Hepatocyte steatosis is an important predictor of response to interferon (IFN) monotherapy in Japanese patients infected with HCV genotype 2a: Virological features of IFN-resistant cases with hepatocyte steatosis

The role of hepatocyte steatosis in interferon (IFN) resistance is still unclear, especially in patients infected with hepatitis C virus (HCV) genotype 2a. The present study was conducted in 364 consecutive non-cirrhotic naive patients infected with genotype 2a, who were evaluated for the severity of steatosis and response to IFN monotherapy after a 24-week median duration of therapy. The patients were examined for factors associated with steatosis and treatment efficacy according to the grade of steatosis. Early viral kinetics was also evaluated in 64 patients for predictors of response to therapy. Nine IFN-resistant patients were assessed for the relationship between amino acid sequence of HCV core region/NS5A and severity of steatosis. Multivariate analysis identified two independent factors associated with steatosis; serum ferritin ≥200 μg/l and body mass index ≥25.0 kg/m2. The sustained virological response rate in patients with high-grade steatosis was significantly lower than in the low-grade group. Study of early viral kinetics showed a significantly lower cumulative HCV-RNA negative rate for the high-grade than low-grade steatosis group. Sequence analysis of HCV core region/NS5A in IFN-resistant patients with or without steatosis failed to identify steatosis-specific amino acid substitutions associated with resistance. This study of HCV genotype 2a suggested that steatosis is associated with excess iron storage, and that it is an important predictor of efficacy of IFN monotherapy. Further large-scale studies are warranted to examine the role of amino acid substitutions on IFN resistance specific for steatosis. J. Med. Virol. 75:550–558, 2005. © 2005 Wiley-Liss, Inc.