Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Liver Transpl. 2011 Apr;17(4):456-65. doi: 10.1002/lt.22226.
A considerable proportion of liver transplantation recipients who receive hepatitis B immunoglobulin (HBIG) monotherapy for hepatitis B virus (HBV) prophylaxis develop resistance to HBIG. We retrospectively assessed the efficacy of HBV prophylaxis in 1524 patients who received primary high-dose HBIG monotherapy (n = 1463) or with a preemptive antiviral add-on as secondary combination therapy (n = 61). At a median follow-up time of 57 months, 106 (7.3%) patients receiving HBIG monotherapy experienced HBV recurrence, with a 10-year HBV recurrence rate of 9.8%, compared to none of the patients receiving preemptive combination therapy (P = 0.047). Thirteen patients (12.3%) with HBV recurrence failed antiviral therapy, leading to death or retransplantation. Response rates to rescue therapy before and after use of adefovir/entecavir were 44.4% and 91.8%, respectively. Acute exacerbation was not associated with treatment failure, but required prolonged treatment. Of 84 surviving patients with HBV recurrence, 44 (52.4%) showed no evidence of blood HBV DNA. The Gly145Arg mutation was found in 11 of 15 (73.3%) patients, whereas 25 of 71 (35.2%), 2 of 29 (6.9%), and 4 of 8 (50%) patients were resistant to lamivudine, adefovir, and entecavir, respectively. In conclusion, our finding of a 10-year HBV recurrence rate of 9.8% in patients receiving high-dose HBIG monotherapy indicates that this treatment is effective but requires complementary measures. Strict surveillance following HBIG monotherapy is necessary to enhance responses to rescue antiviral therapy. Preemptive conversion to combination therapy has a complementary role in prophylaxis with primary high-dose HBIG monotherapy, especially for patients at high risk of HBV recurrence.
相当一部分接受乙型肝炎免疫球蛋白（HBIG）单药治疗预防乙型肝炎病毒（HBV）的肝移植受者会对 HBIG 产生耐药性。我们回顾性评估了 1524 例患者的 HBV 预防效果，这些患者接受了初始高剂量 HBIG 单药治疗（n=1463）或作为二线联合治疗的预防性抗病毒附加治疗（n=61）。在中位随访时间为 57 个月时，106 例（7.3%）接受 HBIG 单药治疗的患者发生 HBV 复发，10 年 HBV 复发率为 9.8%，而接受预防性联合治疗的患者无一例复发（P=0.047）。13 例（12.3%）HBV 复发患者抗病毒治疗失败，导致死亡或再次肝移植。阿德福韦酯/恩替卡韦治疗前和治疗后的挽救治疗应答率分别为 44.4%和 91.8%。急性加重与治疗失败无关，但需要延长治疗时间。在 84 例 HBV 复发的存活患者中，44 例（52.4%）无血液 HBV DNA 证据。在 15 例患者中发现了 Gly145Arg 突变 11 例（73.3%），而对拉米夫定、阿德福韦酯和恩替卡韦耐药的分别为 25 例（35.2%）、2 例（6.9%）和 4 例（50%）。结论，我们发现接受高剂量 HBIG 单药治疗的患者 10 年 HBV 复发率为 9.8%，这表明该治疗有效，但需要补充措施。HBIG 单药治疗后进行严格监测，有助于增强对挽救性抗病毒治疗的应答。在高剂量 HBIG 单药预防的基础上，预防性转换为联合治疗对预防具有互补作用，特别是对 HBV 复发风险高的患者。
