Applicability, Tolerability and Efficacy of Preemptive Antiviral Therapy in Hepatitis C‐Infected Patients Undergoing Liver Transplantation
Applicability, Tolerability and Efficacy of Preemptive Antiviral Therapy in Hepatitis C‐Infected Patients Undergoing Liver Transplantation
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丙型肝炎感染肝移植患者预防性抗病毒治疗的适用性、耐受性和有效性
DOI：
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发表时间：
2005
影响因子：
8.8
通讯作者：
N. Terrault
中科院分区：
文献类型：
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作者：
A. Shergill;M. Khalili;Stephanie D. Straley;K. Bollinger;J. Roberts;Nancy A. Ascher;N. Terrault
初步研究表明，肝移植受者的抢先抗HCV治疗可能会提高病毒清除率，但抢先治疗的适用性和耐受性尚未在当代队列中进行评估。在这项随机化研究中，在移植后2-6周开始评估抢先标准（IFN）或聚乙二醇化（PEG-IFN）干扰素α-2b（每周3次，每次3 MU或每周1.5 μg/kg）或IFN/PEG-IFN加利巴韦林（每日600 mg，增加至1.0-1.2 g）的安全性和耐受性，并持续总计48周。在124例移植受者中，只有51例（41%）符合预先治疗的条件;符合条件的患者在移植前的终末期肝病（MELD）模型和查尔兹-Pugh评分较低，并且比不符合条件的患者更频繁地接受活体供体移植。分别有85%和37%的患者需要减量和停药，27%的患者发生严重不良事件。在研究的后半部分，生长因子（GF）（促红细胞生成素和GCSF）的使用未显著影响剂量降低的频率。只有15%的患者能够在治疗期间实现全剂量治疗。治疗结束和持续病毒学应答分别为13.6%和9.1%，联合治疗组应答者最多。我们的结论是，先发制人的抗病毒治疗只适用于一部分移植受者，与“病情较重”的患者不太可能通过这种方法来管理。活体肝移植受者比已故供体受者更容易接受治疗。病毒学应答率较低，可能与治疗耐受性差和未能达到目标药物剂量有关。未来的研究应侧重于替代给药方案，更积极地使用辅助治疗，包括GF。
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 μg/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.
影响因子：
29.4
作者：
Shiffman, ML;Di Bisceglie, AM;Everhart, JE
通讯作者：
Everhart, JE
影响因子：
29.4
作者：
Forman, LM;Lewis, JD;Lucey, MR
通讯作者：
Lucey, MR
影响因子：
29.4
作者：
McHutchison, JG;Manns, M;Albrecht, JK
通讯作者：
Albrecht, JK