• hepatocellular carcinoma;
  • interferon;
  • retrospective cohort study;
  • risk factor;
  • sustained virological response


Background and Aim:  Hepatitis C virus (HCV)-infected patients who responded to interferon (IFN) treatment with clearance of serum HCV RNA may rarely develop hepatocellular carcinoma (HCC). The aim of the present study was to elucidate the risk factors for liver carcinogenesis among such patients.

Methods:  In total, 126 patients with chronic hepatitis C (CHC) who achieved a sustained virological response (SVR) to IFN monotherapy, which was defined as the absence of detectable HCV RNA in the serum at 6 months after completion of treatment, were enrolled and possible risk factors for HCC were analyzed.

Results:  During the observation period of 66 ± 36 months after cessation of IFN treatment, five (4.0%) of the 126 patients developed HCC. The cumulative incidence of HCC at 3, 5 and 10 years was estimated to be 0.9, 4.7 and 7.5%, respectively. The cumulative incidence of HCC was significantly higher among patients with severe fibrosis (F3 or F4) than among patients with no or mild fibrosis (F0 to F2) in the liver before treatment (= 0.007); among patients with alcohol intake of ≥ 27 g/day than among patients with that of < 27 g/day (= 0.015); and among patients who were ≥ 65 years old than among patients who were < 65 years old at the start of treatment (= 0.026).

Conclusions:  Patients with CHC who had severe fibrosis, who had regularly taken moderate amounts of alcohol, or who were ≥ 65 years at the start of IFN treatment should be carefully followed to detect small and controllable HCC, even after eradication of HCV.