Precore and basal core promoter mutations in Asian American patients with hepatitis B e antigen-positive chronic hepatitis B

Aliment Pharmacol Ther. 2013 Feb;37(4):464-72. doi: 10.1111/apt.12193. Epub 2012 Dec 22.

Abstract

Background: Prior studies have shown that precore mutations abolish and basal core promoter (BCP) mutations down-regulate hepatitis B e antigen (HBeAg) production. Thus, the presence of precore and BCP mutations in HBeAg-positive patients indicates an infection with a mixed viral population of wild-type and precore and/or BCP mutant hepatitis B virus (HBV). To date, there has been limited study of the prevalence and clinical significance of precore and BCP mutations in patients with HBeAg-positive chronic hepatitis B.

Aim: To determine the prevalence, predictors and clinical characteristics of mixed wild-type and precore/BCP HBV infection, through a cross-sectional study, in a US cohort of patients with chronic hepatitis B.

Methods: We conducted a retrospective study of 828 chronic hepatitis B patients with HBV genotype and mutation panel testing seen at three US gastroenterology and liver clinics from June 2005 to September 2009.

Results: A majority of our patients (92.3%) were either Vietnamese or Chinese American. In the HBeAg-positive cohort, 17% of patients had precore mutations only, 28% had BCP mutations only and 5% had both BCP and precore mutations. On multivariate analyses, HBV genotype C, increasing age, lower HBV DNA level and an ALT quotient >2 were independent predictors for the presence of precore and/or BCP mutations.

Conclusions: The current distinction and management recommendations for HBeAg-positive vs. HBeAg-negative patients with chronic hepatitis B should be reassessed. Additional biomarkers and treatment endpoints should be studied for their usefulness in predicting continued viral suppression after treatment discontinuation.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Asian / genetics
  • DNA, Viral / genetics
  • Female
  • Genotype
  • Hepatitis B e Antigens / blood*
  • Hepatitis B virus / genetics*
  • Hepatitis B virus / immunology
  • Hepatitis B, Chronic / virology*
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Mutation*
  • Promoter Regions, Genetic / genetics*
  • Retrospective Studies
  • United States
  • Viral Load
  • Young Adult

Substances

  • DNA, Viral
  • Hepatitis B e Antigens