Hepatocellular carcinoma is typically associated with hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. Cirrhosis of the liver is an important preneoplastic condition, although HBV-related tumors can develop in patients without cirrhosis. Treatment of HBV and HCV infection with interferon-alfa often does not achieve sustained virologic benefit; however, the antitumor effects of interferon may differ from its antiviral effect at any stage of disease development. Thus, little is actually known about the effectiveness of interferon-alfa in delaying or preventing hepatocellular carcinoma independent of its antiviral effect in patients with cirrhosis. Baffis and associates reviewed the literature to discuss the impact of interferon-alfa on hepatocellular carcinoma in patients with cirrhosis, review the pathology of hepatocellular carcinoma in patients with HBV-and HCV-related cirrhosis, and summarize the clinical studies addressing both.

A search of the MEDLINE database for appropriate English-language studies concerning cirrhosis treatment and progression to hepatocellular carcinoma was conducted. Interferon-alfa appears to prevent hepatocellular carcinoma in patients with HCV-related cirrhosis, but little is known about whether a measurable virologic response is needed to realize this benefit. In HBV infection, ongoing viral replication is associated with a less favorable clinical outcome independent of cancer. Patients with chronic liver disease, especially cirrhosis, are at increased risk for hepatocellular carcinoma, possibly related to regenerative nodule formation promoting malignant transformation. Early cellular genetic alterations may also play a role in the development of carcinoma. In HCV infection, progressive infection follows an orderly course from chronic hepatitis to cirrhosis, and carcinoma occurs almost exclusively among patients with cirrhosis. The core protein of HCV may modulate gene transcription, resulting in the induction of adenomas in mice similar to hepatic carcinomas.

The literature suggests that interferon-alfa may be effective in preventing hepatocellular carcinoma in patients with cirrhosis who have HBV or HCV infection. Patients with HBV-related cirrhosis appeared to have a slightly lower incidence of hepatocellular carcinoma that was clearly associated with virologic response. Those with HCV-related cirrhosis showed a consistent decrease in hepatocellular carcinoma risk independent of the antiviral effect.

The authors conclude that interferon-alfa monotherapy appears to delay or prevent hepatocellular carcinoma in patients with either type of hepatitis infection, although patients with HCV infection experienced a greater benefit. Additional randomized controlled studies would be useful to confirm this finding before definitive recommendations for interferon-alfa monotherapy are instituted.