title: The role of previous hepatitis B virus infection and heavy smoking in hepatitis C virus-related hepatocellular carcinoma.
abstract: OBJECTIVE
  Worldwide epidemiological studies have demonstrated that hepatitis C virus (HCV) probably is a causative agent of hepatocellular carcinoma (HCC). However, there are no available reports that clearly identify the risk factors for the development of HCC in HCV-related chronic liver disease (CLD). The aim of the present study is to explore the risk factors for hepatocarcinogenesis in HCV-related CLD.
  
  
  METHODS
  We prospectively observed 412 patients with anti-HCV-positive CLD but without co-infection of hepatitis B virus (232 patients with chronic hepatitis and 180 with liver cirrhosis) for between 0.5 and 15.8 yr (median: 4.9 yr). Risk factors for hepatocarcinogenesis were identified with a Cox proportional-hazard model.
  
  
  RESULTS
  Sixty-three patients (15.3%) developed HCC during the observation period; the cumulative occurrence rates at the end of the 5th, 10th, and 15th yr was 3.7%, 12.1%, and 12.1%, respectively, for chronic hepatitis patients and 23.3%, 49.4%, and 90.7%, respectively, for 180 cirrhotic patients. The Cox proportional-hazard model showed that the risk of hepatocarcinogenesis increased almost 5-fold in cirrhotic patients (risk ratio, 5.14; 95% confidence interval, 2.52-10.46, p = 0.0001), 2-fold in patients with positive antibodies against hepatitis B surface antigen and/or antibodies against hepatitis B core antigen (risk ratio, 2.14; 95% confidence interval, 1.13-4.07, p = 0.0201), and 2.5-fold in heavy smokers (risk ratio, 2.46; 95% confidence interval, 1.11-5.49, p = 0.0276).
  
  
  CONCLUSIONS
  These epidemiological results indicate that previous infection with hepatitis B virus and heavy smoking (in addition to liver cirrhosis, a known risk factor) play important roles as risk factors for carcinogenesis in HCV-related CLD.
authors.affiliation: Department of Medicine, University of Tsukuba, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Chiba
authors.forename: Y
authors.initials: Y
authors.lastname: Matsuzaki
authors.forename: M
authors.initials: M
authors.lastname: Abei
authors.forename: J
authors.initials: J
authors.lastname: Shoda
authors.forename: N
authors.initials: N
authors.lastname: Tanaka
authors.forename: T
authors.initials: T
authors.lastname: Osuga
authors.forename: T
authors.initials: T
authors.lastname: Aikawa
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000209:etiology*; D002908:Chronic Disease; D005260:Female; D005500:Follow-Up Studies; D006509:Hepatitis B / Q000150:complications* / Q000453:epidemiology; D006526:Hepatitis C / Q000150:complications* / Q000453:epidemiology; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008103:Liver Cirrhosis / Q000150:complications / Q000453:epidemiology; D008113:Liver Neoplasms / Q000453:epidemiology / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects* / Q000453:epidemiology; D013997:Time Factors