Sustained hepatitis B e antigen seroconversion in patients with chronic hepatitis B after adefovir dipivoxil treatment: analysis of precore and basal core promoter mutants

Clin Infect Dis. 2008 Nov 15;47(10):1305-11. doi: 10.1086/592570.

Abstract

Background: This study evaluated the persistence of hepatitis B e antigen (HBeAg) seroconversion (which is considered to be an important therapeutic end point) after adefovir dipivoxil treatment.

Methods: Forty-five patients who experienced confirmed HBeAg seroconversion and had a serum hepatitis B virus DNA level < 10(5) copies/mL while receiving 10 mg of adefovir dipivoxil in a prior study were enrolled in the present study. At the time of the last dose of adefovir dipivoxil (baseline), the median age of the patients was 35 years, 64% were male, 73% were Asian, 27% were white, the median alanine aminotransferase level was 25 IU/L, and the median serum hepatitis B virus DNA level was 3.0 log copies/mL. The median follow-up time was 150 weeks (range, 13-252 weeks).

Results: Forty-one patients maintained sustained seroconversion at the last 2 assessments, and 4 experienced seroreversion at weeks 12 (3 patients) and 16 (1 patient) of follow-up. Approximately 50% of patients had a hepatitis B virus DNA level < 1000 copies/mL at the last visit of the study period. Of 13 patients who were viremic and had available samples at the last visit, 11 had basal core promoter and/or precore mutations. Notably, 8 of these 11 patients had basal core promoter and/or precore mutations before adefovir dipivoxil therapy despite being HBeAg positive. The median duration of adefovir dipivoxil treatment was shorter before seroconversion (48 vs. 108 weeks; P = .03) and longer after seroconversion (41 vs. 22 weeks; P = .02) for patients who experienced sustained seroconversion, compared with the patients who experienced seroreversion.

Conclusions: Prolonged adefovir dipivoxil therapy after HBeAg seroconversion appeared to increase the likelihood of sustained HBeAg seroconversion. Most patients who experienced HBeAg seroconversion and had viremia had precore and/or basal core promoter mutants, which usually existed before initiation of adefovir dipivoxil therapy.

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / therapeutic use
  • Adult
  • Alanine Transaminase / blood
  • Asian People
  • DNA Mutational Analysis
  • DNA, Viral / blood
  • Female
  • Hepatitis B e Antigens / blood*
  • Hepatitis B virus / genetics*
  • Hepatitis B virus / isolation & purification
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / virology*
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Mutation*
  • Organophosphonates / therapeutic use*
  • Promoter Regions, Genetic*
  • White People

Substances

  • DNA, Viral
  • Hepatitis B e Antigens
  • Organophosphonates
  • Alanine Transaminase
  • Adenine
  • adefovir dipivoxil