Interferon therapy reduces the risk for hepatocellular carcinoma: Nationalsurveillance program of cirrhotic and noncirrhotic patients with chronic hepatitis C in Japan

Background: Previous studies on the effect of interferon therapy on the inc idence of hepatocellular carcinoma have not sufficiently assessed degree of liver fibrosis, a major risk factor for hepatocellular carcinoma. Objective: To evaluate the effect of interferon therapy on incidence of hep atocellular carcinoma, adjusting for risk factors, including the degree of liver fibrosis. Design: Retrospective cohort study. Setting: Seven university hospitals and one regional core hospital in Japan . Patients: 2890 patients with chronic hepatitis C who had undergone liver bi opsy since 1986. Of these patients, 2400 received interferon and 490 were u ntreated. Measurements: The degree of liver fibrosis was assessed from stage F0 (no f ibrosis) to stage F4 (cirrhosis). Response to interferon was determined vir ologically and biochemically. Screening for development of hepatocellular c arcinoma was performed periodically during an average follow-up of 4.3 year s. Effect of interferon therapy on the risk for hepatocellular carcinoma wa s analyzed by using Cox proportional hazards regression. Results: Hepatocellular carcinoma developed in 89 interferon-treated patien ts and in 59 untreated patients. Among untreated patients, the annual incid ence of hepatocellular carcinoma increased with the degree of liver fibrosi s, from 0.5% among patients with stage F0 or F1 fibrosis to 7.9% among pati ents with stage F4 fibrosis. The cumulative incidence in treated and untrea ted patients differed significantly for patients with stage F2 fibrosis (P = 0.0128) and for those with stage F3 fibrosis (P = 0.0011). In multivariat e analysis, interferon therapy was associated with a reduced risk for hepat ocellular carcinoma (adjusted risk ratio, 0.516 [95% CI, 0.358 to 0.742]; P < 0.001), especially among patients with sustained virologic response (ris k ratio, 0.197 [CI, 0.099 to 0.392]), among those with persistently normal serum alanine aminotransferase levels (risk ratio, 0.197 [CI, 0.104 to 0.37 5]), and among those with alanine aminotransferase levels less than two tim es the upper limit of normal (risk ratio, 0.358 [CI, 0.206 to 0.622]). Conclusions: Interferon therapy significantly reduces the risk for hepatoce llular carcinoma, especially among virologic or biochemical responders.