Antiviral therapy for cirrhotic hepatitis C: association with reduced hepatocellular carcinoma development and improved survival

Ann Intern Med. 2005 Jan 18;142(2):105-14. doi: 10.7326/0003-4819-142-2-200501180-00009.


Background: Although cirrhosis is a major risk factor for development of hepatocellular carcinoma, no definitive prospective analyses have assessed the long-term efficacy of antiviral therapy in cirrhotic patients.

Objective: To elucidate the role of antiviral therapy in the suppression of liver tumors and survival over a long-term follow-up period.

Design: Prospective cohort study.

Setting: 25 clinical centers.

Patients: 345 patients with chronic hepatitis C and cirrhosis enrolled in previous trials.

Intervention: 271 patients received 6 to 9 million U of interferon 3 times weekly for 26 to 88 weeks; 74 received no treatment.

Measurements: Blood tests and abdominal ultrasonography were done regularly to detect hepatocellular carcinoma.

Results: Hepatocellular carcinoma was detected in 119 patients during a 6.8-year follow-up: 84 (31%) in the interferon-treated group and 35 (47%) in the untreated group. Cumulative incidence of hepatocellular carcinoma among interferon-treated patients was significantly lower than in untreated patients (Cox model: age-adjusted hazard ratio, 0.65 [95% CI, 0.43 to 0.97]; P = 0.03), especially sustained virologic responders. A total of 69 patients died during follow-up: 45 (17%) in the treated group and 24 (32%) in the untreated group. Interferon-treated patients had a better chance of survival than the untreated group (Cox model: age-adjusted hazard ratio, 0.54 [CI, 0.33 to 0.89]; P = 0.02). This was especially evident in sustained virologic responders.

Limitation: This was not a randomized, controlled study. Patients enrolled in the control group had declined to receive interferon treatment even though they were eligible for treatment.

Conclusion: Interferon therapy for cirrhotic patients with chronic hepatitis C, especially those in whom the infection had been cured, inhibited the development of hepatocellular carcinoma and improved survival.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Antiviral Agents / therapeutic use*
  • Carcinoma, Hepatocellular / diagnosis
  • Carcinoma, Hepatocellular / prevention & control*
  • Carcinoma, Hepatocellular / therapy
  • Cause of Death
  • Female
  • Follow-Up Studies
  • Hepacivirus / genetics
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / mortality
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use*
  • Liver Cirrhosis / drug therapy*
  • Liver Cirrhosis / etiology
  • Liver Cirrhosis / mortality
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / prevention & control*
  • Liver Neoplasms / therapy
  • Male
  • Middle Aged
  • Prospective Studies
  • RNA, Viral / blood
  • Recombinant Proteins
  • Risk Factors
  • Viral Load


  • Antiviral Agents
  • Interferon alpha-2
  • Interferon-alpha
  • RNA, Viral
  • Recombinant Proteins