hepatitis lecture 2021.pptdgvhehnvnjvfvlfv

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1. Pharmacotherapy of
Hepatitis

2. Liver: Anatomy
•Theliveristhelargestvisceralorganinthe
bodyandisprimarilyintheright
hypochondriumandepigastricregion,
extendingintothelefthypochondrium(or
intherightupperquadrant,extending
intotheleftupperquadrant).
•Surfacesoftheliverinclude:
•adiaphragmaticsurfaceintheanterior,
superior,andposteriordirections;
•avisceralsurfaceintheinferiordirection
2

3. Position of the liver in the abdomen: Diaphragmatic surface
3

4. 4

5. Liver anatomy: Visceral surface
5

6. 6

7. The Liver
•Is located in the upper right quadrant of the abdomen
•Cleans the blood
•Regulates hormones
•Helps with blood clotting
•Produces bile
•Produces important proteins
•Maintains blood sugar levels
•And much, much, more
•The liver is essential
for life !

8. Evaluation of Liver Function
8

9. Laboratory Studies
Serumenzymes
•Hepaticdisordersassociatedpredominantlywith
elevationinaminotransferasesarereferredtoas
hepatocellular;hepaticdisorderswithpredominant
elevationinalkalinephosphatase(AP)arereferredtoas
cholestatic.
•Alkalinephosphataseisanenzymethatispresentina
varietyoftissues(bone,intestine,kidney,leukocytes,
liver,andplacenta).
•Elevationofserumaspartateandalanine
aminotransferases(ASTandALT,respectively)indicates
hepatocellularinjuryandnecrosis.
•TheratioofserumASTtoALTistypically>2inalcoholic
liverdisease.Inviralhepatitis,thisratiois
characteristically<1.
9

10. Synthetic products
•Serumalbuminconcentrationisfrequently
decreasedinchronicliverdisease.
•However,chronicinflammation,expanded
plasmavolume,andgastrointestinalor
renallossesmayalsoleadto
hypoalbuminemia.
•Becausethehalf-lifeofalbuminisrelatively
long(20days),serumlevelsmaybe
normalinacuteliverdisease.
10

11. Synthetic products
•Cholesterolissynthesizedintheliver.
•Patientswithadvancedliverdiseasemay
haveverylowcholesterollevels.
•However,inprimarybiliarycirrhosis,
levelsofserumcholesterolmaybe
markedlyelevated.
11

12. Excretory products
•Bilirubinisadegradationproductof
hemoglobin.
•Totalserumbilirubiniscomposedof
conjugated(direct)andunconjugated
(indirect)fractions.
•Unconjugatedhyperbilirubinemiaoccursas
aresultofexcessivebilirubinproduction
(neonatalorphysiologicjaundice,
hemolysisand hemolytic anemias,
ineffectiveerythropoiesis,andresorptionof
12

13. Excretory products
•Bileacidsareproducedintheliverandare
secretedintotheintestine,wheretheyare
requiredforlipiddigestionandabsorption.
•Elevatedlevelsofserumbileacidsare
specificbutnotsensitivemarkersof
hepatobiliarydisease.
•Levelsofindividualbileacidsarenotuseful
inthedifferentialdiagnosisofliver
disorders.
13

14. Imaging
•Ultrasonographyisusedtoscreenfordilationof
thebiliarytreeandtodetectgallstonesand
cholecystitisinpatientswithright-sided
abdominalpainassociatedwithabnormalliver
bloodtests.
•Itcanrevealandcharacterizelivermasses,
abscesses,andcysts.
•Color-flowdopplerultrasonographycanassess
patency(opennessofvessel)anddirectionof
bloodflowintheportalandhepaticveins.
•Ultrasonographyisafrequentlyusedmodality
forscreeningofhepatocellularcarcinoma.
14

15. Imaging
•Magneticresonanceimaging(MRI)offers
informationsimilartothatprovidedbyCT
scanandtheadditionaladvantageofbetter
characterizationofliverlesions,fatty
infiltration,andirondeposition.
•Itisthemodalityofchoiceinpatientswithan
allergytoiodinatedcontrastandrenalfailure.
15

16. Liver Biopsy
•Percutaneous liver biopsy can be performed
with or without radiographic (ultrasound or
CT) guidance.
•Suspicious liver lesions are usually biopsied
with ultrasonographic or CT guidance.
16

17. Viral Hepatitis

18. What Is Hepatitis?
•Hepatitismeans inflammation of the liver
•Hepat(liver) + itis(inflammation)= Hepatitis
•Viral hepatitis means there is a specific virus
that is causing your liver to inflame (swell or
become larger than normal)

