New Zealand Liver Transplant Unit, Auckland Hospital, Auckland, New Zealand.
Liver Transpl. 2013 Mar;19(3):268-74. doi: 10.1002/lt.23600.
Without effective prophylaxis, liver transplantation for hepatitis B virus (HBV)-related liver disease is frequently complicated by severe and rapidly progressive HBV recurrence. Combination prophylaxis with hepatitis B immune globulin (HBIG) and lamivudine (LAM) reduces long-term recurrence rates below 10%; however, HBIG is costly and inconvenient to administer. We, therefore, conducted a multicenter, prospective study of outcomes with an HBIG-sparing regimen of LAM plus adefovir dipivoxil (ADV) initiated at the time of listing for liver transplantation and continued after transplantation. Twenty-six patients were recruited into this study at the time of listing for transplantation, and 20 subsequently underwent transplantation. Twelve of the 26 patients had LAM exposure before the study baseline, but none had LAM resistance. The median HBV viral load before the institution of antiviral therapy was approximately 4.0 log(10) IU/mL (range=2.3-7.5 log(10) IU/mL). To the 20 patients who underwent transplantation, 800 IU of intramuscular HBIG was given immediately after transplantation and daily for 7 days only (total HBIG dose=6400 IU). All transplant patients remained alive without HBV recurrence (they were negative for hepatitis B surface antigen, and HBV DNA was undetectable) after a median follow-up of 57 months after transplantation (range=27-83 months). The median serum creatinine level in these patients rose from 81 to 119 μmol/L over the course of the study. No patient required dose reduction or cessation. After the completion of this prospective study, the regimen was modified so that no perioperative HBIG was administered if the pretransplant serum HBV DNA level was suppressed below 3 log(10) IU/mL. Another 28 patients with HBV-related liver disease underwent transplantation (18 without HBIG). All remained alive and well without HBV recurrence after a median follow-up of 22 months after transplantation (range=10-58 months). In conclusion, a combination of LAM and ADV initiated at the time of wait listing provides safe and effective protection against recurrent HBV infection without the high costs and inconvenience associated with long-term HBIG therapy.
在没有有效预防措施的情况下，乙型肝炎病毒（HBV）相关肝病的肝移植常常会出现严重且快速进展的 HBV 复发。乙型肝炎免疫球蛋白（HBIG）和拉米夫定（LAM）联合预防可将长期复发率降低至 10%以下；然而，HBIG 成本高且给药不便。因此，我们开展了一项多中心前瞻性研究，评估在肝移植等待名单时即开始应用拉米夫定加阿德福韦酯（ADV）的 HBIG 节省方案，并在移植后继续应用该方案的效果。在移植等待名单时，共有 26 例患者入组该研究，其中 20 例随后接受了移植。26 例患者中有 12 例在研究基线时有 LAM 暴露史，但均无 LAM 耐药。开始抗病毒治疗前的中位 HBV 病毒载量约为 4.0 log10 IU/mL（范围=2.3-7.5 log10 IU/mL）。20 例接受移植的患者在移植后立即接受 800 IU 肌内注射 HBIG，仅连续 7 天（总 HBIG 剂量=6400 IU）。中位随访 57 个月（范围=27-83 个月）后，所有移植患者均存活且未出现 HBV 复发（乙型肝炎表面抗原阴性，HBV DNA 不可检测）。这些患者的中位血清肌酐水平在研究过程中从 81 μmol/L 升高至 119 μmol/L。无患者需要减少剂量或停药。在完成这项前瞻性研究后，如果移植前血清 HBV DNA 水平低于 3 log10 IU/mL，则修改该方案，不再给予围手术期 HBIG。另外 28 例 HBV 相关肝病患者接受了移植（18 例无 HBIG）。中位随访 22 个月（范围=10-58 个月）后，所有患者均存活且未出现 HBV 复发。总之，在等待名单时开始应用 LAM 和 ADV 的联合方案可提供安全有效的预防 HBV 再感染的作用，且不会带来长期 HBIG 治疗的高成本和不便。
