Prevalence and types of drug-resistant variants in Chinese patients with acute hepatitis B

J Med Virol. 2015 Sep;87(9):1527-31. doi: 10.1002/jmv.24006. Epub 2015 May 29.

Abstract

The presence of therapy-associated hepatitis B virus (HBV) variants is the main drawback of antiviral therapy for HBV infection. Moreover, drug-resistant variants are more insensitive to a second agent and more therapy-associated mutations will be present. To apply better nucleos(t)ide analogues (NA) and reduce the occurrence of resistance, the prevalence and types of drug-resistant mutations in acute hepatitis B patients were investigated in this study. One hundred three HBV DNA-positive patients with symptomatic acute hepatitis B that were observed from 2011 to 2013 were enrolled. Direct polymerase chain reaction sequencing was used firstly to screen HBV reverse-transcriptase domain to detect HBV mutants. Five lamivudine-resistant variants were identified. Clonal sequencing was performed for 5 resistance-positive samples and 10 other random samples. Interestingly, all detected samples harbored drug-resistant mutations, although with different percentage. Thirteen harbored lamivudine-related alone (five) or together with other NA related mutations (five with adefovir, one with entecavir, and one with telbivudine), and two of them harbored adefovir-related mutations. Also, mutations associated with four currently used NA were all detected, and the frequency is in accordance with the popularity of NA used in clinical practice. These data suggest that drug-resistant variants are present in patients with acute hepatitis B and NA should be applied more carefully for chronic hepatitis B patients developed from acute hepatitis B.

Keywords: acute hepatitis B; drug-resistant; hepatitis B virus; nucleos(t)ide analogues.

MeSH terms

  • Adenine / analogs & derivatives
  • Adenine / pharmacology
  • Adenine / therapeutic use
  • Adult
  • Antiviral Agents / pharmacology*
  • Antiviral Agents / therapeutic use
  • China / epidemiology
  • DNA, Viral / genetics
  • Drug Resistance, Viral* / genetics
  • Female
  • Genetic Variation / drug effects*
  • Guanine / analogs & derivatives
  • Guanine / pharmacology
  • Guanine / therapeutic use
  • Hepatitis B / drug therapy
  • Hepatitis B / virology*
  • Hepatitis B virus / classification
  • Hepatitis B virus / genetics*
  • Hepatitis B, Chronic / drug therapy
  • Hepatitis B, Chronic / virology
  • Humans
  • Lamivudine / pharmacology
  • Lamivudine / therapeutic use
  • Male
  • Middle Aged
  • Mutation, Missense
  • Organophosphonates / pharmacology
  • Organophosphonates / therapeutic use
  • Prevalence
  • RNA-Directed DNA Polymerase / genetics
  • Telbivudine
  • Thymidine / analogs & derivatives
  • Thymidine / pharmacology
  • Thymidine / therapeutic use
  • Time Factors
  • Young Adult

Substances

  • Antiviral Agents
  • DNA, Viral
  • Organophosphonates
  • Telbivudine
  • Lamivudine
  • entecavir
  • Guanine
  • adefovir
  • RNA-Directed DNA Polymerase
  • Adenine
  • Thymidine