Hepatitis B, Chronic

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

Demographics

• Chronic hepatitis B afflicts 248 million people worldwide and 2.2 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

  • Occasional patients (only 1% of treated and untreated patients per year) reach the HBsAg-negative phase, in which

    • Anti-HBe may remain

    • Serum ALT levels are normal

    • HBV DNA is undetectable in serum but remains present in the liver

    • In some cases, anti-HBs ...