19. Inflammation
Walls of
scar
tissue
begin to
form
Healthy liver cells
become trapped
by a wall of scar
tissue

20. Viral Hepatitis
5 types:
A: fecal-oral transmission
B: sexual fluids & blood to blood
C: blood to blood
D: travels with B
E: fecal–oraltransmission Vaccine
Preventable
Adapted from Corneil, 2003

21. Clinical Terms
•Acute Viral Hepatitis: symptoms last less than 6
months
•Acute Hepatic Failure: Massive hepatic necrosis with
impaired consciousness within 8 wks of onset of
illness.
•Chronic Hepatitis: Inflammation of liver for at least 6
months
•Cirrhosis:Replacement of liver tissuefibrosis,
scar tissue
•Fulminant Hepatitis: severe impairment of hepatic
functions or severe necrosis of hepatocytes in the
absence of preexisting liver disease

22. Pathophysiology
Targets of the hepatic viruses are hepatocytes:
•Hepatocyte uptake involves a receptor on the
plasma membrane of the cell
•After entry into the cell, viral RNA is uncoated,
and host ribosomes bind to form polysomes.
•Viral proteins are synthesized, and the viral
genome is copied by a viral RNA polymerase
•Lymphocytic infiltrate; varying degree of
necrosis.

24. Classic presentation: infectious hepatitis
•Phase 1 -Viral replication; Patients are
asymptomatic during this phase.
•Phase 2 –Prodromal
•Phase 3 -Icteric phase
•Phase 4 -Convalescent phase; symptoms and
icterus resolve. Liver enzymes return to normal.

25. Clinical Evaluation: Acute Viral Hepatitis
1. Prodromal phase:
•Patients experience anorexia, nausea, vomiting,
alterations in taste, arthralgias, malaise, fatigue,
urticaria, and pruritus.
•When seen by a health care provider during this
phase, patients are often diagnosed as having
gastroenteritis or a viral syndrome.
2. Icteric Phase
•Jaundice, Patients may note dark urine, followed
by pale-colored stools.
•In addition to the predominant gastrointestinal
symptoms and malaise, patients become icteric
and may develop right upper quadrant pain with
hepatomegaly.

26. Clinical….
•Severe cases may result in Fulminant
Hepatitis:
1.Hepatic Encephalopathy: palmar
erythema, spider angioma
2.Hepatorenalsyndrome
3.Bleeding diathesis

27. Clinical Evaluation: Chronic Hepatitis
-Occurs after acute Hepatitis in >80% of
people with HCV
-Some are asymptomatic, or have mild
symptoms; others may only present
with late complications (cirrhosis/HCC)
-Categorized based on grade of
inflammation, stage of fibrosis, and
etiology of disease

28. Physical Exam
•Low-grade fever.
•Significant vomiting and anorexia dehydration such
as tachycardia, dry mucous membranes, loss of skin
turgor, and delayed capillary refill.
•Icteric phase: icterus of the scleraeor mucous
membranes or discoloration of the tympanic
membranes.
•The skin may be jaundiced and may reveal urticarial
rashes.
•Liver may be tender and diffusely enlarged with a firm,
sharp, smooth edge.

29. Imaging Studies
•No specific imaging studies needed for diagnosis
•Appropriate diagnostic imaging studies (eg, ultrasound,
CT) if the differential diagnosis favors gallbladder
disease, biliary obstruction, or liver abscess.
Liver biopsy usually in cases of:
o The diagnosis is uncertain.
o Other coinfections or disease may be present.
o The patient is immunocompromised.
o Asses severity of chronic hepatitis B or chronic
hepatitis C.

30. •LFT: Elevation of serum transaminases not diagnostic, but useful
a)ALT elevated more than AST
b)Acute Hepatitis: ALT > 1000
c)Chronic HCV: ALT is generally lower than 1000
* Urine analysis: presence of bilirubin.
* Serum bilirubin: Total bilirubin may be elevated in infectious
hepatitis. Bilirubin levels higher than 30 mg/dL indicate more severe
disease.
* Alkaline phosphatase: if elevated significantly, consider
abscess or biliary obstruction.
* Prothrombin time (PT) if prolonged impaired synthetic
function of the liver.
* BUN & serum creatinine decreased renal function suggests
fulminant hepatic disease.
* Serum ammonia in patients with evidence of hepatic
encephalopathy.
* CBC: lymphocytosis
Lab Studies:

31. Differentials:
•Pancreatitis
•Cholangitis
•Cholecystitis and Biliary Colic
•Cholelithiasis
•Gastritis and PUD
•Gastroenteritis

32. Hepatitis A
•Common cause of acute hepatitis
•Single-stranded, RNA enterovirus
•Transmission fecal-oral route; Contaminated
water and food
•The incubation period of hepatitis A virus is 2-7
weeks,
•AST & ALT levels usually return to reference
ranges over 5-20 weeks.

