Randomised trial of effects of interferon-alpha on incidence of hepatocellular carcinoma in chronic active hepatitis C with cirrhosis

Lancet. 1995 Oct 21;346(8982):1051-5. doi: 10.1016/s0140-6736(95)91739-x.


Patients with chronic active hepatitis C and cirrhosis often develop hepatocellular carcinoma. Interferon (IFN) seems to be effective in some patients but whether it prevents carcinogenesis is unknown. In a prospective randomised controlled trial, we evaluated the effects of IFN-alpha in cirrhotic patients with HCV infection because of their high risk of hepatocellular carcinoma. 90 patients with compensated chronic active hepatitis C with cirrhosis were randomly allocated to receive IFN-alpha (6 MU three times weekly for 12-24 weeks) (45 patients) or symptomatic treatment (45 controls), and were followed up for 2-7 years. In nine controls, alanine aminotransferase (ALT) decreased to less than 80 IU/L but did not stay in the normal range. In 19 patients given IFN-alpha, ALT decreased to less than 80 IU/L (in seven patients, it became and stayed normal; p = 0.011, Wilcoxon rank-sum test). However, the mean change in ALT was not significantly different between the two groups. The mean change in peak alpha-fetoprotein values was smaller in patients given IFN-alpha than in controls (p = 0.021). The mean change in the serum albumin level was higher in the IFN-alpha group (p < 0.001). The histological activity index in the 12 IFN-alpha patients undergoing a second biopsy after therapy was improved (p = 0.031). Hepatitis C viral RNA disappeared in seven (16%) of the 45 IFN-alpha patients (95% CI, 7-29%) and in none of the 45 controls (0-8%; p = 0.018). Hepatocellular carcinoma was detected in two (4%, 1-15%) IFN-alpha patients and 17 (38%, 24-54%) controls (p = 0.002, Wilcoxon signed-rank test). The risk ratio of IFN-alpha treatment versus symptomatic treatment was 0.067 (0.009-0.530; p = 0.010 Cox's proportional hazards). IFN-alpha improved liver function in chronic active hepatitis C with cirrhosis, and its use was associated with a decreased incidence of hepatocellular carcinoma.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / therapeutic use*
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / therapeutic use*
  • Carcinoma, Hepatocellular / diagnosis
  • Carcinoma, Hepatocellular / epidemiology
  • Carcinoma, Hepatocellular / prevention & control*
  • Female
  • Follow-Up Studies
  • Hepatitis C / complications
  • Hepatitis C / therapy*
  • Hepatitis, Chronic / complications
  • Hepatitis, Chronic / therapy*
  • Humans
  • Incidence
  • Interferon-alpha / administration & dosage
  • Interferon-alpha / therapeutic use*
  • Liver Cirrhosis / complications*
  • Liver Function Tests
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / epidemiology
  • Liver Neoplasms / prevention & control*
  • Male
  • Middle Aged
  • Prospective Studies
  • Risk Factors


  • Antineoplastic Agents
  • Antiviral Agents
  • Interferon-alpha