Hepatocarcinogenesis in chronic hepatitis C patients achieving a sustained virological response to interferon: significance of lifelong periodic cancer screening for improving outcomes

Due to advances in interferon (IFN) therapy for chronic hepatitis C, most elderly patients, and even many of those with advanced hepatic fibrosis, now achieve a sustained virological response (SVR). However, carcinogenesis remains problematic in these patients. Hence, we aimed to elucidate risk factors for hepatocarcinogenesis in SVR patients and to present an appropriate follow-up protocol for improving outcomes. We retrospectively studied 562 consecutive SVR patients for a median observation period of 4.8 years. Hepatocellular carcinoma was diagnosed in 31 patients (5.5 %). Respective cumulative incidences were 3.1, 10.1, and 15.9 % at 5, 10, and 15 years after completion of IFN therapy. The proportional hazards model identified moderate or advanced fibrosis stage, advanced age, habitual alcohol consumption, and alpha-fetoprotein elevation as determinants of carcinogenesis, with hazard ratios of 10.7 (p < 0.001), 4.1 (p < 0.01), 3.9 (p < 0.01), and 2.6 (p < 0.05), respectively. Carcinoma was diagnosed in 26 % of patients more than 10 years after completion of IFN therapy. Unexpectedly, F2 fibrosis was detected in 42 % of these patients. The 5-year survival rate was 93 % in the patients who had received periodic cancer screening but only 60 % in those who had not. We recommend that SVR patients be observed at 6-month intervals, at a minimum, to facilitate diagnosis at an early stage, for as long as possible after completion of therapy even if not at an advanced stage of fibrosis.