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目的 分析原位肝移植(OLT)术后HBV再感染的相关因素,评价联合应用乙型肝炎免疫球蛋白(HBIG)和核苷(酸)类似物预防HBV再感染的疗效.方法 收集2003年10月-2007年8月在中山大学附属第三医院行OLT治疗的160例HBV相关性终末期肝病患者,117例患者术前服用核苷(酸)类似物.所有患者术后长期肌肉注射HBIG,并联合服用核苷(酸)类似物,采用回顾性调查方法分析患者术前资料,并前瞻性长期随访OLT术后HBV再感染情况.正态分布计量资料2组间的比较采用独立样本t检验;组间率的比较采用Fisher's精确概率检验,P<0.05表示差异具有统计学意义.结果 160例患者中,19例患者出现HBV再感染,再感染率为11.88%(19/160).患者术前HBV DNA载量、HBeAg状态及抗病毒治疗时间与OLT术后HBV再感染之间无显著相关性(r值分别为0.108、0.127和0.033,P值均>0.05).19例HBV再感染患者中有17例是长期使用拉米夫定治疗的患者,其中8例酪氨酸-蛋氨酸-天门冬氨酸-天门冬氨酸(YMDD)变异株阳性,其HBV DNA载量为(7.0±2.0)log拷贝/mL,而YMDD变异阴性组为(3.2±2.5)log拷贝/mL,2组比较差异有统计学意义(t=3.531,P=0.003).17例长期服用拉米夫定治疗的患者中,12例加用阿德福韦酯,3例改用恩替卡韦,均获得满意疗效.结论 OLT术后长期小剂量肌肉注射HBIG,并联合核苷(酸)类似物可有效预防HBV再感染.OLT术后使用拉米夫定易出现YMDD变异,而YMDD变异是HBV再感染的重要因素,临床上要予以重视.

Objective To investigate the risk factors of hepatitis B virus(HBV) re-infection after orthotopic liver transplantation(OLT)and to evaluate the therapeutic efficacy of hepatitis B immunoglobulin(HBIG)combined with nucleos(t)ide analogues. Methods The study included 160 patients with HBVrelated liver diseases who underwent OLT in the Third Affiliated Hospital of Sun Yat-sen University from October 2003 to Augest 2007, 117 of whom were treated with nucleos(t)ide analogues before OLT;and all patients were received HBIG i. m and nucleos(t)ide analogues treatment after OLT. Preoperative data of the patients were retrospectively reviewed, and HBV re-infection was assessed prospectively. Independent t test was used to compare normally distributed data and Fisher's exact test was used for the comparison of rates among groups. Results HBV re-infection Was observed in 19 patients after OLT with a rate of 11. 88%(19/160), which was not correlated with HBV DNA loads, HBeAg and the duration of antiviral therapy before OLT(r=0.108, 0.127 and 0.033, P>0.05). Of 19 patients with HBV re-infection, 17 were treated with lamivudine after OLT, and HBV YMDD mutants were detected in 8. The YMDD positive group had a higher HBV DNA level than YMDD negative group(7.0 ± 2.0 log copies/mL vs 3.2 ± 2.5 log copies/mL, t = 3.531, P=0.003). Among above 17 patients, 12 received adefovir add-on treatment, and3 received entecavir instead of lamivadine; all achieved satisfactory responses. Conclusions Low dose of HBIG combined with long-term use of nucleos(t)ide analogues can effectively prevent HBV re-infection after OLT. HBV YMDD mutation may be the primary reason for HBV re-infection in the patients treated with lamivudine after OLT.