Long-term continuous entecavir therapy in nucleos(t)ide-naïve chronic hepatitis B patients

J Hepatol. 2012 Sep;57(3):508-14. doi: 10.1016/j.jhep.2012.04.037. Epub 2012 May 30.

Abstract

Background & aims: We determined the antiviral potency and viral resistance rate after 4 years of continuous entecavir treatment in patients with chronic hepatitis B (CHB) infection.

Methods: The cumulative rates of undetectable hepatitis B virus DNA (HBV DNA;<2.6 log(10) copies/ml), hepatitis B e antigen (HBeAg) seronegativity, seroconversion, alanine aminotransferase (ALT) normalization, and entecavir signature mutations were calculated in 474 nucleos(t)ide-naïve CHB patients (HBeAg-positive: 47%) on continuous entecavir treatment for 4 years.

Results: Median age was 47 years and follow-up period was 2.4 years, with 403, 281, 165, and 73 patients followed-up for at least 1, 2, 3, and 4 years, respectively. Incremental increases were observed in the rates of undetectable HBV DNA, HBeAg seroclearance and seroconversion, and ALT normalization, reaching 96%, 42%, 38% and 93%, respectively, by the fourth year. In all, 100% and 93% of patients negative and positive for HBeAg, respectively, had undetectable HBV DNA at year 4. Of 165 patients, HBV DNA was detectable in nine patients after 3 years. Multivariate analysis identified HBV DNA level (≤7.6 log(10) copies/ml, OR=15.8; 95% CI=43.1-79.9, P=0.001) as an independent predictor of undetectable HBV DNA at year 3. Five patients experienced virological breakthrough including two (0.4%) who developed entecavir-resistance mutations.

Conclusions: Continuous treatment of nucleos(t)ide-naïve CHB patients with entecavir over 4 years was associated with 96% chance of undetectable HBV DNA and only 0.4% chance of emerging entecavir-resistant mutations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Alanine Transaminase / blood
  • Antiviral Agents / therapeutic use*
  • Confidence Intervals
  • DNA, Viral / blood
  • Drug Resistance, Viral*
  • Female
  • Genotype
  • Guanine / analogs & derivatives*
  • Guanine / therapeutic use
  • Hepatitis B e Antigens / blood
  • Hepatitis B virus / genetics*
  • Hepatitis B, Chronic / blood
  • Hepatitis B, Chronic / drug therapy*
  • Humans
  • Kaplan-Meier Estimate
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Mutation
  • Odds Ratio
  • Retrospective Studies
  • Time Factors
  • Young Adult

Substances

  • Antiviral Agents
  • DNA, Viral
  • Hepatitis B e Antigens
  • entecavir
  • Guanine
  • Alanine Transaminase