Hepatitis B viral surface mutations in patients with adefovir resistant chronic hepatitis B with A181T/V polymerase mutations

J Korean Med Sci. 2010 Feb;25(2):257-64. doi: 10.3346/jkms.2010.25.2.257. Epub 2009 Jan 19.

Abstract

The hepatitis B virus (HBV) polymerase gene has overlapping reading frames with surface genes, which allows to alter the amino acid codon of the surface genes. In adefovir (ADV) treated chronic hepatitis B patients carrying rtA181T/rtA181V mutations, overlap with surface gene mutations such as sW172stop/sL173F has been reported. However, the clinical consequences of such surface mutations have not been determined. The aim of this study was to determine the surface gene sequence in ADV-resistant patients carrying the A181T/V mutation and to describe the clinical significance. Of the 22 patients included in this study, 13 were ADV-resistant with rtA181T/V mutations (polymerase mutation group, Group P) and nine were antiviral treatment-naïve (control group, Group C). The Pre-S1 gene mutation, V60A, was detected in 11 patients (Group P=8, Group C=3). A start codon mutation in the Pre-S2 gene was found in five patients (Group P=3, Group C=2). An S gene mutation, sA184V, was found in nine patients, all of whom were in group P. Although sW172stop and sL173F mutations were detected, reduced HBsAg titer was not observed. Further study of these mutations and their clinical implications are needed.

Keywords: Adefovir; Hepatitis B Surface Antigens; Hepatitis B, Chronic.

Publication types

  • Case Reports

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / therapeutic use
  • Adult
  • Aged
  • Amino Acid Sequence
  • Amino Acid Substitution
  • Antiviral Agents / therapeutic use*
  • Codon, Initiator
  • DNA-Directed DNA Polymerase / genetics*
  • Demography
  • Drug Resistance, Viral / genetics
  • Female
  • Genotype
  • Hepatitis B Surface Antigens / genetics*
  • Hepatitis B Surface Antigens / metabolism
  • Hepatitis B, Chronic / drug therapy*
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Organophosphonates / therapeutic use*
  • Point Mutation
  • Viral Proteins / genetics*

Substances

  • Antiviral Agents
  • Codon, Initiator
  • Hepatitis B Surface Antigens
  • Organophosphonates
  • Viral Proteins
  • adefovir
  • DNA-Directed DNA Polymerase
  • Adenine