This document discusses hepatitis, primarily caused by five hepatotropic viruses - hepatitis A, B, C, D, and E viruses. Hepatitis A virus and hepatitis B virus are the most common causes of acute viral hepatitis in children in India. Most cases of acute viral hepatitis improve spontaneously without treatment. Prolongation of prothrombin time is a reliable laboratory marker of worsening liver function or potential liver failure. Chronic infection with hepatitis B or C can potentially lead to chronic hepatitis.

1. HEPATITIS
By Dr Robin Thomas
Resident in Pediatrics
JJMMC, Davangere

2. Introduction
• Acute hepatitis- Inflammatory disorder of liver, usually associated with complete clinical &
histological recovery within 4 to 6 weeks.
• Children most commonly caused by hepatotrophic viruses, followed by drugs & metabolic
liver diseases.
• Acute viral hepatitis- self limited mild disease, does not require any active treatment.
• Sometimes leads to fulminant hepatitis & may need liver transplantation.
• Infection with Hepatotropic viruses [HAV, HBV, HCV, HDV, HEV].
• Non Hepatotropic viruses- mumps, measles, rubella, CMV, HSV, VZV, Dengue virus.
• Salmonella typhi, Plasmodium.
• Drugs- ATT, Antiepileptics, Halothane.
• Autoimmune Hepatitis.

3. • Acute viral hepatitis- HAV, HEV.
• Chronic viral hepatitis- [>6months]- HBV,HCV,HDV.

4. Epidemiology
• Viral hepatitis occurs in all parts of world, higher in resource poor countries of Asia
&Africa.
• High population density, poor water quality & sanitation, financial constraints, lack
of education.
• India- HAV & HEV infection common.
• 1-3%- chronic HBV infection.
• 0.5-1.5%- chronic HCV infection.
• 10-20% of chronic HBV infection carries HDV infection.

5. Various hepatotrophic viruses
Feature HAV HBV HCV HDV HEV
Virus size
(nm)
28 42 50 35-37 32-34
Nucleic acid RNA DNA RNA RNA RNA
Disease
frequency
Most common Second most
common
Uncommon Uncommon in
india
Uncommon
Routes of
transmission
Fecal oral Parenteral, mother
to child, sexual.
Parenteral,
mother to child,
sexual.
Parenteral, sexual. Fecal oral.
Incubation
period
14-28 45-180 15-150 30-180 15-60
Clinical AVH, ALF AVH, ALF,
chronic hepatitis
Chronic hepatitis,
AVH.
HBV-HDV
coinfection.
AVH, ALF, chronic
hepatitis.
Chronicity No Yes, cirrhosis &
HCC.
Yes, cirrhosis &
HCC.
Yes with chronic
HBV infection.
Rare, in transplant
recipients &
immunosuppressed.

6. Feature HAV HBV HCV HDV HEV
Diagnostic tests IgM anti HAV
antibody.
HbsAg
(acute/chronic),
IgM anti HBc
antibody(acute
infection).
Anti HCV, HCV
RNA.
IgM anti HDV
antibody, HDV
RNA.
IgM anti HEV
antibody.
Treatment Supportive Oral nucleotide
analogs,
interferons.
Pegylated
interferon &
Ribavirin.
Pegylated
interferon.
Supportive for
acute hepatitis &
Ribavirin for
chronic
infection.
Vaccine Yes Yes None Yes (HBV
vaccine)
Developed , not
yet available.

7. Etiology
• Hepatotropic viruses A,B,C,D,E.
• Hepatitis A virus
• Most common cause of AVH- 60 %
• HAV infected children below 2 yrs- asymptomatic & above 5 yrs-
symptomatic.
• Fecal oral route

8. • Hepatitis B virus
• Acute & chronic hepatitis, acute liver failure.
• Second most common cause of AVH.
• Liver cirrhosis & hepatocellular carcinoma.
• Parenteral, mother to infant, sexual transmission.

9. • Hepatitis C virus
• Hepatitis D virus
• Hepatitis E virus

10. Pathogenesis
• Hepatitis A virus
• Enter body by feco-oral route.
• Multiply in hepatocytes & excretion in stools.
• No cytopathic effect on hepatocyte ie does not cause much hepatocyte
damage.

11. • Hepatitis B virus
• HBV[ DNA virus ], enters into hepatocyte nucleus .
• Integrates with host DNA- forms covalently closed circular DNA
(cccDNA).
• cccDNA remains inside the body for rest of life- Chronic HBV
infection.

