Liver Disease in Pregnancy powerpoint presentation.pdf
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About This Presentation
Liver disease in pregnancy
Slide Content
Liver Disease in Liver Disease in
Pregnancy Pregnancy
Luis S. Marsano, MD Luis S. Marsano, MD
Profes
sor of Medicine
Profes
sor of Medicine
Division of Gastroenterolo
gy, Hepatology and Nutrition
Division of Gastroenterolo
gy, Hepatology and Nutrition
University of Louisville, Louisville V
A
MC, and Jewish
University of Louisville, Louisville V
A
MC, and Jewish
Hospital Hospital
Pregnancy Pregnancy
Luis S. Marsano, MD Luis S. Marsano, MD
Profes
sor of Medicine
Profes
sor of Medicine
Division of Gastroenterolo
gy, Hepatology and Nutrition
Division of Gastroenterolo
gy, Hepatology and Nutrition
University of Louisville, Louisville V
A
MC, and Jewish
University of Louisville, Louisville V
A
MC, and Jewish
Hospital Hospital
Contents Contents
¾¾
Dis
eas
es Unique to Pregnancy
Dis
eas
es Unique to Pregnancy
zz
Intrahepatic Cholestasis of Intrahepatic Cholestasis of Pregnancy Pregnancy
zz
Hyperemesis Gravidarum Hyperemesis Gravidarum
zz
HELLP Syndrome HELLP Syndrome
zz
PrePre
--
Ecla
mpsia/Eclampsia
Ecla
mpsia/Eclampsia
zz
Acute fatty liver of Pregnancy Acute fatty liver of Pregnancy
¾¾
Dis
eas
es During Pregnancy
Dis
eas
es During Pregnancy
zz
Gallstone disease Gallstone disease
zz
Viral Hepatitis (A,B,C,D,E,HSV) Viral Hepatitis (A,B,C,D,E,HSV)
zz
Primary Biliary Cirrhosis Primary Biliary Cirrhosis
zz
Primary Sclerosing Cholangitis Primary Sclerosing Cholangitis
zz
AutoAuto
--
Immune Hepatitis
¾¾
Pregnancy in Cirrhosis Pregnancy in Cirrhosis
zz
Esophageal Varices Esophageal Varices
zz
As
cites
As
cites
zz
Hepatic Encephalopathy Hepatic Encephalopathy
zz
Splenic ar
tery aneurism rupture
Splenic ar
tery aneurism rupture
zz
Po
st
Po
st
--
par
tum Uterine Hemor
r
hage
par
tum Uterine Hemor
r
hage
¾¾
Pregnancy after Liver Pregnancy after Liver Trans
plant
Trans
plant
Immune Hepatitis
¾¾
Dis
eas
es Unique to Pregnancy
Dis
eas
es Unique to Pregnancy
zz
Intrahepatic Cholestasis of Intrahepatic Cholestasis of Pregnancy Pregnancy
zz
Hyperemesis Gravidarum Hyperemesis Gravidarum
zz
HELLP Syndrome HELLP Syndrome
zz
PrePre
--
Ecla
mpsia/Eclampsia
Ecla
mpsia/Eclampsia
zz
Acute fatty liver of Pregnancy Acute fatty liver of Pregnancy
¾¾
Dis
eas
es During Pregnancy
Dis
eas
es During Pregnancy
zz
Gallstone disease Gallstone disease
zz
Viral Hepatitis (A,B,C,D,E,HSV) Viral Hepatitis (A,B,C,D,E,HSV)
zz
Primary Biliary Cirrhosis Primary Biliary Cirrhosis
zz
Primary Sclerosing Cholangitis Primary Sclerosing Cholangitis
zz
AutoAuto
--
Immune Hepatitis
¾¾
Pregnancy in Cirrhosis Pregnancy in Cirrhosis
zz
Esophageal Varices Esophageal Varices
zz
As
cites
As
cites
zz
Hepatic Encephalopathy Hepatic Encephalopathy
zz
Splenic ar
tery aneurism rupture
Splenic ar
tery aneurism rupture
zz
Po
st
Po
st
--
par
tum Uterine Hemor
r
hage
par
tum Uterine Hemor
r
hage
¾¾
Pregnancy after Liver Pregnancy after Liver Trans
plant
Trans
plant
Immune Hepatitis
Effects of Pregnancy in Hepatobiliary Effects of Pregnancy in Hepatobiliary
System System
¾¾
Bile compos
ition: cholesterol supersaturation, decreased
Bile compos
ition: cholesterol supersaturation, decreased
chenodexycholic acid. increased cholic acid, and increased bile chenodexycholic acid. increased cholic acid, and increased bile
acid acid
pool. pool.
¾¾
Greater residual GB volume in fa
sting and fed state, with less G
Greater residual GB volume in fa
sting and fed state, with less G
B B
contractibility. Prevalence of GB stones is 2.5 contractibility. Prevalence of GB stones is 2.5
--
12%.12%.
¾¾
Progressive increase in blood volume, with peak at week 30, with Progressive increase in blood volume, with peak at week 30, with 50% greater
volume, due to increased renin, aldosterone, and
50% greater
volume, due to increased renin, aldosterone, and
steroid hormones. steroid hormones.
¾¾
Decreased serum protein concentration by hemodilution; 20% by 2 Decreased serum protein concentration by hemodilution; 20% by 2
ndnd
trimester. Raising AFP. trimester. Raising AFP.
¾¾
Accelerated synthesis of CYP
P450 gene superfamily products,
Accelerated synthesis of CYP
P450 gene superfamily products,
coagulation products, globulins and ceruloplasmin. coagulation products, globulins and ceruloplasmin.
¾¾
Progressive elevation of Alkali
ne phosphatase with peak of 2X UL
Progressive elevation of Alkali
ne phosphatase with peak of 2X UL
N N
by end of pregnancy. by end of pregnancy.
¾¾
GGT normal or slightly decreased. GGT normal or slightly decreased.
¾¾
Spider nevi & palmar erythema in 50% Spider nevi & palmar erythema in 50%
System System
¾¾
Bile compos
ition: cholesterol supersaturation, decreased
Bile compos
ition: cholesterol supersaturation, decreased
chenodexycholic acid. increased cholic acid, and increased bile chenodexycholic acid. increased cholic acid, and increased bile
acid acid
pool. pool.
¾¾
Greater residual GB volume in fa
sting and fed state, with less G
Greater residual GB volume in fa
sting and fed state, with less G
B B
contractibility. Prevalence of GB stones is 2.5 contractibility. Prevalence of GB stones is 2.5
--
12%.12%.
¾¾
Progressive increase in blood volume, with peak at week 30, with Progressive increase in blood volume, with peak at week 30, with 50% greater
volume, due to increased renin, aldosterone, and
50% greater
volume, due to increased renin, aldosterone, and
steroid hormones. steroid hormones.
¾¾
Decreased serum protein concentration by hemodilution; 20% by 2 Decreased serum protein concentration by hemodilution; 20% by 2
ndnd
trimester. Raising AFP. trimester. Raising AFP.
¾¾
Accelerated synthesis of CYP
P450 gene superfamily products,
Accelerated synthesis of CYP
P450 gene superfamily products,
coagulation products, globulins and ceruloplasmin. coagulation products, globulins and ceruloplasmin.
¾¾
Progressive elevation of Alkali
ne phosphatase with peak of 2X UL
Progressive elevation of Alkali
ne phosphatase with peak of 2X UL
N N
by end of pregnancy. by end of pregnancy.
¾¾
GGT normal or slightly decreased. GGT normal or slightly decreased.
¾¾
Spider nevi & palmar erythema in 50% Spider nevi & palmar erythema in 50%
Physiologic changes in Pregnancy Physiologic changes in Pregnancy
TestTest
Effect of Pregnancy Effect of Pregnancy
Bilirubin Bilirubin
Unchanged Unchanged
ALS & AST ALS & AST
Unchanged Unchanged
Prothrombin time Prothrombin time
Unchanged Unchanged
Alkaline phosphatase Alkaline phosphatase
Increase 2 Increase 2
--
4 fold (2 X ULN) (placenta) 4 fold (2 X ULN) (placenta)
Bile acids Bile acids
Increase 2 Increase 2
--
3 fold 3 fold
(glycochol
ate, taurochol
a
te, chenodeoxychol
ate)
(glycochol
ate, taurochol
a
te, chenodeoxychol
ate)
Fibrinogen Fibrinogen
Increases 50% Increases 50%
Globulins Globulins
Increases alpha & beta; Decreases gamma Increases alpha & beta; Decreases gamma
Alpha fetoprotein Alpha fetoprotein
Increases (specially with twins) Increases (specially with twins)
Hemoglobin Hemoglobin
Decrease in late pregnancy Decrease in late pregnancy
Leukocyte count Leukocyte count
Increases Increases
Ceruloplasmin Ceruloplasmin
Increase Increase
Cholesterol Cholesterol
Increases 2 Increases 2
--
foldfold
Triglycerides Triglycerides
Increase Increase
TestTest
Effect of Pregnancy Effect of Pregnancy
Bilirubin Bilirubin
Unchanged Unchanged
ALS & AST ALS & AST
Unchanged Unchanged
Prothrombin time Prothrombin time
Unchanged Unchanged
Alkaline phosphatase Alkaline phosphatase
Increase 2 Increase 2
--
4 fold (2 X ULN) (placenta) 4 fold (2 X ULN) (placenta)
Bile acids Bile acids
Increase 2 Increase 2
--
3 fold 3 fold
(glycochol
ate, taurochol
a
te, chenodeoxychol
ate)
(glycochol
ate, taurochol
a
te, chenodeoxychol
ate)
Fibrinogen Fibrinogen
Increases 50% Increases 50%
Globulins Globulins
Increases alpha & beta; Decreases gamma Increases alpha & beta; Decreases gamma
Alpha fetoprotein Alpha fetoprotein
Increases (specially with twins) Increases (specially with twins)
Hemoglobin Hemoglobin
Decrease in late pregnancy Decrease in late pregnancy
Leukocyte count Leukocyte count
Increases Increases
Ceruloplasmin Ceruloplasmin
Increase Increase
Cholesterol Cholesterol
Increases 2 Increases 2
--
foldfold
Triglycerides Triglycerides
Increase Increase
Timing of Diseases Unique to, Timing of Diseases Unique to,
or Triggered by Pregnancy or Triggered by Pregnancy
Disease Disease
Trimester Trimester
Hyperemesis gravidarum Hyperemesis gravidarum
11
stst
..
Intrahepatic cholestasis of pregnancy Intrahepatic cholestasis of pregnancy
22
ndnd
& 3& 3
rdrd
..
HELLP syndrome HELLP syndrome
Late 2 Late 2
ndnd
& 3& 3
rdrd
..
Preeclampsia Preeclampsia
Late 2 Late 2
ndnd
& 3& 3
rdrd
..
Acute fatty liver of pregnancy Acute fatty liver of pregnancy
33
rdrd
..
BuddBudd
--
Chiari syndrome Chiari syndrome
Post partum Post partum
or Triggered by Pregnancy or Triggered by Pregnancy
Disease Disease
Trimester Trimester
Hyperemesis gravidarum Hyperemesis gravidarum
11
stst
..
Intrahepatic cholestasis of pregnancy Intrahepatic cholestasis of pregnancy
22
ndnd
& 3& 3
rdrd
..
HELLP syndrome HELLP syndrome
Late 2 Late 2
ndnd
& 3& 3
rdrd
..
Preeclampsia Preeclampsia
Late 2 Late 2
ndnd
& 3& 3
rdrd
..
Acute fatty liver of pregnancy Acute fatty liver of pregnancy
33
rdrd
..
BuddBudd
--
Chiari syndrome Chiari syndrome
Post partum Post partum
Hyperemesis Gravidarum (HG) Hyperemesis Gravidarum (HG)
¾¾
Occurs in 0.3% of pregnancies. Occurs in 0.3% of pregnancies.
¾¾
Clinical Features: Clinical Features:
zz
Intractable vomiting in 1 Intractable vomiting in 1
stst
trimester, requiring IV trimester, requiring IV
hydration. hydration.
zz
Starts between 4 Starts between 4
--
10 week of pregnancy and resolves 10 week of pregnancy and resolves
by week 20. In 10% persists until delivery. by week 20. In 10% persists until delivery.
¾¾
Risk factors: Risk factors:
zz
Hyperthyroidism, Hyperthyroidism,
zz
psychiatric illness, psychiatric illness,
zz
molar pregnancy, molar pregnancy,
zz
preexisting diabetes, and preexisting diabetes, and
zz
multiple pregnancies. multiple pregnancies.
¾¾
Occurs in 0.3% of pregnancies. Occurs in 0.3% of pregnancies.
¾¾
Clinical Features: Clinical Features:
zz
Intractable vomiting in 1 Intractable vomiting in 1
stst
trimester, requiring IV trimester, requiring IV
hydration. hydration.
zz
Starts between 4 Starts between 4
--
10 week of pregnancy and resolves 10 week of pregnancy and resolves
by week 20. In 10% persists until delivery. by week 20. In 10% persists until delivery.
¾¾
Risk factors: Risk factors:
zz
Hyperthyroidism, Hyperthyroidism,
zz
psychiatric illness, psychiatric illness,
zz
molar pregnancy, molar pregnancy,
zz
preexisting diabetes, and preexisting diabetes, and
zz
multiple pregnancies. multiple pregnancies.
Hyperemesis Gravidarum (HG) Hyperemesis Gravidarum (HG)
¾¾
Pathogenesis: Immunological, hormonal, and Pathogenesis: Immunological, hormonal, and psychological factors associated with pregnancy may psychological factors associated with pregnancy may play an etiologic role. play an etiologic role.
zz
Increased levels of human chorionic gonadotropin (HCG) in HG Increased levels of human chorionic gonadotropin (HCG) in HG may cause stimulation of
secretory processes of the upper
may cause stimulation of
secretory processes of the upper
gastrointestinal tract and stimul
ation of the thyroid gland.
gastrointestinal tract and stimul
ation of the thyroid gland.
zz
Elevations of estrogen, decreas
es in prolactin levels
, and
Elevations of estrogen, decreas
es in prolactin levels
, and
overactivity of the hypothalamic overactivity of the hypothalamic
--
pituitary pituitary
--
adrenal axis. adrenal axis.
zz
Immune and inflammatory mechanis
ms may als
o
contribute to
Immune and inflammatory mechanis
ms may als
o
contribute to
HG. Increased levels of tumor ne
crosis factor alpha have been
HG. Increased levels of tumor ne
crosis factor alpha have been
observed in HG patients.
Higher levels
of immunoglobulin G
observed in HG patients.
Higher levels
of immunoglobulin G
(IgG), immunoglobulin M (IgM), C3, and C4 lev
e
ls, as well as
(IgG), immunoglobulin M (IgM), C3, and C4 lev
e
ls, as well as
increased lymphoc
yte counts and natural killer and extra
increased lymphoc
yte counts and natural killer and extra
--
thymic thymic
T cell levels have been observed in HG patients. T cell levels have been observed in HG patients.
¾¾
Pathogenesis: Immunological, hormonal, and Pathogenesis: Immunological, hormonal, and psychological factors associated with pregnancy may psychological factors associated with pregnancy may play an etiologic role. play an etiologic role.
zz
Increased levels of human chorionic gonadotropin (HCG) in HG Increased levels of human chorionic gonadotropin (HCG) in HG may cause stimulation of
secretory processes of the upper
may cause stimulation of
secretory processes of the upper
gastrointestinal tract and stimul
ation of the thyroid gland.
gastrointestinal tract and stimul
ation of the thyroid gland.
zz
Elevations of estrogen, decreas
es in prolactin levels
, and
Elevations of estrogen, decreas
es in prolactin levels
, and
overactivity of the hypothalamic overactivity of the hypothalamic
--
pituitary pituitary
--
adrenal axis. adrenal axis.
zz
Immune and inflammatory mechanis
ms may als
o
contribute to
Immune and inflammatory mechanis
ms may als
o
contribute to
HG. Increased levels of tumor ne
crosis factor alpha have been
HG. Increased levels of tumor ne
crosis factor alpha have been
observed in HG patients.
Higher levels
of immunoglobulin G
observed in HG patients.
Higher levels
of immunoglobulin G
(IgG), immunoglobulin M (IgM), C3, and C4 lev
e
ls, as well as
(IgG), immunoglobulin M (IgM), C3, and C4 lev
e
ls, as well as
increased lymphoc
yte counts and natural killer and extra
increased lymphoc
yte counts and natural killer and extra
--
thymic thymic
T cell levels have been observed in HG patients. T cell levels have been observed in HG patients.
Hyperemesis Gravidarum (HG) Hyperemesis Gravidarum (HG)
¾¾
Laboratory: Laboratory:
zz
Liver dysfunction occurs in 50% patients with aminotransferases Liver dysfunction occurs in 50% patients with aminotransferases
up to up to
2020
--
fold elevation (ALT 400 fold elevation (ALT 400
--
1000 U/L) and with occasional jaundice. 1000 U/L) and with occasional jaundice.
zz
Other complications include disturbances in electrolytes and in Other complications include disturbances in electrolytes and in
water water
and acid and acid
--
base balance that can usually be treated adequately with base balance that can usually be treated adequately with
hydration. hydration.
zz
Liver biopsy normal or with bland cholestasis. Needed only to ex Liver biopsy normal or with bland cholestasis. Needed only to ex
clude clude
more serious disease. more serious disease.
¾¾
Effect in Fetus: Not clear. Effect in Fetus: Not clear.
zz
Increased rates of fetal abnormalities including undescended tes Increased rates of fetal abnormalities including undescended tes
ticles, ticles,
hip dysplasia, and Down Syndrome have been reported. hip dysplasia, and Down Syndrome have been reported.
zz
In one large cohort study, infants of HG mothers were found to h In one large cohort study, infants of HG mothers were found to h
ave ave
lower birth weights and higher rates of being small for gestatio lower birth weights and higher rates of being small for gestatio
nal age nal age
¾¾
Laboratory: Laboratory:
zz
Liver dysfunction occurs in 50% patients with aminotransferases Liver dysfunction occurs in 50% patients with aminotransferases
up to up to
2020
--
fold elevation (ALT 400 fold elevation (ALT 400
--
1000 U/L) and with occasional jaundice. 1000 U/L) and with occasional jaundice.
zz
Other complications include disturbances in electrolytes and in Other complications include disturbances in electrolytes and in
water water
and acid and acid
--
base balance that can usually be treated adequately with base balance that can usually be treated adequately with
hydration. hydration.
zz
Liver biopsy normal or with bland cholestasis. Needed only to ex Liver biopsy normal or with bland cholestasis. Needed only to ex
clude clude
more serious disease. more serious disease.
¾¾
Effect in Fetus: Not clear. Effect in Fetus: Not clear.
zz
Increased rates of fetal abnormalities including undescended tes Increased rates of fetal abnormalities including undescended tes
ticles, ticles,
hip dysplasia, and Down Syndrome have been reported. hip dysplasia, and Down Syndrome have been reported.
zz
In one large cohort study, infants of HG mothers were found to h In one large cohort study, infants of HG mothers were found to h
ave ave
lower birth weights and higher rates of being small for gestatio lower birth weights and higher rates of being small for gestatio
nal age nal age
Hyperemesis Gravidarum (HG) Hyperemesis Gravidarum (HG)
¾¾
Treatment: Treatment:
zz
Hospitaliz
ation is necessary fo
r rehydration, nutritional suppor
Hospitaliz
ation is necessary fo
r rehydration, nutritional suppor
t, t,
and symptomatic measures with antiemetics; occasionally and symptomatic measures with antiemetics; occasionally steroids are used. steroids are used.
zz
Eat small, frequent, low Eat small, frequent, low
--
fat meals. fat meals.
zz
NasoNaso
--
jejunal feeding can be very helpful. jejunal feeding can be very helpful.
¾¾
Treatment: Treatment:
zz
Hospitaliz
ation is necessary fo
r rehydration, nutritional suppor
Hospitaliz
ation is necessary fo
r rehydration, nutritional suppor
t, t,
and symptomatic measures with antiemetics; occasionally and symptomatic measures with antiemetics; occasionally steroids are used. steroids are used.
zz
Eat small, frequent, low Eat small, frequent, low
--
fat meals. fat meals.
zz
NasoNaso
--
jejunal feeding can be very helpful. jejunal feeding can be very helpful.
Safety of drugs used in pregnancy Safety of drugs used in pregnancy
--
associated associated
liver diseases liver diseases
(Drug FD
A pregnancy category Comments)
(Drug FD
A pregnancy category Comments)
¾¾
Antiemetics Antiemetics
zz
Promethazine Promethazine
CC
Poss
ible respiratory depres
sion if drug is
Poss
ible respiratory depres
sion if drug is
administered near time of delivery administered near time of delivery
zz
Metoclopramide Metoclopramide
BB
Available evidenc
e suggests safe use during
Available evidenc
e suggests safe use during
pregnancy pregnancy
zz
Ondansetron Ondansetron
BB
Additional studies are needed to determine Additional studies are needed to determine
safety to the fetus, particul
arly during the first trimester
safety to the fetus, particul
arly during the first trimester
zz
Prochlorperazine Prochlorperazine
CC
There are isolated repor
ts of congenital
There are isolated repor
ts of congenital
anomalies; however, some incl
uded exposures to other drugs.
anomalies; however, some incl
uded exposures to other drugs.
Jaundice, extrapyramidal signs, hyper Jaundice, extrapyramidal signs, hyper
--
/hyporeflexes have been /hyporeflexes have been
noted in newborns noted in newborns
From: Lee MN, and Brady CW. World J Gastroenterol
2009 February 28; 15(8): 897-906
--
associated associated
liver diseases liver diseases
(Drug FD
A pregnancy category Comments)
(Drug FD
A pregnancy category Comments)
¾¾
Antiemetics Antiemetics
zz
Promethazine Promethazine
CC
Poss
ible respiratory depres
sion if drug is
Poss
ible respiratory depres
sion if drug is
administered near time of delivery administered near time of delivery
zz
Metoclopramide Metoclopramide
BB
Available evidenc
e suggests safe use during
Available evidenc
e suggests safe use during
pregnancy pregnancy
zz
Ondansetron Ondansetron
BB
Additional studies are needed to determine Additional studies are needed to determine
safety to the fetus, particul
arly during the first trimester
safety to the fetus, particul
arly during the first trimester
zz
Prochlorperazine Prochlorperazine
CC
There are isolated repor
ts of congenital
There are isolated repor
ts of congenital
anomalies; however, some incl
uded exposures to other drugs.
anomalies; however, some incl
uded exposures to other drugs.
Jaundice, extrapyramidal signs, hyper Jaundice, extrapyramidal signs, hyper
--
/hyporeflexes have been /hyporeflexes have been
noted in newborns noted in newborns
From: Lee MN, and Brady CW. World J Gastroenterol
2009 February 28; 15(8): 897-906
Intrahepatic Cholestasis of Pregnancy (ICP) Intrahepatic Cholestasis of Pregnancy (ICP)
¾¾
In USA in 0.1% of pregnanc
ies
;
20% have jaundice.
In USA in 0.1% of pregnanc
ies
;
20% have jaundice.
¾¾
Clinical Features: Clinical Features:
zz
Severe pruritus usually with onset at week 25 or later, generali Severe pruritus usually with onset at week 25 or later, generali
zed, but zed, but
most severe in palms and soles, worse at night. most severe in palms and soles, worse at night.
zz
Only 20% have mild jaundice, us
ually less than 5 mg/dL. Jaundice
Only 20% have mild jaundice, us
ually less than 5 mg/dL. Jaundice
without pruritus is rare. without pruritus is rare.
zz
More common with advanced maternal age & multiparity. More common with advanced maternal age & multiparity.
zz
May have clinical or subclinical steatorrhea that may cause defi May have clinical or subclinical steatorrhea that may cause defi
ciency of ciency of
fat soluble vitamins, specially vit K. fat soluble vitamins, specially vit K.
zz
There is increased risk of gallstone formation. There is increased risk of gallstone formation.
zz
Cholestasis disappears after delivery and recurs in 60 Cholestasis disappears after delivery and recurs in 60
--
70% of 70% of
pregnancies. pregnancies.
zz
If cholestasis does not disappear with delivery, should suspect If cholestasis does not disappear with delivery, should suspect
PBC or PBC or
PSC. PSC.
zz
Cholecystectomy increases risk of recurrence. Have increased ris Cholecystectomy increases risk of recurrence. Have increased ris
k of k of
cholestasis when taking oral contraceptives. cholestasis when taking oral contraceptives.
¾¾
In USA in 0.1% of pregnanc
ies
;
20% have jaundice.
In USA in 0.1% of pregnanc
ies
;
20% have jaundice.
