Journal of Gastroenterology

, Volume 46, Issue 3, pp 391–400

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

Authors

  • Zhihui Xu
    • Viral Hepatitis Research LaboratoryBeijing Institute of Infectious Diseases
    • Liver Failure Research CenterBeijing 302 Hospital
  • Xiaoqiang Ren
    • Viral Hepatitis Research LaboratoryBeijing Institute of Infectious Diseases
    • Liver Failure Research CenterBeijing 302 Hospital
  • Yan Liu
    • Viral Hepatitis Research LaboratoryBeijing Institute of Infectious Diseases
    • Liver Failure Research CenterBeijing 302 Hospital
  • Xiaodong Li
    • Viral Hepatitis Research LaboratoryBeijing Institute of Infectious Diseases
    • Liver Failure Research CenterBeijing 302 Hospital
  • Siyu Bai
    • Viral Hepatitis Research LaboratoryBeijing Institute of Infectious Diseases
    • Liver Failure Research CenterBeijing 302 Hospital
  • Yanwei Zhong
    • Viral Hepatitis Research LaboratoryBeijing Institute of Infectious Diseases
    • Liver Failure Research CenterBeijing 302 Hospital
  • Lin Wang
    • Viral Hepatitis Research LaboratoryBeijing Institute of Infectious Diseases
    • Liver Failure Research CenterBeijing 302 Hospital
  • Panyong Mao
    • Viral Hepatitis Research LaboratoryBeijing Institute of Infectious Diseases
    • Liver Failure Research CenterBeijing 302 Hospital
  • Huifen Wang
    • Viral Hepatitis Research LaboratoryBeijing Institute of Infectious Diseases
    • Liver Failure Research CenterBeijing 302 Hospital
  • Shaojie Xin
    • Viral Hepatitis Research LaboratoryBeijing Institute of Infectious Diseases
    • Liver Failure Research CenterBeijing 302 Hospital
  • Vincent Wai-Sun Wong
    • Department of Medicine and Therapeutics and Institute of Digestive DiseaseThe Chinese University of Hong Kong
  • Henry Lik-Yuen Chan
    • Department of Medicine and Therapeutics and Institute of Digestive DiseaseThe Chinese University of Hong Kong
  • Fabien Zoulim
    • INSERM, U871
    • Department of Hepatology and Gastroenterology, Hospices Civils de LyonHôtel Dieu Hospital
    • Viral Hepatitis Research LaboratoryBeijing Institute of Infectious Diseases
    • Liver Failure Research CenterBeijing 302 Hospital
Original Article—Liver, Pancreas, and Biliary Tract

DOI: 10.1007/s00535-010-0315-4

Cite this article as:
Xu, Z., Ren, X., Liu, Y. et al. J Gastroenterol (2011) 46: 391. doi:10.1007/s00535-010-0315-4

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 virusBasal core promoter mutationPrecore mutationGenotypeAcute-on-chronic liver failure

Abbreviations

ACLF

Acute-on-chronic liver failure

ALF

Acute liver failure

ALT

Alanine aminotransferase

BCP

Basal core promoter

CHB-M

Mild chronic hepatitis B

CHB-S

Severe chronic hepatitis B

HBV

Hepatitis B virus

HCC

Hepatocellular carcinoma

LC

Liver cirrhosis

PC

Precore

PTA

Prothrombin activity

TBIL

Total bilirubin

PCR

Polymerase chain reaction

Copyright information

© Springer 2010