Original Article—Liver, Pancreas, and Biliary Tract

Journal of Gastroenterology

, Volume 46, Issue 3, pp 391-400

First online:

Association of hepatitis B virus mutations in basal core promoter and precore regions with severity of liver disease: an investigation of 793 Chinese patients with mild and severe chronic hepatitis B and acute-on-chronic liver failure

  • Zhihui XuAffiliated withViral Hepatitis Research Laboratory, Beijing Institute of Infectious DiseasesLiver Failure Research Center, Beijing 302 Hospital
  • , Xiaoqiang RenAffiliated withViral Hepatitis Research Laboratory, Beijing Institute of Infectious DiseasesLiver Failure Research Center, Beijing 302 Hospital
  • , Yan LiuAffiliated withViral Hepatitis Research Laboratory, Beijing Institute of Infectious DiseasesLiver Failure Research Center, Beijing 302 Hospital
  • , Xiaodong LiAffiliated withViral Hepatitis Research Laboratory, Beijing Institute of Infectious DiseasesLiver Failure Research Center, Beijing 302 Hospital
  • , Siyu BaiAffiliated withViral Hepatitis Research Laboratory, Beijing Institute of Infectious DiseasesLiver Failure Research Center, Beijing 302 Hospital
  • , Yanwei ZhongAffiliated withViral Hepatitis Research Laboratory, Beijing Institute of Infectious DiseasesLiver Failure Research Center, Beijing 302 Hospital
  • , Lin WangAffiliated withViral Hepatitis Research Laboratory, Beijing Institute of Infectious DiseasesLiver Failure Research Center, Beijing 302 Hospital
  • , Panyong MaoAffiliated withViral Hepatitis Research Laboratory, Beijing Institute of Infectious DiseasesLiver Failure Research Center, Beijing 302 Hospital
  • , Huifen WangAffiliated withViral Hepatitis Research Laboratory, Beijing Institute of Infectious DiseasesLiver Failure Research Center, Beijing 302 Hospital
    • , Shaojie XinAffiliated withViral Hepatitis Research Laboratory, Beijing Institute of Infectious DiseasesLiver Failure Research Center, Beijing 302 Hospital
    • , Vincent Wai-Sun WongAffiliated withDepartment of Medicine and Therapeutics and Institute of Digestive Disease, The Chinese University of Hong Kong
    • , Henry Lik-Yuen ChanAffiliated withDepartment of Medicine and Therapeutics and Institute of Digestive Disease, The Chinese University of Hong Kong
    • , Fabien ZoulimAffiliated withINSERM, U871Department of Hepatology and Gastroenterology, Hospices Civils de Lyon, Hôtel Dieu Hospital
    • , Dongping XuAffiliated withViral Hepatitis Research Laboratory, Beijing Institute of Infectious DiseasesLiver Failure Research Center, Beijing 302 Hospital Email author 

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Abstract

Objective

To investigate the features of hepatitis B virus (HBV) basal core promoter/precore (BCP/PC) mutations and genotypes in a large number of mild/severe chronic hepatitis B (CHB-M/CHB-S), and acute-on-chronic liver failure (ACLF) patients and analyze the clinical implications of the virologic features.

Patients and methods

Sera of 793 (325 CHB-M, 170 CHB-S, and 298 ACLF) patients admitted to or who had visited Beijing 302 Hospital from January 2005 to December 2008 were collected and successfully amplified for the HBV BCP/PC and a 1225-bp-long S/Pol (nt 54–1278) gene regions. Biochemical and serological parameters and HBV DNA level were routinely performed. Viral DNA was extracted and subjected to a nested PCR. Genotypes/subgenotypes were determined based on complete genomic sequence or on analysis of the 1225-bp-long S/Pol-gene sequence. HBV genotyping was performed by direct PCR sequencing followed by molecular evolutionary analysis of the viral sequences. A P value of <0.05 (two-sided) was considered to be statistically significant.

Conclusions

Our findings suggest that CHB patients infected with BCP/PC mutant viruses are more susceptible to severe hepatitis and ACLF than those with the BCP/PC wild-type virus and that ACLF patients with PC mutant viruses have an increased risk of death. As such, the HBV PC mutation is a potential predictive indicator of ACLF outcome.

Keywords

Hepatitis B virus Basal core promoter mutation Precore mutation Genotype Acute-on-chronic liver failure