核苷类药物对肝移植受者肝门淋巴结内乙肝病毒分子病毒学状态的影响

摘要

目的 研究核苷类药物对乙肝相关的肝移植受者肝门淋巴结内乙肝病毒(HBV)分子存在状态和复制的影响.方法 选择2010年6月至2011年3月因乙肝相关肝病行肝移植的患者36例,其中男性32例,女性4例,平均年龄(54±7)岁.根据术前是否应用核苷类药物,分为用药组和未用药组,其中用药组分为用药时间＞3个月和≤3个月两个亚组.于肝移植术中采集患者肝门淋巴结,利用巢式或半巢式PCR检测肝门淋巴结内HBV DNA和病毒复制中间体HBV cccDNA.数据采用Fisher精确概率法分析.结果 HBV DNA阳性率用药组为72.7％ (16/22),未用药组为14/14,差异无统计学意义(P =0.062),用药组中用药时间＞3个月与≤3个月的患者HBV DNA阳性率差异无统计学意义(10/14比6/8,P=1.000).HBV cccDNA阳性率用药组为22.7％ (5/22),低于未用药组的12/14(P =0.000),用药组中用药时间＞3个月的患者低于≤3个月的患者(1/14比4/8,P=0.039).结论 乙肝相关的肝移植受者术前应用核苷类药物3个月以上,能有效地抑制肝门淋巴结内HBV的复制.%Objective To investigate the effects of nucleoside analogues on hepatitis B virus (HBV) in hepatic lymph nodes of hepatitis B related liver transplantation recipients who were hepatitis B surface antigen (HBsAg) positive but negative for serum HBV DNA.Methods From June 2010 to March 201 1,thirty-six cases of hepatitis B related liver transplantation recipients [ 32 males,4 females,average age (54 ± 7) years ] were divided into drug treatment group and non-drug treatment group according to the utility of nucleoside analogues. Drug treatment group was divided into two subgroups:drug treatment ＞3 months group and drug treatment ≤ 3 months group. The hepatic lymph nodes in the hepatoduodenal ligament were taken during the operation of liver transplant. Using nested or semi-nested PCR,HBV DNA and the replicative form HBV cccDNA in hepatic lymph nodes were detected. Data were analyzed by Fisher's exact test.Results The positive rate of HBV DNA:the difference was not statistically significant between drug treatment group ( 72.7％,16/22) and non-drug treatment group ( 14/14 ) ( P =0.062 ),the difference was not statistically significant between drug treatment ＞ 3 months group (10/14) and drug treatment ≤3 months group (6/8) in the subgroups of drug treatment group (P =1.000).The positive rate of HBV cccDNA:drug treatment group (22.7％,5/22) was significantly lower than the non-drug treatment (12/14) ( P =0.000),drug treatment ＞ 3 months group (1/14) was significantly lower than drug treatment ≤3 months group (4/8) in the subgroups of drug treatment group (P =0.039).Conclusions Hepatic lymph nodes maybe one of the extrahepatic HBV reservoirs.Treating with nucleoside analogues more than 3 months can significantly decrease the replication of HBV in hepatic lymph nodes of HBV associated liver transplantation recipients.