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

  • Zhihui Xu
  • Xiaoqiang Ren
  • Yan Liu
  • Xiaodong Li
  • Siyu Bai
  • Yanwei Zhong
  • Lin Wang
  • Panyong Mao
  • Huifen Wang
  • Shaojie Xin
  • Vincent Wai-Sun Wong
  • Henry Lik-Yuen Chan
  • Fabien Zoulim
  • Dongping Xu
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

Authors and Affiliations

  • Zhihui Xu
    • 1
    • 2
  • Xiaoqiang Ren
    • 1
    • 2
  • Yan Liu
    • 1
    • 2
  • Xiaodong Li
    • 1
    • 2
  • Siyu Bai
    • 1
    • 2
  • Yanwei Zhong
    • 1
    • 2
  • Lin Wang
    • 1
    • 2
  • Panyong Mao
    • 1
    • 2
  • Huifen Wang
    • 1
    • 2
  • Shaojie Xin
    • 1
    • 2
  • Vincent Wai-Sun Wong
    • 3
  • Henry Lik-Yuen Chan
    • 3
  • Fabien Zoulim
    • 4
    • 5
  • Dongping Xu
    • 1
    • 2
  1. 1.Viral Hepatitis Research LaboratoryBeijing Institute of Infectious DiseasesBeijingChina
  2. 2.Liver Failure Research CenterBeijing 302 HospitalBeijingChina
  3. 3.Department of Medicine and Therapeutics and Institute of Digestive DiseaseThe Chinese University of Hong KongHong KongChina
  4. 4.INSERM, U871LyonFrance
  5. 5.Department of Hepatology and Gastroenterology, Hospices Civils de LyonHôtel Dieu HospitalLyonFrance