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

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

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Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China.



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.


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).


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.


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.

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