Case-control study on hepatitis C virus (HCV) as a risk factor for hepatocellular carcinoma: The role of HCV genotypes and the synergism with hepatitis B virus and alcohol

We performed a case-control study to evaluate the risk of hepatocellular ca rcinoma (HCC) for hepatitis C virus (HCV) infection. A total of 305 newly d iagnosed HCC cases (80% males) and 610 subjects (81% males) unaffected by c linically evident hepatic disease admitted to the 2 main hospitals in Bresc ia, North Italy, were recruited as cases and controls, respectively. Among the 122 HCC cases positive for HCV RNA, genotype 1b was found in 83 patient s (68%), genotype 2 in 36 (29.5%) and genotype la in 3 (2.5%). Among the co ntrols, 15 were infected with genotype Ib and 15 with type 2. Analysis of H CV envelope I nucleotide sequence among 25 cases and 8 controls infected wi th genotype 2 showed subtype 2c in 96% of cases and in all controls, and su btype 2a in I HCC case. The odds ratio (OR) for HCV RNA positivity adjusted for hepatitis B virus (HBV) markers and alcohol intake was 26.3 [95% confi dence interval (CI): 15.8-44], and it was higher for genotype Ib (OR = 34.2 ) than type 2 (OR = 14.4). The OR for HCV RNA was 35.6 (95% CI: 14.5-87.1) when the HBV markers were all negative and 132 (15.3-890) when HBsAg positi vity was present; the OR was 26.1 (95% CI: 12.6-54.0) among subjects with a lcohol intake of 0-40 g/day and increased to 62.6 (23.3-168) and 126 (42.8- 373) with an alcohol intake of 41-80 and >80 g/day, respectively. In conclu sion, synergism was found between HCV infection and HBV infection and alcoh ol intake in causing HCC. (C) 1999 Wiley-Liss, Inc.