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Hepatitis B

Patricia D. Jones, M.D.

November 13, 2009
Hepatitis B
 Prototype member of the Hepadnaviridae family

 DNA virus

 Outer lipoprotein envelope with 3 glycoproteins

– Hep B surface antigens (HBsAg)

 Viral nucleocapsid protein - Hep B core antigen


 Soluble nucleocapsid protein-Hepatitis B e

antigen (HBeAg)
 Worldwide:
 Affects 350-400 million persons
 Endemic areas: Asia, Africa
 1 million worldwide deaths per year
 Acquired perinatally and in childhood

 United States:
 Affects 1.25 million persons
 4000-5000 deaths per year
 Acquired via sexual activity, then IVDU and
occupational exposure
Primary Infection
 Incubation Period 4-10 weeks
 During the prodromal period, patient may have a serum sickness-like
 Constitutional symptoms, anorexia, nausea, RUQ discomfort and jaundice.
 30 % develop icteric hepatitis.
 70% develop anicteric or subclinical hepatitis.
 0.5-1% develop fulminant liver failure.
 Symptoms and jaundice disappear in 1-3 months, though fatigue may persist.
Infection in Children vs. Adults
 Children
 In neonates, the immature immune system does not recognize a difference between
the virus and the host.
 Cellular immune responses to hepatocyte-membrane HBV proteins do not occur.
 Risk of developing chronic HBV infection is 90% in infants born to HBeAg positive
mothers. In children under 5, risk is 25-30%.

 Adults:
 Tend to have a more vigorous immune response.
 Less than 5% of those infected develop continual viremia and persistent infection.
Serologic Diagnosis
HBsAg HBeAg Anti-HBc IgM Anti-HBc IgG Anti-HBe HBsAb HBV DNA

Early + + + +++
Window + +
Recovery + + + +/-
Replicative + + + +++
Nonreplicative + + + +/-
Flare + +/- + + +
Precore/core + + + ++
promoter mutants
Chronic Hepatitis B Infection
 Early Replicative Phase: Immune Tolerance
 Perinatally acquired infection
 High levels of HBV DNA, HBeAg present
 No liver disease—normal ALT, asymptomatic, Stage 0-1 fibrosis
 Lasts 10-30 years

 Replicative Phase: Immune Clearance

 Spontaneous clearance of HBeAg
 Often characterized by periods of increased HBV DNA and increased ALT due to immune-mediated lysis of
infected hepatocytes, i.e. flares

 Nonreplication Phase: Inactive Carrier State

 HBeAg negative, anti-Hep B e positive, HBV DNA undetectable
 ALT levels normalize, however some patients may have active inflammation
Chronic Hepatitis B Infection
 HBeAg-negative Chronic Hepatitis
 Precore/Core Promoter Mutations
 Moderate levels HBV DNA
 Active liver disease and elevated ALT
 Older patients

 Resolution
 Hallmark is the clearance of HbSAg
 Does not preclude development of cirrhosis, HCC or failure.
 Patients may still produce HBV DNA, which has implications in the
Sequelae of Chronic HBV Infection
 Cirrhosis
 Hepatocellular Carcinoma
 Hepatic Decompensation
 Extrahepatic Manifestations
 Death
 Prognosis is worse in endemic areas:
 Prolonged replicative phase
 Clearance of HBeAg causes a 2 fold
decrease in death rate.
 Patients who reactivate have worse
Extrahepatic Manifestations
 Occur in 10-20% of patients with
Chronic Hep B.

 Serum Sickness
 Polyarteritis Nodosa
 Membranous and

 Genotype B associated with HBeAg seroconversion at an earlier age, more sustained remission, less active
hepatic necroinflammation, a slower rate of progression to cirrhosis and lower rate of HCC development
when compared with Genotype C.

 Genotypes A and B are associated with higher rates of seroconversion with pegIFN-alpha than C and D.
Indications for Therapy
Acute Hepatitis
 One trial demonstrated no biochemical or clinical benefit in patients treated with
Lamivudine vs. placebo in 12 months.

 General Rule:
 Coagulopathy INR>1.5
 Persistent symptoms or marked jaundice (bilirubin >10 mg/dl) for more than 4 weeks after
 Fulminant Hepatic Failure
 Concomitant infection with Hep C or D
Indications for Therapy
HBeAg-positive patients:
 HBeAg-positive patients with persistently normal ALT
should be tested for ALT at 3-6 month intervals
 HBeAg status should be checked every 6-12 months.
 HBeAg positive with HBV DNA levels >20,000 IU/mL after a
3-6 month and ALT 1-2 x ULN OR are >40 years liver
biopsy w/ treatment if biopsy shows moderate/severe
inflammation or significant fibrosis.
 Patients who remain HBeAg positive with HBV
DNAlevels>20,000 IU/mL after a 3-6month period of
elevated ALT levels >2 ULN should be considered for

HBeAg-negative patients:
 HBeAg-negative patients with normal ALT and HBV DNA
<2,000 IU/mL: Tested ALT q 3months during the first year to
verify true “inactive carrier state” and then every 6-12
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 Lok ASF, McMahon BJ. Chronic Hepatitis B: Update 2009. Hepatology 2009;
3: 1-36.
 Lok ASF. Clinical manifestations and natural history of hepatitis B virus
infection. UpToDate