拉米夫定抗乙型肝炎治疗中发生YMDD变异的因素研究

Study of factors on the emergence of hepatitis B virus YMDD mutants during lamivudine therapy in chronic hepatitis B

目的 探讨拉米夫定治疗慢性乙型肝炎YMDD变异的发生与血清HBVDNA水平、HBeAg、ALT的关系。方法以295例慢性乙型肝炎患者为研究对象，分别于接受拉米夫定治疗前测定慢性乙型肝炎患者血清HBVDNA水平、HBeAg、ALT等指标；经过12个月随访，期间每3个月检测患者血清HBVDNA水平和YMDD变异等。结果在接受拉米夫定治疗12个月后，295例慢性乙型肝炎患者中有63例发生YMDD变异（21．36％），YMDD变异组治疗前血清HBVDNA水平显著高于未发生YMDD变异组[（7．16±0．34）：（6．20±0．63）log10拷贝／mL，P〈0．01]，YMDD变异组患者的HBeAg阳性率与未发生YMDD变异组患者的HBeAg阳性率相比，差异具有统计学意义（61．90％：40．95％，P〈0．01）；YMDD变异组患者治疗前ALT水平显著高于未发生YMDD变异组患者[（174．9±108．1）：（96．1±54．4）IU／L，P〈0．01]。结论拉米夫定治疗慢性乙型肝炎YMDD变异的发生与血清HBVDNA水平、HBeAg、ALT等具有密切的相关性；在拉米夫定治疗前对慢性乙型肝炎患者进行血清HBVDNA、HBeAg、ALT等检测，具有重要的指导意义。

Objective To evaluate the effect of HBV DNA, HBeAg and ALT on the emergence of HBV YMDD mutants. Methods 295 chronic hepatitis B patients treated with lamivudine for more than one year were enrolled in the study. HBV DNA, HBeAg and ALT were measured in every three months during lamivudine treatment. Results Among them, 63 patients with YMDD mutants against lamivudine were detected after 12 months. The serum HBV DNA level in pretreatment patients with YMDD mutants were significantly higher than those in patients without YMDD mutants[ （7.16 ±0.54）：（6.20± 0.63） log10copies/mL, P 〈 0.01 ]. There was statistical difference in HBeAg positive rate between pretreatment patients with and without YMDD mutants（61.90 % ：40.95 %, P 〈 0.01 ）. The ALT levels in pretreatmeut patients with YMDD mutants were significantly higher than those in patients without YMDD mutants [（ 174.9± 108.1）： （96.1 ±54.4） IU/L, P 〈 0.01 ]. Conclusions HBeAg status, HBV DNA levels and ALT levels are the major determinants for the YMDD mutation during lamivudine therapy, and should be considered before lamivudine therapy.