The role of previous hepatitis B virus infection and heavy smoking in hepatitis C virus-related hepatocellular carcinoma

Am J Gastroenterol. 1996 Jun;91(6):1195-203.


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).

Conclusion: 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.

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Hepatocellular / epidemiology
  • Carcinoma, Hepatocellular / etiology*
  • Chronic Disease
  • Female
  • Follow-Up Studies
  • Hepatitis B / complications*
  • Hepatitis B / epidemiology
  • Hepatitis C / complications*
  • Hepatitis C / epidemiology
  • Humans
  • Japan / epidemiology
  • Liver Cirrhosis / complications
  • Liver Cirrhosis / epidemiology
  • Liver Neoplasms / epidemiology
  • Liver Neoplasms / etiology*
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Factors
  • Smoking / adverse effects*
  • Smoking / epidemiology
  • Time Factors