RELATION OF INTERFERON THERAPY AND HEPATOCELLULAR-CARCINOMA IN PATIENTS WITH CHRONIC HEPATITIS-C

Background: The effect of interferon therapy on the incidence of hepat ocellular carcinoma in chronic hepatitis C is poorly defined. Objectiv e: To compare the incidence of hepatocellular carcinoma in interferon- treated patients with chronic hepatitis C to that of historical contro ls and to examine whether response to therapy is related to incidence of hepatocellular carcinoma in patients with chronic hepatitis C. Desi gn: Retrospective cohort study. Setting: One university hospital and s even university-affiliated hospitals. Patients: 419 consecutive patien ts with chronic hepatitis C who started interferon therapy between Jan uary 1992 and December 1993 (interferon group) and 144 patients with c hronic hepatitis C who had liver biopsy between January 1986 and Decem ber 1989 and did not receive interferon (controls). Intervention: Pati ents in the interferon group received human lymphoblastoid interferon, recombinant interferon-alpha 2a, or recombinant interferon-alpha 2b f or 6 months. Measurements: The end point was development of hepatocell ular carcinoma on abdominal ultrasonography or computed tomography. Su stained response was defined as persistent normalization of alanine am inotransferase (ALT) levels during interferon therapy and follow-up. R elapse was defined as a normal serum ALT revel at the end of treatment with an increase to an abnormal level after cessation of treatment. N onresponse included all other ALT patterns. Results: Median follow-up in the interferon and control groups was 47.6 and 46.8 months, respect ively. During follow-up, hepatocellular carcinoma was found in 28 inte rferon-treated patients and 19 controls. Cox proportional hazards regr ession analysis that included all patients revealed that interferon th erapy (P = 0.041), older age (P = 0.003), greater histologic activity (P = 0.029), and higher histologic stage (P = 0.049) were independent factors associated with the development of hepatocellular carcinoma. T he risk ratios for development of hepatocellular carcinoma in patients with sustained response, relapse, and nonresponse were 0.06 (95% CI, 0.01 to 0.46), 0.51 (CI, 0.20 to 1.27), and 0.95 (CI, 0.48 to 1.84), r espectively, compared with controls. Conclusions: The incidence of hep atocellular carcinoma was lower in patients with sustained response to interferon therapy than historical controls and nonresponders. Interf eron therapy may decrease the risk for hepatocellular carcinoma in pat ients with chronic hepatitis C.