12. • Hepatitis C virus
• 70% leads to chronic infection.
• High degree of genetic variability & mutations.

13. • Histopathology- chronic viral hepatitis
• Inflammatory cells (lymphocytes).
• Necro inflammation.
• Liver fibrosis.
• Regenerating nodules.
• Cirrhosis.

14. Clinical features
• Hepatotropic viruses- 3 possible courses-
• 1.Acute viral hepatitis
• 2.Chronic viral hepatitis.
• 3.Acute liver failure.

15. • Acute viral hepatitis- runs a triphasic course-
• 1.Prodromal phase.
• 2.Icteric phase.
• 3.Convalescent phase.

16. Prodromal phase
Symptoms Signs Laboratory
Precedes jaundice No icterus Normal bilirubin
Anorexia, nausea, abdominal discomfort Right upper quadrant tenderness Marked elevation of
ALT & AST(>10 fold)
Low grade fever, malaise, myalgia Mild soft hepatomegaly ALP slightly raised
Lasts for 5-7 days. Arthritis, skin rash (HBV) Normal or mildly
deranged PT
Occasional mild splenomegaly

17. Icteric phase
Symptoms Signs Laboratory
Yellow discoloration of eyes &
urine.
Jaundice of variable severity High serum bilirubin-conjugated
Improvement of appetite. Mildly ,soft hepatomegaly Moderately elevated ALT & AST.
Feeling well & active. Occasional mild, soft, splenomegaly
Lasts for 6 weeks. Scratch marks, if itching

18. Convalescent phase
Symptoms Signs Laboratory
Complete recovery of symptoms Icterus-moderate to mild Near normal bilirubin
Mild icterus & fatigue Normalization of urine color Normal or slightly elevated ALT
& AST.
Few weeks Regression of organomegaly Normal ALP.

19. Atypical features of Acute Hepatitis A
• 1.Cholestatic hepatitis
• 2.Relapsing hepatitis
• 3.Autoimmune hepatitis
• 4.Extrahepatic manifestations

20. • Cholestatic hepatitis
• Recovering from acute HAV.
• Deep icterus & intense pruritus during convalescent phase.
• Few weeks to months.
• Counseling & antipruritic measures.

21. • Relapsing hepatitis
• Reinfection due to prolonged enterohepatic circulation of HAV.
• Second attack of hepatitis 4-8 weeks following initial recovery.
• Subclinical elevation of transaminases .
• Either mildly symptomatic disease or full blown hepatitis attack.

22. • Extra hepatic manifestations
• Renal- proteinuria, AGN, nephrotic syndrome, ARF.
• Nervous system- aseptic meningitis, encephalitis, seizures.
• Pancreatobiliary system- acalculous cholecystitis, acute pancreatitis.
• Hematological- autoimmune hemolytic anemia, aplastic anemia

23. Differential diagnosis
• Malaria
• Dengue hepatitis
• Enteric hepatitis
• Chronic liver disease
• Liver abscess
• Cholangitis

24. Approach to Diagnosis
Prodromal symptoms
Jaundice
ALT/AST markedly
elevated
No risk factor for hepatitis
Suspected acute viral
hepatitis
No features of hepatic
encephalopathy.
Normal PT.
Acute viral hepatitis
Tests for HBsAg &
IgM anti HAV
IgM anti HAV
positive
Confirmed Acute
HAV
No acute liver failure

25. HBs Ag positive
IgM anti HBc test
IgM anti HBc positive
Confirmed Acute HBV
IgM anti HBc negative
Probably chronic HBV
with super added infection
IgM anti HDV positrive
HDV super infection
IgM anti HAV negative
HBsAg negative
IgM anti HEV positive
Confirmed Acute HEV

28. Management
• Supportive therapy
• Antipyretics, analgesics & antiemetics
• Light physical activity. no role for bed rest.
• Hygienic measures prevent spread to other family members.

29. • No role for vitamin k, appetizers, antibiotics & hepatoprotective medications
• ( Liv-52, Ursodeoxycholic acid ).
• Dietary restrictions of fat, milk, turmeric, pickles, spices offer no benefit.

30. Counselling
• Parents counseled about :
• 1. benign nature of illness.
• 2. likelihood of complete natural recovery.
• 3. avoidance of restrictions on physical activity & diet.
• 4. lack of role for drugs.
• 5. for hepatitis B & C follow up for chronicity.

31. • Monitoring
• Monitored for complications like ALF, hepatic encephalopathy.
• Subtle signs of hepatic encephalopathy- flapping tremors, altered sleep
pattern, excessive irritability, inconsolable cry.
Prolongation of PT- most reliable & early marker of worsening liver function
or liver failure.

