Analysis of Risk Factors for Hepatocellular Carcinoma in Patients With HBs Antigen‐ and Anti‐HCV Antibody‐Negative Alcoholic Cirrhosis: Clinical Significance of Prior Hepatitis B Virus Infection

BACKGROUND: The hepatitis B virus (HBV) or hepatitis C virus (HCV) markers frequently are detected in alcoholic patients with hepatocellular carcinoma (HCC). However, risk factors for the development of HCC in patients with HBs antigen (Ag)- and anti-HCV antibody (anti-HCV)-negative alcoholic cirrhosis have not been clearly documented. The present study was conducted to elucidate the occurrence rates of HCC in HBs Ag- and anti-HCV-negative male alcoholic cirrhosis and to assess the risk factors for hepatocellular carcinogenesis. METHOD: We prospectively studied 91 consecutive patients with HBs Ag- and anti-HCV-negative alcoholic cirrhosis for 0.5 to 12.5 years (median 5.9 years). Potential risk factors assessed for liver carcinogenesis included the following six variables: age, total alcohol intake, association of continuing alcohol intake after diagnosis, indocyanine green retention rate at 15 min, anti-HB core antibodies (anti-HBc), and association of diabetes mellitus. RESULTS: Cumulative occurrence rates of HCC were 6.4%, 18.9%, and 28.7% at the end of the 5th, 7th and 10th years, respectively. When classified by anti-HBc, the occurrence rates of HCC in 31 patients with anti-HBc and 60 patients without anti-HBc were 15.6% and 2.9% at the 5th year, 28.4% and 13.5% at the 7th year, and 40.4% and 22.1% at the 10th year, respectively. The occurrence rates of HCC were also significantly related to the cumulative alcohol intake. Cox proportional hazard model identified that cumulative alcohol intake (p = 0.0047) and positive anti-HBc antibodies (p = 0.0598) were independently associated with the occurrence rates of HCC. CONCLUSION: These epidemiologic results suggest that heavy cumulative alcohol intake and prior exposure to HBV infection are risk factors for the development of HCC in patients with HBs Ag- and anti-HCV-negative alcoholic cirrhosis.