Introduction: Previously, we reported that Hepatitis C Virus (HCV) infection had effects for lipid metabolism in patients with Chronic Hepatitis C (CHC). Recently, HCV with substitutions in amino acids (aa) 70 and/or 91 in the core region of HCV (HCV-C) has been reported to be more difficult to treat than HCV without aa 70 and 91 substitutions. The aim of this study was to clarify whether aa 70 or 91 substitution in the HCV-C influenced serum cholesterol fractions in patients with CHC genotype 1b and high viral load. Patients and Methods: Twenty-two patients infected with genotype 1b and high viral loads, whose serum samples taken before the start of therapy had been stored at -80°centigrade, and in whom aa 70 and 91 substitutions in the HCV-C could be detected, were selected. Patients without aa 70 and 91 substitutions in the HCV-C were assigned to wild (n=12), those with aa 70 substitution in the HCV-C assigned to mutant-70 (n=6), and those with aa 91 substitution in the HCV-C were assigned to mutant-91 (n=4). All patients received interferon (IFN)- based therapy. Fasting serum total cholesterol (C) and its fractions were compared before starting IFN therapy and at 24 weeks after the End of Therapy (EOT). When serum HCV-RNA was negative at 24 weeks after EOT, the patient was defined as having SVR. RESULTS: The SVR rates were 42% (5/12) in the wild, and 17i¼Â… (1/6) in the mutant-70, and 0% (0/4) in the mutant-91. Serum levels of LDL-C were significantly lower and those of HDL-C were significantly higher in the mutant-70 patients than in the wild patients before starting therapy. Only serum level of VLDL-C increased significantly at 24 weeks after EOT than before starting therapy in the wild patients. Conclusions: It was clarified that the mutant-70 influenced serum cholesterol fractions before starting therapy.