¾¾
Clinical Features: Clinical Features:
zz
Severe pruritus usually with onset at week 25 or later, generali Severe pruritus usually with onset at week 25 or later, generali
zed, but zed, but
most severe in palms and soles, worse at night. most severe in palms and soles, worse at night.
zz
Only 20% have mild jaundice, us
ually less than 5 mg/dL. Jaundice
Only 20% have mild jaundice, us
ually less than 5 mg/dL. Jaundice
without pruritus is rare. without pruritus is rare.
zz
More common with advanced maternal age & multiparity. More common with advanced maternal age & multiparity.
zz
May have clinical or subclinical steatorrhea that may cause defi May have clinical or subclinical steatorrhea that may cause defi
ciency of ciency of
fat soluble vitamins, specially vit K. fat soluble vitamins, specially vit K.
zz
There is increased risk of gallstone formation. There is increased risk of gallstone formation.
zz
Cholestasis disappears after delivery and recurs in 60 Cholestasis disappears after delivery and recurs in 60
--
70% of 70% of
pregnancies. pregnancies.
zz
If cholestasis does not disappear with delivery, should suspect If cholestasis does not disappear with delivery, should suspect
PBC or PBC or
PSC. PSC.
zz
Cholecystectomy increases risk of recurrence. Have increased ris Cholecystectomy increases risk of recurrence. Have increased ris
k of k of
cholestasis when taking oral contraceptives. cholestasis when taking oral contraceptives.
Intrahepatic Cholestasis of Pregnancy (ICP) Intrahepatic Cholestasis of Pregnancy (ICP)
¾¾
Laboratory Features: Laboratory Features:
zz
Have high fasting bile acids, sometimes 100 fold, which correlat Have high fasting bile acids, sometimes 100 fold, which correlat
e with e with
fetal risk. Increase in cholic acid and decrease in chenodeoxych fetal risk. Increase in cholic acid and decrease in chenodeoxych
olic acid olic acid
leads to a marked elevation in the cholic/ chenodeoxycholic acid leads to a marked elevation in the cholic/ chenodeoxycholic acid
ratio. ratio.
The glycine/taurine ratio is also reduced. The glycine/taurine ratio is also reduced.
zz
Bilirubinuria may be present, serum alkaline phosphatase modest
l
Bilirubinuria may be present, serum alkaline phosphatase modest
l
y y
elevated, GGT is normal or marginally high. elevated, GGT is normal or marginally high.
zz
Serum ALT & AST usually mildly elevated, but as high as 1000 U/L Serum ALT & AST usually mildly elevated, but as high as 1000 U/L
or or
more (10 more (10
--
20 X ULN) 20 X ULN)
zz
Liver Bx shows bland cholestasis with none or minimal hepatocell Liver Bx shows bland cholestasis with none or minimal hepatocell
ular ular
necrosis. necrosis.
¾¾
Fetal Risk: Fetal Risk:
zz
Have increased risk of fetal distress, stillbirt
h
and premature
Have increased risk of fetal distress, stillbirt
h
and premature
delivery (up delivery (up
to 60%). to 60%).
zz
Should monitor for placental insufficiency. Should monitor for placental insufficiency.
zz
Fetal or perinatal mortality 0.4 Fetal or perinatal mortality 0.4
--
1.4%. 1.4%.
¾¾
Laboratory Features: Laboratory Features:
zz
Have high fasting bile acids, sometimes 100 fold, which correlat Have high fasting bile acids, sometimes 100 fold, which correlat
e with e with
fetal risk. Increase in cholic acid and decrease in chenodeoxych fetal risk. Increase in cholic acid and decrease in chenodeoxych
olic acid olic acid
leads to a marked elevation in the cholic/ chenodeoxycholic acid leads to a marked elevation in the cholic/ chenodeoxycholic acid
ratio. ratio.
The glycine/taurine ratio is also reduced. The glycine/taurine ratio is also reduced.
zz
Bilirubinuria may be present, serum alkaline phosphatase modest
l
Bilirubinuria may be present, serum alkaline phosphatase modest
l
y y
elevated, GGT is normal or marginally high. elevated, GGT is normal or marginally high.
zz
Serum ALT & AST usually mildly elevated, but as high as 1000 U/L Serum ALT & AST usually mildly elevated, but as high as 1000 U/L
or or
more (10 more (10
--
20 X ULN) 20 X ULN)
zz
Liver Bx shows bland cholestasis with none or minimal hepatocell Liver Bx shows bland cholestasis with none or minimal hepatocell
ular ular
necrosis. necrosis.
¾¾
Fetal Risk: Fetal Risk:
zz
Have increased risk of fetal distress, stillbirt
h
and premature
Have increased risk of fetal distress, stillbirt
h
and premature
delivery (up delivery (up
to 60%). to 60%).
zz
Should monitor for placental insufficiency. Should monitor for placental insufficiency.
zz
Fetal or perinatal mortality 0.4 Fetal or perinatal mortality 0.4
--
1.4%. 1.4%.
Laboratory in ICP Laboratory in ICP
% Abnormal
Mean
Range
Bilirubin
25
2.9
0.4-8.4
Alk. Phosphatase
70
2.4 fold
Nl –
1
2.5 fold
AST
60
119
Nl –
7
36
ALT
55
131
Nl –
1
030
Bile acids
90
47 mcM
Nl –
4
30
Cholic acid
70
17 mcM
Nl -
1
09
% Abnormal
Mean
Range
Bilirubin
25
2.9
0.4-8.4
Alk. Phosphatase
70
2.4 fold
Nl –
1
2.5 fold
AST
60
119
Nl –
7
36
ALT
55
131
Nl –
1
030
Bile acids
90
47 mcM
Nl –
4
30
Cholic acid
70
17 mcM
Nl -
1
09
Intrahepatic Cholestasis of Pregnancy (ICP) Intrahepatic Cholestasis of Pregnancy (ICP)
¾¾
Pathogenesis: Pathogenesis:
Unknown. Unknown.
zz
Most common in Chile and Scand
inavia, and many have family
Most common in Chile and Scand
inavia, and many have family
history of ICP (genetic predis
pos
ition?).
history of ICP (genetic predis
pos
ition?).
zz
More common in winter, and with low serum selenium and More common in winter, and with low serum selenium and selenoenzyme glutathione peroxidase activity (environmental selenoenzyme glutathione peroxidase activity (environmental factors). factors).
zz
Elevated estrogen and/or proges
terone can cause ICP in non
Elevated estrogen and/or proges
terone can cause ICP in non
--
pregnant women, and some patients have impaired pregnant women, and some patients have impaired detoxification by the sulfat
ion pathway (metabolic ?).
detoxification by the sulfat
ion pathway (metabolic ?).
zz
Mutations in the phospholipid tr
anslocator known as the ATP
Mutations in the phospholipid tr
anslocator known as the ATP
--
cassette transporter B4 (ABCB4) or
multidrug resistant protein
cassette transporter B4 (ABCB4) or
multidrug resistant protein
--
3 3
(MDR
3) are associated with 15% of cases of ICP.
(MDR
3) are associated with 15% of cases of ICP.
zz
Increased fetal death may be due to bile acid mediated Increased fetal death may be due to bile acid mediated vasospasm of placental vessels
, causing asphyxia.
vasospasm of placental vessels
, causing asphyxia.
¾¾
Pathogenesis: Pathogenesis:
Unknown. Unknown.
zz
Most common in Chile and Scand
inavia, and many have family
Most common in Chile and Scand
inavia, and many have family
history of ICP (genetic predis
pos
ition?).
history of ICP (genetic predis
pos
ition?).
zz
More common in winter, and with low serum selenium and More common in winter, and with low serum selenium and selenoenzyme glutathione peroxidase activity (environmental selenoenzyme glutathione peroxidase activity (environmental factors). factors).
zz
Elevated estrogen and/or proges
terone can cause ICP in non
Elevated estrogen and/or proges
terone can cause ICP in non
--
pregnant women, and some patients have impaired pregnant women, and some patients have impaired detoxification by the sulfat
ion pathway (metabolic ?).
detoxification by the sulfat
ion pathway (metabolic ?).
zz
Mutations in the phospholipid tr
anslocator known as the ATP
Mutations in the phospholipid tr
anslocator known as the ATP
--
cassette transporter B4 (ABCB4) or
multidrug resistant protein
cassette transporter B4 (ABCB4) or
multidrug resistant protein
--
3 3
(MDR
3) are associated with 15% of cases of ICP.
(MDR
3) are associated with 15% of cases of ICP.
zz
Increased fetal death may be due to bile acid mediated Increased fetal death may be due to bile acid mediated vasospasm of placental vessels
, causing asphyxia.
vasospasm of placental vessels
, causing asphyxia.
Intrahepatic Cholestasis of Pregnancy (ICP) Intrahepatic Cholestasis of Pregnancy (ICP) ¾¾
Management: Management:
zz
Mother: Mother:
palliative. palliative.
••
UDCA 20 UDCA 20
--
25 mg/kg helps itching by changing bile acid 25 mg/kg helps itching by changing bile acid
content in maternal serum, and amniotic fluid, and also content in maternal serum, and amniotic fluid, and also increasing placental bile acid transport. Also decreases bile increasing placental bile acid transport. Also decreases bile acids in the fetus. acids in the fetus.
••
Exogenous progesterone must be discontinue. Exogenous progesterone must be discontinue.
••
Cholestyramine 8 Cholestyramine 8
--
24 g/d may help, but worsens steatorrhea 24 g/d may help, but worsens steatorrhea
and fat and fat
--
soluble vitamin deficienc
y; does not help the fetus.
soluble vitamin deficienc
y; does not help the fetus.
••
SAMe has mixed therapeutic results. SAMe has mixed therapeutic results.
••
Ultraviolet B light may also help. Ultraviolet B light may also help.
Management: Management:
zz
Mother: Mother:
palliative. palliative.
••
UDCA 20 UDCA 20
--
25 mg/kg helps itching by changing bile acid 25 mg/kg helps itching by changing bile acid
content in maternal serum, and amniotic fluid, and also content in maternal serum, and amniotic fluid, and also increasing placental bile acid transport. Also decreases bile increasing placental bile acid transport. Also decreases bile acids in the fetus. acids in the fetus.
••
Exogenous progesterone must be discontinue. Exogenous progesterone must be discontinue.
••
Cholestyramine 8 Cholestyramine 8
--
24 g/d may help, but worsens steatorrhea 24 g/d may help, but worsens steatorrhea
and fat and fat
--
soluble vitamin deficienc
y; does not help the fetus.
soluble vitamin deficienc
y; does not help the fetus.
••
SAMe has mixed therapeutic results. SAMe has mixed therapeutic results.
••
Ultraviolet B light may also help. Ultraviolet B light may also help.
Intrahepatic Cholestasis of Pregnancy (ICP) Intrahepatic Cholestasis of Pregnancy (ICP) ¾¾
Management: Management:
zz
Fetus: Fetus:
••
Close monitoring for chronic placental ins
u
fficiency.
Close monitoring for chronic placental ins
u
fficiency.
••
Fetal complications correlate wi
th maternal bile acid (BA)
Fetal complications correlate wi
th maternal bile acid (BA)
levels. levels.
••
Premature deliv
e
ry, asphyxial
events, and
meconium staining
Premature deliv
e
ry, asphyxial
events, and
meconium staining
occur only in the 19% of ca
ses with maternal BA levels
occur only in the 19% of ca
ses with maternal BA levels
greater than 40 mol/L. greater than 40 mol/L.
••
Delivery of baby as soon as is mature. Delivery of baby as soon as is mature.
••
Dexamethasone (12 mg/day for 7 days) has been use to Dexamethasone (12 mg/day for 7 days) has been use to promote fetal lung maturity. promote fetal lung maturity.
Management: Management:
zz
Fetus: Fetus:
••
Close monitoring for chronic placental ins
u
fficiency.
Close monitoring for chronic placental ins
u
fficiency.
••
Fetal complications correlate wi
th maternal bile acid (BA)
Fetal complications correlate wi
th maternal bile acid (BA)
levels. levels.
••
Premature deliv
e
ry, asphyxial
events, and
meconium staining
Premature deliv
e
ry, asphyxial
events, and
meconium staining
occur only in the 19% of ca
ses with maternal BA levels
occur only in the 19% of ca
ses with maternal BA levels
greater than 40 mol/L. greater than 40 mol/L.
••
Delivery of baby as soon as is mature. Delivery of baby as soon as is mature.
••
Dexamethasone (12 mg/day for 7 days) has been use to Dexamethasone (12 mg/day for 7 days) has been use to promote fetal lung maturity. promote fetal lung maturity.
Safety of drugs used in pregnancy Safety of drugs used in pregnancy
--
associated associated
liver diseases liver diseases
(Drug FD
A pregnancy category Comments)
(Drug FD
A pregnancy category Comments)
¾¾
Intrahepatic cholestasis Intrahepatic cholestasis
zz
Ursodeoxycholic
acid
Ursodeoxycholic
acid
BB
Relatively low risk Relatively low risk
zz
SS
--
adenosyl adenosyl
--
LL
--
methionine methionine
Not evaluated by FDA
Relatively low
Not evaluated by FDA
Relatively low
riskrisk
zz
Cholestyramine Cholestyramine
CC
Cholestyramine is not absorbed Cholestyramine is not absorbed
systemically
,
but may interfere with vitamin absorption
systemically
,
but may interfere with vitamin absorption
From: Lee MN, and Brady CW. World J Gastroenterol
2009 February 28; 15(8): 897-906
--
associated associated
liver diseases liver diseases
(Drug FD
A pregnancy category Comments)
(Drug FD
A pregnancy category Comments)
¾¾
Intrahepatic cholestasis Intrahepatic cholestasis
zz
Ursodeoxycholic
acid
Ursodeoxycholic
acid
BB
Relatively low risk Relatively low risk
zz
SS
--
adenosyl adenosyl
--
LL
--
methionine methionine
Not evaluated by FDA
Relatively low
Not evaluated by FDA
Relatively low
riskrisk
zz
Cholestyramine Cholestyramine
CC
Cholestyramine is not absorbed Cholestyramine is not absorbed
systemically
,
but may interfere with vitamin absorption
systemically
,
but may interfere with vitamin absorption
From: Lee MN, and Brady CW. World J Gastroenterol
2009 February 28; 15(8): 897-906
Preeclampsia & Eclampsia Preeclampsia & Eclampsia
¾¾
Hy
pertens
ion, edema & proteinuria in late 2
Hy
pertens
ion, edema & proteinuria in late 2
ndnd
, or
3
, or
3
rdrd
trimester. trimester.
¾¾
Occurs in 3 Occurs in 3
--
10% of pregnanc
ies.
10% of pregnanc
ies.
¾¾
Hypertension: Hypertension:
zz
systolic pressure greater
than 1
40 mmHg and a diastolic pressure
systolic pressure greater
than 1
40 mmHg and a diastolic pressure
greater
than
greater
than
90 mmHg 90 mmHg
zz
on at least two occa
sion
s that
are at least 4 to 6 h apart
on at least two occa
sion
s that
are at least 4 to 6 h apart
zz
in a previously normotensive patient, after
the 20
in a previously normotensive patient, after
the 20
thth
week of pregnancy week of pregnancy
zz
BP should be measured in a sitt
ing position for
ambulatory patie
BP should be measured in a sitt
ing position for
ambulatory patie
nts or in a semi nts or in a semi
--
reclining position for
hospita
lized patients, with the
reclining position for
hospita
lized patients, with the
right ar
m being in a roughly
right ar
m being in a roughly
horizontal position at hear
t level.
horizontal position at hear
t level.
¾¾
Proteinuria: Proteinuria:
equal to or greater than 300 mg of protein in a 24 h equal to or greater than 300 mg of protein in a 24 h
urine collection, or 1+ protein
or greater on urine dipstick tes
urine collection, or 1+ protein
or greater on urine dipstick tes
ting of ting of
two random urine samples collec
ted at least 4 to 6 h apart.
two random urine samples collec
ted at least 4 to 6 h apart.
¾¾
Eclampsia: Eclampsia:
preeclamps
ia + neurologic symptoms such as
preeclamps
ia + neurologic symptoms such as
headaches, visual disturbances, and seiz
ures or coma.
headaches, visual disturbances, and seiz
ures or coma.
¾¾
Hy
pertens
ion, edema & proteinuria in late 2
Hy
pertens
ion, edema & proteinuria in late 2
ndnd
, or
3
, or
3
rdrd
trimester. trimester.
¾¾
Occurs in 3 Occurs in 3
--
10% of pregnanc
ies.
10% of pregnanc
ies.
¾¾
Hypertension: Hypertension:
zz
systolic pressure greater
than 1
40 mmHg and a diastolic pressure
systolic pressure greater
than 1
40 mmHg and a diastolic pressure
greater
than
greater
than
90 mmHg 90 mmHg
zz
on at least two occa
sion
s that
are at least 4 to 6 h apart
on at least two occa
sion
s that
are at least 4 to 6 h apart
zz
in a previously normotensive patient, after
the 20
in a previously normotensive patient, after
the 20
thth
week of pregnancy week of pregnancy
zz
BP should be measured in a sitt
ing position for
ambulatory patie
BP should be measured in a sitt
ing position for
ambulatory patie
nts or in a semi nts or in a semi
--
reclining position for
hospita
lized patients, with the
reclining position for
hospita
lized patients, with the
right ar
m being in a roughly
right ar
m being in a roughly
horizontal position at hear
t level.
horizontal position at hear
t level.
¾¾
Proteinuria: Proteinuria:
equal to or greater than 300 mg of protein in a 24 h equal to or greater than 300 mg of protein in a 24 h
urine collection, or 1+ protein
or greater on urine dipstick tes
urine collection, or 1+ protein
or greater on urine dipstick tes
ting of ting of
two random urine samples collec
ted at least 4 to 6 h apart.
two random urine samples collec
ted at least 4 to 6 h apart.
¾¾
Eclampsia: Eclampsia:
preeclamps
ia + neurologic symptoms such as
preeclamps
ia + neurologic symptoms such as
headaches, visual disturbances, and seiz
ures or coma.
headaches, visual disturbances, and seiz
ures or coma.
Preeclampsia & Eclampsia Preeclampsia & Eclampsia
¾¾
Risk factors Risk factors
nulliparity, extremes of maternal age, nulliparity, extremes of maternal age,
insulin resistance, obesity, and infection. insulin resistance, obesity, and infection.
¾¾
Liver involvement is infrequent. Indicates severe Liver involvement is infrequent. Indicates severe preeclampsia with significant perinatal morbidity and preeclampsia with significant perinatal morbidity and mortality. mortality.
¾¾
Is the commonest cause of hepatic tenderness without Is the commonest cause of hepatic tenderness without hepatomegaly, and liver dysfunction in pregnancy. hepatomegaly, and liver dysfunction in pregnancy.
¾¾
Laboratory: Laboratory:
zz
Aminotransferases are variable, from mild to 10 Aminotransferases are variable, from mild to 10
--
fold to 20 fold to 20
--
fold fold
elevations. elevations.
zz
Bilirubin is usually less than 5 mg/dL Bilirubin is usually less than 5 mg/dL
zz
May be complicated by HELLP Syndrome. May be complicated by HELLP Syndrome.
¾¾
Risk factors Risk factors
nulliparity, extremes of maternal age, nulliparity, extremes of maternal age,
insulin resistance, obesity, and infection. insulin resistance, obesity, and infection.
¾¾
Liver involvement is infrequent. Indicates severe Liver involvement is infrequent. Indicates severe preeclampsia with significant perinatal morbidity and preeclampsia with significant perinatal morbidity and mortality. mortality.
¾¾
Is the commonest cause of hepatic tenderness without Is the commonest cause of hepatic tenderness without hepatomegaly, and liver dysfunction in pregnancy. hepatomegaly, and liver dysfunction in pregnancy.
¾¾
Laboratory: Laboratory:
zz
Aminotransferases are variable, from mild to 10 Aminotransferases are variable, from mild to 10
--
fold to 20 fold to 20
--
fold fold
elevations. elevations.
zz
Bilirubin is usually less than 5 mg/dL Bilirubin is usually less than 5 mg/dL
zz
May be complicated by HELLP Syndrome. May be complicated by HELLP Syndrome.
Preeclampsia & Eclampsia Preeclampsia & Eclampsia
¾¾
Liver histology: Liver histology:
hepatic sinusoidal deposition of fibrin hepatic sinusoidal deposition of fibrin
along with periportal hemorrhage, liver cell necrosis, and along with periportal hemorrhage, liver cell necrosis, and in severe cases, infarction; these changes are likely due in severe cases, infarction; these changes are likely due to vasoconstriction of hepatic vasculature. Microvesicular to vasoconstriction of hepatic vasculature. Microvesicular fatty infiltration has also been observed in some cases of fatty infiltration has also been observed in some cases of preeclampsia, suggesting a possible overlap with acute preeclampsia, suggesting a possible overlap with acute fatty liver of pregnancy fatty liver of pregnancy
¾¾
Pathophysiology: Pathophysiology:
procoagulant and pro procoagulant and pro
--
inflammatory inflammatory
states that create glomerular endotheliosis, increased states that create glomerular endotheliosis, increased vascular permeability, and a systemic inflammatory vascular permeability, and a systemic inflammatory response that results in end response that results in end
--
organ damage and organ damage and
hypoperfusion. hypoperfusion.
¾¾
Liver histology: Liver histology:
hepatic sinusoidal deposition of fibrin hepatic sinusoidal deposition of fibrin
along with periportal hemorrhage, liver cell necrosis, and along with periportal hemorrhage, liver cell necrosis, and in severe cases, infarction; these changes are likely due in severe cases, infarction; these changes are likely due to vasoconstriction of hepatic vasculature. Microvesicular to vasoconstriction of hepatic vasculature. Microvesicular fatty infiltration has also been observed in some cases of fatty infiltration has also been observed in some cases of preeclampsia, suggesting a possible overlap with acute preeclampsia, suggesting a possible overlap with acute fatty liver of pregnancy fatty liver of pregnancy
¾¾
Pathophysiology: Pathophysiology:
procoagulant and pro procoagulant and pro
--
inflammatory inflammatory
states that create glomerular endotheliosis, increased states that create glomerular endotheliosis, increased vascular permeability, and a systemic inflammatory vascular permeability, and a systemic inflammatory response that results in end response that results in end
--
organ damage and organ damage and
hypoperfusion. hypoperfusion.
Preeclampsia & Eclampsia Preeclampsia & Eclampsia
¾¾
Maternal mortality: Maternal mortality:
zz
rare in developed countries; rare in developed countries;
zz
up to 15% up to 15%
--
20% in developing countries. 20% in developing countries.
¾¾
Fetal mortality rate is rare, occurring in 1% Fetal mortality rate is rare, occurring in 1%
--
2% of births. 2% of births.
¾¾
Maternal and neonatal morbidity may include: Maternal and neonatal morbidity may include:
zz
placental abruption, placental abruption,
zz
preterm delivery, preterm delivery,
zz
fetal growth restriction or fetal growth restriction or
zz
maternal renal failure pulmonary edema, or cerebrovascular accid maternal renal failure pulmonary edema, or cerebrovascular accid
ent.ent.
¾¾
Maternal mortality: Maternal mortality:
zz
rare in developed countries; rare in developed countries;
zz
up to 15% up to 15%
--
20% in developing countries. 20% in developing countries.
¾¾
Fetal mortality rate is rare, occurring in 1% Fetal mortality rate is rare, occurring in 1%
--
2% of births. 2% of births.
¾¾
Maternal and neonatal morbidity may include: Maternal and neonatal morbidity may include:
zz
placental abruption, placental abruption,
zz
preterm delivery, preterm delivery,
zz
fetal growth restriction or fetal growth restriction or
zz
maternal renal failure pulmonary edema, or cerebrovascular accid maternal renal failure pulmonary edema, or cerebrovascular accid
ent.ent.
Preeclampsia & Eclampsia Preeclampsia & Eclampsia
¾¾
Treatment for preeclampsia is delivery of the fetus and Treatment for preeclampsia is delivery of the fetus and placenta. placenta.
¾¾
If mild preeclampsia is evident before fetal lung maturity If mild preeclampsia is evident before fetal lung maturity at 36 wk gestation, consider expectant management with at 36 wk gestation, consider expectant management with intensive monitoring. intensive monitoring.
¾¾
Pharmacological agents used in preeclampsia include Pharmacological agents used in preeclampsia include
zz
antihy
pertensives such as
calcium channel blockers and
antihy
pertensives such as
calcium channel blockers and
zz
lowlow
--
dose aspirin. dose aspirin.
¾¾
Magnesium sulfate may be administered if eclampsia Magnesium sulfate may be administered if eclampsia develops. develops.
¾¾
Treatment for preeclampsia is delivery of the fetus and Treatment for preeclampsia is delivery of the fetus and placenta. placenta.
¾¾
If mild preeclampsia is evident before fetal lung maturity If mild preeclampsia is evident before fetal lung maturity at 36 wk gestation, consider expectant management with at 36 wk gestation, consider expectant management with intensive monitoring. intensive monitoring.
¾¾
Pharmacological agents used in preeclampsia include Pharmacological agents used in preeclampsia include
zz
antihy
pertensives such as
calcium channel blockers and
antihy
pertensives such as
calcium channel blockers and
zz
lowlow
--
dose aspirin. dose aspirin.
¾¾
Magnesium sulfate may be administered if eclampsia Magnesium sulfate may be administered if eclampsia develops. develops.
