Analysis of HBV genotype, drug resistant mutations, and pre-core/basal core promoter mutations in Korean patients with acute hepatitis B

J Med Virol. 2015 Jun;87(6):993-8. doi: 10.1002/jmv.24148. Epub 2015 Feb 24.

Abstract

Acute hepatitis B, caused by hepatitis B virus (HBV) strains with drug resistant mutations or pre-core/basal core promoter (PC/BCP) mutations, is a public health concern, because this infection is often associated with poor disease outcome or difficulty in therapeutic choice. The HBV genotype, the prevalence of drug resistant mutations, and PC/BCP mutations in Korean patients with acute hepatitis B were studied. From 2006 to 2008, 36 patients with acute hepatitis B were enrolled prospectively in four general hospitals. Among them, 20 showed detectable HBV DNA (median value was 4.8 log copies/mL). HBV genotyping and analysis of HBV mutations that conferred resistance against lamivudine, adefovir, or entecavir and of PC/BCP mutations were performed using highly sensitive restriction fragment mass polymorphism (RFMP) analysis. All 20 patients were infected with HBV genotype C, which causes almost all cases of chronic hepatitis B in Korea. No patient showed mutations that conferred resistance against lamivudine (L180M, M204V/I), adefovir (A181T, N236S), or entecavir (I169M, A184T/V, S202I/G, M250V/I/L). However, four patients had BCP mutations, and two had PC mutations. Platelet counts were significantly lower in the four patients with PC/BCP mutations compared to those with wild type. In this study, all acute hepatitis B patients had genotype C HBV strains with no drug resistant mutations. However, 20% showed PC/BCP mutations. This highlights the need for further study on the significance of PC/BCP mutations.

Keywords: Korea; acute hepatitis B; genotype; mutation.

MeSH terms

  • Adenine / analogs & derivatives
  • Adenine / pharmacology
  • Adenine / therapeutic use
  • Adult
  • Aged
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use
  • DNA, Viral / genetics
  • DNA, Viral / isolation & purification
  • Drug Resistance, Viral / genetics*
  • Female
  • Genotype
  • Guanine / analogs & derivatives
  • Guanine / pharmacology
  • Guanine / therapeutic use
  • Hepatitis B / drug therapy
  • Hepatitis B / virology*
  • Hepatitis B Core Antigens / genetics*
  • Hepatitis B virus / drug effects
  • Hepatitis B virus / genetics*
  • Hepatitis B virus / physiology
  • Humans
  • Lamivudine / pharmacology
  • Lamivudine / therapeutic use
  • Male
  • Middle Aged
  • Mutation*
  • Organophosphonates / pharmacology
  • Organophosphonates / therapeutic use
  • Promoter Regions, Genetic*
  • Prospective Studies
  • Republic of Korea
  • Viral Core Proteins / genetics*
  • Virus Replication

Substances

  • Antiviral Agents
  • DNA, Viral
  • Hepatitis B Core Antigens
  • Organophosphonates
  • Viral Core Proteins
  • Lamivudine
  • entecavir
  • Guanine
  • adefovir
  • Adenine