title: 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.
abstract: 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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Jikei University School of Medicine, Koyabe, Yokosukashi, Kanagawaken, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Uetake
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Yamauchi
authors.forename: Shuji
authors.initials: S
authors.lastname: Itoh
authors.forename: Osamu
authors.initials: O
authors.lastname: Kawashima
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Takeda
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Ohata
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000453:epidemiology / Q000276:immunology; D015984:Causality; D003920:Diabetes Mellitus / Q000175:diagnosis / Q000453:epidemiology / Q000276:immunology; D005500:Follow-Up Studies; D006509:Hepatitis B / Q000175:diagnosis* / Q000453:epidemiology / Q000276:immunology; D006510:Hepatitis B Antibodies / Q000097:blood; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D018937:Hepatitis C Antibodies / Q000097:blood*; D006801:Humans; D007564:Japan; D008104:Liver Cirrhosis, Alcoholic / Q000175:diagnosis* / Q000453:epidemiology / Q000276:immunology; D008111:Liver Function Tests; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000453:epidemiology / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D018937:Hepatitis C Antibodies