HELLP Syndrome HELLP Syndrome
¾¾
Severe preeclampsia is complicated by HELLP Severe preeclampsia is complicated by HELLP Syndrome in 2% Syndrome in 2%
--
12% of cases (0.2% 12% of cases (0.2%
--
0.6% of all 0.6% of all
pregnancies). pregnancies).
¾¾
Diagnostic criteria: Diagnostic criteria:
zz
HH
: Abnormal smear (microangiopathy),
LDH > 600 U/L, High
: Abnormal smear (microangiopathy),
LDH > 600 U/L, High
Indirect Bilirubin Indirect Bilirubin
zz
ELEL
: AST > 70 U/L,
(AST/ALT elevation up to 10
: AST > 70 U/L,
(AST/ALT elevation up to 10
--
20 fold) 20 fold)
zz
LPLP
: plat < 150,000; : plat < 150,000;
••
Class 1: <
50K,
Class 1: <
50K,
••
Class 2: 50 Class 2: 50
--
99K, 99K,
••
Class 3: 100 Class 3: 100
--
149K) 149K)
¾¾
Severe preeclampsia is complicated by HELLP Severe preeclampsia is complicated by HELLP Syndrome in 2% Syndrome in 2%
--
12% of cases (0.2% 12% of cases (0.2%
--
0.6% of all 0.6% of all
pregnancies). pregnancies).
¾¾
Diagnostic criteria: Diagnostic criteria:
zz
HH
: Abnormal smear (microangiopathy),
LDH > 600 U/L, High
: Abnormal smear (microangiopathy),
LDH > 600 U/L, High
Indirect Bilirubin Indirect Bilirubin
zz
ELEL
: AST > 70 U/L,
(AST/ALT elevation up to 10
: AST > 70 U/L,
(AST/ALT elevation up to 10
--
20 fold) 20 fold)
zz
LPLP
: plat < 150,000; : plat < 150,000;
••
Class 1: <
50K,
Class 1: <
50K,
••
Class 2: 50 Class 2: 50
--
99K, 99K,
••
Class 3: 100 Class 3: 100
--
149K) 149K)
HELLP Syndrome HELLP Syndrome
¾¾
Symptoms: Symptoms:
zz
Epigas
tric and/or RUQ abdomin
al pain and tenderness, nausea
Epigas
tric and/or RUQ abdomin
al pain and tenderness, nausea
and vomiting, malaise, headache, edema and weight gain, and vomiting, malaise, headache, edema and weight gain, hypertens
ion, and proteinuria;
hypertens
ion, and proteinuria;
zz
Less commonly renal failure (with increased uric acid), diabetes Less commonly renal failure (with increased uric acid), diabetes ins
ipidus, and antiphospholipid syndrome.
ins
ipidus, and antiphospholipid syndrome.
zz
Late findings include Late findings include
intravascular coagulopathy (DIC), intravascular coagulopathy (DIC),
pulmonary pulmonary
edema, placental abrupti
on, and retinal detachment.
edema, placental abrupti
on, and retinal detachment.
zz
Jaundice is uncommon (5%); T. bili < 5 mg/dL unless has Jaundice is uncommon (5%); T. bili < 5 mg/dL unless has massive liver necrosis massive liver necrosis
zz
Some patients have no obvious preeclamps
ia
Some patients have no obvious preeclamps
ia
¾¾
Symptoms: Symptoms:
zz
Epigas
tric and/or RUQ abdomin
al pain and tenderness, nausea
Epigas
tric and/or RUQ abdomin
al pain and tenderness, nausea
and vomiting, malaise, headache, edema and weight gain, and vomiting, malaise, headache, edema and weight gain, hypertens
ion, and proteinuria;
hypertens
ion, and proteinuria;
zz
Less commonly renal failure (with increased uric acid), diabetes Less commonly renal failure (with increased uric acid), diabetes ins
ipidus, and antiphospholipid syndrome.
ins
ipidus, and antiphospholipid syndrome.
zz
Late findings include Late findings include
intravascular coagulopathy (DIC), intravascular coagulopathy (DIC),
pulmonary pulmonary
edema, placental abrupti
on, and retinal detachment.
edema, placental abrupti
on, and retinal detachment.
zz
Jaundice is uncommon (5%); T. bili < 5 mg/dL unless has Jaundice is uncommon (5%); T. bili < 5 mg/dL unless has massive liver necrosis massive liver necrosis
zz
Some patients have no obvious preeclamps
ia
Some patients have no obvious preeclamps
ia
HELLP Syndrome HELLP Syndrome
¾¾
Most patients present between 27 and 36 weeks Most patients present between 27 and 36 weeks
’’
gestation, but 25% gestation, but 25%
present in postpartum period. present in postpartum period.
¾¾
HELLP is commoner in white pat
ients, multiparous, and
older
HELLP is commoner in white pat
ients, multiparous, and
older
patients but can occur with any parity and age. patients but can occur with any parity and age.
¾¾
Pathogenesis: Pathogenesis:
zz
alterations in platelet activation, alterations in platelet activation,
zz
increa
se
in proinfla
mmatory cytokines,
increa
se
in proinfla
mmatory cytokines,
zz
segmental vasospasm with
vascular endothelial damage.
segmental vasospasm with
vascular endothelial damage.
zz
association with a defect in long association with a defect in long
--
chain 3 chain 3
--
hydroxyacyl hydroxyacyl
--
coe
n
zyme A
coe
n
zyme A
dehydrogenase (LCHAD)
has been described.
dehydrogenase (LCHAD)
has been described.
¾¾
Families with known Fatty Acid Oxidation (FAO)
deficiencies have
Families with known Fatty Acid Oxidation (FAO)
deficiencies have
shown a high incidence of HELLP, but
babies of mothers with
shown a high incidence of HELLP, but
babies of mothers with
HELLP do not have a proven increased risk of FAO deficiencies. HELLP do not have a proven increased risk of FAO deficiencies.
¾¾
Most patients present between 27 and 36 weeks Most patients present between 27 and 36 weeks
’’
gestation, but 25% gestation, but 25%
present in postpartum period. present in postpartum period.
¾¾
HELLP is commoner in white pat
ients, multiparous, and
older
HELLP is commoner in white pat
ients, multiparous, and
older
patients but can occur with any parity and age. patients but can occur with any parity and age.
¾¾
Pathogenesis: Pathogenesis:
zz
alterations in platelet activation, alterations in platelet activation,
zz
increa
se
in proinfla
mmatory cytokines,
increa
se
in proinfla
mmatory cytokines,
zz
segmental vasospasm with
vascular endothelial damage.
segmental vasospasm with
vascular endothelial damage.
zz
association with a defect in long association with a defect in long
--
chain 3 chain 3
--
hydroxyacyl hydroxyacyl
--
coe
n
zyme A
coe
n
zyme A
dehydrogenase (LCHAD)
has been described.
dehydrogenase (LCHAD)
has been described.
¾¾
Families with known Fatty Acid Oxidation (FAO)
deficiencies have
Families with known Fatty Acid Oxidation (FAO)
deficiencies have
shown a high incidence of HELLP, but
babies of mothers with
shown a high incidence of HELLP, but
babies of mothers with
HELLP do not have a proven increased risk of FAO deficiencies. HELLP do not have a proven increased risk of FAO deficiencies.
Clinical Characteristics of Clinical Characteristics of
HELLP Syndrome HELLP Syndrome
Symptoms, Signs, & Symptoms, Signs, &
Complications Complications
%%
RUQ/Epigastric Pain RUQ/Epigastric Pain
6565
Nausea & Vomiting Nausea & Vomiting
3636
Headache Headache
3131
Bleeding Bleeding
99
Jaundice Jaundice
55
Disseminated Intravasc Disseminated Intravasc CoagCoag
2121
Abruptio placentae Abruptio placentae
1616
Acute Kidney Injury Acute Kidney Injury
88
Hepatic hematoma Hepatic hematoma
11
Death Death
11
Laboratory Findings Laboratory Findings
% Ab
nl
% Ab
nl
Median Median
Ra
nge
Ra
nge
ALTALT
100100
239239
4949
--
700*700*
ASTAST
9999
250250
7070
--
630*630*
T. Bilirubin T. Bilirubin
4242
1.51.5
0.50.5
--
2525
Platelets Platelets
100100
5757
77
--
9999
Am J Obstet Gynecol 169:1000; 1993
*
A
ST up to 2300, ALT up to
700 have been reported
HELLP Syndrome HELLP Syndrome
Symptoms, Signs, & Symptoms, Signs, &
Complications Complications
%%
RUQ/Epigastric Pain RUQ/Epigastric Pain
6565
Nausea & Vomiting Nausea & Vomiting
3636
Headache Headache
3131
Bleeding Bleeding
99
Jaundice Jaundice
55
Disseminated Intravasc Disseminated Intravasc CoagCoag
2121
Abruptio placentae Abruptio placentae
1616
Acute Kidney Injury Acute Kidney Injury
88
Hepatic hematoma Hepatic hematoma
11
Death Death
11
Laboratory Findings Laboratory Findings
% Ab
nl
% Ab
nl
Median Median
Ra
nge
Ra
nge
ALTALT
100100
239239
4949
--
700*700*
ASTAST
9999
250250
7070
--
630*630*
T. Bilirubin T. Bilirubin
4242
1.51.5
0.50.5
--
2525
Platelets Platelets
100100
5757
77
--
9999
Am J Obstet Gynecol 169:1000; 1993
*
A
ST up to 2300, ALT up to
700 have been reported
HELLP Syndrome HELLP Syndrome
¾¾
Computed tomography or MRI of
the liver may show subcapsular
Computed tomography or MRI of
the liver may show subcapsular
hematomas, intraparenchymal hemo
rrhage, or infarction or hepatic
hematomas, intraparenchymal hemo
rrhage, or infarction or hepatic
rupture (thrombocytopenia of less than 20,000). rupture (thrombocytopenia of less than 20,000).
¾¾
Management: Management:
zz
Hospitalize for
antepar
tum stab
ilization of hyper
tension, manage
Hospitalize for
antepar
tum stab
ilization of hyper
tension, manage
ment of DIC, ment of DIC,
seizure prophylaxis, and
fetal monitoring.
seizure prophylaxis, and
fetal monitoring.
zz
Transfer to a tertiary ca
re center
if possible.
Transfer to a tertiary ca
re center
if possible.
zz
Obtain hepatic computed tomography (limited views). Obtain hepatic computed tomography (limited views).
zz
If fetus greater
than 34 weeks
If fetus greater
than 34 weeks
’’
gestation or
if there is a
ny evidence of multiorgan
gestation or
if there is a
ny evidence of multiorgan
dysfunction, DIC, renal failure,
abruptio placentae, or
fetal di
dysfunction, DIC, renal failure,
abruptio placentae, or
fetal di
stress, here is stress, here is
consensus that immediate
delivery should be effected.
consensus that immediate
delivery should be effected.
zz
If fetus < 34 weeks and case is m
ild, give IV betamethasone or
d
If fetus < 34 weeks and case is m
ild, give IV betamethasone or
d
examethasone examethasone
for 24 for 24
--
48 h before deli
v
e
r
y.
48 h before deli
v
e
r
y.
zz
WellWell
--
established labor
should be allow
ed to proceed in the absence of
established labor
should be allow
ed to proceed in the absence of
obstetric obstetric
complications or
DIC, but many patients (40%
complications or
DIC, but many patients (40%
--
50%)
will require caesarean
50%)
will require caesarean
section. section.
¾¾
Computed tomography or MRI of
the liver may show subcapsular
Computed tomography or MRI of
the liver may show subcapsular
hematomas, intraparenchymal hemo
rrhage, or infarction or hepatic
hematomas, intraparenchymal hemo
rrhage, or infarction or hepatic
rupture (thrombocytopenia of less than 20,000). rupture (thrombocytopenia of less than 20,000).
¾¾
Management: Management:
zz
Hospitalize for
antepar
tum stab
ilization of hyper
tension, manage
Hospitalize for
antepar
tum stab
ilization of hyper
tension, manage
ment of DIC, ment of DIC,
seizure prophylaxis, and
fetal monitoring.
seizure prophylaxis, and
fetal monitoring.
zz
Transfer to a tertiary ca
re center
if possible.
Transfer to a tertiary ca
re center
if possible.
zz
Obtain hepatic computed tomography (limited views). Obtain hepatic computed tomography (limited views).
zz
If fetus greater
than 34 weeks
If fetus greater
than 34 weeks
’’
gestation or
if there is a
ny evidence of multiorgan
gestation or
if there is a
ny evidence of multiorgan
dysfunction, DIC, renal failure,
abruptio placentae, or
fetal di
dysfunction, DIC, renal failure,
abruptio placentae, or
fetal di
stress, here is stress, here is
consensus that immediate
delivery should be effected.
consensus that immediate
delivery should be effected.
zz
If fetus < 34 weeks and case is m
ild, give IV betamethasone or
d
If fetus < 34 weeks and case is m
ild, give IV betamethasone or
d
examethasone examethasone
for 24 for 24
--
48 h before deli
v
e
r
y.
48 h before deli
v
e
r
y.
zz
WellWell
--
established labor
should be allow
ed to proceed in the absence of
established labor
should be allow
ed to proceed in the absence of
obstetric obstetric
complications or
DIC, but many patients (40%
complications or
DIC, but many patients (40%
--
50%)
will require caesarean
50%)
will require caesarean
section. section.
HELLP Syndrome HELLP Syndrome
¾¾
Maternal mortality f
r
om HELLP is 1%.
Maternal mortality f
r
om HELLP is 1%.
¾¾
Perinatal mortality rate ranges from 7% Perinatal mortality rate ranges from 7%
--
22% and may be due to 22% and may be due to
premature detachment of placenta, intrauterine asphyxia, and premature detachment of placenta, intrauterine asphyxia, and prematurity. prematurity.
¾¾
Liv
e
r transplantation need is ra
re: persisting bleeding from a
Liv
e
r transplantation need is ra
re: persisting bleeding from a
hematoma or hepatic rupture or
li
ver failure from extens
ive necr
hematoma or hepatic rupture or
li
ver failure from extens
ive necr
os
is
.
os
is
.
¾¾
Hepatic hemorrhage without rupture is managed conservatively
in
Hepatic hemorrhage without rupture is managed conservatively
in
a a
hemodynamically stable patient with close hemodynamic monitoring hemodynamically stable patient with close hemodynamic monitoring in an intensive care unit: in an intensive care unit:
zz
correction of coagulopathy, correction of coagulopathy,
zz
avoid all trauma: abdominal palpa
tion, convulsions, emesis, unne
avoid all trauma: abdominal palpa
tion, convulsions, emesis, unne
cessar
y
cessar
y
transportation. transportation.
zz
immediate availability of large
volume transfusion of blood prod
immediate availability of large
volume transfusion of blood prod
ucts, ucts,
zz
immediate intervention for
ruptur
e or
rapid expansion of hematom
immediate intervention for
ruptur
e or
rapid expansion of hematom
a, on a, on
diagnostic hepatic imaging. diagnostic hepatic imaging.
¾¾
Maternal mortality f
r
om HELLP is 1%.
Maternal mortality f
r
om HELLP is 1%.
¾¾
Perinatal mortality rate ranges from 7% Perinatal mortality rate ranges from 7%
--
22% and may be due to 22% and may be due to
premature detachment of placenta, intrauterine asphyxia, and premature detachment of placenta, intrauterine asphyxia, and prematurity. prematurity.
¾¾
Liv
e
r transplantation need is ra
re: persisting bleeding from a
Liv
e
r transplantation need is ra
re: persisting bleeding from a
hematoma or hepatic rupture or
li
ver failure from extens
ive necr
hematoma or hepatic rupture or
li
ver failure from extens
ive necr
os
is
.
os
is
.
¾¾
Hepatic hemorrhage without rupture is managed conservatively
in
Hepatic hemorrhage without rupture is managed conservatively
in
a a
hemodynamically stable patient with close hemodynamic monitoring hemodynamically stable patient with close hemodynamic monitoring in an intensive care unit: in an intensive care unit:
zz
correction of coagulopathy, correction of coagulopathy,
zz
avoid all trauma: abdominal palpa
tion, convulsions, emesis, unne
avoid all trauma: abdominal palpa
tion, convulsions, emesis, unne
cessar
y
cessar
y
transportation. transportation.
zz
immediate availability of large
volume transfusion of blood prod
immediate availability of large
volume transfusion of blood prod
ucts, ucts,
zz
immediate intervention for
ruptur
e or
rapid expansion of hematom
immediate intervention for
ruptur
e or
rapid expansion of hematom
a, on a, on
diagnostic hepatic imaging. diagnostic hepatic imaging.
HELLP Syndrome HELLP Syndrome
¾¾
Hepatic rupture mortality is 50%, with 10 Hepatic rupture mortality is 50%, with 10
--
60% perinatal 60% perinatal
mortality. mortality.
¾¾
BuddBudd
--
Chiari syndrome can occur with HELLP syndrome. Chiari syndrome can occur with HELLP syndrome.
¾¾
Recurrence: Recurrence:
44
--
19%. Subsequent pregnancies in 19%. Subsequent pregnancies in
patients with HELLP syndrome carry a high risk of patients with HELLP syndrome carry a high risk of complications: complications:
zz
prepre
--
eclamps
ia,
eclamps
ia,
zz
recurrent HELLP, recurrent HELLP,
zz
prematurity, prematurity,
zz
intrauterine growth retardation, intrauterine growth retardation,
zz
abruptio plac
entae,
abruptio plac
entae,
zz
No long No long
--
term effect
on renal function has been noted.
term effect
on renal function has been noted.
¾¾
Hepatic rupture mortality is 50%, with 10 Hepatic rupture mortality is 50%, with 10
--
60% perinatal 60% perinatal
mortality. mortality.
¾¾
BuddBudd
--
Chiari syndrome can occur with HELLP syndrome. Chiari syndrome can occur with HELLP syndrome.
¾¾
Recurrence: Recurrence:
44
--
19%. Subsequent pregnancies in 19%. Subsequent pregnancies in
patients with HELLP syndrome carry a high risk of patients with HELLP syndrome carry a high risk of complications: complications:
zz
prepre
--
eclamps
ia,
eclamps
ia,
zz
recurrent HELLP, recurrent HELLP,
zz
prematurity, prematurity,
zz
intrauterine growth retardation, intrauterine growth retardation,
zz
abruptio plac
entae,
abruptio plac
entae,
zz
No long No long
--
term effect
on renal function has been noted.
term effect
on renal function has been noted.
Safety of drugs used in pregnancy Safety of drugs used in pregnancy
--
associated liver associated liver
diseases diseases
(Drug FDA pregnancy category Comments) (Drug FDA pregnancy category Comments)
¾¾
Antihypertensives Antihypertensives
zz
ACE inhibitors ACE inhibitors
C/DC/D
First trimester exposure to ACE inhibitors First trimester exposure to ACE inhibitors
may cause major congenital ma
lformations. Second and third
may cause major congenital ma
lformations. Second and third
trimester use of an ACE inhibitor is associated with trimester use of an ACE inhibitor is associated with oligohydramnios and anuria, hypot
ension, renal failure, skull
oligohydramnios and anuria, hypot
ension, renal failure, skull
hypoplasia, and death
in the fetus/neonate
hypoplasia, and death
in the fetus/neonate
zz
Beta blockers Beta blockers
C/DC/D
Fetal bradycardia, hypotension, risk of Fetal bradycardia, hypotension, risk of
intrauterine growth retardation intrauterine growth retardation
zz
Calcium channel blockers Calcium channel blockers
CC
Teratogenic and embryotoxic Teratogenic and embryotoxic
effects have been demons
trated in small animals. There are no
effects have been demons
trated in small animals. There are no
adequate and well adequate and well
--
controlled studies in pregnant women controlled studies in pregnant women
From: Lee MN, and Brady CW. World J Gastroenterol
2009 February 28; 15(8)
: 897-906
--
associated liver associated liver
diseases diseases
(Drug FDA pregnancy category Comments) (Drug FDA pregnancy category Comments)
¾¾
Antihypertensives Antihypertensives
zz
ACE inhibitors ACE inhibitors
C/DC/D
First trimester exposure to ACE inhibitors First trimester exposure to ACE inhibitors
may cause major congenital ma
lformations. Second and third
may cause major congenital ma
lformations. Second and third
trimester use of an ACE inhibitor is associated with trimester use of an ACE inhibitor is associated with oligohydramnios and anuria, hypot
ension, renal failure, skull
oligohydramnios and anuria, hypot
ension, renal failure, skull
hypoplasia, and death
in the fetus/neonate
hypoplasia, and death
in the fetus/neonate
zz
Beta blockers Beta blockers
C/DC/D
Fetal bradycardia, hypotension, risk of Fetal bradycardia, hypotension, risk of
intrauterine growth retardation intrauterine growth retardation
zz
Calcium channel blockers Calcium channel blockers
CC
Teratogenic and embryotoxic Teratogenic and embryotoxic
effects have been demons
trated in small animals. There are no
effects have been demons
trated in small animals. There are no
adequate and well adequate and well
--
controlled studies in pregnant women controlled studies in pregnant women
From: Lee MN, and Brady CW. World J Gastroenterol
2009 February 28; 15(8)
: 897-906
Safety of drugs used in pregnancy Safety of drugs used in pregnancy
--
associated associated
liver diseases liver diseases
(Drug FD
A pregnancy category Comments)
(Drug FD
A pregnancy category Comments)
¾¾
Anticoagulation Anticoagulation
zz
Aspirin Aspirin
CC
(1st/2nd trimesters) (1st/2nd trimesters)
DD
(3rd trimester). Adverse effects (3rd trimester). Adverse effects
in the fetus include intrauterine growth retardation, salicylate in the fetus include intrauterine growth retardation, salicylate intoxic
a
tion, bleeding abnormali
ties, and neonatal acidos
is. Use
intoxic
a
tion, bleeding abnormali
ties, and neonatal acidos
is. Use
of aspirin close to deliv
e
ry may cause premature closure of the
of aspirin close to deliv
e
ry may cause premature closure of the
ductus arteriosus. Data have shown low ductus arteriosus. Data have shown low
--
dos
e aspirin (60
dos
e aspirin (60
--
150 150
mg/day) may be safe in pregnancy mg/day) may be safe in pregnancy
zz
Enoxaparin Enoxaparin
BB
No adequate and well No adequate and well
--
controlled studies using controlled studies using
enoxaparin. Postmarketing reports include congenital enoxaparin. Postmarketing reports include congenital abnormalities and als
o
fetal death
abnormalities and als
o
fetal death
zz
Heparin Heparin
CC
Does not cross the placenta Does not cross the placenta
From: Lee MN, and Brady CW. World J Gastroenterol
2009 February 28; 15(8): 897-906
--
associated associated
liver diseases liver diseases
(Drug FD
A pregnancy category Comments)
(Drug FD
A pregnancy category Comments)
¾¾
Anticoagulation Anticoagulation
zz
Aspirin Aspirin
CC
(1st/2nd trimesters) (1st/2nd trimesters)
DD
(3rd trimester). Adverse effects (3rd trimester). Adverse effects
in the fetus include intrauterine growth retardation, salicylate in the fetus include intrauterine growth retardation, salicylate intoxic
a
tion, bleeding abnormali
ties, and neonatal acidos
is. Use
intoxic
a
tion, bleeding abnormali
ties, and neonatal acidos
is. Use
of aspirin close to deliv
e
ry may cause premature closure of the
of aspirin close to deliv
e
ry may cause premature closure of the
ductus arteriosus. Data have shown low ductus arteriosus. Data have shown low
--
dos
e aspirin (60
dos
e aspirin (60
--
150 150
mg/day) may be safe in pregnancy mg/day) may be safe in pregnancy
zz
Enoxaparin Enoxaparin
BB
No adequate and well No adequate and well
--
controlled studies using controlled studies using
enoxaparin. Postmarketing reports include congenital enoxaparin. Postmarketing reports include congenital abnormalities and als
o
fetal death
abnormalities and als
o
fetal death
zz
Heparin Heparin
CC
Does not cross the placenta Does not cross the placenta
From: Lee MN, and Brady CW. World J Gastroenterol
2009 February 28; 15(8): 897-906
Acute Fatty Liver of Pregnancy Acute Fatty Liver of Pregnancy
¾¾
Sudden, catastrophic illness with hepatic failure, Sudden, catastrophic illness with hepatic failure, manifested as coagulopathy and hepatic manifested as coagulopathy and hepatic encephalopathy, in a pregnant woman without known encephalopathy, in a pregnant woman without known liver disease, liver biopsy sh
owing microvesicular fatty
liver disease, liver biopsy sh
owing microvesicular fatty
infiltration. infiltration.
¾¾
Occurs in the third trimester of pregnancy (wk 34 Occurs in the third trimester of pregnancy (wk 34
--
37). 37).
Rarely occurs after delivery. Rarely occurs after delivery.
¾¾
Incidence of 1 in 10 000 to 1 in 15000 pregnancies. Incidence of 1 in 10 000 to 1 in 15000 pregnancies.
¾¾
Maternal mortality rate of 18% and a fetal mortality rate Maternal mortality rate of 18% and a fetal mortality rate of 23%. of 23%.
