A Long-term Follow-up Study on Risk Factors for Hepatocellular Carcinoma among Japanese Patients with Liver Cirrhosis

To identify virological parameters (serostatus of hepatitis B surface antigen HBsAg] and antibodies to hepatitis C virus anti-HCV], HCV genotypes and HCV-RNA titer) and other clinico-biological and lifestyle variables that may influence or predict the development of hepatocellular carcinoma (HCC) in cirrhosis, we followed 100 cirrhotic patients without HCC, who visited Kyushu University Hospital between 1985 and 1987, until the end of 1995 (follow-up rate: 98%; average follow-up period: 5.3 years). After elimination of 4 patients who developed HCC or were censored within the initial 6 months, 37 (39%) out of 96 patients developed HCC during follow-up. As compared with HBsAg(+) patients, anti-HCV(+) HBsAg(–) patients demonstrated significantly elevated HCC risk (adjusted hazard ratio HR]=5.85, 95% confidence interval CI] 1.65–20.67). Genotype 1 HCV infection was not associated with increased risk compared with genotype 2 (HR = 0.64, 95% CI 0.21–1.99). For genotype 1 HCV infection, patients with HCV-RNA levels <1 Meq/ml tended to present lower risk than patients with ≥1 Meq/ml ( P = 0.03). Male sex, advanced Child's class, lower serum albumin, and higher serum aminotransferase and α-fetoprotein were also found to be strong predictors. Overall, drinking and smoking habits were not associated with significantly elevated risk. Among virological parameters, anti-HCV positivity and, possibly high HCV-RNA titer, were predictive of HCC occurrence in cirrhosis in our clinical setting.