33. Hepatitis A..
•High risk Travellers: vaccinations;
passive immunoglobinsgiven to those
exposed
•Mild self-limited disease and confers
lifelong immunity to hepatitis A virus.
•Chronic infection with hepatitis A virus
does not occur.
•Treatment: supportive

34. Diagnosis of HAV
•**Serum Serology: presence of serum
antigens and immunoglobins
•HAV: IgM anti-HAV: positive at the time of
onset of symptoms; results remain positive
for 3-6 months after the primary infection
•Anti-HAV IgG appears soon after IgM and
generally persists for many years.

35. Hepatitis C
•Spherical, enveloped, single-stranded RNA
virus
•170 million infected worldwide
•Parenteral Transmission: IV drug users
•Most common indication for liver
transplantation

36. Hepatitis C
•Usually clinically mild, does not cause
significant acute illness
•Fluctuating elevations of AST & ALT
•20% likelihood of developing cirrhosis
•50% likelihood of developing chronic
hepatitis
•Incubation period: 15-150 days, with
symptoms developing anywhere from 5-12
weeks after exposure.

37. Diagnosis of HCV
•HCV: Anti-HCV; cannot distinguish acute from chronic
infection
•EIA: antibodies against core protein and nonstructural
proteins; may appear 3 –5 months after infection
PCR: used to detect viral RNA HCV
80% of cases: patients are asymptomaticand do not
develop icterus.
Treatment: Interferon alpha, Ribavirin; PEG-IFNs (better
sustained absorption, a slower rate of clearance, and a
longer half-life than those of unmodified IFN)

38. Hepatitis E
•Hepatitis E virus (HEV) RNA virus
•Enterically transmitted infection; fecal-oral
route, typically self-limited
•Most outbreaks occur in developing
countries.
•Incubation period of hepatitis E virus is 2-9
weeks
•Case fatality rate is 4%

39. Hepatitis E: diagnosis
•Serum, liver, and stool samples can be
tested for HEV RNA
•Anti-HEV antibodies:
-IgM (acute)
-IgG (chronic)
AST & ALT are elevated several days before
the onset of symptoms; return to normal
within 1-2 months after the peak severity of
disease.
Treatment: supportive

40. Hepatitis: B & D

41. Hepatitis B(HBV)--EPIDEMIOLOGY
•HBV is a DNA virus
•2 billion people worldwide have past or present
infections
•400 million people are chronicHBV carriers.
•Eight genotypes of HBV identified and re-labeled A
through H.
•HBV is the cause of 60% to 80% of worldwide
Hepatocellular Carcinoma(HCC).
•500,000 to 1 million deaths worldwide are attributed
to it.
•5% to 10% of all liver transplants are attributed to HBV.

42. AT Risk Groups
•IV drug users
•People receiving multiple blood
transfusions
•Sexual promiscuity
•People in contact with HBV carriers
•Resident and employees of residential
care facilities
•Health Care Workers

43. Pathophysiology
Transmission 3 main ways:
•Parenterally/percutaneous route----IV Drug
Users, needle sticks, Hemodialysis patients
•Sexually
•Vertical/ Perinatal route

44. Serology
HBsAg
•Present in acute of infection
•Detectable 1 to 2 weeks after infection
HBeAg(Soluble core associated antigen )
•Appears shortly after HBsAg
•Indicates viral Replication and Infectivity
HBsAB(Anti-HBS)
•Present after vaccination or clearance of HBsAg(Usually 1 to
3 months)
•Indicates immunity to HBV
Hb core Antibody(IgM anti-Hbcor IgG anti-HBc)
•Only Serological marker of HBV during "Window Period"

46. Diagnosis
•Serology
•Liver Chemistry tests
•AST, ALT, ALP, and total Bilirubin
•HBV Viral DNA--Most accurate marker of
viral DNA and detected by PCR
•Liver Biopsy--to determine
grade(Inflammation) and stage(Fibrosis) in
chronic Hepatitis

48. Progression
•Incubation Period:30-180 days
•Acute HBV Infection:90% resolve by themselves;
less than 1% develop fulminant hepatitic failure
•Chronic HBV Infection: 2-10% progress to chronic
state
•90% in under five children progress to chronic
state
•Risk ofLiver Cirrhosis:5 year accumulation risk
of 8% to 20%
•5% to 10% of people progress to HCC with or
without preceding cirrhosis; less than
5%achieve a chronic carrier state

