title: The Effect of HBV Genotype C on the Development of HCC Differs Between Wild-Type Viruses and Those With BCP Double Mutations (T(1762)A(1764)).
abstract: BACKGROUND
  Association of hepatitis B virus (HBV) genotype C with hepatocellular carcinoma (HCC) development remains controversial. HBV basal core promoter (BCP) double mutations (T(1762)A(1764)) are very strong confounding factors of genotypes B and C in HCC development.
  
  
  OBJECTIVE
  To investigate the association of HBV genotype C with HCC development after controlling for BCP double mutations.
  
  
  METHODS
  Four hundred and two serum samples from patients with HCC, liver cirrhosis (LC) and chronic hepatitis (CH) and also from asymptomatic HBsAg carriers were analyzed.
  
  
  RESULTS
  Genotypes B (31.1%), C (62.8%), and I (6.1%) were detected. With the severity of liver disease the prevalence of genotype B decreased, but genotype C increased. No trend was found for genotype I. The prevalence of BCP double mutations in genotypes C and I viruses was significantly higher than genotype B. BCP double mutations are risk factors for CH, LC and HCC. Genotype C was not identified as a particular risk factor for HCC prior to the stratification analysis but after that genotype C viruses with BCP double mutations were found to be a particular risk factor for HCC (P = 0.008, OR = 17.19 [95% CI: 2.10 - 140.41]), but those with the wild-type BCP were not. In the interaction analysis, genotype C and BCP double mutations were found to have a synergistic effect on HCC development (P < 0.0001, OR = 52.56 [95% CI: 11.49-240.52]).
  
  
  CONCLUSIONS
  The effect of HBV genotype C on the development of HCC differs between wild-type viruses and those with BCP double mutations, suggesting that not all individuals infected with genotype C HBV are at increased risk of HCC.
authors.affiliation: Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Nanning, China.
authors.forename: Qin-Yan
authors.initials: QY
authors.lastname: Chen
authors.affiliation: Division of Medicine, Faculty of Medical Sciences, University College London, London, UK.
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Harrison
authors.affiliation: Research Department of Infection and Population Health, UCL Medical School, London, UK.
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Sabin
authors.affiliation: Department of Public Health of Guangxi Zhuang Autonomous Region, Nanning, China.
authors.forename: Guo-Jian
authors.initials: GJ
authors.lastname: Li
authors.affiliation: School of Public Health, Guangxi Medical University, Nanning, China.
authors.forename: Gao-Ming
authors.initials: GM
authors.lastname: Huang
authors.affiliation: Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Nanning, China.
authors.forename: Jin-Ye
authors.initials: JY
authors.lastname: Yang
authors.affiliation: Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Nanning, China.
authors.forename: Xue-Yan
authors.initials: XY
authors.lastname: Wang
authors.affiliation: Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Nanning, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Li
authors.affiliation: Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Nanning, China ; School of Preclinical Medicine, Guangxi Medical University, Nanning, China.
authors.forename: Mo-Han
authors.initials: MH
authors.lastname: Liu
authors.affiliation: Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Nanning, China ; School of Preclinical Medicine, Guangxi Medical University, Nanning, China.
authors.forename: Zhong-Liao
authors.initials: ZL
authors.lastname: Fang
keywords: Basal Core Promoter Double Mutations; Genotypes; Hepatitis B Virus; Hepatocellular Carcinoma