live diseases in pregnency and approach .pptx

liver diseases in prengency,intrahepatic cholestasis in pregnency

1. Liver Disease in Pregnancy DR SAMBIT KUMAR PATEL

2. Classification of disease Diseases Unique to Pregnancy Intercurrent liver disease in pregnancy Chronic liver disease revealed by pregnancy Pregnancy after Liver Transplant

3. I) Diseases Unique to Pregnancy Hyepremeis gravidarum Intraheptic cholestatis of pregnancy Preeclampsia liver disorders HELLP syndrome Acute fatty liver of pregnancy

4. Disease Trimester Hyperemesis gravidarum 1 st Intrahepatic cholestasis of pregnancy 2 nd & 3 rd HELLP syndrome Late 2 nd & 3 rd Preeclampsia Late 2 nd & 3 rd Acute fatty liver of pregnancy 3 rd Budd- Chiari syndrome Post partum

5. Hyperemeis gravidarum Morning sickness present in over 50% of all preganancy Hyperemesis gravidarum in about 1.5% of pranancy >3 episodes of vomiting/day accompanying ketonuria and weigh loss of >3kg or %5of pre-pregnancy bodyweight Risk factor young age Multiple gestation History of HG Asian and black ethnicity Female fetus Thyroid and parathyrioid dysfunction Hypercholesteremia Type I DM

6. Pathophysiology Complex process and exact cause is unknown Increased levels of human chorionic gonadotropin (HCG) in HG may cause stimulation of secretory processes of the upper gastrointestinal tract and stimulation of the thyroid gland.   Elevations of estrogen , decreases in prolactin levels, and over activity of the hypothalamic-pituitary-adrenal axis

7. Clinical and biochemical finding During 4-10 gestation week Resolve by 20 th week, regardless of therapy Mild elevation of aminotransferase SGPT>SGOT Up to 1000 IU/l Bilirubin may increase Liver biopsy rarely perform-no inflammation, centrilobular vacuolization, necrosis with cell dropout

8. Maternal and fetal outcome FETAL COMPLICATION Low pregnancy weight gain <7 kg Low birth weight Small for gestational age Pre-term birth Poor 5min Apgar score MATERNAL COMPLICATION Weight loss Dehydration Micro-nutrient deficiency Mallory- weiss tears Wernics encephalopathy Retinal hemorrhage Spontaneous pneumomediastinum

9. THERAPY Non pharmacological alternatives Acupressure, ginger, frequent small meals, avoid food that delay gastric emptying Rehydration and gut rest Diet rich in carbohydrates and low in fat Thiamine supplementation Ondensetron Antihistamines (H1 receptor antagonist- promethazine , cyclizine , doxylamine ) and metoclopramide Intravenous corticosteroids

10. Intrahepatic Cholestasis of Pregnancy Present in 2 nd and 3 rd trimester Risk factor- advanced age, personal and family history, history of cholestatis secondary to OC pill, hepatitis C Severe pruritus , generalized, but most severe in palms and soles, worse at night.  Only 10% have jaundice, usually less than 5 mg/ dL and preceded by pruritus ICP with Jaundice but without pruritus is rare and warrents additional diagnosis  May have clinical or subclinical steatorrhea that may cause deficiency of fat soluble vitamins, specially vit K.   Cholestasis disappears after delivery and recurs in 60-70% of pregnancies.  If cholestasis does not disappear with delivery, should suspect PBC or PSC.  

11. Biochemical findings Total bile acid level-increased >10 micromol /L SGPT- elevated, some times up to >1000 U/L GGT-slightly elevated or normal Cholic acid increased and chenodeoxycholic acid decreased Corelation between maternal bile acid level and fetal distress. TBA concentration >40 micromol / L predict fetal distress. PT is normal except in vit k deficiency in severe cholastasis . Liver Bx shows bland cholestasis predominantly in zone 3 with none or minimal hepatocellular necrosis

12. Maternal and fetal outcomes Long term maternal prognosis is excellent Fetal distress, preterm labor , prematurity, IUD Treatments Early delivery at 37 week is encouraged UDCA- 500 mg bd or 10-15 mg/kg per day Increased expression of bile salt export pumps Increased placental bile transporters.

