Aim: Hepatic steatosis is linked to development of hepatocellular carcinoma (HCC) in non-viral liver disease such as non-alcoholic steatohepatitis. The present study aimed to assess whether hepatic steatosis is associated with the development of HCC in chronic hepatitis C.

Methods: We studied a retrospective cohort of 1279 patients with chronic hepatitis C who received interferon (IFN) therapy between 1994 and 2005 at a single regional hospital in Japan. Of these patients, 393 had a sustained virological response (SVR) and 886 had non-SVR to IFN therapy. After IFN therapy, these patients were screened for development of HCC every 6 months. The average period of observation was 4.5 years.

Results: HCC developed in 68 patients. The annual incidence of HCC was 2.73% for patients with a steatosis grade of 10% or greater and 0.69% for patients with a steatosis grade of 0-9%. On multivariate analysis, higher grade of steatosis was a significant risk factor for HCC independent of older age, male sex, higher body mass index (BMI), advanced fibrosis stage and non-SVR to IFN therapy. The adjusted risk ratio of hepatic steatosis was 3.04 (confidence interval 1.82-5.06, P < 0.0001), which was higher than that of older age (1.09), male sex (2.12), non-SVR to IFN (2.43) and higher BMI (1.69).

Conclusion: Hepatic steatosis is a significant risk factor for development of HCC in chronic hepatitis C independent of other known risk factors, which suggest the possibility that amelioration of hepatic steatosis may prevent hepatocarcinogenesis. �