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For further information, see CMDT Part 16-06: Chronic Viral Hepatitis

Key Features

Essentials of Diagnosis

  • Chronic inflammatory reaction of the liver of more than 3–6 months' duration

  • Repeated detection of hepatitis B surface antigen (HBsAg) in serum, often with elevated serum aminotransferase levels

General Considerations

  • Early in the course, hepatitis Be antigen (HBeAg) and hepatitis B virus (HBV) DNA are present in serum

    • Indicative of active viral replication and necroinflammatory activity in the liver

    • These persons are at risk for progression to cirrhosis and for hepatocellular carcinoma

    • Low-level IgM anti-HBc is also present in about 70%

  • Clinical and biochemical improvement may coincide with

    • Disappearance of HBeAg and HBV DNA from serum

    • Appearance of anti-HBe

    • Integration of the HBV genome into the host genome in infected hepatocytes

  • If cirrhosis has not yet developed, such persons are at a lower risk for cirrhosis and hepatocellular carcinoma

  • Chronic hepatitis is characterized on the basis of

  • The etiology

    • The grade of portal, periportal, and lobular inflammation (minimal, mild, moderate, or severe)

    • The stage of fibrosis (none, mild, moderate, severe, cirrhosis)

  • Five phases of chronic HBV infection are recognized

    • Immune tolerant phase

    • Immune active (or immune clearance) phase

    • Inactive HBsAg carrier state

    • Reactivated chronic hepatitis B phase

    • HBsAg-negative phase


  • Afflicts 248 million people worldwide (2 billion overall have been infected; endemic areas include Asia and sub-Saharan Africa) and an estimated 2.4 million (predominantly males) in the United States

Clinical Findings

Symptoms and Signs

  • Clinically indistinguishable from chronic hepatitis due to other causes

  • Immune active phase (HBeAg-positive chronic hepatitis B)

    • HBeAg and HBV DNA are present in serum, indicative of active viral replication

    • Serum aminotransferase levels are normal, with little necroinflammation in the liver

    • This phase is common in infants and young children whose immature immune system fails to mount an immune response to HBV

  • Inactive HBsAg carrier state (HBeAg-negative chronic HBV infection)

    • Patients have entered this phase when biochemical improvement follows immune clearance and cirrhosis has not yet developed

    • Patients in this phase are at a low risk for cirrhosis and hepatocellular carcinoma

    • Patients with persistently normal serum aminotransferase levels infrequently have histologically significant liver disease

  • Reactivated chronic hepatitis B phase (HBeAg-negative chronic hepatitis B)

    • Risk factors for reactivation include

      • Male sex and HBV genotype C

      • Advanced age

      • Alcohol use

      • Cigarette smoking

      • Coinfection with HCV or HDV

    • In patients with either HBeAg-positive or HBeAg-negative chronic hepatitis B, the risk of cirrhosis and of hepatocellular carcinoma correlates with the serum HBV DNA level

    • HIV coinfection is also associated with an increased frequency of cirrhosis when the CD4 count is low

  • HBsAg-negative phase

    • Occasional patients reach the HBsAg-negative phase, in which

      • Anti-HBe remains the only serologic marker of HBV infection

      • Serum ALT levels are normal

      • HBV DNA is undetectable in serum ...

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