Relationship of hepatitis C virus genotypes and viremia levels with development of hepatocellular carcinoma among Japanese.

: The roles of hepatitis C virus (HCV) genotypes and viremia levels in the pathogenesis of hepatocellular carcinoma (HCC) were examined in case-control analyses of 69 patients with HCC, 55 patients with liver cirrhosis (LC) without HCC, and 30 controls undergoing health examinations. Major HCV genotypes (genotypes 1 and 2) were determined by both reverse transcription-polymerase chain reaction (RT-PCR)-based and serological assays, and the HCV-RNA level by a branched DNA assay. Genotype 1 was detected in 68-82% of HCCs, 71-73% of LCs, and 50-72% of controls. Based on RT-RCR, the relative risk for genotype 1 vs. 2 contrasting either HCC or LC patients with controls was estimated at 3.6 (95% confidence interval: 1.1-12.5) for HCC and 4.8 (1.1-20.4) for LC, whereas no risk excess was evident for the occurrence of HCC in LC (relative risk: 0.7). The corresponding association based on the serological assay was somewhat weaker and statistically insignificant. No significant difference in age or time lapse after blood transfusion was observed according to the genotype. The HCV-RNA titer for genotype 1 was significantly lower among HCC patients than among LC patients or controls. Genotype 1 HCV may be associated with HCC through affecting relatively early stages of liver diseases progression prior to the establishment of LC.