¾¾
AFLP is more commonly seen in nulliparous (40 AFLP is more commonly seen in nulliparous (40
--
50%) 50%)
women and with twin or multiple gestation. women and with twin or multiple gestation.
¾¾
Sudden, catastrophic illness with hepatic failure, Sudden, catastrophic illness with hepatic failure, manifested as coagulopathy and hepatic manifested as coagulopathy and hepatic encephalopathy, in a pregnant woman without known encephalopathy, in a pregnant woman without known liver disease, liver biopsy sh
owing microvesicular fatty
liver disease, liver biopsy sh
owing microvesicular fatty
infiltration. infiltration.
¾¾
Occurs in the third trimester of pregnancy (wk 34 Occurs in the third trimester of pregnancy (wk 34
--
37). 37).
Rarely occurs after delivery. Rarely occurs after delivery.
¾¾
Incidence of 1 in 10 000 to 1 in 15000 pregnancies. Incidence of 1 in 10 000 to 1 in 15000 pregnancies.
¾¾
Maternal mortality rate of 18% and a fetal mortality rate Maternal mortality rate of 18% and a fetal mortality rate of 23%. of 23%.
¾¾
AFLP is more commonly seen in nulliparous (40 AFLP is more commonly seen in nulliparous (40
--
50%) 50%)
women and with twin or multiple gestation. women and with twin or multiple gestation.
Acute Fatty Liver of Pregnancy Acute Fatty Liver of Pregnancy
¾¾
Presentation: Presentation:
from asymptomatic to fulminant liver from asymptomatic to fulminant liver
failure. failure.
zz
Typical patient has 1 to 2
weeks of anorexia, nausea and
Typical patient has 1 to 2
weeks of anorexia, nausea and
vomiting, headache, and right upper quadrant pain, and is ill vomiting, headache, and right upper quadrant pain, and is ill
--
look
ing with jaundice, hypertens
ion, edema, ascites, a small
look
ing with jaundice, hypertens
ion, edema, ascites, a small
liver, and hepatic encephalopathy
. Pruritus may be an early
liver, and hepatic encephalopathy
. Pruritus may be an early
symptom. symptom.
zz
Intrauterine death may occur. Intrauterine death may occur.
zz
About 50% (21 About 50% (21
--
64%) of patients with AFLP have preeclampsia, 64%) of patients with AFLP have preeclampsia,
and there is some overlap with the HELLP syndrome. and there is some overlap with the HELLP syndrome.
zz
The fetus ratio male:female is 2.7:1 The fetus ratio male:female is 2.7:1
¾¾
Presentation: Presentation:
from asymptomatic to fulminant liver from asymptomatic to fulminant liver
failure. failure.
zz
Typical patient has 1 to 2
weeks of anorexia, nausea and
Typical patient has 1 to 2
weeks of anorexia, nausea and
vomiting, headache, and right upper quadrant pain, and is ill vomiting, headache, and right upper quadrant pain, and is ill
--
look
ing with jaundice, hypertens
ion, edema, ascites, a small
look
ing with jaundice, hypertens
ion, edema, ascites, a small
liver, and hepatic encephalopathy
. Pruritus may be an early
liver, and hepatic encephalopathy
. Pruritus may be an early
symptom. symptom.
zz
Intrauterine death may occur. Intrauterine death may occur.
zz
About 50% (21 About 50% (21
--
64%) of patients with AFLP have preeclampsia, 64%) of patients with AFLP have preeclampsia,
and there is some overlap with the HELLP syndrome. and there is some overlap with the HELLP syndrome.
zz
The fetus ratio male:female is 2.7:1 The fetus ratio male:female is 2.7:1
Acute Fatty Liver of Pregnancy Acute Fatty Liver of Pregnancy
¾¾
Laboratory: Laboratory:
zz
ALT & AST from near ALT & AST from near
--
normal to 1000, usuall
y about 300 to 500; as
normal to 1000, usuall
y about 300 to 500; as
high as 1300 high as 1300
zz
high ammonia high ammonia
zz
bilirubin usually less than 5mg/
dL but higher in severe or
bilirubin usually less than 5mg/
dL but higher in severe or
complicated diseas
e (
e
levated
in 98%, up to 36 mg/dL)
complicated diseas
e (
e
levated
in 98%, up to 36 mg/dL)
zz
hypoglycemia in 25% hypoglycemia in 25%
zz
hyperuricemia in 81%
(up to 18.5 mg/dL)
hyperuricemia in 81%
(up to 18.5 mg/dL)
zz
normochromic,
normocytic anemia,
normochromic,
normocytic anemia,
zz
high white blood cell count in 97%,
high white blood cell count in 97%,
zz
normal to low platelets (low in 86%, as low as 5000), normal to low platelets (low in 86%, as low as 5000),
zz
coagulopathy with or without DIC
,
coagulopathy with or without DIC
,
zz
metabolic acidosis, metabolic acidosis,
zz
renal dysfunction (often progressi
ng to oliguric renal failure)
renal dysfunction (often progressi
ng to oliguric renal failure)
in 75%, in 75%,
zz
biochemical pancreatitis in 33% biochemical pancreatitis in 33%
¾¾
Laboratory: Laboratory:
zz
ALT & AST from near ALT & AST from near
--
normal to 1000, usuall
y about 300 to 500; as
normal to 1000, usuall
y about 300 to 500; as
high as 1300 high as 1300
zz
high ammonia high ammonia
zz
bilirubin usually less than 5mg/
dL but higher in severe or
bilirubin usually less than 5mg/
dL but higher in severe or
complicated diseas
e (
e
levated
in 98%, up to 36 mg/dL)
complicated diseas
e (
e
levated
in 98%, up to 36 mg/dL)
zz
hypoglycemia in 25% hypoglycemia in 25%
zz
hyperuricemia in 81%
(up to 18.5 mg/dL)
hyperuricemia in 81%
(up to 18.5 mg/dL)
zz
normochromic,
normocytic anemia,
normochromic,
normocytic anemia,
zz
high white blood cell count in 97%,
high white blood cell count in 97%,
zz
normal to low platelets (low in 86%, as low as 5000), normal to low platelets (low in 86%, as low as 5000),
zz
coagulopathy with or without DIC
,
coagulopathy with or without DIC
,
zz
metabolic acidosis, metabolic acidosis,
zz
renal dysfunction (often progressi
ng to oliguric renal failure)
renal dysfunction (often progressi
ng to oliguric renal failure)
in 75%, in 75%,
zz
biochemical pancreatitis in 33% biochemical pancreatitis in 33%
Acute Fatty Liver of Pregnancy Acute Fatty Liver of Pregnancy
¾¾
Definitive diagnosis Definitive diagnosis
: is histological; : is histological;
zz
frozen tissue stained with oil frozen tissue stained with oil
--
red O shows mic
r
ovesicular fatty
red O shows mic
r
ovesicular fatty
infiltration (free fatty acids)
predominantly in zone 3 with lob
infiltration (free fatty acids)
predominantly in zone 3 with lob
ular
ular
dis
a
rray and mild portal inflammation with cholestasis .
dis
a
rray and mild portal inflammation with cholestasis .
zz
Occasionally the histologic
al picture, cannot be differentiated
Occasionally the histologic
al picture, cannot be differentiated
from viral hepatitis or preeclampsia. from viral hepatitis or preeclampsia.
¾¾
Presumptive diagnosis Presumptive diagnosis
: :
zz
In presence of coagulopathy precl
uding biopsy, the diagnosis is
In presence of coagulopathy precl
uding biopsy, the diagnosis is
made on compatible clinical an
d laboratory features, and the
made on compatible clinical an
d laboratory features, and the
need for expeditious therapy. need for expeditious therapy.
zz
Imaging studies, including ultrasound and computed tomography Imaging studies, including ultrasound and computed tomography (CT), are incons
istent in detecting fatty infiltration.
(CT), are incons
istent in detecting fatty infiltration.
¾¾
Definitive diagnosis Definitive diagnosis
: is histological; : is histological;
zz
frozen tissue stained with oil frozen tissue stained with oil
--
red O shows mic
r
ovesicular fatty
red O shows mic
r
ovesicular fatty
infiltration (free fatty acids)
predominantly in zone 3 with lob
infiltration (free fatty acids)
predominantly in zone 3 with lob
ular
ular
dis
a
rray and mild portal inflammation with cholestasis .
dis
a
rray and mild portal inflammation with cholestasis .
zz
Occasionally the histologic
al picture, cannot be differentiated
Occasionally the histologic
al picture, cannot be differentiated
from viral hepatitis or preeclampsia. from viral hepatitis or preeclampsia.
¾¾
Presumptive diagnosis Presumptive diagnosis
: :
zz
In presence of coagulopathy precl
uding biopsy, the diagnosis is
In presence of coagulopathy precl
uding biopsy, the diagnosis is
made on compatible clinical an
d laboratory features, and the
made on compatible clinical an
d laboratory features, and the
need for expeditious therapy. need for expeditious therapy.
zz
Imaging studies, including ultrasound and computed tomography Imaging studies, including ultrasound and computed tomography (CT), are incons
istent in detecting fatty infiltration.
(CT), are incons
istent in detecting fatty infiltration.
Acute Fatty Liver of Pregnancy Acute Fatty Liver of Pregnancy
¾¾
Etiology: Etiology:
It is unknown. It is unknown.
zz
LCHAD (long chain 3 LCHAD (long chain 3
--
hydroxyacyl hydroxyacyl
--
CoA dehydrogenase deficiency) has CoA dehydrogenase deficiency) has
been identified in about 20% of babies of mothers with AFLP. been identified in about 20% of babies of mothers with AFLP.
zz
Maternal heterozygosity for LCHAD deficiency may reduce the mate Maternal heterozygosity for LCHAD deficiency may reduce the mate
rnal rnal
capacity to oxidize long capacity to oxidize long
--
chain fatty acids both in liver and placenta, and chain fatty acids both in liver and placenta, and
this, together with the metabolic stress of pregnancy and fetal this, together with the metabolic stress of pregnancy and fetal homozygosity for LCHAD deficiency, may causes accumulation in th homozygosity for LCHAD deficiency, may causes accumulation in th
e e
maternal circulation of potentia
lly hepatotoxic LCHAD metabolite
maternal circulation of potentia
lly hepatotoxic LCHAD metabolite
s. s.
zz
Even with a normal maternal genotype, a fetus with at least one Even with a normal maternal genotype, a fetus with at least one G1528C or E474Q mutation causing LCHAD, can produce AFLP in the G1528C or E474Q mutation causing LCHAD, can produce AFLP in the mother. mother.
zz
Carnitine palmitoyltransferase I deficiency has been associated Carnitine palmitoyltransferase I deficiency has been associated
with with
AFLP. AFLP.
zz
Prenat
al diagnosis can be done by chorionic villous sampling.
Prenat
al diagnosis can be done by chorionic villous sampling.
zz
Perhaps external factors, such as carnitine deficiency or other Perhaps external factors, such as carnitine deficiency or other
dietary dietary
factors, exacerbate this situation. factors, exacerbate this situation.
¾¾
Etiology: Etiology:
It is unknown. It is unknown.
zz
LCHAD (long chain 3 LCHAD (long chain 3
--
hydroxyacyl hydroxyacyl
--
CoA dehydrogenase deficiency) has CoA dehydrogenase deficiency) has
been identified in about 20% of babies of mothers with AFLP. been identified in about 20% of babies of mothers with AFLP.
zz
Maternal heterozygosity for LCHAD deficiency may reduce the mate Maternal heterozygosity for LCHAD deficiency may reduce the mate
rnal rnal
capacity to oxidize long capacity to oxidize long
--
chain fatty acids both in liver and placenta, and chain fatty acids both in liver and placenta, and
this, together with the metabolic stress of pregnancy and fetal this, together with the metabolic stress of pregnancy and fetal homozygosity for LCHAD deficiency, may causes accumulation in th homozygosity for LCHAD deficiency, may causes accumulation in th
e e
maternal circulation of potentia
lly hepatotoxic LCHAD metabolite
maternal circulation of potentia
lly hepatotoxic LCHAD metabolite
s. s.
zz
Even with a normal maternal genotype, a fetus with at least one Even with a normal maternal genotype, a fetus with at least one G1528C or E474Q mutation causing LCHAD, can produce AFLP in the G1528C or E474Q mutation causing LCHAD, can produce AFLP in the mother. mother.
zz
Carnitine palmitoyltransferase I deficiency has been associated Carnitine palmitoyltransferase I deficiency has been associated
with with
AFLP. AFLP.
zz
Prenat
al diagnosis can be done by chorionic villous sampling.
Prenat
al diagnosis can be done by chorionic villous sampling.
zz
Perhaps external factors, such as carnitine deficiency or other Perhaps external factors, such as carnitine deficiency or other
dietary dietary
factors, exacerbate this situation. factors, exacerbate this situation.
Acute Fatty Liver of Pregnancy Acute Fatty Liver of Pregnancy
¾¾
Management: Management:
zz
delivery of the fetus. delivery of the fetus.
zz
many laboratory abnormalities may persist after delivery and many laboratory abnormalities may persist after delivery and may initially worsen during the first postpartum week. may initially worsen during the first postpartum week.
zz
rarely patients progress to fulminant hepatic failure needing li rarely patients progress to fulminant hepatic failure needing li
ver ver
transplantation. transplantation.
zz
infant should be watched for risk
of cardiomyopathy, neuropathy,
infant should be watched for risk
of cardiomyopathy, neuropathy,
myopathy, non myopathy, non
--
ketotic hypoglycemia, hepatic failure, and death ketotic hypoglycemia, hepatic failure, and death
associated with fatty acid ox
idation defects in newborns.
associated with fatty acid ox
idation defects in newborns.
zz
affected patients should be scre
ened for defects in fatty acid
affected patients should be scre
ened for defects in fatty acid
oxidation as recurrence in s
ubsequent children is 25%, and
oxidation as recurrence in s
ubsequent children is 25%, and
recurrence of AFLP in mothers is also possible. recurrence of AFLP in mothers is also possible.
zz
mother, father and child should
be tested for LCHAD (G1528C
or
mother, father and child should
be tested for LCHAD (G1528C
or
E474Q), and Carnitine palmito
yltransferase
I de
ficiency
E474Q), and Carnitine palmito
yltransferase
I de
ficiency
¾¾
Management: Management:
zz
delivery of the fetus. delivery of the fetus.
zz
many laboratory abnormalities may persist after delivery and many laboratory abnormalities may persist after delivery and may initially worsen during the first postpartum week. may initially worsen during the first postpartum week.
zz
rarely patients progress to fulminant hepatic failure needing li rarely patients progress to fulminant hepatic failure needing li
ver ver
transplantation. transplantation.
zz
infant should be watched for risk
of cardiomyopathy, neuropathy,
infant should be watched for risk
of cardiomyopathy, neuropathy,
myopathy, non myopathy, non
--
ketotic hypoglycemia, hepatic failure, and death ketotic hypoglycemia, hepatic failure, and death
associated with fatty acid ox
idation defects in newborns.
associated with fatty acid ox
idation defects in newborns.
zz
affected patients should be scre
ened for defects in fatty acid
affected patients should be scre
ened for defects in fatty acid
oxidation as recurrence in s
ubsequent children is 25%, and
oxidation as recurrence in s
ubsequent children is 25%, and
recurrence of AFLP in mothers is also possible. recurrence of AFLP in mothers is also possible.
zz
mother, father and child should
be tested for LCHAD (G1528C
or
mother, father and child should
be tested for LCHAD (G1528C
or
E474Q), and Carnitine palmito
yltransferase
I de
ficiency
E474Q), and Carnitine palmito
yltransferase
I de
ficiency
Acute Fatty Liver of Pregnancy Acute Fatty Liver of Pregnancy
¾¾
Evolution & Prognosis : Evolution & Prognosis :
zz
patients are better
managed in an ICU with liv
er failure experti
patients are better
managed in an ICU with liv
er failure experti
se
.
se
.
zz
most patients improve in 1 to 4 weeks postpartum, most patients improve in 1 to 4 weeks postpartum,
zz
a cholestatic phase with rising
bilirubin and alkaline phosphata
a cholestatic phase with rising
bilirubin and alkaline phosphata
se se
may persist. may persist.
zz
recovery can occur in days or
be delayed for months but is
recovery can occur in days or
be delayed for months but is
complete with no signs of chronic liver dis
eas
e.
complete with no signs of chronic liver dis
eas
e.
zz
With good supportive management, the maternal mortality is With good supportive management, the maternal mortality is now 7% now 7%
--
18% and fetal mortality 9% 18% and fetal mortality 9%
--
23%. 23%.
zz
infectious and bleeding complic
a
tions remain the most life
infectious and bleeding complic
a
tions remain the most life
threatening threatening
¾¾
Evolution & Prognosis : Evolution & Prognosis :
zz
patients are better
managed in an ICU with liv
er failure experti
patients are better
managed in an ICU with liv
er failure experti
se
.
se
.
zz
most patients improve in 1 to 4 weeks postpartum, most patients improve in 1 to 4 weeks postpartum,
zz
a cholestatic phase with rising
bilirubin and alkaline phosphata
a cholestatic phase with rising
bilirubin and alkaline phosphata
se se
may persist. may persist.
zz
recovery can occur in days or
be delayed for months but is
recovery can occur in days or
be delayed for months but is
complete with no signs of chronic liver dis
eas
e.
complete with no signs of chronic liver dis
eas
e.
zz
With good supportive management, the maternal mortality is With good supportive management, the maternal mortality is now 7% now 7%
--
18% and fetal mortality 9% 18% and fetal mortality 9%
--
23%. 23%.
zz
infectious and bleeding complic
a
tions remain the most life
infectious and bleeding complic
a
tions remain the most life
threatening threatening
ICPICP
HGHG
PE/EPE/E
HELLP HELLP
AFLPAFLP
% Preg % Preg
0.10.1
0.30.3
33
--
1010
0.20.2
--
0.60.6
0.005 0.005
--
0.010.01
Onset Onset
2525
--
32 w32 w
44
--
10 w10 w
After 20 w After 20 w
2727
--
36 w36 w
3434
--
37 W37 W
Fam. Hx Fam. Hx
Often Often
NoNo
NoNo
NoNo
Occa
sio
nal
Occa
sio
nal
PrePre
--
eclamp eclamp
NoNo
NoNo
Ye
s
Ye
s
Ye
s
Ye
s
50%50%
Clinical Clinical
Features Features
Pruri
tus, hi
gh
Pruri
tus, hi
gh
bile acids bile acids
Nausea/ Nausea/ vomi
ting
vomi
ting
H
B
P, edema
H
B
P, edema
proteinuria proteinuria
Hemolysi
s, l
o
w
Hemolysi
s, l
o
w
pl
at, high Liver
pl
at, high Liver
enzymes enzymes
ALF, coagulop ALF, coagulop hi
gh amm
o
nia
hi
gh amm
o
nia
& uric aci
d
& uric aci
d
AST & AST &
ALTALT
Mild Mild
--
20X20X
Normal Normal
--
20X20X
Normal Normal
--
20X20X
Mild Mild
--
20X20X
Mild Mild
--
1000 1000
UU
Bilirubin Bilirubin
< 5 mg/dL < 5 mg/dL
Occasional Occasional
< 5 mg/dL < 5 mg/dL
< 5 mg/dL < 5 mg/dL
< 5 (up to 25) < 5 (up to 25)
< 5 (up to 25) < 5 (up to 25)
Maternal Maternal mortality mortality
00
RareRare
Rare (15 Rare (15
--
20% 20%
in 3in 3
rdrd
W)W)
11
--
25 %25 %
77
--
18 %18 %
Fetal/perin Fetal/perin
mortality mortality
0.40.4
--
1.2 % 1.2 %
RareRare
11
--
2 %2 %
44
--
19 %19 %
99
--
23%23%
HGHG
PE/EPE/E
HELLP HELLP
AFLPAFLP
% Preg % Preg
0.10.1
0.30.3
33
--
1010
0.20.2
--
0.60.6
0.005 0.005
--
0.010.01
Onset Onset
2525
--
32 w32 w
44
--
10 w10 w
After 20 w After 20 w
2727
--
36 w36 w
3434
--
37 W37 W
Fam. Hx Fam. Hx
Often Often
NoNo
NoNo
NoNo
Occa
sio
nal
Occa
sio
nal
PrePre
--
eclamp eclamp
NoNo
NoNo
Ye
s
Ye
s
Ye
s
Ye
s
50%50%
Clinical Clinical
Features Features
Pruri
tus, hi
gh
Pruri
tus, hi
gh
bile acids bile acids
Nausea/ Nausea/ vomi
ting
vomi
ting
H
B
P, edema
H
B
P, edema
proteinuria proteinuria
Hemolysi
s, l
o
w
Hemolysi
s, l
o
w
pl
at, high Liver
pl
at, high Liver
enzymes enzymes
ALF, coagulop ALF, coagulop hi
gh amm
o
nia
hi
gh amm
o
nia
& uric aci
d
& uric aci
d
AST & AST &
ALTALT
Mild Mild
--
20X20X
Normal Normal
--
20X20X
Normal Normal
--
20X20X
Mild Mild
--
20X20X
Mild Mild
--
1000 1000
UU
Bilirubin Bilirubin
< 5 mg/dL < 5 mg/dL
Occasional Occasional
< 5 mg/dL < 5 mg/dL
< 5 mg/dL < 5 mg/dL
< 5 (up to 25) < 5 (up to 25)
< 5 (up to 25) < 5 (up to 25)
Maternal Maternal mortality mortality
00
RareRare
Rare (15 Rare (15
--
20% 20%
in 3in 3
rdrd
W)W)
11
--
25 %25 %
77
--
18 %18 %
Fetal/perin Fetal/perin
mortality mortality
0.40.4
--
1.2 % 1.2 %
RareRare
11
--
2 %2 %
44
--
19 %19 %
99
--
23%23%
Gallstone Disease Gallstone Disease
¾¾
Biliary sludge and gallstones is
associated with parity. Stones
Biliary sludge and gallstones is
associated with parity. Stones
or or
sludge develop by the postpartu
m period in 10% of pregnanc
ies
.
sludge develop by the postpartu
m period in 10% of pregnanc
ies
.
¾¾
Prevalence of gallstones in pregnancy is: Prevalence of gallstones in pregnancy is:
zz
18.4% 18.4%
--
19.3% in m
u
lti
parous women and
19.3% in m
u
lti
parous women and
zz
6.9%6.9%
--
8.4% in nulliparous women. 8.4% in nulliparous women.
zz
Symptomatic stones in 0.1 Symptomatic stones in 0.1
--
0.3% of pregnancies 0.3% of pregnancies
¾¾
Etiology for biliary sludge and gallstones in pregnancy is Etiology for biliary sludge and gallstones in pregnancy is multifactorial: multifactorial:
zz
Increased estrogen leve
ls, especially in t
he second and third tr
Increased estrogen leve
ls, especially in t
he second and third tr
imesters, lead
to increased
imesters, lead
to increased
cholesterol secretion and
supersaturation of bile
cholesterol secretion and
supersaturation of bile
zz
increased progesterone levels cause
a decrease in small intestin
increased progesterone levels cause
a decrease in small intestin
al motility al motility
zz
fasting and postprandial gallb
ladder volume
s are larger
fasting and postprandial gallb
ladder volume
s are larger
zz
gallbladder emptying
time is reduced.
gallbladder emptying
time is reduced.
¾¾
The large residual volume of supersaturated bile in the pregnant The large residual volume of supersaturated bile in the pregnant woman leads to biliary sludge and
the formation of gallstones.
woman leads to biliary sludge and
the formation of gallstones.
¾¾
Biliary sludge and gallstones is
associated with parity. Stones
Biliary sludge and gallstones is
associated with parity. Stones
or or
sludge develop by the postpartu
m period in 10% of pregnanc
ies
.
sludge develop by the postpartu
m period in 10% of pregnanc
ies
.
¾¾
Prevalence of gallstones in pregnancy is: Prevalence of gallstones in pregnancy is:
zz
18.4% 18.4%
--
19.3% in m
u
lti
parous women and
19.3% in m
u
lti
parous women and
zz
6.9%6.9%
--
8.4% in nulliparous women. 8.4% in nulliparous women.
zz
Symptomatic stones in 0.1 Symptomatic stones in 0.1
--
0.3% of pregnancies 0.3% of pregnancies
¾¾
Etiology for biliary sludge and gallstones in pregnancy is Etiology for biliary sludge and gallstones in pregnancy is multifactorial: multifactorial:
zz
Increased estrogen leve
ls, especially in t
he second and third tr
Increased estrogen leve
ls, especially in t
he second and third tr
imesters, lead
to increased
imesters, lead
to increased
cholesterol secretion and
supersaturation of bile
cholesterol secretion and
supersaturation of bile
zz
increased progesterone levels cause
a decrease in small intestin
increased progesterone levels cause
a decrease in small intestin
al motility al motility
zz
fasting and postprandial gallb
ladder volume
s are larger
fasting and postprandial gallb
ladder volume
s are larger
zz
gallbladder emptying
time is reduced.
gallbladder emptying
time is reduced.
