Effects of Alcohol Consumption on Hepatocarcinogenesis in Japanese Patients With Fatty Liver Disease

BACKGROUND & AIMS: The effect of ethanol consumption on hepatocarcinogenesis in patients with fatty liver disease (FLD) is not clear. We aimed to investigate the influence of alcohol consumption on hepatocarcinogenesis and determine the risk factors for hepatocellular carcinoma (HCC) in a large number of Japanese patients with FLD without viral hepatitis. METHODS: This multicenter, retrospective cohort study was conducted at a specialized center for hepatology in Japan and included 9959 patients with FLD without viral hepatitis, diagnosed by ultrasonography from January 1997 through December 2011. The patients' level of ethanol consumption was divided into 4 categories: <20 g/day (n = 6671), 20-39 g/day (n = 753), 40-69 g/day (n = 1589), and >= 70 g/day (n = 946). The primary endpoint was the onset of HCC. Statistical analyses performed included the Kaplan-Meier method and Cox proportional hazard analysis. The median follow-up period was 5.4 years. RESULTS: Of the study cohort, 49 cases (0.49%) developed HCC during the follow-up period. The annual incidence rate of HCC was 0.05% in patients with FLD and a daily ethanol consumption <20 g/day. Increasing levels of ethanol consumption were associated with increased annual incidence rates of HCC: 0.06% for patients with 20-39 g/day ethanol consumption (hazard ratio [HR], 1.54; 95% confidence interval [CI], 0.34-7.04), 0.16% for patients with 40-69 g/day ethanol consumption (HR, 3.49; 95% CI, 1.50-8.12), and 0.22% for patients with >= 70 g/day ethanol consumption (HR, 10.58; 95% CI, 5.06-22.13), compared with patients with ethanol consumption <20 g/day. Multivariate analysis showed that ethanol consumption >= 40 g/day was an independent risk factor for HCC: for 40-69 g/day the HR was 2.48 (95% CI, 1.01-6.05; P < .047) and for >= 70 g/day the HR was 12.61 (95% CI, 5.68-28.00; P < .001). CONCLUSIONS: Based on a multicenter, retrospective analysis of almost 10,000 patients with FLD, ethanol consumption >= 40 g/day is an independent risk factor for HCC.