拉米夫定治疗中乙肝病毒聚合酶YMDD变异的早期预测因子研究

Predictive factors of variations in hepatitis B virus polymerase responsible for lamivudine resistance

目的：建立ＨＢＶ多聚酶ＹＭＤＤ变异的快速检测方法，并藉此进行临床流行病学研究，以了解应用拉米夫定治疗乙肝过程中ＹＭＤＤ变异的发生率及其早期预测因子。方法：收集９１例应用拉米夫定治疗的慢性ＨＢＶ感染者临床资料及系列血清。应用ｍｐＰＣＲＲＦＬＰ技术检测治疗过程中ＨＢＶ ＤＮＡ复现患者的ＹＭＤＤ变异情况，并采用ＳＰＳＳ软件进行统计学分析。结果：检出ＹＭＤＤ变异３５例（３８．５％），其累计发生率在治疗１２和１８个月时分别为２０．４８％、５３．４６％。拉米夫定治疗前诊断为肝硬变者ＹＭＤＤ变异出现较早（Ｐ＝０．０２７９），在慢性肝炎中ＨＢｅＡｇ阳性者ＹＭＤＤ出现较早（Ｐ＝０．０２９６）。Ｃｏｘ比例风险模型显示：肝硬变（Ｐ＝０．００９２）和ＨＢｅＡｇ阳性（Ｐ＝０．０７７８）与ＹＭＤＤ变异有关。结论：慢性肝炎中ＨＢｅＡｇ阳性和肝炎肝硬变可作为拉米夫定治疗过程中ＹＭＤＤ变异的早期预测因子。

Objective:To study the incidence and the predicti ve factors of HBV polymerase YMDD variati ons during lamivudine therapy.Methods:The clinical data and seri al sera of chronic HBV infected patients treated with lamivudine were collected. YMDD variations were detected by mispairing PCR RFLP assay. The data were anal ysed with SPSS software.Results:Of 91 patients treated with lami vudine for at least 6 months, 35(38.5%) had YMDD variations in HBV P gene. The c umul ative rate of variation was 20.48% and 53.46% after 12 and 18 months of trea tmen t, respectively. In liver cirrhosis group, YMDD variation occurred earlier than in CHB group (P<0.05). In CHB group, YMDD variation in HBeAg posit ive patients occurred earlier than in negative ones (P<0.05). C o x's proportional hazard model represented: liver cirrhosis (P<0.01 ) and HBeAg positivity (P>0.05) relate to YMDD variation. Conc lusion:Liver cirrhosis and positive HBeAg seem to be statistically signifi cant in predicting the appearance of YMDD variation.