13. Preeclampsia liver disorders Occurs in 3-10% of pregnancies Hypertension, edema & proteinuria in late 2 nd , or 3 rd trimester.  Hypertension: BP >140/90 mmhg   in a previously normotensive patient, after the 20 th week of pregnancy. Proteinuria : >/=300 mg of protein in a 24 h urine collection, or 1+ protein or greater on urine dipstick testing Eclampsia : preeclampsia + neurologic symptoms such as headaches, visual disturbances, and seizures or coma  

14. Risk factors- Nulliparity extremes of maternal age, insulin resistance, obesity, infection. Hepatic involement Indicates severe preeclampsia with significant perinatal morbidity and mortality. Is the commonest cause of hepatic tenderness without hepatomegaly , and liver dysfunction in pregnancy.

15. Laboratory:   Aminotransferases are variable, from mild to 10-fold to 20-fold elevations.   Bilirubin is usually less than 5 mg/ dL   May be complicated by HELLP Syndrome. Maternal mortality: rare in developed countries; up to 15%-20% in developing countries. Fetal mortality rate is rare, occurring in 1%-2% of births .  

16. Treatment for preeclampsia is delivery of the fetus and placenta.   If mild preeclampsia is evident before fetal lung maturity at 36 wk gestation, consider expectant management with intensive monitoring.   Pharmacological agents used in preeclampsia include   antihypertensives such as calcium channel blockers   low-dose aspirin.   Magnesium sulfate may be administered if eclampsia develops.

17. HELLP syndrome Typically present b/t 28 to 36 week of gestation. 30% manifest symptoms in first week of pregnancy  HELLP syndrome characterized by H : hemolysis Abnormal smear ( microangiopathy ), LDH > 600 U/L, High Indirect Bilirubin EL : AST > 70 U/L, (AST/ALT elevation up to 10-20 fold) LP : platelete count < 1,00,000 HELLP syndrome affect minority of pregnancy Severe preeclampsia is complicated by HELLP Syndrome in 20% of cases.

18. Symptoms and biochemical finding Epigastric and/or RUQ abdominal pain and tenderness, nausea and vomiting, malaise, headache, edema and weight gain, hypertension, and proteinuria ; Less commonly renal failure (with increased uric acid), diabetes insipidus , and antiphospholipid syndrome. Late findings include intravascular coagulopathy (DIC),pulmonary edema , placental abruption, and retinal detachment. Jaundice is uncommon (5%); T. bili < 5 mg/ dL unless has massive liver necrosis

19. Cross sectional imaging shoud be consider when the ALT or AST is >1000 or abdominal pain radiates to right shoulder. Computed tomography or MRI of the liver may show subcapsular hematomas, intraparenchymal hemorrhage , or infarction or hepatic rupture (thrombocytopenia of less than 20,000).  

20. Management stabilization of hypertension, management of DIC, seizure prophylaxis, and fetal monitoring. Transfer to a tertiary care center if possible. Obtain hepatic computed tomography (limited views).   If fetus >34 weeks gestation or if there is any evidence of multiorgan dysfunction, DIC, renal failure, abruptio placentae , or fetal distress immediate delivery should be prefered . If fetus < 34 weeks and case is mild, give IV betamethasone or dexamethasone for 24-48 h before delivery.

21. Acute fatty liver of preganacy 3 rd trimester, median age – 36 week Rare, life threatning condition charecterized by microvesicular fatty infilteration of liver leading to liver failure Risk factor Twin prenancy Low BMI Clinical feature Nausea, vomiting , abdominal pain Concomitant preeclampsia is present in half of patient. Hepatic dysfunction can progress to acute hepatic failure-encephalopathy, coagulopathy and hypoglycemia .

22. Hepatic failure, pancreatitis and renal dysfunction may occure as a complication. Thromocytopenia Elevation of aminotransferase Hyperbilirubinemia PT- increased in severe case USG Abdomen- increased echogenicity of liver CT Abdomen-liver density is lower, equal or lower HU compared to spleen.

