Prevention of hepatitis B virus-related hepatocellular carcinoma with antiviral therapy

Hepatology. 2013 Jan;57(1):399-408. doi: 10.1002/hep.25937.


Chronic hepatitis B (CHB) infection is the major cause of hepatocellular carcinoma (HCC). Primary prevention of hepatitis B infection by vaccination is effective in reducing the incidence of HCC. In persons with CHB infection, the two accepted treatment modalities are interferon alpha (IFN-α) given subcutaneously for a limited period and nucleoside/nucleotide analogs given orally on a long-term basis. These treatments are effective in suppressing viral activity and improving disease markers in short-term studies. The long-term effect on the development of liver cancers with these two forms of treatment appears to be different. However, there are no studies directly comparing IFN-α and nucleoside/nucleotide analogs. Comparisons across studies are inevitably limited by differences in the baseline characteristics of the study cohorts. Long-term follow-up studies of IFN-α therapy show inconsistent results. The beneficial effect in reducing the development of liver cancer is observed mainly in treatment responders who have preexisting cirrhosis of the liver. The long-term studies of lamivudine (and adefovir) show a consistent reduction in the development of liver cancers in patients with, and without, cirrhosis. This beneficial effect is blunted by the development of resistance. The effects of the newer nucleoside/nucleotide analogs, with higher potency and minimal risk of resistance development, are, as yet, unknown.

Publication types

  • Review

MeSH terms

  • Antiviral Agents / therapeutic use*
  • Carcinoma, Hepatocellular / prevention & control*
  • Carcinoma, Hepatocellular / virology
  • Hepatitis B / complications*
  • Hepatitis B / drug therapy
  • Humans
  • Interferon-alpha / therapeutic use*
  • Liver Neoplasms / prevention & control*
  • Liver Neoplasms / virology
  • Risk Factors


  • Antiviral Agents
  • Interferon-alpha