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

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.

• Authors: I-Chin Wu, Mitchell L Shiffman, Myron J Tong, Patrick Marcellin, Elsa Mondou, David Frederick, Andrea Snow-Lampart, Jeff Sorbel, Franck Rousseau, Ting-Tsung Chang
• Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 47 Issue 10 Pg. 1305-11 (Nov 15 2008) ISSN: 1537-6591 [Electronic] United States
• PMID: 18840078 (Publication Type: Journal Article)

Chemical References

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

Topics

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