实时荧光定量PCR法检测乙型肝炎病毒YMDD变异的临床意义

Clinical significance of YMDD mutations of HBV detected by quantitative real-time PCR

目的:探讨拉米夫定治疗慢性乙型肝炎期间发生乙型肝炎病毒HBV YMDD变异情况及其与病毒载量、肝功能的关系。方法:对慢乙肝患者分别检测血清HBV YMDD变异、HBV DNA载量及肝功能,并对检验结果进行分析。结果:3年间共发生HBV YMDD变异共59例,其中HBV YIDD变异29例(49.15%),HBV YVDD变异41(69.49%)例,2者共同变异11(18.64%)例,YIDD与YVDD变异比较差异有统计学意义(χ2=5.057,P<0.05)。发生变异的慢乙肝患者HBV DNA阳性率为59/59(100%),同期对照未发生变异HBV DNA阳性率为40/150(26.67%),2组比较,差异有统计学意义(χ2=91.34,P<0.05)。发生不同变异各组与未发生变异组病毒载量比较,差异有显著性(组间F=11.175,P<0.05),而变异组之间HBV DNA之间不存在显著性差异,肝功能仅TBIL结果单独YIDD变异组与未变异组有统计学差异。结论:本地区HBV YMDD变异以HBV YVDD为主;变异各组HBV DNA阳性率及HBV载量都显著高于未变异组,表明YMDD变异株HBV DNA复制活跃。肝功能除了TBIL,变异与否与肝功能水平高低无关,提示不同的HBV YMDD突变模式可能与患者病情无关。

Objective：To explore the status of YMDD mutations of HBV during lamivudine antiviral therapy of hepatitis B and its associations with HBV viral load and liver function. Methods：Serum HBV YMDD mutations, HBV viral load and liver functions were detected and analyzed from chronic hepatitis B patients visiting Wuhu Third People＇s Hospital from April 2013 to April 2016. Results： Totally 59 cases of HBV YMDD mutations occurred during the 3-year investigation, which included 29 YIDD mutations （49.15% ） ,41 YVDD mutations （69.49%） and 11 YIDD/YVDD dual mutations （18.64% }. The difference between YIDD mutations and YVDD mutations was significant （ X2 = 5. 057, P 〈 0.05 ）. The positive rate of HBV DNA of hepatitis B patients with YMDD mutations was 100% （59/59） , whereas for those in controls without YMDD mutations, the positive rate of HBV DNA was 26.67% （40/150）. There was significant difference between the 2 groups （ X2 = 91.34, P 〈 0.05 ）. In comparison of HBV viral loads between the group without mutations and the groups with diverse mutations, the difference was significant （inter-groups F = 11. 175 ,P 〈0.005） , and no difference were found among groups with mutations. In addition, among parameters of liver function, only TBIL results exhibited difference between YIDD mutation group and negative control group. Conclusion： In Wuhu city, the majority of HBV YMDD mutations are YVDD ones. HBV DNA positivity and HBV viral load in mutation groups are significantly higher than in the negative control group, which indicates that active replication of HBV DNA is present in HBV variants with YMDD mutations. Except for TBIL, other liver function parameters have no associations with YMDD mutations, which hints that different modes of HBV YMDD mutations are inde- pendent of progression of chronic hepatitis B.