Effect of interferon therapy on the incidence of hepatocellular carcinoma and mortality of patients with chronic hepatitis C: A retrospective cohort study of 738 patients

The effect of interferon on the long-term clinical outcome of patients with chronic hepatitis C remains unclear. This study included 594 patients with chronic hepatitis C who received interferon-alpha therapy (Interferon grou p) and 144 patients with chronic hepatitis C who did not receive interferon (Control group). The patients in the Interferon group were classified into the following three groups based on the response of the serum aminotransam inase level of the patient during and after completion of the therapy proto col: sustained responders (n = 175), transient responders (n = 165), and no n-responders (n = 254). The age, sex, serum aminotransaminase level, platel et count, histological staging, hepatitis C virus (HCV) subtype, and HCV co ncentration at baseline were adjusted with the Cox proportional hazards mod el. The length of follow-up for assessment of the risk for developing hepat ocellular carcinoma (HCC) was 57.2 +/- 13.9 months in the Interferon group and 67.7 +/- 28.7 months in the Control group. Multivariate analysis showed that interferon therapy decreased the risk for developing HCC by 48% compa red with that in the Control group (P = 0.064). The older the age, being ma le, having a low platelet count, and higher histological stage were indepen dent factors associated with the development of HCC. The hazard rate ratio for development of HCC in the sustained responders, transient responders, a nd non-responders was 0.16 (95% confidence interval Cell: 0.04-0.62), 0.27 (95% CI: 0.09-0.79), and 0.74 (95% CI: 0.37-1.48), respectively. During fol low-up, 18 patients in the Interferon group died(10 from liver-related dise ases) and 17 patients in the Control group died (10 from liver-related dise ases). No sustained responder or transient responder in the Interferon grou p died of liver-related disease. The cumulative survival rates of the Inter feron and Control groups were nearly identical during the first 5 years fol lowing diagnosis. Thereafter, the cumulative survival rate of the Control g roup declined, resulting in an 1-year survival rate in the Interferon and C ontrol groups of 97% and 81%, respectively (P = 0.061). Similar trends were seen in the survival analysis of those who had died of liver disease: the I-year survival rates of the Interferon and Control groups were 98% and 88% , respectively (P = 0.32). Our study demonstrated that interferon therapy s ignificantly lowered the incidence of HCC among patients with chronic hepat itis C who showed sustained normalization and among patients who showed tra nsient normalization of the serum aminotransferase level after completion o f interferon therapy. The survival analyses and determination of cause of d eath suggested that interferon therapy improves the long-term survival of c hronic hepatitis C patients who respond to this therapy, possibly by decrea sing mortality from liver-related diseases. (C) 2000 Wiley-Liss, Inc.