The Transplant Institute, Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden.
Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
PLoS One. 2019 Feb 22;14(2):e0211437. doi: 10.1371/journal.pone.0211437. eCollection 2019.
Direct antiviral agents (DAA) has dramatically improved the therapy outcome of hepatitis C-virus (HCV) infection, both on the waiting-list and post liver transplantation (LT). DAA are generally well-tolerated in patients with mild to moderate liver and kidney failure, but some DAAs are contraindicated in patients with severe dysfunction of these organs. Today there are few studies of peri-LT DAA use and treatment is commonly discontinued at the time of LT. We report here our experience of DAA therapy given continuously in the perioperative LT period in a real-life setting in Sweden.
In total 10 patients with HCV-cirrhosis, with or without hepatocellular carcinoma, and a median age of 60.5 years (range, 52-65) were treated with DAAs on the waiting list for LT, and continued in the early postoperative period without any interruption, on the basis of not having reached a full treatment course at the time of LT. Sofosbuvir and a NS5A inhibitor with or without ribavirin, or sofosbuvir and ribavirin only, were given. The distribution of genotypes was genotype 1 and 3, in 4 and 6 patients, respectively. Six of the 10 patients had previously been treated with IFN-based therapy.
There were no adverse events leading to premature DAA discontinuation. All recipients achieved a sustained viral response 12 weeks after end-of-treatment (SVR12). At the time of LT the median MELD-score was 16.5 (range 7-21), CTP-score 9.0 (range 5-10), creatinine 82.5 μmol/L (range 56-135, reference 60-105), bilirubin 33 μmol/L (range 16-79, reference 5-25) and PK-INR 1.5 (range 1.1-1.8). The median duration of DAA therapy was 60 days (range 18-132) pre-LT, 54 days post-LT (range 8-111 days) and in total 15.5 weeks (range 12-30 weeks).
Interferon-free DAA therapy of HCV-infection given in the immediate pre- and post-operative LT period is safe, well-tolerated and yields high SVR rates.
直接抗病毒药物（DAA）显著改善了丙型肝炎病毒（HCV）感染的治疗效果，无论是在等待肝移植（LT）期间还是移植后。在轻度至中度肝肾功能衰竭患者中，DAA 通常耐受性良好，但某些 DAA 对这些器官严重功能障碍的患者禁用。目前，关于 LT 期间 DAA 使用的研究较少，治疗通常在 LT 时停止。我们在此报告了我们在瑞典真实环境中连续进行 LT 围手术期 DAA 治疗的经验。
共有 10 名 HCV 肝硬化患者，无论是否合并肝细胞癌，中位年龄为 60.5 岁（范围，52-65 岁），在 LT 等待期间接受 DAA 治疗，并在没有完全完成治疗疗程的情况下继续在术后早期进行治疗，而无需中断治疗。使用了索非布韦和一种 NS5A 抑制剂联合或不联合利巴韦林，或索非布韦和利巴韦林。10 名患者中有 4 名和 6 名患者分别为基因型 1 和 3。其中 6 名患者之前接受过 IFN 为基础的治疗。
没有导致提前停止 DAA 治疗的不良事件。所有受者在治疗结束后 12 周（SVR12）均达到持续病毒应答。LT 时，中位 MELD 评分 16.5（范围 7-21），CTP 评分 9.0（范围 5-10），肌酐 82.5μmol/L（范围 56-135，参考值 60-105），胆红素 33μmol/L（范围 16-79，参考值 5-25）和 PK-INR 1.5（范围 1.1-1.8）。LT 前 DAA 治疗的中位持续时间为 60 天（范围 18-132），LT 后 54 天（范围 8-111 天），总疗程为 15.5 周（范围 12-30 周）。
在 LT 围手术期立即给予无干扰素的 DAA 治疗 HCV 感染是安全的，耐受性良好，并且产生高 SVR 率。