49. Treatment of HBV
1)Interferon therapy –First Line
•Method of action is the inhibition of viral replication of
cells thus assisting the immune system
•Interferon alpha: SUB-Q5 million units q D or 10 million
units 3x weekly Sub-Q
•Side effects: "Flulike Symptoms", alopecia, rash, diarrhea
•pINF-alpha(pegylatedinterferon-alpha):180ug q weekly
SUB-Q
•Better Choice than IFN-Alpha--Greater
Bioavailability,Longer half life, Better treatment schedule

50. Treatment cont.
2) Nucleoside Analogues--Lamivudine, Entecavir, Telbivudine
Method of action is the inhibition of viral reverse transcriptase
•Lamivudine
•Dose:100 mg PO q daily
•Good for reducing the risk of progression to hepatic decompensation in
patients with cirrhosis or advanced fibrosis
•Problem: High rates of resistant mutations
•Side effect: lactic acidosis
•Entecavir–1
st
line
•0.5 to 1mg PO
•very effective; low resistance andgreater than 90%HBV DNA clearance rate
in HBeAG positive Px's.
•more effective than lamivudine
•Side effect: lactic acidosis
•Telbivudine
•Dose: 600mg q daily
•Worse resistant profile than Entecavir
•Side effect: lactic acidosis

51. Treatment cont.
3) Nucleotide analogues
Method of action is the inhibition of viral reverse
transcriptase
•Tenovir
•Dose: 300mg qd
•Highly effective with low resistance
•Well tolerated
•Adefovir–1
st
line
•Dose: 10mg daily
•Resistance less than Tenovir
•Side effect: nephrotoxicity and lactic acidosis

52. When to Treat for Chronic Hepatitis
HBV DNA(copies/ml) ALT Recommendation
<10
5
Normal No treatment , monitor,
considered inactive
>10
5
Normal No treatment, current tx
is limited benefit
>10
5
Elevated(greater than
2 x ULN)
Oral Agents, not PEG IFN
compensated
cirrhosis
Normal or elevatedOral Agents, not PEG IFN
uncompensated
cirrhosis
Normal or elevatedOral agents and refer for
treatment
1) HBeAg positive

53. When to Treat for Chronic Hepatitis
2)HBeAG negative
HBV DNA(copies/ml) ALT Recommendation
<10
4
Normal No tx necessary,
inactive carrier
>10
4
Normal Liver Biopsy , treat
ifabnormal
>10
4
Elevated Oral agents or PEG IFN
compensated cirrhosisElevated or normal Oral agents, not PEG IFN
uncompensated
cirrhosis
Elevated or normalOral agents, not PEG IFN

54. Prophylaxis
HBV Vaccine
•Indicated for everyone and especially those in high risk groups
•IM injection at 0,1,6 months in infants and adults
•Response greater than 90% after 3rd dose
HBV Pregnant Mothers
•Give 1st dose of Hip B vaccine and Hip B
Immunoglobulin(HBIG)o.5 ml within 12 hours of birth.
•2nd dose at 1 month, 3rd at 6 months
•Recheck at 12 months for active infection
•95% lifetime immunity
•Not Done---leads to 90% chronic HBV
•Transmittedthrough birth canalduring birth or through
umbilical cord.
Others i.e. those receiving a needle stick
•Should receive0.04 to 0.7 ml/kgof HBIG and 1st dose vaccine
within48and no later than a week.

55. Transplant
•Last resort forthose with advanced Liver Disease
and HCC due to infection

56. HEPATITIS D
Transmission
•Only as co-infection with acute HBV or with
superinfection in chronic HBV carrier
•Requires outer envelope of HBsAG for replication
and transmission
•Can progress to chronic disease
•Incubation Period 30 to 150 days
Serology
•Hepatitis D antibody(Anti-HDV)
•Indicates HDV superinfection
•Ab not always present in acute infection---requires
repeat testing

57. HEPATITIS D
Risk Factors-Same high risk groups as those for Hip B
Prevention -Avoidance of Hip B and/or Hip B vaccine
DX -HDV antigen in serum or finding Ab to HDV
antigen
Clinical
•Coinfection-self limited
•Superinfection-acute HBV carrierspresent with
severe acute hepatitis infection w/ increased risk
forHDV infection.
Fatality Rate -2% to 10%
Cirrhosis –None
TX:IFN-alpha

58. Other Causes of Hepatitis
•Alcoholic Hepatitis
•Drug induced Hepatitis
•Autoimmune Hepatitis
•Ischemic Hepatitis

59. A hepatitis panel is ordered for a 27 year old female
as part of a routine workup for abdominal pain.
Results of serological testing a negative for HBeAg
and HBsAg, but positive for HBsAb and IgG HBcAb.
The patient has been exposed to Hep B.
a.Patient has recovered
b.Patient is in acute infective disease state
c.Window period
d.Chronically infected
e.Patient was never infected
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