Sustained hepatitis B e antigen seroconversion in patients with chronic hepatitis B after adefovir dipivoxil treatment: analysis of precore and basal core promoter mutants.
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.
Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China.
I-Chin
IC
Wu
Mitchell L
ML
Shiffman
Myron J
MJ
Tong
Patrick
P
Marcellin
Elsa
E
Mondou
David
D
Frederick
Andrea
A
Snow-Lampart
Jeff
J
Sorbel
Franck
F
Rousseau
Ting-Tsung
TT
Chang
D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D044466:Asian People; D004252:DNA Mutational Analysis; D004279:DNA, Viral / Q000097:blood; D005260:Female; D006513:Hepatitis B e Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000235:genetics* / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009154:Mutation; D063065:Organophosphonates / Q000627:therapeutic use*; D011401:Promoter Regions, Genetic; D044465:White People
D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D063065:Organophosphonates; D000410:Alanine Transaminase; D000225:Adenine; C106812:adefovir dipivoxil