Changes in serum hepatitis B e antigen (HBeAg) levels associated with the emergence of YMDD mutants in HBeAg non-seroconverted patients during lamivudine therapy.
BACKGROUND
To elucidate the associations between the changing patterns of hepatitis B e antigen (HBeAg) levels and the emergence of tyrosine-methionine-aspartate-aspartate (YMDD) mutants in HBeAg non-seroconverted patients undergoing lamivudine therapy.


METHODS
This study analysed 76 HBeAg-positive naïve chronic hepatitis B patients treated with lamivudine. The median duration of therapy was 52 weeks. The YMDD mutants were detected in 35 patients. The changing patterns of HBeAg levels were categorized into three groups: Descending, Descending-Ascending and Fluctuation. HBeAg breakthrough was defined as progressive HBeAg decreasing to <10% of pretreatment levels, followed by increases exceeding 50 S/Co [the ratio of the sample (S) to the cut-off (Co)] above nadir levels.


RESULTS
Of 76 patients, the sensitivity and specificity for predicting YMDD mutants by the Descending-Ascending pattern were 66 and 100% respectively. Of 17 patients with YMDD mutants in the Descending-Ascending group, hepatitis B virus (HBV) DNA first increased, followed by increased HBeAg levels and finally by biochemical breakthrough. The median intervals between virological breakthrough and HBeAg breakthrough, between HBeAg breakthrough and biochemical breakthrough and between virological breakthrough and biochemical breakthrough were 4, 24 and 33 weeks respectively.


CONCLUSIONS
Serial HBeAg levels are useful in predicting YMDD mutant emergence in HBeAg non-seroconverted patients during lamivudine therapy.
Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Taiwan.
Yi-Hao
YH
Yen
Sheng-Nan
SN
Lu
Chien-Hung
CH
Chen
Jing-Houng
JH
Wang
Chun-Mei
CM
Wu
Chao-Hung
CH
Hung
Po-Lin
PL
Tseng
Tsung-Hui
TH
Hu
Chi-Sin
CS
Changchien
Chuan-Mo
CM
Lee
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D004279:DNA, Viral / Q000097:blood; D024882:Drug Resistance, Viral / Q000187:drug effects / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006510:Hepatitis B Antibodies / Q000097:blood; D006513:Hepatitis B e Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics* / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011237:Predictive Value of Tests; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*
D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D006513:Hepatitis B e Antigens; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D000410:Alanine Transaminase