Vasudevan Abhinav, Ardalan Zaid S, Ahmed Navera, Apostolov Ross, Gow Paul J, Testro Adam G, Gane Ed J, Angus Peter W
Liver Transplant Unit Victoria Austin Health Melbourne Australia.
New Zealand Liver Transplant Unit Auckland City Hospital New Zealand.
JGH Open. 2018 Sep 19;2(6):288-294. doi: 10.1002/jgh3.12086. eCollection 2018 Dec.
Limitations to the use of long-term Hepatitis B Immunoglobulin (HBIg) following liver transplantation for hepatitis B (HBV) have led to the substitution of HBIg with oral nucleo(s)tide analogue prophylaxis. We prospectively assessed the long-term safety and efficacy of switching to tenofovir disoproxil fumarate (TDF) from HBIg.
An open-label, multicenter switch study was conducted to evaluate the substitution of TDF for HBIg whilst continuing lamivudine (LAM) therapy in preventing the recurrence of HBV in patients who had been maintained as hepatitis B surface antigen (HBsAg)-negative posttransplantation for at least 12 months.
Eighteen patients were enrolled (median age 66 years, range 42-78 years); 84% were male, and 78% on calcineurin inhibitors. Median time after transplantation was 14 years (range 5-19), and median duration of HBIg/LAM prior to the switch was 10 years (range 1-14). Median follow-up was 5 years (range 5-8). Of 18 patients, 16 (89%) remained HBsAg and HBV DNA negative at the end of follow-up. Two patients had re-emergence of HBsAg without a detectable HBV DNA and no clinical sequelae. Creatinine clearance significantly reduced (median 59 mL/min to 51 mL/min, = 0.03), necessitating dose reduction of TDF in six (33%) participants, with two eventually ceasing TDF. One patient switched back to HBIg by choice. All patients who changed therapy maintained an undetectable HBsAg.
Substitution of HBIg with TDF in patients on LAM is well tolerated and effective for the long-term prevention of HBV recurrence posttransplantation. Renal dysfunction occurs frequently in the posttransplant setting and can require dose adjustment of TDF or change of therapy.
肝移植治疗乙型肝炎（HBV）后长期使用乙型肝炎免疫球蛋白（HBIg）存在局限性，这导致用口服核苷类似物预防方案替代HBIg。我们前瞻性评估了从HBIg转换为替诺福韦酯（TDF）的长期安全性和疗效。
开展了一项开放标签、多中心转换研究，以评估在继续使用拉米夫定（LAM）治疗的同时，用TDF替代HBIg预防肝移植后已维持至少12个月乙型肝炎表面抗原（HBsAg）阴性的患者HBV复发的情况。
共纳入18例患者（中位年龄66岁，范围42 - 78岁）；84%为男性，78%使用钙调神经磷酸酶抑制剂。移植后的中位时间为14年（范围5 - 19年），转换前HBIg/LAM的中位使用时间为10年（范围1 - 14年）。中位随访时间为5年（范围5 - 8年）。18例患者中，16例（89%）在随访结束时HBsAg和HBV DNA仍为阴性。2例患者HBsAg再次出现，但未检测到HBV DNA，且无临床后遗症。肌酐清除率显著降低（中位值从59 mL/min降至51 mL/min，P = 0.03），6例（33%）参与者需要减少TDF剂量，其中2例最终停用TDF。1例患者自行选择换回HBIg。所有改变治疗方案的患者HBsAg均未检测到。
在接受LAM治疗的患者中，用TDF替代HBIg耐受性良好，对长期预防移植后HBV复发有效。移植后肾功能障碍常见，可能需要调整TDF剂量或改变治疗方案。
