拉米夫定耐药突变相关慢性重型乙型肝炎27例分析

目的 研究在拉米夫定治疗慢性乙型肝炎的过程中出现拉米夫定耐药突变相关的慢性重型乙型肝炎的临床特点.方法 回顾性分析27例在拉米夫定治疗过程中出现耐药突变的慢性重型乙型肝炎病例,分析其临床特征,用基因芯片法或基因测序法检测YMDD突变类型,对8例施行肝移植术后的离体肝组织分析其病理特点.采用χ2检验进行统计学分析.结果 27例拉米夫定耐药患者的YMDD突变类型分别为:YVDD突变5例,YVDD突变+L180M突变2例,YIDD突变13例,YIDD+L180M突变4例,YVDD突变+YIDD突变1例,YVDD突变+Y1DD突变+L180M突变2例,单独L180M突变未检出.根据治疗前是否存在肝硬化,分为肝硬化组和非肝硬化组.与肝硬化组相比,非肝硬化组慢性重型乙型肝炎的发生率低,预后好,年龄小,HBeAg阳性率高.8例离体肝组织病理分析显示两种主要病理类型,一种主要表现为活动性肝硬化,另一种为大块或亚大块坏死,肝脏显著萎缩.结论 肝硬化为拉米夫定耐药突变相关的慢性重型乙型肝炎的高危因素.拉米夫定耐药突变相关的慢性重型乙型肝炎可能存在两种发病机制.

Analysis of 27 cases with lamivudine-resistant mutation associated chronic severe hepatitis B

Objective To study the characteristics of lamivudine-resistant mutation associated chronic severe hepatitis B during lamivudine treatment.Methods Twenty-seven patients with lamivudine-resistant mutation associated chronic severe hepatitis B during lamivudine treatment were analyzed retrospectively.YMDD motif mutation was detected by gene chips or DNA sequencing.The pathological features of liver tissues from 8 patients undergoing liver transplantation were analyzed.The X2 test were used to perform the stafistical analysis.Results The YMDD motif mutations of 27 lamivudine-resistant patients were 5 cases of YVDD mutation,2 of YVDD+L180M,13 of YIDD mutation,4 of YIDD+L180M,1 of YVDD+YIDD mutations,2 of YVDD+YIDD+L180M,and there was no single L180 M mutation among patients.Twenty-seven patients were divided into cirrhotic group and noncirrhotic group according to whether they were diagnosed with cirrhosis before treatment.Compared to cirrhotic group,incidence of severe hepatitis was lower,prognosis was better,the age of patients was younger and hepatitis Be antigen(HBeAg)positive rate was higher in noncirrhotic group.There were two types of pathological features of liver tissues from 8 patients,which were active hepatic cirrhosis and massive or submassive hepatic necrosis with liver shrinking significantly.Conclusions Hepatic cirrhosis is a risk factor of lamivudine-resistant mutation associated chronic severe hepatitis B.There may be two mechanisms in lamivudine-resistant mutation associated chronic severe hepatitis B.