Molecular diagnosis and treatment of drug-resistant hepatitis B virus

World J Gastroenterol. 2014 May 21;20(19):5708-20. doi: 10.3748/wjg.v20.i19.5708.

Abstract

Oral antiviral agents have been developed in the last two decades for the treatment of chronic hepatitis B (CHB). However, antiviral resistance remains an important challenge for long-term CHB therapy. All of the clinically available oral antiviral agents are nucleoside or nucleotide analogues that target the activity of viral reverse transcriptase (RT), and all are reported to have resistant mutations. Since the hepatitis B virus (HBV) RT, like other viral polymerases, lacks proofreading activity, the emergence of drug-resistance occurs readily under selective pressure from the administration of antiviral agents. The molecular diagnosis of drug-resistant HBV is based on sequence variations, and current diagnostic methods include sequencing, restriction fragment polymorphism analysis, and hybridization. Here, we will discuss the currently available molecular diagnosis tools, in vitro phenotypic assays for validation of drug-resistant HBV, and treatment options for drug-resistant HBV.

Keywords: Antiviral treatment; Chronic hepatitis B; Drug-resistance; Hepatitis B virus; Molecular diagnosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenine / analogs & derivatives
  • Adenine / therapeutic use
  • Antiviral Agents / therapeutic use
  • Drug Resistance, Viral*
  • Guanine / analogs & derivatives
  • Guanine / therapeutic use
  • Hepatitis B virus / genetics*
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / virology
  • Humans
  • Lamivudine / therapeutic use
  • Molecular Diagnostic Techniques
  • Mutation
  • Nucleic Acid Hybridization
  • Organophosphonates / therapeutic use
  • Phenotype
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • RNA-Directed DNA Polymerase / metabolism
  • Sequence Analysis, DNA
  • Tenofovir
  • Treatment Outcome

Substances

  • Antiviral Agents
  • Organophosphonates
  • Lamivudine
  • entecavir
  • Guanine
  • Tenofovir
  • RNA-Directed DNA Polymerase
  • Adenine