¾¾
The large residual volume of supersaturated bile in the pregnant The large residual volume of supersaturated bile in the pregnant woman leads to biliary sludge and
the formation of gallstones.
woman leads to biliary sludge and
the formation of gallstones.
Gallstone Disease Gallstone Disease
¾¾
PrePre
--
pregnancy risk factors : pregnancy risk factors :
zz
high body mass index, high body mass index,
zz
high serum leptin levels, high serum leptin levels,
zz
low high low high
--
density lipoprotein (HDL) levels, and density lipoprotein (HDL) levels, and
zz
insu
lin resi
stance
insu
lin resi
stance
¾¾
Clinical Presentation: Clinical Presentation:
zz
Biliary colic: causes 5% of
jaundice episodes in pr
egnancy
Biliary colic: causes 5% of
jaundice episodes in pr
egnancy
zz
Gallstone pancr
eatitis: 50% of wo
men <
30 with pancreatitis are
Gallstone pancr
eatitis: 50% of wo
men <
30 with pancreatitis are
pregnant; 0.05 pregnant; 0.05
--
0.1% of pregnancies. 0.1% of pregnancies.
zz
Acute c
holecystitis: Least common pres
entation
Acute c
holecystitis: Least common pres
entation
zz
right upper quadrant pain that
may radiate to the flank, scapula
right upper quadrant pain that
may radiate to the flank, scapula
, or
shoulder.
, or
shoulder.
zz
nausea, vomiting, nausea, vomiting,
zz
anorexia, anorexia,
zz
fatty food intolerance, fatty food intolerance,
zz
lowlow
--
grade fever
.
grade fever
.
¾¾
PrePre
--
pregnancy risk factors : pregnancy risk factors :
zz
high body mass index, high body mass index,
zz
high serum leptin levels, high serum leptin levels,
zz
low high low high
--
density lipoprotein (HDL) levels, and density lipoprotein (HDL) levels, and
zz
insu
lin resi
stance
insu
lin resi
stance
¾¾
Clinical Presentation: Clinical Presentation:
zz
Biliary colic: causes 5% of
jaundice episodes in pr
egnancy
Biliary colic: causes 5% of
jaundice episodes in pr
egnancy
zz
Gallstone pancr
eatitis: 50% of wo
men <
30 with pancreatitis are
Gallstone pancr
eatitis: 50% of wo
men <
30 with pancreatitis are
pregnant; 0.05 pregnant; 0.05
--
0.1% of pregnancies. 0.1% of pregnancies.
zz
Acute c
holecystitis: Least common pres
entation
Acute c
holecystitis: Least common pres
entation
zz
right upper quadrant pain that
may radiate to the flank, scapula
right upper quadrant pain that
may radiate to the flank, scapula
, or
shoulder.
, or
shoulder.
zz
nausea, vomiting, nausea, vomiting,
zz
anorexia, anorexia,
zz
fatty food intolerance, fatty food intolerance,
zz
lowlow
--
grade fever
.
grade fever
.
Gallstone Disease Gallstone Disease
¾¾
Medic
a
l Management:
Medic
a
l Management:
zz
Conservative management is recommended initially, especially dur Conservative management is recommended initially, especially dur
ing the first ing the first
and thir
d trimesters, in which su
rgical intervention may confer
and thir
d trimesters, in which su
rgical intervention may confer
risk of abor
tion or
risk of abor
tion or
premature labor, respectively. premature labor, respectively.
zz
Medical management involves intr
avenous fluids, correction of el
Medical management involves intr
avenous fluids, correction of el
ectrolytes, ectrolytes,
bowel rest, pain management, and
broad spectr
um antibiotics.
bowel rest, pain management, and
broad spectr
um antibiotics.
zz
R
e
laps
e r
a
tes
(
4
0%
R
e
laps
e r
a
tes
(
4
0%
--
90%)
are high during pregnancy; thus, surgical intervention
90%)
are high during pregnancy; thus, surgical intervention
may be warranted. may be warranted.
¾¾
Surgic
al Management:
Surgic
al Management:
zz
Laparascopic cholecystectomy
in th
e second trimester
is prefer
re
Laparascopic cholecystectomy
in th
e second trimester
is prefer
re
d.; d.;
••
should be done in all
symptomatic patients
who present in 2
should be done in all
symptomatic patients
who present in 2
ndnd
trimes
ter.
trimes
ter.
••
COCO
22
insuflati
o
n shoul
d
be minimized, and
insuflati
o
n shoul
d
be minimized, and
••
hyperventilation should be induce
d to minimize aci
d
osis and PaCO
hyperventilation should be induce
d to minimize aci
d
osis and PaCO
22
in mother. in mother.
zz
ERCP may also be required if t
here are concerns about choledocho
ERCP may also be required if t
here are concerns about choledocho
lithia
si
s, and
lithia
si
s, and
this can be per
for
m
ed safely in
pr
egnancy by shielding the fetus
this can be per
for
m
ed safely in
pr
egnancy by shielding the fetus
and minimizing and minimizing
fluoroscopy time fluoroscopy time
¾¾
Medic
a
l Management:
Medic
a
l Management:
zz
Conservative management is recommended initially, especially dur Conservative management is recommended initially, especially dur
ing the first ing the first
and thir
d trimesters, in which su
rgical intervention may confer
and thir
d trimesters, in which su
rgical intervention may confer
risk of abor
tion or
risk of abor
tion or
premature labor, respectively. premature labor, respectively.
zz
Medical management involves intr
avenous fluids, correction of el
Medical management involves intr
avenous fluids, correction of el
ectrolytes, ectrolytes,
bowel rest, pain management, and
broad spectr
um antibiotics.
bowel rest, pain management, and
broad spectr
um antibiotics.
zz
R
e
laps
e r
a
tes
(
4
0%
R
e
laps
e r
a
tes
(
4
0%
--
90%)
are high during pregnancy; thus, surgical intervention
90%)
are high during pregnancy; thus, surgical intervention
may be warranted. may be warranted.
¾¾
Surgic
al Management:
Surgic
al Management:
zz
Laparascopic cholecystectomy
in th
e second trimester
is prefer
re
Laparascopic cholecystectomy
in th
e second trimester
is prefer
re
d.; d.;
••
should be done in all
symptomatic patients
who present in 2
should be done in all
symptomatic patients
who present in 2
ndnd
trimes
ter.
trimes
ter.
••
COCO
22
insuflati
o
n shoul
d
be minimized, and
insuflati
o
n shoul
d
be minimized, and
••
hyperventilation should be induce
d to minimize aci
d
osis and PaCO
hyperventilation should be induce
d to minimize aci
d
osis and PaCO
22
in mother. in mother.
zz
ERCP may also be required if t
here are concerns about choledocho
ERCP may also be required if t
here are concerns about choledocho
lithia
si
s, and
lithia
si
s, and
this can be per
for
m
ed safely in
pr
egnancy by shielding the fetus
this can be per
for
m
ed safely in
pr
egnancy by shielding the fetus
and minimizing and minimizing
fluoroscopy time fluoroscopy time
Viral Hepatitis Viral Hepatitis
¾¾
Viral hepatitis, due to hepatitis A,
B, C, D, E, herpes simplex,
Viral hepatitis, due to hepatitis A,
B, C, D, E, herpes simplex,
cytomegalovirus, and Epstein cytomegalovirus, and Epstein
--
Barr viruses, accounts fo
r 40% of
Barr viruses, accounts fo
r 40% of
jaundice in pregnant women in the United States. jaundice in pregnant women in the United States.
¾¾
Hepatitis A,
B, and C have the sa
me frequency in the pregnant a
Hepatitis A,
B, and C have the sa
me frequency in the pregnant a
nd nd
nonpregnant populations and during ea
ch of the 3 trimesters of
nonpregnant populations and during ea
ch of the 3 trimesters of
pregnancy. pregnancy.
zz
Acute Acute
hepatitis A occurs in 1 per
1000,
hepatitis A occurs in 1 per
1000,
zz
Acute hepatitis B in 2 per
Acute hepatitis B in 2 per
1000 pregnant women, and 1000 pregnant women, and
zz
Hepatitis D is rare. Hepatitis D is rare.
¾¾
The clinic
al and serologic course of acute hepatitis in the West
The clinic
al and serologic course of acute hepatitis in the West
ern ern
world is generally the same as in the nonpregnant patient world is generally the same as in the nonpregnant patient
¾¾
Viral hepatitis, due to hepatitis A,
B, C, D, E, herpes simplex,
Viral hepatitis, due to hepatitis A,
B, C, D, E, herpes simplex,
cytomegalovirus, and Epstein cytomegalovirus, and Epstein
--
Barr viruses, accounts fo
r 40% of
Barr viruses, accounts fo
r 40% of
jaundice in pregnant women in the United States. jaundice in pregnant women in the United States.
¾¾
Hepatitis A,
B, and C have the sa
me frequency in the pregnant a
Hepatitis A,
B, and C have the sa
me frequency in the pregnant a
nd nd
nonpregnant populations and during ea
ch of the 3 trimesters of
nonpregnant populations and during ea
ch of the 3 trimesters of
pregnancy. pregnancy.
zz
Acute Acute
hepatitis A occurs in 1 per
1000,
hepatitis A occurs in 1 per
1000,
zz
Acute hepatitis B in 2 per
Acute hepatitis B in 2 per
1000 pregnant women, and 1000 pregnant women, and
zz
Hepatitis D is rare. Hepatitis D is rare.
¾¾
The clinic
al and serologic course of acute hepatitis in the West
The clinic
al and serologic course of acute hepatitis in the West
ern ern
world is generally the same as in the nonpregnant patient world is generally the same as in the nonpregnant patient
Viral Hepatitis Viral Hepatitis
¾¾
With few exceptions, hepatitis usually does not appear to With few exceptions, hepatitis usually does not appear to affect the pregnant state adversely affect the pregnant state adversely
zz
Hepatitis A during the second or third trimesters may increase Hepatitis A during the second or third trimesters may increase gestational complications. gestational complications.
zz
Hepatitis E is extremely rare in the United States but is endemi Hepatitis E is extremely rare in the United States but is endemi
c to large c to large
areas of Asia, Africa, and Central America, where, in the third areas of Asia, Africa, and Central America, where, in the third
trimester trimester
of pregnancy, it becomes fulminant with a high mortality (up to of pregnancy, it becomes fulminant with a high mortality (up to
25%), 25%),
probably influenced by malnutrition. probably influenced by malnutrition.
zz
Herpes simplex hepatitis is rare but must be diagnosed because Herpes simplex hepatitis is rare but must be diagnosed because antiviral therapy with acyclovir or vidarabine is life antiviral therapy with acyclovir or vidarabine is life
--
saving; these patients saving; these patients
present with a severe or fulminant present with a severe or fulminant
““
anicteric anicteric
””
hepatitis in the third hepatitis in the third
trimester. trimester.
¾¾
With few exceptions, hepatitis usually does not appear to With few exceptions, hepatitis usually does not appear to affect the pregnant state adversely affect the pregnant state adversely
zz
Hepatitis A during the second or third trimesters may increase Hepatitis A during the second or third trimesters may increase gestational complications. gestational complications.
zz
Hepatitis E is extremely rare in the United States but is endemi Hepatitis E is extremely rare in the United States but is endemi
c to large c to large
areas of Asia, Africa, and Central America, where, in the third areas of Asia, Africa, and Central America, where, in the third
trimester trimester
of pregnancy, it becomes fulminant with a high mortality (up to of pregnancy, it becomes fulminant with a high mortality (up to
25%), 25%),
probably influenced by malnutrition. probably influenced by malnutrition.
zz
Herpes simplex hepatitis is rare but must be diagnosed because Herpes simplex hepatitis is rare but must be diagnosed because antiviral therapy with acyclovir or vidarabine is life antiviral therapy with acyclovir or vidarabine is life
--
saving; these patients saving; these patients
present with a severe or fulminant present with a severe or fulminant
““
anicteric anicteric
””
hepatitis in the third hepatitis in the third
trimester. trimester.
Viral Hepatitis Viral Hepatitis
¾¾
Management of the patient with
acute viral hepatitis is supporti
Management of the patient with
acute viral hepatitis is supporti
ve, ve,
and viral hepatitis is not an indication for termination of preg and viral hepatitis is not an indication for termination of preg
nancy, nancy,
caesarean section, or discourag
ement for breastfeeding.
caesarean section, or discourag
ement for breastfeeding.
¾¾
Congenital m
a
lformations in the fetus occur only with early
Congenital m
a
lformations in the fetus occur only with early
cytomegalovirus infection. cytomegalovirus infection.
¾¾
Vertical transmission of hepatitis A and D is rare and occurs on Vertical transmission of hepatitis A and D is rare and occurs on
ly ly
with high viral levels at the time of delivery. with high viral levels at the time of delivery.
¾¾
Newborns of mothers with hepatitis
A in the third trimester shou
Newborns of mothers with hepatitis
A in the third trimester shou
ld be ld be
giv
en passiv
e
immunoprophy
laxis with immune globulin within 48
giv
en passiv
e
immunoprophy
laxis with immune globulin within 48
hours of birth. hours of birth.
¾¾
Hepatitis E is associated with intrauterine death and abortion, Hepatitis E is associated with intrauterine death and abortion,
in any in any
trimester. Maternal trimester. Maternal
--
fetal transmission can occur, and give neonatal fetal transmission can occur, and give neonatal
hepatitis. hepatitis.
¾¾
Management of the patient with
acute viral hepatitis is supporti
Management of the patient with
acute viral hepatitis is supporti
ve, ve,
and viral hepatitis is not an indication for termination of preg and viral hepatitis is not an indication for termination of preg
nancy, nancy,
caesarean section, or discourag
ement for breastfeeding.
caesarean section, or discourag
ement for breastfeeding.
¾¾
Congenital m
a
lformations in the fetus occur only with early
Congenital m
a
lformations in the fetus occur only with early
cytomegalovirus infection. cytomegalovirus infection.
¾¾
Vertical transmission of hepatitis A and D is rare and occurs on Vertical transmission of hepatitis A and D is rare and occurs on
ly ly
with high viral levels at the time of delivery. with high viral levels at the time of delivery.
¾¾
Newborns of mothers with hepatitis
A in the third trimester shou
Newborns of mothers with hepatitis
A in the third trimester shou
ld be ld be
giv
en passiv
e
immunoprophy
laxis with immune globulin within 48
giv
en passiv
e
immunoprophy
laxis with immune globulin within 48
hours of birth. hours of birth.
¾¾
Hepatitis E is associated with intrauterine death and abortion, Hepatitis E is associated with intrauterine death and abortion,
in any in any
trimester. Maternal trimester. Maternal
--
fetal transmission can occur, and give neonatal fetal transmission can occur, and give neonatal
hepatitis. hepatitis.
Viral Hepatitis B Viral Hepatitis B
¾¾
All pregnant women are tested fo
r hepatitis B on first antenatal
All pregnant women are tested fo
r hepatitis B on first antenatal
visit; visit;
¾¾
Pregnant women without immune antibodies and at high risk for Pregnant women without immune antibodies and at high risk for HBV infection during pregnancy (for example, multiple sex partne HBV infection during pregnancy (for example, multiple sex partne
rs, rs,
intravenous drug use), vaccine can be giv
en in pregnancy with li
intravenous drug use), vaccine can be giv
en in pregnancy with li
ttle ttle
risk to the fetus. risk to the fetus.
¾¾
Perinatal transmission of hepatitis
B is highest in those with a
Perinatal transmission of hepatitis
B is highest in those with a
cu
te
cu
te
hepatitis, especially with hepatitis
B e antigen positiv
ity in t
hepatitis, especially with hepatitis
B e antigen positiv
ity in t
he third he third
trimester (50% trimester (50%
--
80%). 80%).
¾¾
Trans
mission is lower in mothers with anti
Trans
mission is lower in mothers with anti
--
HBe (25%), and lowest in HBe (25%), and lowest in
carriers (5%); 80% carriers (5%); 80%
--
90% of these babies have persistent hepatitis B 90% of these babies have persistent hepatitis B
surface antigen positivity. surface antigen positivity.
¾¾
Hepatitis B virus DNA levels typically increase late in pregnan Hepatitis B virus DNA levels typically increase late in pregnan
cy or cy or
in the early postpartum period, with 1 retrospective study showi in the early postpartum period, with 1 retrospective study showi
ng a
ng a
mean increase of 0.4 log mean increase of 0.4 log
¾¾
All pregnant women are tested fo
r hepatitis B on first antenatal
All pregnant women are tested fo
r hepatitis B on first antenatal
visit; visit;
¾¾
Pregnant women without immune antibodies and at high risk for Pregnant women without immune antibodies and at high risk for HBV infection during pregnancy (for example, multiple sex partne HBV infection during pregnancy (for example, multiple sex partne
rs, rs,
intravenous drug use), vaccine can be giv
en in pregnancy with li
intravenous drug use), vaccine can be giv
en in pregnancy with li
ttle ttle
risk to the fetus. risk to the fetus.
¾¾
Perinatal transmission of hepatitis
B is highest in those with a
Perinatal transmission of hepatitis
B is highest in those with a
cu
te
cu
te
hepatitis, especially with hepatitis
B e antigen positiv
ity in t
hepatitis, especially with hepatitis
B e antigen positiv
ity in t
he third he third
trimester (50% trimester (50%
--
80%). 80%).
¾¾
Trans
mission is lower in mothers with anti
Trans
mission is lower in mothers with anti
--
HBe (25%), and lowest in HBe (25%), and lowest in
carriers (5%); 80% carriers (5%); 80%
--
90% of these babies have persistent hepatitis B 90% of these babies have persistent hepatitis B
surface antigen positivity. surface antigen positivity.
¾¾
Hepatitis B virus DNA levels typically increase late in pregnan Hepatitis B virus DNA levels typically increase late in pregnan
cy or cy or
in the early postpartum period, with 1 retrospective study showi in the early postpartum period, with 1 retrospective study showi
ng a
ng a
mean increase of 0.4 log mean increase of 0.4 log
HBV & Pregnancy HBV & Pregnancy
¾¾
Pregnancy is well tolerated by HBV carriers Pregnancy is well tolerated by HBV carriers
¾¾
HBV reactivation with exacerbation of disease is rare HBV reactivation with exacerbation of disease is rare during pregnancy or post during pregnancy or post
--
partum. partum.
¾¾
Intrauterine transmission of HBV is rare, but may occur Intrauterine transmission of HBV is rare, but may occur during during
““
threatened abortion threatened abortion
””
by transplacental leakage. by transplacental leakage.
¾¾
Transmission by amniocentesis is low (</= 4%). Transmission by amniocentesis is low (</= 4%).
¾¾
If mother is HBeAg(+), risk of vertical transmission is If mother is HBeAg(+), risk of vertical transmission is 90% without prophylaxis. 90% without prophylaxis.
¾¾
PostPost
--
partum partum
““
flare up flare up
””
is common and due to decrease is common and due to decrease
of cortisol levels. Up to 12 of cortisol levels. Up to 12
--
17% may have post 17% may have post
--
partum partum
““
ee
””
seroconversion. seroconversion.
¾¾
Pregnancy is well tolerated by HBV carriers Pregnancy is well tolerated by HBV carriers
¾¾
HBV reactivation with exacerbation of disease is rare HBV reactivation with exacerbation of disease is rare during pregnancy or post during pregnancy or post
--
partum. partum.
¾¾
Intrauterine transmission of HBV is rare, but may occur Intrauterine transmission of HBV is rare, but may occur during during
““
threatened abortion threatened abortion
””
by transplacental leakage. by transplacental leakage.
¾¾
Transmission by amniocentesis is low (</= 4%). Transmission by amniocentesis is low (</= 4%).
¾¾
If mother is HBeAg(+), risk of vertical transmission is If mother is HBeAg(+), risk of vertical transmission is 90% without prophylaxis. 90% without prophylaxis.
¾¾
PostPost
--
partum partum
““
flare up flare up
””
is common and due to decrease is common and due to decrease
of cortisol levels. Up to 12 of cortisol levels. Up to 12
--
17% may have post 17% may have post
--
partum partum
““
ee
””
seroconversion. seroconversion.
HBV & Pregnancy HBV & Pregnancy
¾¾
If mother has HBV If mother has HBV
--
DNA < 10 DNA < 10
88
IU/ml: IU/ml:
zz
neonatal immuno neonatal immuno
--
prophylaxis [HBIG + HBV prophylaxis [HBIG + HBV
immunization] prevents transmission in 95%. immunization] prevents transmission in 95%.
¾¾
Cesarean section decreases vertical Cesarean section decreases vertical transmission rate, but: transmission rate, but:
zz
is not indicated because [HBIG + HBV immunization] is not indicated because [HBIG + HBV immunization] is very effective. is very effective.
¾¾
If mother is If mother is
““
highly infectious highly infectious
””
with HBV with HBV
--
DNA > DNA >
1010
88
IU/mL IU/mL
zz
risk of HBV transmission is 30 risk of HBV transmission is 30
--
40% despite [HBIG + 40% despite [HBIG +
HBV immunization] HBV immunization]
¾¾
If mother has HBV If mother has HBV
--
DNA < 10 DNA < 10
88
IU/ml: IU/ml:
zz
neonatal immuno neonatal immuno
--
prophylaxis [HBIG + HBV prophylaxis [HBIG + HBV
immunization] prevents transmission in 95%. immunization] prevents transmission in 95%.
¾¾
Cesarean section decreases vertical Cesarean section decreases vertical transmission rate, but: transmission rate, but:
zz
is not indicated because [HBIG + HBV immunization] is not indicated because [HBIG + HBV immunization] is very effective. is very effective.
¾¾
If mother is If mother is
““
highly infectious highly infectious
””
with HBV with HBV
--
DNA > DNA >
1010
88
IU/mL IU/mL
zz
risk of HBV transmission is 30 risk of HBV transmission is 30
--
40% despite [HBIG + 40% despite [HBIG +
HBV immunization] HBV immunization]
HBV & Pregnancy HBV & Pregnancy
¾¾
If mother is infected with HBeAg( If mother is infected with HBeAg(
--
) and HBV ) and HBV
--
DNA > 10 DNA > 10
8 8
IU/mL ( IU/mL (
““
very high load precore mutant HBV very high load precore mutant HBV
””
): ):
zz
infant is at risk of fulminant hepatitis B during initial 2 to 4 infant is at risk of fulminant hepatitis B during initial 2 to 4
months months
of life. of life.
¾¾
Mothers with HBV/HDV co Mothers with HBV/HDV co
--
infection: infection:
zz
may vertically transmit both infections to the neonate. may vertically transmit both infections to the neonate.
zz
HBIG + HBV immuniz
a
tion can protect from both.
HBIG + HBV immuniz
a
tion can protect from both.
¾¾
PostPost
--
vaccination testing of infant should be done at age vaccination testing of infant should be done at age
99
--
15 months. 15 months.
¾¾
Telbivudine and Tenofovir ar
e safe during pregnancy.
Telbivudine and Tenofovir ar
e safe during pregnancy.
Lamivudine has been used safely in the 3 Lamivudine has been used safely in the 3
rdrd
trimester. trimester.
¾¾
If mother is infected with HBeAg( If mother is infected with HBeAg(
--
) and HBV ) and HBV
--
DNA > 10 DNA > 10
8 8
IU/mL ( IU/mL (
““
very high load precore mutant HBV very high load precore mutant HBV
””
): ):
zz
infant is at risk of fulminant hepatitis B during initial 2 to 4 infant is at risk of fulminant hepatitis B during initial 2 to 4
months months
of life. of life.
¾¾
Mothers with HBV/HDV co Mothers with HBV/HDV co
--
infection: infection:
zz
may vertically transmit both infections to the neonate. may vertically transmit both infections to the neonate.
zz
HBIG + HBV immuniz
a
tion can protect from both.
HBIG + HBV immuniz
a
tion can protect from both.
¾¾
PostPost
--
vaccination testing of infant should be done at age vaccination testing of infant should be done at age
99
--
15 months. 15 months.
¾¾
Telbivudine and Tenofovir ar
e safe during pregnancy.
Telbivudine and Tenofovir ar
e safe during pregnancy.
Lamivudine has been used safely in the 3 Lamivudine has been used safely in the 3
rdrd
trimester. trimester.
Effect of Lamivudine on HBV Vertical Transmission from Effect of Lamivudine on HBV Vertical Transmission from
Highly Infectious Mothers Highly Infectious Mothers
Xu WM et al
. AASLD Abstr # 246, 2004
Xu WM et al
. AASLD Abstr # 246, 2004
Xu WM et al. J. Viral Hepat 2009:16, 94 Xu WM et al. J. Viral Hepat 2009:16, 94
--
103103
¾¾
Multicenter, double blind, randomized, placebo Multicenter, double blind, randomized, placebo controlled. controlled.
¾¾
Population Population
: 114 pregnant women with HBsAg(+) & : 114 pregnant women with HBsAg(+) &
HBVHBV
--
DNA > 10 DNA > 10
99
genome Eq/mL (Chiron bDNA) (aprox genome Eq/mL (Chiron bDNA) (aprox
> 200 million IU/mL). > 200 million IU/mL).