23. Acute fatty liver of pregnancy in a 24-year-old primipara . This woman had experienced nausea and vomiting, abdominal pains, and jaundice in late pregnancy. A transvenous liver biopsy was performed postpartum showing: (A) intact lobular architecture ( hematoxylin and eosin, original ×200), and (B) typical microvesicular fatty infiltration in hepatocytes and features of cholestasis (original ×400). (Courtesy of Dr. Anne de Muret .)

24. Swansea Criteria For Diagnosis of Acute Fatty Liver of Pregnancy. Six or more criteria are required in the absence of another cause. Clinical findings Vomiting Abdominal pain Polydipsia / polyuria Encephalopathy Ascites or bright liver on ultrasound Microvesicular steatosis on liver biopsy Laboratory findings Bilirubin >14 μ mol/L Hypoglycemia <4 mmol /L Uric acid >340 μ mol/L Leukocytosis 0.11 × 106 cells/L AST or ALT >42 μ mol/L Creatinine >150 μ mol/L Prothombin time >14 s Ammonia >47 μ mol/L

25. Pathophysiology Exact pathopysiologhy not known Fetus deficiency of LCHAD(long chain 3-hydroxyAcyle Coenzyme dehydrogenase ). Most common mutation 1528G>C Use in beta oxidation of long chain fatty acid Mother are more likely hetrogenous Fetus are homozygus Fetus of AFLP should be early diagnosed b/c symtops are reversible with energy supply Hypoketotic hypogycemia , infantile cholestatis , hypocalcemia , fatty liver

26. Early recognition, prompt delivery and supportive care are essential to optimize maternal and fetal prognosis, as post partum clinical course is dependent on interval b/w symptoms and termination of pregnancy. If liver function does not rapidly improve, evaluation for liver transplantation offer best chance of survival.

27. II) Intercurrent liver disease in pregnancy Acute viral hepatitis Billiary tract disease and pancreatitis Budd- chiary syndrome Malignant tumors of liver

28. Acute viral hepatitis Response of a pregnant women to acute infection depends on type of virus Hepatitis A Not increased risk of severe disease May risk of premature labor HAV immunoglobulin treatment for neonate if maternal HAV infection within 2 weeks of delivery. Hepatitis B Not a/w increases mortality or teratogenicity Perinatal transmission may occure , especially in acute infection during 3 rd trimester

29. Hepatitis E It is a/w fulminant hepatic failure with mortality rate as high as 25% Vertical transmission also ocure Supportive treatment and liver transplant in ALF Hepatitis caused by HSV High fetal and maternal mortality Affected women has generalised viral symptoms –fever and URTI Marked increased in aminotransferase (thousands), abnormal PT but usually anicteric at presentation

30. Vesicular eruption diagnostic but not be visible at presentation(<50% of cases) Serology RT PCR High index of suspicious should started acyclovir emperically

31. Biliary tract disease and pancreatitis GB stone Decreased GB motility and increased lithogenicity of bile Gall stone and biliary sludge accumulate throughout gestation and resolve after delivery Biliary colic Managed conservatively if fail consider for surgical intervention Cholecystectomy a/w lower maternal and fetal complication Acute cholecystitis Pain a/w fever, vomiting and murphy’s sign '

32. Medical managment is a/w high recurrence with severe complication such as gangrene, Perforation and fistula formation so typical managed with surgery Acute pancreatitis Rare complication of pregnancy Occures in setting of gall stone Pancreatitis or symptomatic cholelithiasis managed by ERCP with sphincterotomy Choledocal cyst Abdominal pain, a mass and jaundice Congenital cyst exacerbate by pregnancy Spontaneous rupture of choledocal cyst reported

33. Budd- chiari syndrome Prevalence of budd-chiary syndrome is 6.7% during preganacy and puerperium . Work up for underlying cause Prognosis is not good. Early recognition and management may improve survival Anticoagulant should be administered Oral anticoagulants are contraindicated LMWH preferred over unfractionated heparine .

