title: Fifteen-year population attributable fractions and causal pies of risk factors for newly developed hepatocellular carcinomas in 11,801 men in Taiwan.
abstract: Development of hepatocellular carcinoma (HCC) is a multi-factorial process. Chronic infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) are important risk factors of HCC. Host factors, such as alcohol drinking, may also play a role. This study aims to provide a synthesis view on the development of HCC by examining multiple risk factors jointly and collectively. Causal-pie modeling technique was applied to analyze a cohort of 11,801 male residents (followed up for 15 years) in Taiwan, during which a total of 298 incident HCC cases were ascertained. The rate ratios adjusted by age were further modeled by an additive Poisson regression. Population attributable fractions (PAFs) and causal-pie weights (CPWs) were calculated. A PAF indicates the magnitude of case-load reduction under a particular intervention scenario, whereas a CPW for a particular class of causal pies represents the proportion of HCC cases attributable to that class. Using PAF we observed a chance to reduce around 60% HCC risk moving from no HBV-related intervention to the total elimination of the virus. An additional ∼15% (or ∼5%) reduction can be expected, if the HBV-related intervention is coupled with an HCV-related intervention (or an anti-drinking campaign). Eight classes of causal pies were found to be significant, including four dose-response classes of HBV (total CPW=52.7%), one independent-effect class of HCV (CPW=14.4%), one HBV-alcohol interaction class (CPW=4.2%), one HBV-HCV interaction class (CPW=1.7%), and one all-unknown class (CPW=27.0%). Causal-pie modeling for HCC helps clarify the relative importance of each viral and host factor, as well as their interactions.
authors.affiliation: Research Center for Genes, Environment and Human Health, and Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
authors.forename: Shu-Fen
authors.initials: SF
authors.lastname: Liao
authors.forename: Hwai-I
authors.initials: HI
authors.lastname: Yang
authors.forename: Mei-Hsuan
authors.initials: MH
authors.lastname: Lee
authors.forename: Chien-Jen
authors.initials: CJ
authors.lastname: Chen
authors.forename: Wen-Chung
authors.initials: WC
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology* / Q000209:etiology / Q000821:virology; D015331:Cohort Studies; D005500:Follow-Up Studies; D016174:Hepacivirus / Q000302:isolation & purification; D006515:Hepatitis B virus / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000150:complications / Q000453:epidemiology; D006526:Hepatitis C / Q000150:complications / Q000453:epidemiology; D006801:Humans; D008113:Liver Neoplasms / Q000453:epidemiology* / Q000209:etiology / Q000821:virology; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D013624:Taiwan / Q000453:epidemiology