课件：抗乙型肝炎病毒新药研究进展.ppt

* * Key message In most patients who continue lamivudine therapy, improvements in serum HBV DNA are maintained, even when YMDD variants are present for 2 years or longer. Points of explanation Samples taken at weeks 52, 104 and 156 were tested for YMDD variant. These data are from patients in all treatment groups (lamivudine 25 mg and lamivudine 100 mg) for whom there is evidence of either: YMDD variant present at 52, 104 and 156 weeks (n=24) or no variant present at all time points (n=95) Patients received continuous lamivudine therapy (25 or 100 mg) throughout the 3 years (as randomised or open label lamivudine 100 mg). Median HBV DNA concentration started to increase from around week 36 but still remained lower than baseline. This increase is probably due to the presence of YMDD variant. However, the first samples for testing of the variant were taken at week 52. In patients with YMDD variant, median serum HBV DNA concentration at week 156 is significantly lower than baseline (5.9 pg/mL vs. 77.2 pg/mL; p0.001). References Leung NWY, Lai CL, Chang TT, et al. Three year lamivudine therapy in chronic HBV. J Hepatol 1999;30:59 (Abstract GS5/25).Leung NWY. Oral presentation: EASL 1999. * Points of explanation Viral variants with mutations in the gene encoding the HBV polymerase (YMDD variants) have been identified following lamivudine treatment. These variants are less sensitive to inhibition by lamivudine in vitro. YMDD variants are less replication competent compared with wild type HBV, most likely due to lower affinity of the viral polymerase for its nucleotide substrates. YMDD variants have been detected in few chronic hepatitis B patients during the first 6 months of lamivudine therapy (10/267 (4%) patients in the study by Lai, et al). The percentages represent the total of mixed wild type + YMDD variant and YMDD variant alone i.e. these percentages are not for YMDD only. The incidence of detectable YMDD variant HBV increases with duration of therapy. Howev