Elsevier

Mayo Clinic Proceedings

Volume 82, Issue 8, August 2007, Pages 967-975
Mayo Clinic Proceedings

REVIEW
Natural History of Hepatitis B Virus Infection: An Update for Clinicians

https://doi.org/10.4065/82.8.967Get rights and content

Hepatitis B virus (HBV) is a common viral pathogen that causes a substantial health burden worldwide. Significant progress has been made in the past few decades in understanding the natural history of HBV infection. A dynamic balance between viral replication and host immune response is pivotal to the pathogenesis of liver disease. In immunocompetent adults, most HBV infections spontaneously resolve, whereas in most neonates and infants they become chronic. Those with chronic HBV may present in 1 of 4 phases of infection: (1) in a state of immune tolerance, (2) with hepatitis B e antigen (HBeAg)-positive chronic hepatitis, (3) as an inactive hepatitis B surface antigen carrier, or (4) with HBeAg-negative chronic hepatitis. Of these, HBeAg-positive and HBeAg-negative chronic hepatitis may progress to cirrhosis and its long-term sequelae including hepatic decompensation and hepatocellular carcinoma. Several prognostic factors, such as serum HBV DNA concentrations, HBeAg status, serum aminotransferases, and certain HBV genotypes, have been identified to predict long-term outcome. These data emphasize the importance of monitoring all patients with chronic HBV infection to identify candidates for and select optimal timing of antiviral treatment, to recognize those at risk of complications, and to implement surveillance for early detection of hepatocellular carcinoma.

Section snippets

PATHOGENESIS OF HBV INFECTION

The observation that many HBV carriers are asymptomatic with minimal liver injury, despite extensive and continuing intrahepatic replication of the virus, supports the concept that HBV is not directly cytotoxic to hepatocytes.8, 9 The severity of hepatocellular injury is modulated by the strength of host immune responses.10, 11, 12 In patients with fulminant HBV infection, rapid viral clearance is achieved after severe liver injury as a result of a vigorous host immune response.10, 11, 12

ACUTE HBV INFECTION

In acute HBV infection, hepatitis B surface antigen (HBsAg) becomes detectable in the serum after an incubation period of 4 to 10 weeks, followed shortly by the appearance of antibody against the hepatitis B core antigen, which is predominantly of the IgM isotope in the early phase.23 Levels of HBV DNA are generally very high, frequently in the range of 200 million IU/mL to 200 billion IU/mL (109–1012 copies/mL).24 Circulating HBeAg can be detected in most patients with acute HBV infection, and

PHASES OF CHRONIC HBV INFECTION

Those with chronic HBV infection may present: (1) in a state of immune tolerance, (2) with HBeAg-positive chronic hepatitis, (3) as an inactive HBsAg carrier, or (4) with HBeAg-negative chronic hepatitis (Figure 1).

Chronic HBV Infection and Cirrhosis

Sequelae of chronic HBV infection may include mild to moderate fibrosis, compensated cirrhosis, hepatic decompensation, and HCC. The annual incidence of cirrhosis in patients with HBeAg-negative chronic hepatitis may be as high as 8% to 10%, compared with 2% to 5% in those with HBeAg-positive chronic hepatitis.62, 94, 95, 96 The higher rate of cirrhosis in patients presenting with HBeAg-negative chronic hepatitis, a late phase in the natural history of chronic HBV infection, is not surprising

SUMMARY AND CONCLUSIONS

The dynamic balance between viral replication and host immune response plays a key role in the pathogenesis of liver disease from HBV infection. Most infections in immunocompetent adults are resolved, whereas most neonates and infants develop chronic HBV infection. Those with chronic HBV infection may present in 1 of 4 phases: (1) in a state of immune tolerance, (2) with HBeAg-positive chronic hepatitis, (3) as an inactive HBsAg carrier, or (4) with HBeAg-negative chronic hepatitis. Of these,

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    This work was supported by grant DK 61617 from the National Institute of Diabetes and Digestive and Kidney Diseases.

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