Definition:

1
Chawla Management of acute hepatitis B

• Definition
• Clinical, biochemical or histological
  manifestations of hepatic injury occurring within
  6 mo of exposure resolution within 6 mo of
  onset
• Diagnosis ? ALT, HBsAg , IgM anti HBc

2
Chawla Management of acute hepatitis B

• Acute viral hepatitis B
• Course I. Pd shorter large viral load
• Anicteric 70, Icteric 30
• Average 2-3 wks (Daysmonths)
• Low grade fever
• Hepatomegaly
• Splenomegaly 5 15
• Extrahepatic manifestations
• Aplastic anemia
• Serum sickness syndrome
• Resolution HBsAg ve, anti- HBs ve

3
Chawla Management of acute hepatitis B

• Laboratory features
• S bilirubin very high, hemolysis, renal
  failure
• ALT Peak ALT precedes ? S bilirubin
• Normalises in 4 weeks
• No correlation with prognosis
• Pro. time Liver related clotting factors
• II, V, VII, IX, X
• Best prognostic indicator
• Reflects viable hepatocyte mass

4
Chawla Management of acute hepatitis B

• Variants
• Fulminant hepatic failure 0.5 - 1
• Definition encephalopathy without preexisting
  HBV infection
• Diagnosis HBsAg , IgM anti HBc 10
• Subacute hepatic failure
• Definition Progressive jaundice with
  unequivocal ascites after 4 wks of onset
• Chronic hepatitis 1- 5

5
SerologyHBV Acute Infection
Chawla Management of acute hepatitis B
Anti HBs

• HBsAg

1000 900 800 700 600 500 400 300 200 100 0
ALT(IU/L) and HBV-DNA (millions/ml)
HBeAg
IgM Anti HBc
ALT
Symptoms
HBV-DNA
0 1 2 3 4 5
6 12 24 36 48
60
0 1 2 3 4 5
6 12 24 36 48
60
Months After Exposure
6
HBV Chronic Infection
Chawla Management of acute hepatitis B

• HBsAg

1000 900 800 700 600 500 400 300 200 100 0
ALT(IU/L) and HBV-DNA (millions/ml)
HBeAg
ALT
HBV-DNA
0 1 2 3 4 5
6 12 24 36 48
60
Months After Exposure
7
Chawla Management of acute hepatitis B

• Etiology
• AVH FHF SAHF
• HAV 4 1.7 -
• HBV 25 28 38
• HEV 51 62 -
• Non A Non B 42

8
Chawla Management of acute hepatitis B

• PGI data Total patients 178, June 02 to Oct 03
• Asymptomatic carriers 40 (e 7)
• Acute Viral Hepatitis 33
• Acute liver failure 02
• Chronic Hepatitis 81
• Cirrhosis
• Compensated 10
• Decompensated 08
• HCC 04

9
Chawla Management of acute hepatitis B

• HBV persistence after AVH
• 19 AVH FU 6 43 mo
• HBsAg ve, anti HBsve 1 yr
• 72 (13/19) HBV DNA 6 mo
• 33 (4/12) HBV DNA 1 yr N ALT
• (Hepatol Res 200325244-53)

10
Chawla Management of acute hepatitis B

• Histology and viral outcome of AVH
• 14 AVH recovered FU 4.3 yrs
• Anti HBs 12/14
• 9 liver biopsies 7.2 yrs Portal fibrosis
  mild inflammation 8
• 3 low serum HBV DNA
• 9 HBV DNA HBxAg on Liver biopsy
• significance ?
• (Hepatology 2003371172-9)

11
Chawla Management of acute hepatitis B

• HBV kinetics during acute infection
• HBV DNA peak (1010 copies/ml) 12747 days
• DNA clearance symptomatic acute hepatitis
• Initial rapid decline
• Slower decline, hepatocyte loss
• HBV production rate 1013 vir/day
• Each infected hepatocyte 200-1000 vir/day
• (J Exp Med 2001193847-53)

