Shergill Amandeep K, Khalili Mandana, Straley Stephanie, Bollinger Kathy, Roberts John P, Ascher Nancy A, Terrault Norah A
Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Am J Transplant. 2005 Jan;5(1):118-24. doi: 10.1111/j.1600-6143.2004.00648.x.
Preliminary studies suggest preemptive anti-HCV therapy in liver transplant recipients may enhance the rates of viral clearance, but the applicability and tolerability of preemptive therapy has not been evaluated in a contemporary cohort. In this randomized study, the safety and tolerability of preemptive standard (IFN) or pegylated (peg-IFN) interferon alfa-2b (3 MU thrice weekly or 1.5 microg/kg weekly), or IFN/peg-IFN plus ribavirin (600 mg increased to 1.0-1.2 g daily) was initiated 2-6 weeks post-transplantation and continued for a total of 48 weeks. Only 51 (41%) of 124 transplant recipients were eligible for preemptive treatment; eligible patients had lower model for end-stage liver disease (MELD) and Childs-Pugh scores pre-transplantation and were more frequently live donor transplant recipients than ineligible patients. Dose reductions and discontinuations were required in 85% and 37% of patients, respectively, and 27% experienced serious adverse events. Growth factor (GF) use (erythropoietin and GCSF) in the latter half of the study did not significantly affect the frequency of dose reductions. Only 15% of patients were able to achieve full-dose treatment during treatment. End-of-treatment and sustained virological responses were 13.6% and 9.1%, respectively, with most responders in the combination therapy group. We conclude that preemptive antiviral therapy is applicable to only a portion of transplant recipients, with 'sicker' patients less likely to be managed by this approach. Living donor liver transplant recipients were more frequently eligible for treatment than deceased donor recipients. Virological response rates are low, likely related to the poor tolerability of therapy and the lack of achievement of target drug doses. Future studies should focus on alternative dosing schedules with more aggressive use of adjuvant therapies, including GFs.
初步研究表明，对肝移植受者进行抢先抗丙型肝炎病毒（HCV）治疗可能会提高病毒清除率，但在当代队列中尚未评估抢先治疗的适用性和耐受性。在这项随机研究中，抢先标准（干扰素）或聚乙二醇化（聚乙二醇干扰素）干扰素α-2b（每周三次，每次3 MU或每周1.5 μg/kg），或干扰素/聚乙二醇干扰素加利巴韦林（每日600 mg增至1.0 - 1.2 g）的安全性和耐受性在移植后2 - 6周开始，并持续共48周。124名移植受者中只有51名（41%）符合抢先治疗条件；符合条件的患者移植前终末期肝病模型（MELD）和Childs-Pugh评分较低，且活体供肝移植受者比不符合条件的患者更常见。分别有85%和37%的患者需要减少剂量和停药，27%的患者发生严重不良事件。在研究后半期使用生长因子（GF）（促红细胞生成素和粒细胞集落刺激因子）并未显著影响减少剂量的频率。治疗期间只有15%的患者能够完成全剂量治疗。治疗结束时和持续病毒学应答率分别为13.6%和9.1%，大多数应答者在联合治疗组。我们得出结论，抢先抗病毒治疗仅适用于一部分移植受者，病情较重的患者不太可能通过这种方法进行治疗。活体供肝移植受者比尸体供肝移植受者更常符合治疗条件。病毒学应答率较低，可能与治疗耐受性差和未达到目标药物剂量有关。未来的研究应侧重于更积极使用包括生长因子在内的辅助治疗的替代给药方案。
