Smoking, Hepatitis B Virus Infection, and Development of Hepatocellular Carcinoma

Abstract

carcinoma in Greenlanders with chronic HBV infection. The authors confirmed that patients with chronic HBV infection had a higher overall and liver-specific mortality than the general population (8.5 times higher for hepatitis B surface antigen [HBsAg]–positive than for HBsAg-negative individuals). However, they also showed that the risk of hepatocellular carcinoma was lower among HBsAg-positive Greenlanders than in other populations throughout the world. The authors speculated that this finding might be partially explained by the prev alent HBV genotypes in Greenland: genotypes D and B6. In fact, among the different genotypes of HBV infection, genotype C has been recognized as an independent predictor of hepatocellular carcinoma development (10,12), whereas the incidence of hepatocellular carcinoma in people infected by genotype B6 has not been documented. Viral load and infection by mutants of HBV are also recognized risk factors for hepatocellular carcinoma (13), but they were not described in this study. The authors also commented that HBV infection in Greenland occurs mainly in adolescents and young adults, although they did not provide evidence for this statement. If true, this infection pattern is unlikely to account for the high chronicity rate because the likelihood of developing chronic HBV infections is highest in newborns and infants (90%) and decreases with time to be less than 1% in young adulthood. Thus, adolescent or young adult infection cannot account for the majority of chronic infections that lead to hepatocellular carcinoma. The authors also considered a number of other possibilities that might account for the difference in risk of hepatocellular carcinoma among Greenlanders chronically infected with HBV, most of which are speculative. However, one factor that probably best accounts for the lower incidence of hepatocellular carcinoma is that the cohort is relatively young. Subjects had a mean age of approximately 30–35 years at inclusion in the study, and most subjects in the cohort were in their 50s when incidence of hepatocellular carcinoma was determined. The peak age of onset of hepatocellular carcinoma in other populations is between 60 and 70 years of age. Therefore, it is possible that most hepatocellular carcinomas in the Greenlandic population are yet to occur. The second study, from a European consortium [Trichopoulos et al. (14)] aimed to determine the attributable risk of various factors in the development of hepatocellular carcinoma. The main strength of the study was that it used a population-based cohort in which attributable fractions for development of