32. Vaccines
• Hepatitis B vaccine
• Surface antigen hepatitis B vaccine –recombinant technology in yeast &
adjuvanted with aluminium salts.
• Stored at 2-8 C.
• Dose- children & adolescents (<18 yrs)- 0.5 ml.
• 18 yrs & older- 1ml.
• Intramuscular –deltoid /anterolateral thigh.

33. Hepatitis B vaccine schedules
• 1. Birth, 6 wks, 14 wks- preferred one.
• 2. 6 wks, 10 wks, 14 wks.
• 3. Birth, 6 wks, 6 months.
• 4. Birth, 6 wks, 10 wks, 14 wks.

34. Hepatitis B immunoglobulin
• Passive immunity
• Indicated along with hepatitis B vaccine in perinatal, occupational, sexual
exposures.
• Neonates/infant dose-0.5 ml, Adult dose- 0.06 ml/kg.
• Stored at 2-8 C.
• Immunocompromised/Nonresponders- 2 doses of HBIG 1 month apart.

35. Management of infant born to hepatitis B positive
mother
• Pregnant women counselled for HBsAg screening.
• 1. Mother is HBsAg negative, Hepatitis B vaccine given at 0, 6 wks, 6 months.
• 2. Mothers HBsAg status not known- hepatitis B vaccine given within few hours of
birth.
• 3. Mother HBsAg positive- baby given HBIG (0.5ml) & hepatitis B vaccine (0.5
ml) within 12 hrs of birth.
• Hepatitis B vaccine -2 more doses given at 6 wks & 6 months.
• If HBIG not available- Hepatitis B vaccine given at birth, 1month, 2 month &
additional dose between 9 months-1 year.

36. Hepatitis A vaccine
• Liposomal adjuvanted inactivated hepatitis A vaccine, derived from RG-SB
strain.
• First dose at 12 mon, second dose at 18 mon. intramuscular route. 0.5 ml.
• Live attenuated vaccine from human diploid cell also available.
• Live vaccine given subcutaneously.

37. Prognosis
• Most cases with AVH - spontaneous & complete recovery.
• ALF cases- high risk of mortality & needs ICU care & liver transplantation.
• Some cases of HBV & HCV develops chronic hepatitis & liver cirrhosis.
• High risk for chronic HBV- infancy & early childhood (<5 yrs).

38. Prevention
Preventive measures HAV HBV HCV HDV HEV
Water & food hygiene, sanitation measures. Yes Yes
Safe injection practices. Yes Yes Yes
Safe blood/blood product transfusion. Yes Yes Yes
Antenatal screening. Yes
Vaccination Yes Yes Hepatitis B
vaccine
Immunoglobulin Yes Yes

39. Preventive measures

41. Autoimmune hepatitis
• Chronic inflammatory disorder affecting liver , responsive to
immunosuppressive treatment or corticosteroids.
• Associated with circulating auto antibodies, hyperglobulinaemia.
• Viruses that triggers AIH- HAV, HCV, measles, EBV, HHV.
• HCV- most commonly associated, molecular structure of HCV resembles
that of cytochrome P450.
• Drugs- alpha methyl dopa, nitrofurantoin causes AIH.

42. • Classification of AIH- Type 1- ANA (Antinuclear antibody), Anti smooth muscle
antibody.
• Type 2- Anti liver-kidney-microsomal antibody.
• Type 3- Anti soluble liver antigen.
• Diagnostic criteria for AIH
• Periportal hepatitis
• Hyper gammaglobulinaemia
• Autoantibodies & female sex.
• Liver biopsy
• Piece meal necrosis- characteristic histological feature.
• Lympho plasmacytic infiltrate- portal tract with lymphocytes & plasma cells.
• Bridging necrosis

44. • Treatment- AIH
• Corticosteroid therapy- Prednisolone- 1-2 mg/kg/day.
• Immunosuppressants- Azathioprine- ( 2 mg/kg/day ) & Cyclosporine.
• Liver transplantation.

45. Summary
• Five hepatotrophic viruses A to E, cause majority of acute viral hepatitis
episodes.
• Hepatitis A virus followed by hepatitis B virus are the common viral
agents for hepatitis in children in India.
• Most patients with AVH improve spontaneously.
• Degree of ALT/AST elevation has no relation with disease severity.
• Prolongation of PT- reliable lab. marker of severity.

46. • Few children progress to liver failure.
• HBV or HCV infection may progress to chronic hepatitis.