12
Chawla Management of acute hepatitis B

• HBV kinetics with coinfections
• 21 AVH 27 coinfections 6-10 days x 4
• HBV DNA ? faster than HBs Ag on f-up
• 6.8 to 5.1 to 4.2 to 3.3 log ge equivalent/ml
• Suppression of HBV DNA faster with HDV
  coinfection, no effect with HCV
• (J Med Virol 200309313-23)

13
Chawla Management of acute hepatitis B

• Predictors of ALF
• INR gt 1.5 or prothrombin time gt 17 secs, PTI lt40
• Discriminant equation 0.891.74x1 (A/B 2 NANB)
  0.056 x total bil mg/dl 0.14 x cholinesterase
  u/ml
• (J Gastroenterol 200237916-21)
• Factor V levels
• IFN ? upregulated CD8 T lymphos
• (J Hepatol 199931579-83)
• IFN ? lt levels high
• (Folio Med 19984046-51)

14
Chawla Management of acute hepatitis B

• Genotype and clinical course of ALF
• 7 ALF Genotype A 1 longer clinical course
• B 1
• C 4 shorter clinical course
• D 1
• Similar results with 25 AVH
• Conclusion Severity depends on genotype
• (Hepatol Res 200326119-24)
• Prolonged AVH genotype A
• (Hepatol Res 200223167-7)

15
Chawla Management of acute hepatitis B

• Genotype and mutations in AVH
• 45 AVH B, 16 ALF B, 531 CLD B, 19 Ac on
  Chr
• Genotype B AVH 39.3 vs 11.7 CLD
• ALF 62.5 vs 31 AVH
• Precore 1896, Core promoter 1753, 1754
• Conclusion Genotype B more severe liver disease
• (Gut 2003521630-7)

16
Chawla Management of acute hepatitis B

• Genome sequence of HBV in ALF
• Precore (1896) CP (1762, 1764) mutations
• 88 ALF 19 AVH
• Nt difference ALF vs AH same infectious source
• nt 493, 998, 1173, 2982, 3067 3078 in ALF
• (J Hepatol 20033884-90)
• Precore mutations 100 ALF
• 75 severe acute hepatitis
• 73 AVH
• (Hepatogastroenterology 2002491352-6)

17
Chawla Management of acute hepatitis B

• Prediction of chronicity
• Persistence of raised ALT gt 4 mo
• HBsAg titres rising 4 wks after onset
• HBeAg titres HBV DNA persistence after 6 wks
• Genotype C
• Chronicity
• Age Perinatal/neonatal 90
• children lt 6 yrs 30 (asympto)
• Adults 1 5
• Immunosuppressive treatment 60 - 100
• HIV 30
• Hemodialysis ?

18
Chawla Management of acute hepatitis B

• Treatment
• Acute viral hepatitis
• Outcome good in immunocompetent
• Antivirals not recommended
• Prolonged acute hepatitis B (gt 8 weeks)
• r IFN ? 3 mu od x 12 weeks
• 4/7 (57)patients cleared HBsAg
• HBeAg Seroconversion 95
• (J Med Virol 200268522-8)

19
Chawla Management of acute hepatitis B

• IFN a in prolonged AVH-B
• 20 patients IFN, 5 mu tiw x 12 weeks
• Loss of HBsAg, HBeAg 80 vs 53 placebo (JAPI
  200048669-70)
• Lamivudine
• Polyarteritis nodosa (NEJM 20013411256-63)
• Aplastic anemia (DDS 2002471782-5)
• Hepatitis post transplant (Transplantation
  1999671288-9)
• 12 patients post transplant? Lamivudine 100 mg
  od
• HBV DNA undetectable 8 wks, ALT normalised
  24 wks
• 45 HBsAg ve and HBV DNA ve by PCR J Hepatol
  199829955-9
• Bile acids UDCA early clearance of HBsAg HBV
  DNA No effect on HBV, but ? transminases
  Cochrane database 20033184)
• Phyllanthus amarus No benefit (Tr Gastro
  199920169-6)

20
Chawla Management of acute hepatitis B

• Conclusions
• Serological patterns in AVH, FHF SAHF
• Prediction of FHF, SAHF chronicity
• Antivirals ? Prolonged AVH
• ? SAHF
• immunosuppressed