¾¾
Treatment Treatment
: Lamivudine 100 mg/d vs. placebo starting @ : Lamivudine 100 mg/d vs. placebo starting @
wk 32 until 4 wks post wk 32 until 4 wks post
--
partum partum
¾¾
All neonates received: HBIG 200 IU + HBV vaccine @ All neonates received: HBIG 200 IU + HBV vaccine @ birth, 4 & 24 weeks. birth, 4 & 24 weeks.
¾¾
EndEnd
--
point point
: HBsAg(+) & HBV : HBsAg(+) & HBV
--
DNA(+) @ age 53 wks DNA(+) @ age 53 wks
Highly Infectious Mothers Highly Infectious Mothers
Xu WM et al
. AASLD Abstr # 246, 2004
Xu WM et al
. AASLD Abstr # 246, 2004
Xu WM et al. J. Viral Hepat 2009:16, 94 Xu WM et al. J. Viral Hepat 2009:16, 94
--
103103
¾¾
Multicenter, double blind, randomized, placebo Multicenter, double blind, randomized, placebo controlled. controlled.
¾¾
Population Population
: 114 pregnant women with HBsAg(+) & : 114 pregnant women with HBsAg(+) &
HBVHBV
--
DNA > 10 DNA > 10
99
genome Eq/mL (Chiron bDNA) (aprox genome Eq/mL (Chiron bDNA) (aprox
> 200 million IU/mL). > 200 million IU/mL).
¾¾
Treatment Treatment
: Lamivudine 100 mg/d vs. placebo starting @ : Lamivudine 100 mg/d vs. placebo starting @
wk 32 until 4 wks post wk 32 until 4 wks post
--
partum partum
¾¾
All neonates received: HBIG 200 IU + HBV vaccine @ All neonates received: HBIG 200 IU + HBV vaccine @ birth, 4 & 24 weeks. birth, 4 & 24 weeks.
¾¾
EndEnd
--
point point
: HBsAg(+) & HBV : HBsAg(+) & HBV
--
DNA(+) @ age 53 wks DNA(+) @ age 53 wks
RESULTS RESULTS
# 246 # 246
18
39
84
61
20
46
0
102030405060708090
100
HBsAg
(
+
)
an
t
i
-
HBs(
+
)
H
BV
-
D
NA(
+
)
LA
M
PL
A
C
EB
O
# 246 # 246
18
39
84
61
20
46
0
102030405060708090
100
HBsAg
(
+
)
an
t
i
-
HBs(
+
)
H
BV
-
D
NA(
+
)
LA
M
PL
A
C
EB
O
CONCLUSION CONCLUSION
Abstr # 246 Abstr # 246
¾¾
In mothers with HBV In mothers with HBV
--
DNA > 10 DNA > 10
99
genome Eq/ml genome Eq/ml
(> 200 million IU/mL), the addition of Lamivudine (> 200 million IU/mL), the addition of Lamivudine 100 mg/d in the 8 weeks prior to delivery plus 4 100 mg/d in the 8 weeks prior to delivery plus 4 weeks post weeks post
--
partum, to the regimen of HBIG & partum, to the regimen of HBIG &
Vaccination, decreased the rate of vertical Vaccination, decreased the rate of vertical transmission of HBV. transmission of HBV.
¾¾
No safety concerns were observed on mothers No safety concerns were observed on mothers nor infants. nor infants.
¾¾
Lamivudine was well tolerated. Lamivudine was well tolerated.
Abstr # 246 Abstr # 246
¾¾
In mothers with HBV In mothers with HBV
--
DNA > 10 DNA > 10
99
genome Eq/ml genome Eq/ml
(> 200 million IU/mL), the addition of Lamivudine (> 200 million IU/mL), the addition of Lamivudine 100 mg/d in the 8 weeks prior to delivery plus 4 100 mg/d in the 8 weeks prior to delivery plus 4 weeks post weeks post
--
partum, to the regimen of HBIG & partum, to the regimen of HBIG &
Vaccination, decreased the rate of vertical Vaccination, decreased the rate of vertical transmission of HBV. transmission of HBV.
¾¾
No safety concerns were observed on mothers No safety concerns were observed on mothers nor infants. nor infants.
¾¾
Lamivudine was well tolerated. Lamivudine was well tolerated.
Vertical Transmission of HCV Vertical Transmission of HCV
(Obstet Gynecol Surv 2006; 61:666 (Obstet Gynecol Surv 2006; 61:666
--
72)72)
¾¾
Risk if mother anti Risk if mother anti
--
HCV(+) is approximately 2%; HCV(+) is approximately 2%;
zz
If mother is HCV If mother is HCV
--
RNA (+), risk is 4 RNA (+), risk is 4
--
5%. 5%.
zz
Scalp electrodes increase risk of transmission. Scalp electrodes increase risk of transmission.
¾¾
Up to 30% of infected neona
tes may have acquired HCV
Up to 30% of infected neona
tes may have acquired HCV
““
in utero in utero
””
(Arch Dis Child Fetal Neonatal Ed 2005;90:F156 (Arch Dis Child Fetal Neonatal Ed 2005;90:F156
--
60)60)
¾¾
A cohort study of 506 HCV A cohort study of 506 HCV
--
positive pregnant women positive pregnant women
found that HCV infection was associated with: found that HCV infection was associated with:
zz
development of gestational diabetes mellitus, development of gestational diabetes mellitus,
zz
lower birth weight, lower birth weight,
zz
lower Apgar scores, lower Apgar scores,
zz
more admis
sions to the neonatal intensive care unit for
more admis
sions to the neonatal intensive care unit for
respiratory problems, prematurity, and infections respiratory problems, prematurity, and infections
(Obstet Gynecol Surv 2006; 61:666 (Obstet Gynecol Surv 2006; 61:666
--
72)72)
¾¾
Risk if mother anti Risk if mother anti
--
HCV(+) is approximately 2%; HCV(+) is approximately 2%;
zz
If mother is HCV If mother is HCV
--
RNA (+), risk is 4 RNA (+), risk is 4
--
5%. 5%.
zz
Scalp electrodes increase risk of transmission. Scalp electrodes increase risk of transmission.
¾¾
Up to 30% of infected neona
tes may have acquired HCV
Up to 30% of infected neona
tes may have acquired HCV
““
in utero in utero
””
(Arch Dis Child Fetal Neonatal Ed 2005;90:F156 (Arch Dis Child Fetal Neonatal Ed 2005;90:F156
--
60)60)
¾¾
A cohort study of 506 HCV A cohort study of 506 HCV
--
positive pregnant women positive pregnant women
found that HCV infection was associated with: found that HCV infection was associated with:
zz
development of gestational diabetes mellitus, development of gestational diabetes mellitus,
zz
lower birth weight, lower birth weight,
zz
lower Apgar scores, lower Apgar scores,
zz
more admis
sions to the neonatal intensive care unit for
more admis
sions to the neonatal intensive care unit for
respiratory problems, prematurity, and infections respiratory problems, prematurity, and infections
Vertical Transmission of HCV Vertical Transmission of HCV
(Obstet Gynecol Surv 2006; 61:666 (Obstet Gynecol Surv 2006; 61:666
--
72)72)
¾¾
In HCV/HIV co In HCV/HIV co
--
infection the transmission risk is infection the transmission risk is
higher (15 higher (15
--
18%) but HAART may decrease the 18%) but HAART may decrease the
risk. risk.
¾¾
HCVHCV
--
RNA viral load >/= 10 RNA viral load >/= 10
1818
U/mL have up to U/mL have up to
36% vertical transmission rate. 36% vertical transmission rate.
¾¾
There is no association between vertical There is no association between vertical transmission of HCV, gestational age at delivery, transmission of HCV, gestational age at delivery, nor chorioamnionitis. nor chorioamnionitis.
¾¾
Data are conflicting about duration of ruptured Data are conflicting about duration of ruptured membranes and risk of HCV transmission membranes and risk of HCV transmission (increased after 6 h ?) (increased after 6 h ?)
(Obstet Gynecol Surv 2006; 61:666 (Obstet Gynecol Surv 2006; 61:666
--
72)72)
¾¾
In HCV/HIV co In HCV/HIV co
--
infection the transmission risk is infection the transmission risk is
higher (15 higher (15
--
18%) but HAART may decrease the 18%) but HAART may decrease the
risk. risk.
¾¾
HCVHCV
--
RNA viral load >/= 10 RNA viral load >/= 10
1818
U/mL have up to U/mL have up to
36% vertical transmission rate. 36% vertical transmission rate.
¾¾
There is no association between vertical There is no association between vertical transmission of HCV, gestational age at delivery, transmission of HCV, gestational age at delivery, nor chorioamnionitis. nor chorioamnionitis.
¾¾
Data are conflicting about duration of ruptured Data are conflicting about duration of ruptured membranes and risk of HCV transmission membranes and risk of HCV transmission (increased after 6 h ?) (increased after 6 h ?)
Vertical Transmission of HCV Vertical Transmission of HCV
Cesarean Section vs Vaginal Delivery Cesarean Section vs Vaginal Delivery
¾¾
The The
““
Cochrane Pregnancy and Childbirth Cochrane Pregnancy and Childbirth
Group Group
’’
s Trial Register s Trial Register
””
, and the , and the
““
Cochrane Cochrane
Central Register of Controlled Trials Central Register of Controlled Trials
””
were were
analyzed until April 2006. analyzed until April 2006.
¾¾
No randomised controlled trials were found No randomised controlled trials were found (Cochrane Database Syst Rev 2006; Oct 18). (Cochrane Database Syst Rev 2006; Oct 18).
¾¾
Systematic review of observational studies Systematic review of observational studies (subject to biases) or RCT (subject to biases) or RCT
’’
s are needed. s are needed.
Cesarean Section vs Vaginal Delivery Cesarean Section vs Vaginal Delivery
¾¾
The The
““
Cochrane Pregnancy and Childbirth Cochrane Pregnancy and Childbirth
Group Group
’’
s Trial Register s Trial Register
””
, and the , and the
““
Cochrane Cochrane
Central Register of Controlled Trials Central Register of Controlled Trials
””
were were
analyzed until April 2006. analyzed until April 2006.
¾¾
No randomised controlled trials were found No randomised controlled trials were found (Cochrane Database Syst Rev 2006; Oct 18). (Cochrane Database Syst Rev 2006; Oct 18).
¾¾
Systematic review of observational studies Systematic review of observational studies (subject to biases) or RCT (subject to biases) or RCT
’’
s are needed. s are needed.
Vertical Transmission of HCV Vertical Transmission of HCV
(Obstet Gynecol Surv 2006; 61:666 (Obstet Gynecol Surv 2006; 61:666
--
72)72)
¾¾
In HCV(+)/HIV( In HCV(+)/HIV(
--
) mothers: ) mothers:
zz
Route of delivery does not influence vertical Route of delivery does not influence vertical transmission. transmission.
zz
There is no need to discourage breast feeding. There is no need to discourage breast feeding.
¾¾
In HCV(+)/HIV(+) mothers: In HCV(+)/HIV(+) mothers:
zz
Mode of delivery should be based in HIV status. Mode of delivery should be based in HIV status.
zz
Breast feeding should be discouraged. Breast feeding should be discouraged.
(Obstet Gynecol Surv 2006; 61:666 (Obstet Gynecol Surv 2006; 61:666
--
72)72)
¾¾
In HCV(+)/HIV( In HCV(+)/HIV(
--
) mothers: ) mothers:
zz
Route of delivery does not influence vertical Route of delivery does not influence vertical transmission. transmission.
zz
There is no need to discourage breast feeding. There is no need to discourage breast feeding.
¾¾
In HCV(+)/HIV(+) mothers: In HCV(+)/HIV(+) mothers:
zz
Mode of delivery should be based in HIV status. Mode of delivery should be based in HIV status.
zz
Breast feeding should be discouraged. Breast feeding should be discouraged.
HSV Hepatitis HSV Hepatitis
¾¾
Subclinical HSV due to Subclinical HSV due to
““
primary primary
””
infection is common. infection is common.
¾¾
Primary infection during pregnancy, specially in the 3 Primary infection during pregnancy, specially in the 3
rdrd
trimester, may cause severe and fulminant hepatitis. trimester, may cause severe and fulminant hepatitis.
¾¾
Clinical presentation: Clinical presentation:
zz
Patient is usually anicteric, obtunded, with high Patient is usually anicteric, obtunded, with high aminotransferases, and coagulopathy. aminotransferases, and coagulopathy.
zz
May have subtle oropharyngeal or genital vesicular lesions
.
May have subtle oropharyngeal or genital vesicular lesions
.
zz
May have associated HSV encephalitis. May have associated HSV encephalitis.
¾¾
Liver Bx shows intracytoplasmic inclusions. Liver Bx shows intracytoplasmic inclusions.
¾¾
Serum HSV by PCR is positive. Serum HSV by PCR is positive.
¾¾
Treatment is urgent, with Acyclovir. Prevents Treatment is urgent, with Acyclovir. Prevents transmission to the fetus. transmission to the fetus.
¾¾
Subclinical HSV due to Subclinical HSV due to
““
primary primary
””
infection is common. infection is common.
¾¾
Primary infection during pregnancy, specially in the 3 Primary infection during pregnancy, specially in the 3
rdrd
trimester, may cause severe and fulminant hepatitis. trimester, may cause severe and fulminant hepatitis.
¾¾
Clinical presentation: Clinical presentation:
zz
Patient is usually anicteric, obtunded, with high Patient is usually anicteric, obtunded, with high aminotransferases, and coagulopathy. aminotransferases, and coagulopathy.
zz
May have subtle oropharyngeal or genital vesicular lesions
.
May have subtle oropharyngeal or genital vesicular lesions
.
zz
May have associated HSV encephalitis. May have associated HSV encephalitis.
¾¾
Liver Bx shows intracytoplasmic inclusions. Liver Bx shows intracytoplasmic inclusions.
¾¾
Serum HSV by PCR is positive. Serum HSV by PCR is positive.
¾¾
Treatment is urgent, with Acyclovir. Prevents Treatment is urgent, with Acyclovir. Prevents transmission to the fetus. transmission to the fetus.
Primary Biliary Cirrhosis (PBC) Primary Biliary Cirrhosis (PBC)
¾¾
PBC is
a chronic cholestatic dise
ase that affects persons in the
PBC is
a chronic cholestatic dise
ase that affects persons in the
ir 30s ir 30s
to 60s. to 60s.
¾¾
Causes destruction of intrahepat
ic bile ducts and is likely
Causes destruction of intrahepat
ic bile ducts and is likely
autoimmune, with than two thirds
of patients having an associate
autoimmune, with than two thirds
of patients having an associate
d d
autoimmune dis
eas
e.
autoimmune dis
eas
e.
¾¾
The course of PBC may be insidious, often presenting with fatigu The course of PBC may be insidious, often presenting with fatigu
e e
and pruritus. and pruritus.
¾¾
Serum aminotransferase, bilirubin,
cholesterol, IgM, and erythro
Serum aminotransferase, bilirubin,
cholesterol, IgM, and erythro
cyte cyte
sedimentation rate levels are
often elevated, and an elevated
sedimentation rate levels are
often elevated, and an elevated
bilirubin level often portends poor prognos
is.
bilirubin level often portends poor prognos
is.
¾¾
Portal hypertens
ion and liver failure may develop.
Portal hypertens
ion and liver failure may develop.
¾¾
PBC is
a chronic cholestatic dise
ase that affects persons in the
PBC is
a chronic cholestatic dise
ase that affects persons in the
ir 30s ir 30s
to 60s. to 60s.
¾¾
Causes destruction of intrahepat
ic bile ducts and is likely
Causes destruction of intrahepat
ic bile ducts and is likely
autoimmune, with than two thirds
of patients having an associate
autoimmune, with than two thirds
of patients having an associate
d d
autoimmune dis
eas
e.
autoimmune dis
eas
e.
¾¾
The course of PBC may be insidious, often presenting with fatigu The course of PBC may be insidious, often presenting with fatigu
e e
and pruritus. and pruritus.
¾¾
Serum aminotransferase, bilirubin,
cholesterol, IgM, and erythro
Serum aminotransferase, bilirubin,
cholesterol, IgM, and erythro
cyte cyte
sedimentation rate levels are
often elevated, and an elevated
sedimentation rate levels are
often elevated, and an elevated
bilirubin level often portends poor prognos
is.
bilirubin level often portends poor prognos
is.
¾¾
Portal hypertens
ion and liver failure may develop.
Portal hypertens
ion and liver failure may develop.
Primary Biliary Cirrhosis (PBC) Primary Biliary Cirrhosis (PBC)
¾¾
Early reports suggested that PBC is associated with reduced fert Early reports suggested that PBC is associated with reduced fert
ility, ility,
amenorrhea,
repeated pregnancy loss, endometriosis, and
amenorrhea,
repeated pregnancy loss, endometriosis, and
premature ovarian failure, as we
ll as worsening liver function d
premature ovarian failure, as we
ll as worsening liver function d
uring uring
the course of pregnancy. More recent data suggest that women wit the course of pregnancy. More recent data suggest that women wit
h h
PBC may be able to have normal pregnancies. PBC may be able to have normal pregnancies.
¾¾
One st
udy o
f
nine pregnancies in six patients with UDCA
One st
udy o
f
nine pregnancies in six patients with UDCA
--
treated treated
PBC showed tha
t
:
PBC showed tha
t
:
zz
all women remained asymptomatic
during pregnancy with no rec
u
rre
all women remained asymptomatic
during pregnancy with no rec
u
rre
nce of nce of
pruritus
.
pruritus
.
zz
improvements were seen in laboratory tests including antimitocho improvements were seen in laboratory tests including antimitocho
ndrial antibody ndrial antibody
titers and levels of alkaline phos
phatase, ALT, serum bile acid,
titers and levels of alkaline phos
phatase, ALT, serum bile acid,
bilirubin, bilirubin,
immunoglobulin G, and immunoglobulin M. immunoglobulin G, and immunoglobulin M.
zz
a flare in disease with increases
in liver biochemistries was ob
a flare in disease with increases
in liver biochemistries was ob
served 3 mo served 3 mo
postpar
tum.
postpar
tum.
zz
UDCA has been shown t
o
be saf
e
in pregnancy.
UDCA has been shown t
o
be saf
e
in pregnancy.
¾¾
Early reports suggested that PBC is associated with reduced fert Early reports suggested that PBC is associated with reduced fert
ility, ility,
amenorrhea,
repeated pregnancy loss, endometriosis, and
amenorrhea,
repeated pregnancy loss, endometriosis, and
premature ovarian failure, as we
ll as worsening liver function d
premature ovarian failure, as we
ll as worsening liver function d
uring uring
the course of pregnancy. More recent data suggest that women wit the course of pregnancy. More recent data suggest that women wit
h h
PBC may be able to have normal pregnancies. PBC may be able to have normal pregnancies.
¾¾
One st
udy o
f
nine pregnancies in six patients with UDCA
One st
udy o
f
nine pregnancies in six patients with UDCA
--
treated treated
PBC showed tha
t
:
PBC showed tha
t
:
zz
all women remained asymptomatic
during pregnancy with no rec
u
rre
all women remained asymptomatic
during pregnancy with no rec
u
rre
nce of nce of
pruritus
.
pruritus
.
zz
improvements were seen in laboratory tests including antimitocho improvements were seen in laboratory tests including antimitocho
ndrial antibody ndrial antibody
titers and levels of alkaline phos
phatase, ALT, serum bile acid,
titers and levels of alkaline phos
phatase, ALT, serum bile acid,
bilirubin, bilirubin,
immunoglobulin G, and immunoglobulin M. immunoglobulin G, and immunoglobulin M.
zz
a flare in disease with increases
in liver biochemistries was ob
a flare in disease with increases
in liver biochemistries was ob
served 3 mo served 3 mo
postpar
tum.
postpar
tum.
zz
UDCA has been shown t
o
be saf
e
in pregnancy.
UDCA has been shown t
o
be saf
e
in pregnancy.
Primary Sclerosing Cholangitis (PSC) Primary Sclerosing Cholangitis (PSC)
¾¾
There are only a few published ca
se reports on PSC in pregnancy;
There are only a few published ca
se reports on PSC in pregnancy;
thus, the natural history of PS
C in pregnancy is not well unders
thus, the natural history of PS
C in pregnancy is not well unders
tood. tood.
¾¾
Pregnant patients with PSC ma
y experience pruritus, biliary
Pregnant patients with PSC ma
y experience pruritus, biliary
strictures and choledocholithiasis
.
strictures and choledocholithiasis
.
¾¾
If a patient with PSC dev
elops
symptoms worrisome for biliary
If a patient with PSC dev
elops
symptoms worrisome for biliary
obstruction, an ultrasound should
be performed, as it is thought
obstruction, an ultrasound should
be performed, as it is thought
to to
be safe in pregnancy and may dete
ct the presence of stones or
be safe in pregnancy and may dete
ct the presence of stones or
dominant strictures. dominant strictures.
¾¾
Endos
copic retrograde cholangi
opancreatography (ERCP
) may be
Endos
copic retrograde cholangi
opancreatography (ERCP
) may be
considered with caution regarding
exposure to radiation and the
considered with caution regarding
exposure to radiation and the
use use
of sedation. of sedation.
¾¾
Empiric use of UDCA should be cons
idered, as it is felt t
o
be sa
Empiric use of UDCA should be cons
idered, as it is felt t
o
be sa
fe in fe in
pregnancy and may improve maternal symptoms and fetal pregnancy and may improve maternal symptoms and fetal complications. complications.
¾¾
There are only a few published ca
se reports on PSC in pregnancy;
There are only a few published ca
se reports on PSC in pregnancy;
thus, the natural history of PS
C in pregnancy is not well unders
thus, the natural history of PS
C in pregnancy is not well unders
tood. tood.
¾¾
Pregnant patients with PSC ma
y experience pruritus, biliary
Pregnant patients with PSC ma
y experience pruritus, biliary
strictures and choledocholithiasis
.
strictures and choledocholithiasis
.
¾¾
If a patient with PSC dev
elops
symptoms worrisome for biliary
If a patient with PSC dev
elops
symptoms worrisome for biliary
obstruction, an ultrasound should
be performed, as it is thought
obstruction, an ultrasound should
be performed, as it is thought
to to
be safe in pregnancy and may dete
ct the presence of stones or
be safe in pregnancy and may dete
ct the presence of stones or
dominant strictures. dominant strictures.
¾¾
Endos
copic retrograde cholangi
opancreatography (ERCP
) may be
Endos
copic retrograde cholangi
opancreatography (ERCP
) may be
considered with caution regarding
exposure to radiation and the
considered with caution regarding
exposure to radiation and the
use use
of sedation. of sedation.
¾¾
Empiric use of UDCA should be cons
idered, as it is felt t
o
be sa
Empiric use of UDCA should be cons
idered, as it is felt t
o
be sa
fe in fe in
pregnancy and may improve maternal symptoms and fetal pregnancy and may improve maternal symptoms and fetal complications. complications.
Autoimmune Hepatitis Autoimmune Hepatitis
¾¾
The natural history of AIH in
pregnant women is variable.
The natural history of AIH in
pregnant women is variable.
¾¾
Candia Candia
et al review
ed 101 cases of AIH in
et al review
ed 101 cases of AIH in
pregnant women reported pregnant women reported
in the literature between 1966 and 2004: in the literature between 1966 and 2004:
zz
47 women experienced AIH flar
es,
with 35 occurring during pregna
47 women experienced AIH flar
es,
with 35 occurring during pregna
ncy and 12 ncy and 12
occurrin
g
after deli
very.
occurrin
g
after deli
very.
zz
fetal deaths occurred in 19% of
pr
egnancies, and the majority of
fetal deaths occurred in 19% of
pr
egnancies, and the majority of
the fetal deaths the fetal deaths
occurred before the 20
th wk of gestation.
occurred before the 20
th wk of gestation.
¾¾
A recent review of 42 pregnancie
s in women with AIH reported a
A recent review of 42 pregnancie
s in women with AIH reported a
fetal loss rate of 24%. R
ange in several studies is 14
fetal loss rate of 24%. R
ange in several studies is 14
--
24%.24%.
¾¾
Fetal death in pregnant women with AIH has been associated with Fetal death in pregnant women with AIH has been associated with the presenc
e of prematurity and low birth weight.
the presenc
e of prematurity and low birth weight.
¾¾
Factors associated with worsening of
AIH in pregnancy include:
Factors associated with worsening of
AIH in pregnancy include:
zz
changes in the r
e
lative concentr
a
tions of various hormones durin
changes in the r
e
lative concentr
a
tions of various hormones durin
g pregnancy g pregnancy
zz
specific autoantibodies, includin
g antibodies to SLA/LP and Ro/S
specific autoantibodies, includin
g antibodies to SLA/LP and Ro/S
SA.SA.
¾¾
The natural history of AIH in
pregnant women is variable.
The natural history of AIH in
pregnant women is variable.