34. Malignant tumour of the liver Not common When present , its associated with extensive tumor spread and growth due to immunosuppressive state. Liver is not palpable in normal pregnant women thus hepatomegaly recquires immediate evaluation. p/w abdominal pain, back pain, rupture of liver or hepatic failure. Common site of metastasis –CA colon, hydatidiform mole

35. III) Chronic liver disease revealed by pregnancy Chronic hepatitis B Chronic hepatitis C Autoimmune hepatitis Wilson’s disease Cirrhosis of liver

36. Chronic hepatitis B Pregnancy is well tolerated by HBV carriers   Intrauterine transmission of HBV is rare, but may occur during “threatened abortion” by transplacental leakage. Transmission by amniocentesis is low (</= 4%).   Post-partum “flare up” is common and due to decrease of cortisol levels.

37. If mother is HBeAg (+), risk of vertical transmission is 70%-90% where as in HBeAg - mother it is 10-40% without treatments. Active-passive immunoprophylaxis with HBIG and hepatitis B vaccination administered immediately after birth (within 12 h) to infants of HBsAg positive mother, followed by 2 additional dose of vaccine within 6-12 months , prevent transmission in 95% Recent studies shows that active –passive immunoprophylaxis fail to prevent HBV transmission in 8-30% children born to highly viremia mother.

38. Women having chronic HBV and high viremia (>2,00,000 IU/ml or >10 6 log copies/ml) should be offered antiviral medicine with tenofovir or telbivudine in 3 rd trimester. C-section should not be performed electivly in HBV positive mother to prevent fatal infection. Allow to breast feeding However avoided in presence of breast pathology such as cracked or bleeding nipples.

39. Hepatitis C HCV has little impact during pregnancy with minimal risk to both mother and child. Higher risk for premature rupture of membrane and gestational diabetes. Viral load fluctuate during pregnancy, peaking during 3 rd trimester then returning to pre-pregnancy level after delivery.

40. Unfortunately there is no perinatal managment strategy to prevent HCV transmission. Vaginal delivery not associated with increased risk of transmission but prolong rupture(>6 h) may increased risk. C-section should not be performed electively to prevent infection. Allowed to breast feeding. Hepatitis C therapy should not be offered to pregnant women to either treat HCV or decreased the risk for vertical transmission.

41. Autoimmune hepatitis The natural history of AIH in pregnant women is variable. AIH is associated with an increased risk of fetal prematurity and fetal loss.  AIH may by exacerbated by pregnancy Intrapartum flare is 12% to 21%. Postpartum flares are 12% to 86%.  Factors associated with worsening of AIH in pregnancy include: changes in the relative concentrations of various hormones during pregnancy. specific autoantibodies , including antibodies to SLA and Ro/SSA.

42. Women of childbearing age with AIH should be advised to consider pregnancy only if their disease is well-controlled Pregnant women with AIH are often treated with a combination of steroids and azathioprine . Azathioprine crosses the placenta, but data have suggested that azathioprine and its metabolites do not have toxic effects on the fetus . Patients must be monitored closely throughout pregnancy and in the early postpartum period because of the unpredictability of the course of AIH in pregnancy

43. Wilsons disease Autosomal recessive disorder of copper metabolism.   Due to a mutation of gene, ATP 7B, on chromosome 13q14. ATP 7B codes for a P type ATPase that controls copper transportation in the liver.   Hepatic disease may present as chronic hepatitis, cirrhosis, or fulminant failure. Neurologic abnormalities occur in 40%-50%.

44.   copper deposition in the uterus may cause miscarriage due to improper implantation of the embryo.   In WD pregnant women, treatment must be maintained throughout the course of pregnancy.   Interruption of treatment during pregnancy has resulted in acute liver failure. Chelating agents (both penicillamine and trientine ) and zinc have been associated with satisfactory outcomes for the mother and fetus .

