Evolution of hepatitis B virus during long-term therapy in patients with chronic hepatitis B

Ann Hepatol. 2011 Oct-Dec;10(4):434-40.

Abstract

Background: Long-term lamivudine (LAM), adefovir (ADV) and entecavir (ETV) treatment induce the emergence of drug-resistant hepatitis B virus (HBV) in patients with chronic hepatitis B infection.

Aim: To evaluate the LAM, ADV and ETV resistance mutations detected in our patient group.

Materials and methods: Twenty patients who had received at least two years of treatment with nucleoside/tide analogues were enrolled in this study. Patients with detectable HBV DNA were analyzed in order to detect resistance mutations and in this group of patients treatment was change.

Results: Three patients developed LAM resistance mutations (2 presented rtM204I and one rtL180M+rtM204V/I) and one patient showed rtN236T ADV resistance mutation. During ADV and LAM treatment, one patient developed ADV plus LAM resistance mutations (rtI163V+rtL180M+rtA181V+rtN236T), in this case, HBV strains harbouring polymerase mutations did not develop LAM associated rtM204V/I primary mutation. In addition, ETV resistance mutations (rtL180M+rtT184A+rtS202G+rtM204V) were detected in one patient.

Conclusions: These findings suggest that monotherapy resulted in a limited virological response and combination strategies including potent antiviral agents should be recommended for patients with resistant mutations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / administration & dosage
  • Adenine / analogs & derivatives*
  • Adult
  • Antiviral Agents / administration & dosage*
  • DNA, Viral / blood
  • Drug Resistance, Viral* / genetics
  • Female
  • Genotype
  • Guanine / administration & dosage
  • Guanine / analogs & derivatives*
  • Hepatitis B virus / drug effects*
  • Hepatitis B virus / genetics
  • Hepatitis B, Chronic / diagnosis
  • Hepatitis B, Chronic / drug therapy*
  • Humans
  • Lamivudine / administration & dosage*
  • Male
  • Middle Aged
  • Mutation
  • Organophosphonates / administration & dosage*
  • Spain
  • Time Factors
  • Treatment Outcome
  • Viral Load

Substances

  • Antiviral Agents
  • DNA, Viral
  • Organophosphonates
  • Lamivudine
  • entecavir
  • Guanine
  • adefovir
  • Adenine