¾¾
Candia Candia
et al review
ed 101 cases of AIH in
et al review
ed 101 cases of AIH in
pregnant women reported pregnant women reported
in the literature between 1966 and 2004: in the literature between 1966 and 2004:
zz
47 women experienced AIH flar
es,
with 35 occurring during pregna
47 women experienced AIH flar
es,
with 35 occurring during pregna
ncy and 12 ncy and 12
occurrin
g
after deli
very.
occurrin
g
after deli
very.
zz
fetal deaths occurred in 19% of
pr
egnancies, and the majority of
fetal deaths occurred in 19% of
pr
egnancies, and the majority of
the fetal deaths the fetal deaths
occurred before the 20
th wk of gestation.
occurred before the 20
th wk of gestation.
¾¾
A recent review of 42 pregnancie
s in women with AIH reported a
A recent review of 42 pregnancie
s in women with AIH reported a
fetal loss rate of 24%. R
ange in several studies is 14
fetal loss rate of 24%. R
ange in several studies is 14
--
24%.24%.
¾¾
Fetal death in pregnant women with AIH has been associated with Fetal death in pregnant women with AIH has been associated with the presenc
e of prematurity and low birth weight.
the presenc
e of prematurity and low birth weight.
¾¾
Factors associated with worsening of
AIH in pregnancy include:
Factors associated with worsening of
AIH in pregnancy include:
zz
changes in the r
e
lative concentr
a
tions of various hormones durin
changes in the r
e
lative concentr
a
tions of various hormones durin
g pregnancy g pregnancy
zz
specific autoantibodies, includin
g antibodies to SLA/LP and Ro/S
specific autoantibodies, includin
g antibodies to SLA/LP and Ro/S
SA.SA.
Autoimmune Hepatitis Autoimmune Hepatitis
¾¾
AIH may by exacerbated by pregnancy AIH may by exacerbated by pregnancy
zz
Intrapartum flare is 12.5% to 21%. Intrapartum flare is 12.5% to 21%.
zz
Postpartum flares are 12.5% to 86%. Postpartum flares are 12.5% to 86%.
zz
Discrepancy in data may be due to
inconsistent alteration of the
Discrepancy in data may be due to
inconsistent alteration of the
rapy rapy
during pregnancy, with dosing being maintained, reduced, or even during pregnancy, with dosing being maintained, reduced, or even discontinued. discontinued.
¾¾
Patients with AIH undergo caesaria
n section at higher rates than
Patients with AIH undergo caesaria
n section at higher rates than
the the
general population, ranging from 16.1% to 43%. general population, ranging from 16.1% to 43%.
¾¾
Women of childbearing age with
AIH should be advised to consider
Women of childbearing age with
AIH should be advised to consider
pregnancy only if their disease is well pregnancy only if their disease is well
--
controlled. controlled.
¾¾
AIH may by exacerbated by pregnancy AIH may by exacerbated by pregnancy
zz
Intrapartum flare is 12.5% to 21%. Intrapartum flare is 12.5% to 21%.
zz
Postpartum flares are 12.5% to 86%. Postpartum flares are 12.5% to 86%.
zz
Discrepancy in data may be due to
inconsistent alteration of the
Discrepancy in data may be due to
inconsistent alteration of the
rapy rapy
during pregnancy, with dosing being maintained, reduced, or even during pregnancy, with dosing being maintained, reduced, or even discontinued. discontinued.
¾¾
Patients with AIH undergo caesaria
n section at higher rates than
Patients with AIH undergo caesaria
n section at higher rates than
the the
general population, ranging from 16.1% to 43%. general population, ranging from 16.1% to 43%.
¾¾
Women of childbearing age with
AIH should be advised to consider
Women of childbearing age with
AIH should be advised to consider
pregnancy only if their disease is well pregnancy only if their disease is well
--
controlled. controlled.
Autoimmune Hepatitis Autoimmune Hepatitis
¾¾
Pregnancy or the contemplation of pregnancy does not Pregnancy or the contemplation of pregnancy does not contraindicate immunosuppressive therapy. contraindicate immunosuppressive therapy.
¾¾
Pregnant women with AIH are ofte
n treated with a combination of
Pregnant women with AIH are ofte
n treated with a combination of
steroids and azathioprine. steroids and azathioprine.
¾¾
Azathioprine crosses the plac
enta,
but data have suggested that
Azathioprine crosses the plac
enta,
but data have suggested that
azathioprine and its metabolites
do not have toxic effects on th
azathioprine and its metabolites
do not have toxic effects on th
e e
fetus. fetus.
¾¾
Expectant mothers typically respond
as well to treatment as othe
Expectant mothers typically respond
as well to treatment as othe
rs, rs,
and there have been only theoretical concerns regarding and there have been only theoretical concerns regarding teratogenic
ity associated with az
athioprine treatment but have n
teratogenic
ity associated with az
athioprine treatment but have n
ot ot
been reflected in the human exper
ience. The use of prednisone
been reflected in the human exper
ience. The use of prednisone
alone during pregnancy el
iminates any concern.
alone during pregnancy el
iminates any concern.
¾¾
Patients must be monitored closel
y throughout pregnancy and in t
Patients must be monitored closel
y throughout pregnancy and in t
he he
early postpartum period given the
unpredictability of the course
early postpartum period given the
unpredictability of the course
of of
AIH in the setting of pregnancy. AIH in the setting of pregnancy.
¾¾
Pregnancy or the contemplation of pregnancy does not Pregnancy or the contemplation of pregnancy does not contraindicate immunosuppressive therapy. contraindicate immunosuppressive therapy.
¾¾
Pregnant women with AIH are ofte
n treated with a combination of
Pregnant women with AIH are ofte
n treated with a combination of
steroids and azathioprine. steroids and azathioprine.
¾¾
Azathioprine crosses the plac
enta,
but data have suggested that
Azathioprine crosses the plac
enta,
but data have suggested that
azathioprine and its metabolites
do not have toxic effects on th
azathioprine and its metabolites
do not have toxic effects on th
e e
fetus. fetus.
¾¾
Expectant mothers typically respond
as well to treatment as othe
Expectant mothers typically respond
as well to treatment as othe
rs, rs,
and there have been only theoretical concerns regarding and there have been only theoretical concerns regarding teratogenic
ity associated with az
athioprine treatment but have n
teratogenic
ity associated with az
athioprine treatment but have n
ot ot
been reflected in the human exper
ience. The use of prednisone
been reflected in the human exper
ience. The use of prednisone
alone during pregnancy el
iminates any concern.
alone during pregnancy el
iminates any concern.
¾¾
Patients must be monitored closel
y throughout pregnancy and in t
Patients must be monitored closel
y throughout pregnancy and in t
he he
early postpartum period given the
unpredictability of the course
early postpartum period given the
unpredictability of the course
of of
AIH in the setting of pregnancy. AIH in the setting of pregnancy.
Autoimmune Hepatitis Autoimmune Hepatitis
¾¾
A modest decrease in immunos
uppres
sion can often be performed
A modest decrease in immunos
uppres
sion can often be performed
after the third month of pregnan
cy, when liver test t
y
pically im
after the third month of pregnan
cy, when liver test t
y
pically im
prove. prove.
Howev
e
r, this is usually follo
wed by a need for increased doses
Howev
e
r, this is usually follo
wed by a need for increased doses
just just
before delivery and in the postpartum period before delivery and in the postpartum period
¾¾
Women with AIH typic
a
lly tolerate pregnancy satisfactorily unles
Women with AIH typic
a
lly tolerate pregnancy satisfactorily unles
s s
their disease is advanced and complicated by ascites and their disease is advanced and complicated by ascites and esophageal varices. Under such ci
rcumstances, the risk of varice
esophageal varices. Under such ci
rcumstances, the risk of varice
al al
hemorrhage may be increased. hemorrhage may be increased.
¾¾
Patients with advanced liv
er disease and portal hypertension are
Patients with advanced liv
er disease and portal hypertension are
commonly amenorrheic and/or infertile, and pregnancy is commonly amenorrheic and/or infertile, and pregnancy is uncommon. uncommon.
¾¾
Effective contraception should
be advised in those rare, activel
Effective contraception should
be advised in those rare, activel
y y
menstruating women with AIH and advanced liver disease. menstruating women with AIH and advanced liver disease.
¾¾
A modest decrease in immunos
uppres
sion can often be performed
A modest decrease in immunos
uppres
sion can often be performed
after the third month of pregnan
cy, when liver test t
y
pically im
after the third month of pregnan
cy, when liver test t
y
pically im
prove. prove.
Howev
e
r, this is usually follo
wed by a need for increased doses
Howev
e
r, this is usually follo
wed by a need for increased doses
just just
before delivery and in the postpartum period before delivery and in the postpartum period
¾¾
Women with AIH typic
a
lly tolerate pregnancy satisfactorily unles
Women with AIH typic
a
lly tolerate pregnancy satisfactorily unles
s s
their disease is advanced and complicated by ascites and their disease is advanced and complicated by ascites and esophageal varices. Under such ci
rcumstances, the risk of varice
esophageal varices. Under such ci
rcumstances, the risk of varice
al al
hemorrhage may be increased. hemorrhage may be increased.
¾¾
Patients with advanced liv
er disease and portal hypertension are
Patients with advanced liv
er disease and portal hypertension are
commonly amenorrheic and/or infertile, and pregnancy is commonly amenorrheic and/or infertile, and pregnancy is uncommon. uncommon.
¾¾
Effective contraception should
be advised in those rare, activel
Effective contraception should
be advised in those rare, activel
y y
menstruating women with AIH and advanced liver disease. menstruating women with AIH and advanced liver disease.
Wilson Disease Wilson Disease
¾¾
Autosomal recessive disorder of copper metabolism. Autosomal recessive disorder of copper metabolism.
¾¾
Occurs in 1:30 000 to 1:50 000 persons, Occurs in 1:30 000 to 1:50 000 persons,
¾¾
Due to a mutation of gene, ATP7B, on chromosome 13q14. ATP7B cod Due to a mutation of gene, ATP7B, on chromosome 13q14. ATP7B cod
es es
for a P type ATPase that controls copper transportation in the l for a P type ATPase that controls copper transportation in the l
iver. More iver. More
than 100 forms of this mutation have been found to cause WD. Thi than 100 forms of this mutation have been found to cause WD. Thi
s s
mutation leads to copper excess and deposition in the liver and mutation leads to copper excess and deposition in the liver and
brain. brain.
¾¾
Hepatic disease may present as chronic hepatitis, cirrhosis, or Hepatic disease may present as chronic hepatitis, cirrhosis, or
fulminant fulminant
failure. failure.
¾¾
Neurologic abnormalities occur in 40% Neurologic abnormalities occur in 40%
--
50% and include an akinetic 50% and include an akinetic
--
rigid rigid
tremor similar to Parkinson tremor similar to Parkinson
’’
s disease, tremor, ataxia, and a dystonic s disease, tremor, ataxia, and a dystonic
syndrome. syndrome.
¾¾
Studies of WD effects on pregnan
cy are limited to small case ser
Studies of WD effects on pregnan
cy are limited to small case ser
ies. ies.
zz
WD may adversely affect fertility
due to horm
onal fluctuations c
WD may adversely affect fertility
due to horm
onal fluctuations c
ausing amenorrhea; ausing amenorrhea;
zz
copper deposition in t
he uterus may cause misc
arriage due to imp
copper deposition in t
he uterus may cause misc
arriage due to imp
roper implantation of the roper implantation of the
em
bryo.
em
bryo.
zz
the rate of recurrent
spontaneous abortions
is higher among untr
the rate of recurrent
spontaneous abortions
is higher among untr
eated wom
e
n with WD,
eated wom
e
n with WD,
compared to those treated. compared to those treated.
¾¾
Autosomal recessive disorder of copper metabolism. Autosomal recessive disorder of copper metabolism.
¾¾
Occurs in 1:30 000 to 1:50 000 persons, Occurs in 1:30 000 to 1:50 000 persons,
¾¾
Due to a mutation of gene, ATP7B, on chromosome 13q14. ATP7B cod Due to a mutation of gene, ATP7B, on chromosome 13q14. ATP7B cod
es es
for a P type ATPase that controls copper transportation in the l for a P type ATPase that controls copper transportation in the l
iver. More iver. More
than 100 forms of this mutation have been found to cause WD. Thi than 100 forms of this mutation have been found to cause WD. Thi
s s
mutation leads to copper excess and deposition in the liver and mutation leads to copper excess and deposition in the liver and
brain. brain.
¾¾
Hepatic disease may present as chronic hepatitis, cirrhosis, or Hepatic disease may present as chronic hepatitis, cirrhosis, or
fulminant fulminant
failure. failure.
¾¾
Neurologic abnormalities occur in 40% Neurologic abnormalities occur in 40%
--
50% and include an akinetic 50% and include an akinetic
--
rigid rigid
tremor similar to Parkinson tremor similar to Parkinson
’’
s disease, tremor, ataxia, and a dystonic s disease, tremor, ataxia, and a dystonic
syndrome. syndrome.
¾¾
Studies of WD effects on pregnan
cy are limited to small case ser
Studies of WD effects on pregnan
cy are limited to small case ser
ies. ies.
zz
WD may adversely affect fertility
due to horm
onal fluctuations c
WD may adversely affect fertility
due to horm
onal fluctuations c
ausing amenorrhea; ausing amenorrhea;
zz
copper deposition in t
he uterus may cause misc
arriage due to imp
copper deposition in t
he uterus may cause misc
arriage due to imp
roper implantation of the roper implantation of the
em
bryo.
em
bryo.
zz
the rate of recurrent
spontaneous abortions
is higher among untr
the rate of recurrent
spontaneous abortions
is higher among untr
eated wom
e
n with WD,
eated wom
e
n with WD,
compared to those treated. compared to those treated.
Wilson Disease Wilson Disease
¾¾
Penicillamine, trientine, and zinc
are drugs approved by the Uni
Penicillamine, trientine, and zinc
are drugs approved by the Uni
ted ted
States Food and Drug Administrati
on (FDA) as treatment for WD.
States Food and Drug Administrati
on (FDA) as treatment for WD.
¾¾
Penicillamine acts by chelation and enabling excretion of copper Penicillamine acts by chelation and enabling excretion of copper
in in
the urine. Penicillamine has been
reported to cause teratogenici
the urine. Penicillamine has been
reported to cause teratogenici
ty in ty in
humans. humans.
¾¾
Trientine works similarly but is
less effective than penicillami
Trientine works similarly but is
less effective than penicillami
ne. ne.
There is one report
of a chromosomal abnormality occurring in a
There is one report
of a chromosomal abnormality occurring in a
baby deliv
ered by a woman with
WD
who took trientine during
baby deliv
ered by a woman with
WD
who took trientine during
pregnancy pregnancy
¾¾
Zinc induces intestinal cell me
tallothionein that binds to coppe
Zinc induces intestinal cell me
tallothionein that binds to coppe
r and r and
prevents transfer of copper
into the blood. Brewer
prevents transfer of copper
into the blood. Brewer
reported that the reported that the
use of zinc in 26 use of zinc in 26
pregnancies of 19 pregnant women with WD pregnancies of 19 pregnant women with WD
resulted in 24 healthy pregnanc
ies; one baby was born with a hea
resulted in 24 healthy pregnanc
ies; one baby was born with a hea
rt rt
defect requiring surgery at 6 mo, and a second baby was born wit defect requiring surgery at 6 mo, and a second baby was born wit
h h
microcephaly. microcephaly.
¾¾
Penicillamine, trientine, and zinc
are drugs approved by the Uni
Penicillamine, trientine, and zinc
are drugs approved by the Uni
ted ted
States Food and Drug Administrati
on (FDA) as treatment for WD.
States Food and Drug Administrati
on (FDA) as treatment for WD.
¾¾
Penicillamine acts by chelation and enabling excretion of copper Penicillamine acts by chelation and enabling excretion of copper
in in
the urine. Penicillamine has been
reported to cause teratogenici
the urine. Penicillamine has been
reported to cause teratogenici
ty in ty in
humans. humans.
¾¾
Trientine works similarly but is
less effective than penicillami
Trientine works similarly but is
less effective than penicillami
ne. ne.
There is one report
of a chromosomal abnormality occurring in a
There is one report
of a chromosomal abnormality occurring in a
baby deliv
ered by a woman with
WD
who took trientine during
baby deliv
ered by a woman with
WD
who took trientine during
pregnancy pregnancy
¾¾
Zinc induces intestinal cell me
tallothionein that binds to coppe
Zinc induces intestinal cell me
tallothionein that binds to coppe
r and r and
prevents transfer of copper
into the blood. Brewer
prevents transfer of copper
into the blood. Brewer
reported that the reported that the
use of zinc in 26 use of zinc in 26
pregnancies of 19 pregnant women with WD pregnancies of 19 pregnant women with WD
resulted in 24 healthy pregnanc
ies; one baby was born with a hea
resulted in 24 healthy pregnanc
ies; one baby was born with a hea
rt rt
defect requiring surgery at 6 mo, and a second baby was born wit defect requiring surgery at 6 mo, and a second baby was born wit
h h
microcephaly. microcephaly.
Wilson Disease Wilson Disease
¾¾
In WD pregnant women, treatment must be In WD pregnant women, treatment must be maintained throughout the course of pregnancy. maintained throughout the course of pregnancy.
¾¾
Interruption of treatment during pregnancy has Interruption of treatment during pregnancy has resulted in acute liver failure. resulted in acute liver failure.
¾¾
Chelating agents (both penicillamine and trientine) and Chelating agents (both penicillamine and trientine) and zinc salts have been associated with satisfactory zinc salts have been associated with satisfactory outcomes for the mother and fetus. outcomes for the mother and fetus.
¾¾
A few birth defects has been noted infrequently in A few birth defects has been noted infrequently in offspring of treated patients; however, the rarity of this offspring of treated patients; however, the rarity of this disorder has made it difficult to determine whether this is disorder has made it difficult to determine whether this is different from the frequency of these defects in the different from the frequency of these defects in the population at large. population at large.
¾¾
In WD pregnant women, treatment must be In WD pregnant women, treatment must be maintained throughout the course of pregnancy. maintained throughout the course of pregnancy.
¾¾
Interruption of treatment during pregnancy has Interruption of treatment during pregnancy has resulted in acute liver failure. resulted in acute liver failure.
¾¾
Chelating agents (both penicillamine and trientine) and Chelating agents (both penicillamine and trientine) and zinc salts have been associated with satisfactory zinc salts have been associated with satisfactory outcomes for the mother and fetus. outcomes for the mother and fetus.
¾¾
A few birth defects has been noted infrequently in A few birth defects has been noted infrequently in offspring of treated patients; however, the rarity of this offspring of treated patients; however, the rarity of this disorder has made it difficult to determine whether this is disorder has made it difficult to determine whether this is different from the frequency of these defects in the different from the frequency of these defects in the population at large. population at large.
Wilson Disease Wilson Disease
¾¾
The dosage of zinc salts is maintained throughout The dosage of zinc salts is maintained throughout without change. without change.
¾¾
Dosages of chelating agents should be reduced to the Dosages of chelating agents should be reduced to the minimum necessary during pregnancy, especially for the minimum necessary during pregnancy, especially for the last trimester to promote better wound healing if last trimester to promote better wound healing if cesarean section is performed. Dose reduction might be cesarean section is performed. Dose reduction might be on the order of 25% on the order of 25%
--
50% of the pre 50% of the pre
--
pregnancy dose. pregnancy dose.
¾¾
Patients should be monitored frequently during Patients should be monitored frequently during pregnancy. pregnancy.
¾¾
Women taking D Women taking D
--
penicillamine should not breast penicillamine should not breast
--
feed feed
because the drug is excreted into breast milk and might because the drug is excreted into breast milk and might harm the infant. harm the infant.
¾¾
Little is known about the safety of trientine and zinc in Little is known about the safety of trientine and zinc in breast milk. breast milk.
¾¾
The dosage of zinc salts is maintained throughout The dosage of zinc salts is maintained throughout without change. without change.
¾¾
Dosages of chelating agents should be reduced to the Dosages of chelating agents should be reduced to the minimum necessary during pregnancy, especially for the minimum necessary during pregnancy, especially for the last trimester to promote better wound healing if last trimester to promote better wound healing if cesarean section is performed. Dose reduction might be cesarean section is performed. Dose reduction might be on the order of 25% on the order of 25%
--
50% of the pre 50% of the pre
--
pregnancy dose. pregnancy dose.
¾¾
Patients should be monitored frequently during Patients should be monitored frequently during pregnancy. pregnancy.
¾¾
Women taking D Women taking D
--
penicillamine should not breast penicillamine should not breast
--
feed feed
because the drug is excreted into breast milk and might because the drug is excreted into breast milk and might harm the infant. harm the infant.
¾¾
Little is known about the safety of trientine and zinc in Little is known about the safety of trientine and zinc in breast milk. breast milk.
Pregnancy in Cirrhosis Pregnancy in Cirrhosis
¾¾
Only 45 cases of cirrhosis occur in every 100,000 women of Only 45 cases of cirrhosis occur in every 100,000 women of reproductive age. reproductive age.
¾¾
Cirrhosis results in metabolic
and hormonal derangements that le
Cirrhosis results in metabolic
and hormonal derangements that le
ad ad
to anovulation and amenorrhea to anovulation and amenorrhea
¾¾
Morbidity and mortality likely rema
ins higher than that of the g
Morbidity and mortality likely rema
ins higher than that of the g
eneral eneral
pregnant population. pregnant population.
¾¾
Spontaneous abortion rate in patient
s with cirrhosis is 30% to 4
Spontaneous abortion rate in patient
s with cirrhosis is 30% to 4
0% 0%
versus 15% to 20% in the general population. versus 15% to 20% in the general population.
¾¾
In patients with extrahepatic por
tal obstruction unrelated to ci
In patients with extrahepatic por
tal obstruction unrelated to ci
rrhosis, rrhosis,
the rate of spontaneous abortion is 3% to 6%. the rate of spontaneous abortion is 3% to 6%.
¾¾
Patients with cirrhosis who have undergone portal decompressive Patients with cirrhosis who have undergone portal decompressive procedures prior to concepti
on have spontaneous abortion rates
procedures prior to concepti
on have spontaneous abortion rates
comparable to patients with extrahepatic obstruction. comparable to patients with extrahepatic obstruction.
¾¾
Only 45 cases of cirrhosis occur in every 100,000 women of Only 45 cases of cirrhosis occur in every 100,000 women of reproductive age. reproductive age.
¾¾
Cirrhosis results in metabolic
and hormonal derangements that le
Cirrhosis results in metabolic
and hormonal derangements that le
ad ad
to anovulation and amenorrhea to anovulation and amenorrhea
¾¾
Morbidity and mortality likely rema
ins higher than that of the g
Morbidity and mortality likely rema
ins higher than that of the g
eneral eneral
pregnant population. pregnant population.
¾¾
Spontaneous abortion rate in patient
s with cirrhosis is 30% to 4
Spontaneous abortion rate in patient
s with cirrhosis is 30% to 4
0% 0%
versus 15% to 20% in the general population. versus 15% to 20% in the general population.
¾¾
In patients with extrahepatic por
tal obstruction unrelated to ci
In patients with extrahepatic por
tal obstruction unrelated to ci
rrhosis, rrhosis,
the rate of spontaneous abortion is 3% to 6%. the rate of spontaneous abortion is 3% to 6%.
¾¾
Patients with cirrhosis who have undergone portal decompressive Patients with cirrhosis who have undergone portal decompressive procedures prior to concepti
on have spontaneous abortion rates
procedures prior to concepti
on have spontaneous abortion rates
comparable to patients with extrahepatic obstruction. comparable to patients with extrahepatic obstruction.
Pregnancy in Cirrhosis Pregnancy in Cirrhosis
¾¾
Termination of pregnancy most often occurs as a result Termination of pregnancy most often occurs as a result of maternal death, variceal hemorrhage, stillbirth, of maternal death, variceal hemorrhage, stillbirth, intrauterine growth retardation, and maternal intrauterine growth retardation, and maternal complications during delivery. complications during delivery.
¾¾
In those pregnancies that do result in live births, the risk In those pregnancies that do result in live births, the risk of prematurity is significantly increased, with a rate of up of prematurity is significantly increased, with a rate of up to 25%, compared with 12.8% in the general population. to 25%, compared with 12.8% in the general population.
¾¾
From old literature, the perinatal death rate is likewise From old literature, the perinatal death rate is likewise elevated and may be as high as 18% versus 1.08% in elevated and may be as high as 18% versus 1.08% in the noncirrhotic population. We do not know if current the noncirrhotic population. We do not know if current outcomes are better. outcomes are better.
¾¾
Termination of pregnancy most often occurs as a result Termination of pregnancy most often occurs as a result of maternal death, variceal hemorrhage, stillbirth, of maternal death, variceal hemorrhage, stillbirth, intrauterine growth retardation, and maternal intrauterine growth retardation, and maternal complications during delivery. complications during delivery.
¾¾
In those pregnancies that do result in live births, the risk In those pregnancies that do result in live births, the risk of prematurity is significantly increased, with a rate of up of prematurity is significantly increased, with a rate of up to 25%, compared with 12.8% in the general population. to 25%, compared with 12.8% in the general population.
