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 naive 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.