Hepatitis C virus infection and risk of hepatocellular carcinoma among Japanese: possible role of type 1b (II) infection.

BACKGROUND Although hepatitis C virus (HCV) infection is recognized as an important risk factor for hepatocellular carcinoma HCC), the strength of this association has been inconsistent. In addition, the role of specific HCV genotypes in HCC progression has not yet been determined. PURPOSE We conducted a case-control study to estimate the relative risk (RR) of HCC in relation to HCV infection among residents of the Fukuoka Prefecture, where HCC risk is among the highest in Japan, and to examine whether the risk differs according to HCV genotypes and/or HCV RNA titers. METHODS Stored serum samples obtained from 91 patients with HCC and 410 healthy control subjects, who had been frequency matched to the patients with regard to sex and age, were tested for antibodies to HCV by use of second-generation immunoradiometric and immunoblot assays. The presence of serum HCV RNA and of specific HCV genotypes was determined by use of polymerase chain reaction-based assays, and HCV RNA titers were measured by use of a branched DNA assay. RESULTS Antibodies to HCV were detected in 71 patients (78.0%) and in 30 control subjects (7.3%), of whom 57 patients and 25 control subjects had serum HCV RNA. One patient was positive for HCV RNA but not for antibodies to HCV. The sex- and age-adjusted RR of HCC among individuals positive for antibodies to HCV was estimated to be 53.7 (95% confidence interval [CI] = 27.1-106.2). Antibodies to HCV were much more prevalent among patients negative for serum, hepatitis B surface antigen (HBsAg) (69 of 72, 95.8 %) than among HBsAg-positive patients (two of 19, 10.5%); the RR increased to 339.6 (95% CI = 96.5-1195.8) in the separate analysis of HBsAg-negative subjects. The most frequent genotype among HCV RNA-positive subjects was type lb (also called type II) (found in 49 [86.0%] of 57 patients and in 15 [60.0%] of 25 control subjects); individuals with type 1b infection experienced a significantly elevated risk (RR = 3.8; 95% CI = 1.0-13.9) compared with the risk observed for individuals with type 2a (also called type III) infection. No statistically significant association between HCV RNA titers and HCC was evident. CONCLUSIONS HCV infection, particularly type 1b infection, plays an important role in the development of HCC among the study population. We estimated that approximately 78% (95% CI = 69%-86%) of the HCCs that occur in this high-risk area are attributable to HCV infection, if we assume that the patients in this study were representative population samples. IMPLICATIONS Further studies are needed to clarify potential risk factors, including specific HCV genotypes, for progression to HCC among HCV carriers.