¾¾
From old literature, the perinatal death rate is likewise From old literature, the perinatal death rate is likewise elevated and may be as high as 18% versus 1.08% in elevated and may be as high as 18% versus 1.08% in the noncirrhotic population. We do not know if current the noncirrhotic population. We do not know if current outcomes are better. outcomes are better.
Pregnancy in Cirrhosis Pregnancy in Cirrhosis
¾¾
Esophageal Varices: Esophageal Varices:
zz
Esophageal variceal bleeding is reported in 18% to 32% of pregna Esophageal variceal bleeding is reported in 18% to 32% of pregna
nt nt
women with cirrhosis and in up to 50% of those with known portal women with cirrhosis and in up to 50% of those with known portal hypertension. hypertension.
zz
With preexisting varices, up to 78% will have gastrointestinal b With preexisting varices, up to 78% will have gastrointestinal b
leeding leeding
during pregnancy, with a mortality rate of 18% to 50%. In non during pregnancy, with a mortality rate of 18% to 50%. In non
--
cirrhotic cirrhotic
portal hypertension with pregnancy, mortality rate is 2 portal hypertension with pregnancy, mortality rate is 2
--
6%.6%.
zz
Bleeding is most common during the second and third trimesters w Bleeding is most common during the second and third trimesters w
hen hen
maternal blood volume is maximally expanded and the larger fetus maternal blood volume is maximally expanded and the larger fetus causes increased compression of the inferior vena cava and colla causes increased compression of the inferior vena cava and colla
teral teral
vasculature vasculature
zz
Primary prophylaxis with nonselective beta blockers such as Primary prophylaxis with nonselective beta blockers such as propranolol, nadolol, or carvedilol (category C), may outweigh propranolol, nadolol, or carvedilol (category C), may outweigh
the risks the risks
of potential fetal harm. Side effects of these drugs include fet of potential fetal harm. Side effects of these drugs include fet
al growth al growth
retardation, neonatal hypoglycemia, and neonatal bradycardia retardation, neonatal hypoglycemia, and neonatal bradycardia
¾¾
Esophageal Varices: Esophageal Varices:
zz
Esophageal variceal bleeding is reported in 18% to 32% of pregna Esophageal variceal bleeding is reported in 18% to 32% of pregna
nt nt
women with cirrhosis and in up to 50% of those with known portal women with cirrhosis and in up to 50% of those with known portal hypertension. hypertension.
zz
With preexisting varices, up to 78% will have gastrointestinal b With preexisting varices, up to 78% will have gastrointestinal b
leeding leeding
during pregnancy, with a mortality rate of 18% to 50%. In non during pregnancy, with a mortality rate of 18% to 50%. In non
--
cirrhotic cirrhotic
portal hypertension with pregnancy, mortality rate is 2 portal hypertension with pregnancy, mortality rate is 2
--
6%.6%.
zz
Bleeding is most common during the second and third trimesters w Bleeding is most common during the second and third trimesters w
hen hen
maternal blood volume is maximally expanded and the larger fetus maternal blood volume is maximally expanded and the larger fetus causes increased compression of the inferior vena cava and colla causes increased compression of the inferior vena cava and colla
teral teral
vasculature vasculature
zz
Primary prophylaxis with nonselective beta blockers such as Primary prophylaxis with nonselective beta blockers such as propranolol, nadolol, or carvedilol (category C), may outweigh propranolol, nadolol, or carvedilol (category C), may outweigh
the risks the risks
of potential fetal harm. Side effects of these drugs include fet of potential fetal harm. Side effects of these drugs include fet
al growth al growth
retardation, neonatal hypoglycemia, and neonatal bradycardia retardation, neonatal hypoglycemia, and neonatal bradycardia
Pregnancy in Cirrhosis Pregnancy in Cirrhosis
¾¾
Esophageal Varices: Esophageal Varices:
zz
Up to 24% of pregnant patients wi
th cirr
hosis will experience he
Up to 24% of pregnant patients wi
th cirr
hosis will experience he
patic patic
decompensation , usually due to vari
ceal bleed. With fulminant f
decompensation , usually due to vari
ceal bleed. With fulminant f
ailure, liver ailure, liver
transplantation may be the only
option, which may be successful
transplantation may be the only
option, which may be successful
for
mother and
for
mother and
fetus. fetus.
zz
Treatment of choice
is Endoscopic Band Ligation, plus cefotaxime
Treatment of choice
is Endoscopic Band Ligation, plus cefotaxime
(categor
y B),
(categor
y B),
plus Octreotide (
c
ategory B)
.
plus Octreotide (
c
ategory B)
.
zz
TIPS placement is gener
ally cont
raindicated during pregnancy bec
TIPS placement is gener
ally cont
raindicated during pregnancy bec
ause of the ause of the
risk of r
adiation exposure to
the fetus. It may be an appr
opriat
risk of r
adiation exposure to
the fetus. It may be an appr
opriat
e r
e
scue therapy .
e rescu
e therapy .
The risk of fetal malfor
mations fr
om radiation increases at dose
The risk of fetal malfor
mations fr
om radiation increases at dose
s above 150 mGy s above 150 mGy
and is negligible if below 50 mG
y. TIPS can be done with as lit
and is negligible if below 50 mG
y. TIPS can be done with as lit
tle as
0.1
tle as
0.1
--
5.49 5.49
mGy
.
mGy
.
zz
Repetitive Valsalva maneuver during labor
increases variceal ble
Repetitive Valsalva maneuver during labor
increases variceal ble
ed risk. Many ed risk. Many
experts advocate elective c experts advocate elective c
--
section or
forceps delivery under ex
tradural
section or
forceps delivery under ex
tradural
analgesia in order
to decr
ease this risk. During C
analgesia in order
to decr
ease this risk. During C
--
section a surgeon with section a surgeon with
experience with cirrhosis should
be available in case of collate
experience with cirrhosis should
be available in case of collate
ral circulation ral circulation
bleed. bleed.
Absorbed dose per
unit of weight is
measured in gray (
G
Y); 1 Gy
=
100 r
a
d
Biological risk depends in type of
radiation, is measured in
sievert (Sv); 1 Sv =
100 rem
¾¾
Esophageal Varices: Esophageal Varices:
zz
Up to 24% of pregnant patients wi
th cirr
hosis will experience he
Up to 24% of pregnant patients wi
th cirr
hosis will experience he
patic patic
decompensation , usually due to vari
ceal bleed. With fulminant f
decompensation , usually due to vari
ceal bleed. With fulminant f
ailure, liver ailure, liver
transplantation may be the only
option, which may be successful
transplantation may be the only
option, which may be successful
for
mother and
for
mother and
fetus. fetus.
zz
Treatment of choice
is Endoscopic Band Ligation, plus cefotaxime
Treatment of choice
is Endoscopic Band Ligation, plus cefotaxime
(categor
y B),
(categor
y B),
plus Octreotide (
c
ategory B)
.
plus Octreotide (
c
ategory B)
.
zz
TIPS placement is gener
ally cont
raindicated during pregnancy bec
TIPS placement is gener
ally cont
raindicated during pregnancy bec
ause of the ause of the
risk of r
adiation exposure to
the fetus. It may be an appr
opriat
risk of r
adiation exposure to
the fetus. It may be an appr
opriat
e r
e
scue therapy .
e rescu
e therapy .
The risk of fetal malfor
mations fr
om radiation increases at dose
The risk of fetal malfor
mations fr
om radiation increases at dose
s above 150 mGy s above 150 mGy
and is negligible if below 50 mG
y. TIPS can be done with as lit
and is negligible if below 50 mG
y. TIPS can be done with as lit
tle as
0.1
tle as
0.1
--
5.49 5.49
mGy
.
mGy
.
zz
Repetitive Valsalva maneuver during labor
increases variceal ble
Repetitive Valsalva maneuver during labor
increases variceal ble
ed risk. Many ed risk. Many
experts advocate elective c experts advocate elective c
--
section or
forceps delivery under ex
tradural
section or
forceps delivery under ex
tradural
analgesia in order
to decr
ease this risk. During C
analgesia in order
to decr
ease this risk. During C
--
section a surgeon with section a surgeon with
experience with cirrhosis should
be available in case of collate
experience with cirrhosis should
be available in case of collate
ral circulation ral circulation
bleed. bleed.
Absorbed dose per
unit of weight is
measured in gray (
G
Y); 1 Gy
=
100 r
a
d
Biological risk depends in type of
radiation, is measured in
sievert (Sv); 1 Sv =
100 rem
Pregnancy in Cirrhosis Pregnancy in Cirrhosis
¾¾
Ascites and SBP Ascites and SBP
zz
Ascites rarely occurs during pregnancy because of increased Ascites rarely occurs during pregnancy because of increased intra intra
--
abdominal pressure, which acts
to resist the extravasation
abdominal pressure, which acts
to resist the extravasation
of fluid from splanchnic vessels and organs. of fluid from splanchnic vessels and organs.
zz
If therapy is required, however,
sodium restriction and diuretic
If therapy is required, however,
sodium restriction and diuretic
s s
can be used, as in nonpregnant
patients with cirrhosis. Amilorid
can be used, as in nonpregnant
patients with cirrhosis. Amilorid
e e
(category B), and Torsemide (c
ategory B) are reasonable
(category B), and Torsemide (c
ategory B) are reasonable
choices. Metolazone and HC
TZ
are also category B, but are
choices. Metolazone and HC
TZ
are also category B, but are
reserved as third line, to
add to other regimens.
reserved as third line, to
add to other regimens.
zz
Cases
of spontaneous bacterial peritonitis have not been
Cases
of spontaneous bacterial peritonitis have not been
reported during pregnancy. reported during pregnancy.
¾¾
Ascites and SBP Ascites and SBP
zz
Ascites rarely occurs during pregnancy because of increased Ascites rarely occurs during pregnancy because of increased intra intra
--
abdominal pressure, which acts
to resist the extravasation
abdominal pressure, which acts
to resist the extravasation
of fluid from splanchnic vessels and organs. of fluid from splanchnic vessels and organs.
zz
If therapy is required, however,
sodium restriction and diuretic
If therapy is required, however,
sodium restriction and diuretic
s s
can be used, as in nonpregnant
patients with cirrhosis. Amilorid
can be used, as in nonpregnant
patients with cirrhosis. Amilorid
e e
(category B), and Torsemide (c
ategory B) are reasonable
(category B), and Torsemide (c
ategory B) are reasonable
choices. Metolazone and HC
TZ
are also category B, but are
choices. Metolazone and HC
TZ
are also category B, but are
reserved as third line, to
add to other regimens.
reserved as third line, to
add to other regimens.
zz
Cases
of spontaneous bacterial peritonitis have not been
Cases
of spontaneous bacterial peritonitis have not been
reported during pregnancy. reported during pregnancy.
Pregnancy in Cirrhosis Pregnancy in Cirrhosis
¾¾
Hepatic Encephalopathy Hepatic Encephalopathy
zz
May develop due to predispos
ing medications, hypotens
ion,
May develop due to predispos
ing medications, hypotens
ion,
hypox
ia, infection, hypoglyce
mia, or gastrointestinal
hypox
ia, infection, hypoglyce
mia, or gastrointestinal
hemorrhage. hemorrhage.
zz
Spinal and general anesthesia should be avoided during delivery Spinal and general anesthesia should be avoided during delivery because of the potential for hy
potension and the risk of
because of the potential for hy
potension and the risk of
precipitating encephalopathy. precipitating encephalopathy.
zz
Treatment remains frequent small
meals, lactulos
e (category B),
Treatment remains frequent small
meals, lactulos
e (category B),
Zinc, L Zinc, L
--
carnitine (category B) and/or rifaximin (category C). carnitine (category B) and/or rifaximin (category C).
Metronidazol is category B, and neomycin is category D Metronidazol is category B, and neomycin is category D
¾¾
Hepatic Encephalopathy Hepatic Encephalopathy
zz
May develop due to predispos
ing medications, hypotens
ion,
May develop due to predispos
ing medications, hypotens
ion,
hypox
ia, infection, hypoglyce
mia, or gastrointestinal
hypox
ia, infection, hypoglyce
mia, or gastrointestinal
hemorrhage. hemorrhage.
zz
Spinal and general anesthesia should be avoided during delivery Spinal and general anesthesia should be avoided during delivery because of the potential for hy
potension and the risk of
because of the potential for hy
potension and the risk of
precipitating encephalopathy. precipitating encephalopathy.
zz
Treatment remains frequent small
meals, lactulos
e (category B),
Treatment remains frequent small
meals, lactulos
e (category B),
Zinc, L Zinc, L
--
carnitine (category B) and/or rifaximin (category C). carnitine (category B) and/or rifaximin (category C).
Metronidazol is category B, and neomycin is category D Metronidazol is category B, and neomycin is category D
Splenic Artery Aneurism Rupture Splenic Artery Aneurism Rupture
¾¾
Splenic artery aneurisms are incr
eased in pregnancy related to:
Splenic artery aneurisms are incr
eased in pregnancy related to:
zz
increased splenic blood flow from both pregnancy and portal increased splenic blood flow from both pregnancy and portal hypertension. hypertension.
zz
high estrogen levels during pregnancy which effects the elastic high estrogen levels during pregnancy which effects the elastic
tissue of tissue of
the tunica media the tunica media
¾¾
Pregnant patients with cirrhosis have an increased risk of
splen
Pregnant patients with cirrhosis have an increased risk of
splen
ic ic
artery aneurysm rupture, whic
h occurs in 2.6%.
artery aneurysm rupture, whic
h occurs in 2.6%.
¾¾
20% of all splenic artery aneurysm
ruptures occur during pregnan
20% of all splenic artery aneurysm
ruptures occur during pregnan
cy, cy,
with 70% occurring during the third trimester. with 70% occurring during the third trimester.
¾¾
Clinical Presentation: Rapid intra Clinical Presentation: Rapid intra
--
abdominal bleeding and abdominal bleeding and
hypov
olemic
shock often ensue, re
sulting in substantial maternal
hypov
olemic
shock often ensue, re
sulting in substantial maternal
and fetal mortality rates of
70% and 80%, respectively.
and fetal mortality rates of
70% and 80%, respectively.
¾¾
Splenic artery aneurisms are incr
eased in pregnancy related to:
Splenic artery aneurisms are incr
eased in pregnancy related to:
zz
increased splenic blood flow from both pregnancy and portal increased splenic blood flow from both pregnancy and portal hypertension. hypertension.
zz
high estrogen levels during pregnancy which effects the elastic high estrogen levels during pregnancy which effects the elastic
tissue of tissue of
the tunica media the tunica media
¾¾
Pregnant patients with cirrhosis have an increased risk of
splen
Pregnant patients with cirrhosis have an increased risk of
splen
ic ic
artery aneurysm rupture, whic
h occurs in 2.6%.
artery aneurysm rupture, whic
h occurs in 2.6%.
¾¾
20% of all splenic artery aneurysm
ruptures occur during pregnan
20% of all splenic artery aneurysm
ruptures occur during pregnan
cy, cy,
with 70% occurring during the third trimester. with 70% occurring during the third trimester.
¾¾
Clinical Presentation: Rapid intra Clinical Presentation: Rapid intra
--
abdominal bleeding and abdominal bleeding and
hypov
olemic
shock often ensue, re
sulting in substantial maternal
hypov
olemic
shock often ensue, re
sulting in substantial maternal
and fetal mortality rates of
70% and 80%, respectively.
and fetal mortality rates of
70% and 80%, respectively.
Splenic Artery Aneurism Rupture Splenic Artery Aneurism Rupture
¾¾
Management options: Management options:
zz
emergency splenectomy, emergency splenectomy,
zz
transcatheter emboliz
ation of the aneurysm, or
transcatheter emboliz
ation of the aneurysm, or
zz
stent stent
--
graft placement. graft placement.
¾¾
Transcatheter embolization, and stent Transcatheter embolization, and stent
--
graft placement, graft placement,
are usually the preferred options in cases of portal are usually the preferred options in cases of portal hypertension, as an extensive collateral circulation in hypertension, as an extensive collateral circulation in these patients makes surgery more difficult. these patients makes surgery more difficult.
¾¾
Management options: Management options:
zz
emergency splenectomy, emergency splenectomy,
zz
transcatheter emboliz
ation of the aneurysm, or
transcatheter emboliz
ation of the aneurysm, or
zz
stent stent
--
graft placement. graft placement.
¾¾
Transcatheter embolization, and stent Transcatheter embolization, and stent
--
graft placement, graft placement,
are usually the preferred options in cases of portal are usually the preferred options in cases of portal hypertension, as an extensive collateral circulation in hypertension, as an extensive collateral circulation in these patients makes surgery more difficult. these patients makes surgery more difficult.
PostPost
--
Partum Uterine Hemorrhage Partum Uterine Hemorrhage
¾¾
Occurs in 7% to 10% of pregnancies in patients with Occurs in 7% to 10% of pregnancies in patients with cirrhosis. cirrhosis.
¾¾
Likely related to a higher incidence of coagulopathy and Likely related to a higher incidence of coagulopathy and thrombocytopenia. thrombocytopenia.
¾¾
Treatment is similar to that in patients without cirrhosis. Treatment is similar to that in patients without cirrhosis.
zz
blood and coagulation factors blood and coagulation factors
zz
oxytocin or other uterine contractile agents. oxytocin or other uterine contractile agents.
zz
surgic
al therapy to ligate the bl
eeding vessels or hysterectomy
surgic
al therapy to ligate the bl
eeding vessels or hysterectomy
is is
indicated when these measures fail. indicated when these measures fail.
--
Partum Uterine Hemorrhage Partum Uterine Hemorrhage
¾¾
Occurs in 7% to 10% of pregnancies in patients with Occurs in 7% to 10% of pregnancies in patients with cirrhosis. cirrhosis.
¾¾
Likely related to a higher incidence of coagulopathy and Likely related to a higher incidence of coagulopathy and thrombocytopenia. thrombocytopenia.
¾¾
Treatment is similar to that in patients without cirrhosis. Treatment is similar to that in patients without cirrhosis.
zz
blood and coagulation factors blood and coagulation factors
zz
oxytocin or other uterine contractile agents. oxytocin or other uterine contractile agents.
zz
surgic
al therapy to ligate the bl
eeding vessels or hysterectomy
surgic
al therapy to ligate the bl
eeding vessels or hysterectomy
is is
indicated when these measures fail. indicated when these measures fail.
Pregnancy after Liver Transplantation Pregnancy after Liver Transplantation
¾¾
As of January 2006, 202 pregnancies and 205 outcomes As of January 2006, 202 pregnancies and 205 outcomes have been reported in 121 female liver transplant have been reported in 121 female liver transplant recipients in the National Transplantation Pregnancy recipients in the National Transplantation Pregnancy Registry. Registry.
¾¾
Children born to female liver transplant recipients have, Children born to female liver transplant recipients have, compared with the regular population: compared with the regular population:
zz
greater risk of prematurity (35% versus 11.0% greater risk of prematurity (35% versus 11.0%
--
12.7%) and 12.7%) and
zz
greater risk of low birth weight (34% versus 8.2%) greater risk of low birth weight (34% versus 8.2%)
¾¾
As of January 2006, 202 pregnancies and 205 outcomes As of January 2006, 202 pregnancies and 205 outcomes have been reported in 121 female liver transplant have been reported in 121 female liver transplant recipients in the National Transplantation Pregnancy recipients in the National Transplantation Pregnancy Registry. Registry.
¾¾
Children born to female liver transplant recipients have, Children born to female liver transplant recipients have, compared with the regular population: compared with the regular population:
zz
greater risk of prematurity (35% versus 11.0% greater risk of prematurity (35% versus 11.0%
--
12.7%) and 12.7%) and
zz
greater risk of low birth weight (34% versus 8.2%) greater risk of low birth weight (34% versus 8.2%)
Pregnancy after Liver Transplantation Pregnancy after Liver Transplantation
¾¾
No associated malformation patterns reported thus far, No associated malformation patterns reported thus far, but recent data indicates that mycophenolate may be but recent data indicates that mycophenolate may be associated with first trimester pregnancy loss and an associated with first trimester pregnancy loss and an increased risk of congenital malformations. increased risk of congenital malformations.
¾¾
Maternal complications are increased in liver transplant Maternal complications are increased in liver transplant recipients: recipients:
zz
pregnancy pregnancy
--
induced hypertension (34% versus 4% induced hypertension (34% versus 4%
--
10%), 10%),
zz
preeclampsia (22% versus 6% preeclampsia (22% versus 6%
--
8%), and 8%), and
zz
caesarian section (35% versus 20% caesarian section (35% versus 20%
--
25%). 25%).
¾¾
No associated malformation patterns reported thus far, No associated malformation patterns reported thus far, but recent data indicates that mycophenolate may be but recent data indicates that mycophenolate may be associated with first trimester pregnancy loss and an associated with first trimester pregnancy loss and an increased risk of congenital malformations. increased risk of congenital malformations.
¾¾
Maternal complications are increased in liver transplant Maternal complications are increased in liver transplant recipients: recipients:
zz
pregnancy pregnancy
--
induced hypertension (34% versus 4% induced hypertension (34% versus 4%
--
10%), 10%),
zz
preeclampsia (22% versus 6% preeclampsia (22% versus 6%
--
8%), and 8%), and
zz
caesarian section (35% versus 20% caesarian section (35% versus 20%
--
25%). 25%).
Pregnancy after Liver Transplantation Pregnancy after Liver Transplantation
¾¾
The incidence of pregnancy The incidence of pregnancy
--
induced or exacerbated induced or exacerbated
hypertension is highest with cyclosporine, followed by hypertension is highest with cyclosporine, followed by tacrolimus and then corticosteroids. tacrolimus and then corticosteroids.
¾¾
The rate of acute rejection in pregnant liver recipients is The rate of acute rejection in pregnant liver recipients is not substantially different, from that of their nonpregnant not substantially different, from that of their nonpregnant counterparts. counterparts.
zz
In 121 liver recipients, 7% developed acute rejection during pre In 121 liver recipients, 7% developed acute rejection during pre
gnancy, gnancy,
and 8% suffered graft loss within 2 years of delivery. and 8% suffered graft loss within 2 years of delivery.
zz
Risk was highest in women who conceived within 6 months of thei Risk was highest in women who conceived within 6 months of thei
r r
transplant. transplant.
¾¾
The incidence of pregnancy The incidence of pregnancy
--
induced or exacerbated induced or exacerbated
hypertension is highest with cyclosporine, followed by hypertension is highest with cyclosporine, followed by tacrolimus and then corticosteroids. tacrolimus and then corticosteroids.
¾¾
The rate of acute rejection in pregnant liver recipients is The rate of acute rejection in pregnant liver recipients is not substantially different, from that of their nonpregnant not substantially different, from that of their nonpregnant counterparts. counterparts.
zz
In 121 liver recipients, 7% developed acute rejection during pre In 121 liver recipients, 7% developed acute rejection during pre
gnancy, gnancy,
and 8% suffered graft loss within 2 years of delivery. and 8% suffered graft loss within 2 years of delivery.
zz
Risk was highest in women who conceived within 6 months of thei Risk was highest in women who conceived within 6 months of thei
r r
transplant. transplant.
Pregnancy after Liver Transplantation Pregnancy after Liver Transplantation
¾¾
Experts recommend that pregnancy be postponed for at Experts recommend that pregnancy be postponed for at least 1 year post least 1 year post
--
transplant, when graft function is transplant, when graft function is
optimal on lower doses of immunosuppression and the optimal on lower doses of immunosuppression and the risks of acute rejection and opportunistic infection are risks of acute rejection and opportunistic infection are lower. Until then, contraception is advised, preferably lower. Until then, contraception is advised, preferably using barrier methods, which confer a lower risk of using barrier methods, which confer a lower risk of infection or potential drug interaction. infection or potential drug interaction.
¾¾
Physicians should discuss with all patients considering Physicians should discuss with all patients considering pregnancy, as part of pretransplant counseling: pregnancy, as part of pretransplant counseling:
zz
the timing of pregnancy, the timing of pregnancy,
zz
methods of contraception, and methods of contraception, and
zz
safety
and adverse effects of immunos
uppres
sants
safety
and adverse effects of immunos
uppres
sants
¾¾
Experts recommend that pregnancy be postponed for at Experts recommend that pregnancy be postponed for at least 1 year post least 1 year post
--
transplant, when graft function is transplant, when graft function is
optimal on lower doses of immunosuppression and the optimal on lower doses of immunosuppression and the risks of acute rejection and opportunistic infection are risks of acute rejection and opportunistic infection are lower. Until then, contraception is advised, preferably lower. Until then, contraception is advised, preferably using barrier methods, which confer a lower risk of using barrier methods, which confer a lower risk of infection or potential drug interaction. infection or potential drug interaction.
¾¾
Physicians should discuss with all patients considering Physicians should discuss with all patients considering pregnancy, as part of pretransplant counseling: pregnancy, as part of pretransplant counseling:
zz
the timing of pregnancy, the timing of pregnancy,
zz
methods of contraception, and methods of contraception, and
zz
safety
and adverse effects of immunos
uppres
sants
safety
and adverse effects of immunos
uppres
sants
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