应用拉米夫定联合肌肉注射乙肝免疫球蛋白预防肝移植术后乙型肝炎再感染:35例分析

Intramuscular injection of hepatitis B immunoglobulin combined with lamivudine to prevent hepatitis B virus reinfection following liver transplantation: An analysis of 35 cases

目的:观察拉米夫定联合肌肉注射乙肝免疫球蛋白预防肝移植术后乙型肝炎再感染的效果。方法:选择2004-10/2006-05在西安交通大学医学院第一附属医院行肝移植的患者35例,均为东亚人种,术前检查乙肝表面抗原和(或)乙肝病毒DNA定量阳性,且术后能按照肝移植术后预防乙肝复发的方案进行预防性治疗。①所有病例术后均采用拉米夫定联合肌肉注射乙肝免疫球蛋白的方案预防术后乙肝再感染。拉米夫定口服100mg/d,术前服用至少2周,术后第1天开始继续服用。乙肝免疫球蛋白术中无肝期给予4000U,术后1周内每天肌注2000U,之后通过检测血液中乙肝表面抗体滴度来决定是否给药,使抗体浓度保持术后3个月内≥500U/L,术后3个月至半年≥300U/L,术后半年以上≥100U/L。长期随访,观察患者肝功、乙肝系列、乙肝病毒DNA定量等血清学指标变化。对于术后乙肝再感染者则加大乙肝免疫球蛋白用量并联用恩替卡维。②选择文献中同为亚洲人种的日本人数据进行对照,其预防肝移植术后乙肝再感染方案为拉米夫定联合静注型乙肝免疫球蛋白。结果:7例患者因死亡而失访。①35例患者平均随访(15.09±6.50)个月,其中随访7～12个月13例,13～18个月8例,19～24个月12例,24个月以上2例。②患者的乙肝再感染率为5.71%(2/35),日本研究数据中患者的乙肝再感染率为0(0/30),两者差异无显著性意义(P=0.37)。结论:应用拉米夫定联合肌肉注射乙肝免疫球蛋白并通过血液中乙肝表面抗体滴度给药的方案预防肝移植术后乙肝再感染,效果与国外应用拉米夫定联合静脉注射乙肝免疫球蛋白效果相似。

AIM： To explore the tactic to prevent the reinfection of hepatitis B virus （HBV） after liver transplantation by use of lamivudine combined with intramuscular injection of hepatitis B immunoglobulin （HBIG）. METHODS： The experiment adopted 35 patients who underwent liver transplantation in the First Hospital of Xi＇an Jiaotong University from October 2004 to May 2006. Preoperatively all the subjects were examined to be positive for hepatitis B surface antibody （HBsAb） and/or HBV-DNA, and they received the postoperative prophylaxis of HBV reinfection, which included lamivudine and HBIG.（1）Lamivudine （100 mg/d） was administered orally every day except the day of operation. Preoperative treatment was lasted for over two weeks. HBIG were administered intramuscularly 4 000 U during anhepatic phase, 2 000 U every day during the first postoperative week, and thereafter when necessary to maintain HBsAb titer 500 U/L within 3 months, ≥300 U/L between 4-6 months and ≥ 100 U/L beyond 6 months after operation. During the follow-up, the patients were examined for the liver function, HBV-DNA and liver biopsy. Increasing dose of HBIG combined entacavir were applied when HBV reinfection appeared. （2）The medical records of Japanese patients reported in the literatures were taken as controls, and they were treated with lamivudine and intravenous injection of HBIG. RESULTS： Seven cases were invalid due to the deaths.（1）Thirty-five patients were followed up for an average of （15.09± 6.50） months, including 13 cases for 7-12 months, 8 cases for 13-18 cases, 12 cases for 19-24 months, and 2 cases for over 24 months. （2）The HBV reinfection rate was 5.71% （2/35） in the patients and 0 （0/30） in Japanese controls. There was no significant difference between the two groups （P =0.37）. CONCLUSION： Combined use of lamivudine and HBIG in intramuscular injection according to the HBsAb may be a reasonable strategy for HBV prophylaxis after liver transplantation, and the effect is identical with that of lamivudine and HBIG in intravenous injection.