45. The dosage of zinc salts is maintained through out without change.   Dosages of chelating agents should be reduced to the minimum necessary level, especially for the last trimester to promote better wound healing if cesarean section is performed. Dose reduction might be of 25%-50% of the pre-pregnancy dose.    Women taking D- penicillamine should not breast-feed because the drug is excreted into breast milk.   Little is known about the safety of trientine and zinc in breast milk.

46. Cirrhosis of liver Cirrhosis results in metabolic and hormonal derangements that lead to anovulation and amenorrhea Spontaneous abortion rate in patients with cirrhosis is higher. Termination of pregnancy most often occurs as a result of maternal death, variceal hemorrhage , stillbirth, intrauterine growth retardation, and maternal complications during delivery.

47. Variceal bleeding Up to 24% of pregnant patients with cirrhosis will experience hepatic decompensation , usually due to variceal bleed. Treatment of choice is Endoscopic Band Ligation, plus cefotaxime (category B) plus Octreotide (category B). TIPS placement is generally contraindicated during pregnancy because of the risk of radiation exposure to the fetus .   Repetitive Valsalva maneuver during labor increases variceal bleed risk. Many experts adviced elective c-section or forceps delivery under extradural analgesia in order to decrease this risk. During C-section a surgeon with experience with cirrhosis should be available in case of collateral circulation bleed.

48. Ascites and SBP   Ascites rarely occurs during pregnancy because of increased intra-abdominal pressure, which acts to resist the extravasation of fluid from splanchnic vessels and organs. If therapy is required sodium restriction and diuretics can be used. Amiloride (category B), and Torsemide (category B) are reasonable choices. Metolazone and HCTZ (category B) are reserved as third line. Cases of spontaneous bacterial peritonitis have not been reported during pregnancy.

49. Hepatic Encephalopathy May develop due to predisposing medications, hypotensnsion , hypoxia, infection, hypoglycemia , or gastrointestinal hemorrhage .   Spinal and general anesthesia should be avoided during delivery because of the potential for hypotension and the risk of precipitating encephalopathy.   Treatment remains frequent small meals, lactulose (category B), Zinc, L- carnitine (category B) and/or rifaximin (category C), Metronidazol is category B, and neomycin is category D.

50. Splenic Artery Aneurism Rupture Splenic artery aneurisms are increased in pregnancy due to: increased splenic blood flow from both pregnancy and portal hypertension. high estrogen levels during pregnancy which effects the elastic tissue of the tunica media Pregnant patients with cirrhosis have an increased risk of splenic artery aneurysm rupture, which occurs in 2.6%. 20% of all splenic artery aneurysm ruptures occur during pregnany , with 70% occurring during the third trimester.

51. Management   emergency splenectomy ,   transcatheter embolization of the aneurysm, or stent-graft placement. Transcatheter embolization , and stent-graft placement, are usually the preferred options in cases of portal hypertension, as an extensive collateral circulation in these patients makes surgery more difficult.

52. Post-Partum Uterine Hemorrhage Occurs in 7% to 10% of pregnancies in patients with cirrhosis.   Likely related to a higher incidence of coagulopathy and thrombocytopenia.   Treatment is similar to that in patients without cirrhosis. blood and coagulation factors replacement.   oxytocin or other uterine contractile agents. surgical therapy to ligate the bleeding vessels or hysterectomy is indicated when these measures fail.

53. Liver transplant and pregnancy Patient who undergone liver transplant regain fertility within weeks or months of surgery. Delayed pregnancy untill 1-2 years post transplant Encourage to use effective contraception. Pregnancy should be consider high risk Maternal complication Hypertensive disorder Gestational diabetes Anemia Thrombocytopenia UTI

54. Fetal complication Prematurity Fatal distress Growth retardation Teratogenicity Immune suppression may be modified early in pregnancy Calcineurin inhibitors will fluctuate with volume If liver test become abnormal , liver biopsy is indicated to establish the nature of the dysfunction.

55. Teratogenicity with standard immunosuppresant agent, prednisone, azathioprine , cyclosporine and tacrolimus is low. MMF should not be used in pregnancy Breastfeeding discouraged Pregnancy is not a contraindication for liver transplant.

56. Thank you