聚乙二醇干扰素联合利巴韦林治疗慢性丙型肝炎的研究进展

Long-term follow-up of ribavirin-free DAA-based treatment in HCV recurrence after orthotopic liver transplantation.

机构信息

Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.

Department of Internal Medicine 2, Division of Gastroenterology and Hepatology, Universitätsklinikum, St. Pölten, Austria.

出版信息

Liver Int. 2018 Jul;38(7):1188-1197. doi: 10.1111/liv.13652. Epub 2018 Jan 31.

DOI:10.1111/liv.13652

PMID:29197145

Abstract

BACKGROUND & AIMS: Excellent efficacy and safety profile of second-generation DAA combinations improved treatment of chronic hepatitis C (HCV) as well as in HCV recurrence after orthotopic liver transplantation (OLT). The need of ribavirin addition is under debate as anaemia and decreased renal function are prevalent in transplant cohorts. The aim of this study was thus to assess safety and long-term efficacy of RBV-free DAA combinations in HCV-recurrent patients after OLT.

PATIENTS & METHODS: A total of 62 OLT recipients (male: 50%/81%; age: 60.7 ± 8.5 years [mean ± SD]; GT - 1: 48, GT - 3: 9, GT - 4: 5; cirrhosis: 34%/55% [7%/21% decompensated], fibrosing cholestatic hepatitis: 1%/2%) received RBV-free treatment with second-generation DAA combinations: sofosbuvir (SOF)/daclatasvir (DCV): 42%/68%, SOF/simeprevir (SMV): 10%/16%, SOF/ledipasvir (LDV): 6%/10% and PrOD: 4%/7%.

RESULTS

Data of at least 96 weeks of FUP after treatment cessation (mean: 120; up to 167 weeks) were analysed. All patients showed on-treatment response. By intention-to-treat (ITT) analysis, SVR12 was 97% (60/62, GT-1a: 11/11 [100%]; 1b: 33/34 [97%]; 1g: 1/1 [100%]; subtype not specified: 2/2 [100%]; GT3a: 9/9 [100%]; GT4: 4/5 [80%]) compared to SVR96 of 89% (55/62). No late relapses occurred. In total, 16 severe adverse events occurred, including two newly diagnosed carcinoma (lung cancer, hepatocellular carcinoma). Six patients died; one at treatment week 24 (HCV-RNA undetectable) and five during treatment-free FUP and after achieving SVR (SVR4: N = 1, SVR12: N = 3, after SVR96: N = 1 respectively). Reasons for death were: multi-organ failure (N = 4), impaired graft function (N = 1) and unknown (N = 1).

CONCLUSION

RBV-free DAA combinations for the treatment of HCV recurrence after OLT are highly efficacious and well tolerated. Our long-term data show that viral eradication is durable but not necessarily translated into beneficial long-term clinical outcome.

摘要

背景与目的

第二代直接作用抗病毒药物（DAA）联合方案具有出色的疗效和安全性，改善了慢性丙型肝炎（HCV）的治疗效果，以及肝移植（OLT）后 HCV 复发的治疗效果。在移植队列中，贫血和肾功能下降较为常见，因此是否需要添加利巴韦林存在争议。本研究旨在评估 OLT 后 HCV 复发患者中无利巴韦林的 DAA 联合方案的安全性和长期疗效。

患者与方法

共有 62 名 OLT 受者（男性：50%/81%；年龄：60.7±8.5 岁[均值±标准差]；GT-1：48，GT-3：9，GT-4：5；肝硬化：34%/55%[7%/21%失代偿]，纤维-胆汁性肝炎：1%/2%）接受了第二代 DAA 联合方案（SOF/DCV：42%/68%，SOF/SMV：10%/16%，SOF/LDV：6%/10%和 PrOD：4%/7%）的无利巴韦林治疗。

结果

对停药后至少 96 周的随访（平均：120 周，最长：167 周）的数据进行了分析。所有患者在治疗期间均显示出应答。意向治疗（ITT）分析中，SVR12 为 97%（60/62，GT-1a：11/11[100%]；1b：33/34[97%]；1g：1/1[100%]；未指定亚型：2/2[100%]；GT3a：9/9[100%]；GT4：4/5[80%]），而 SVR96 为 89%（55/62）。无晚期复发。共有 16 例严重不良事件发生，包括 2 例新诊断的癌症（肺癌、肝细胞癌）。6 例患者死亡；1 例在治疗第 24 周（HCV RNA 不可检测），5 例在无治疗随访期间和达到 SVR 后（SVR4：N=1，SVR12：N=3，SVR96 后：N=1）。死亡原因分别为：多器官功能衰竭（N=4）、移植物功能障碍（N=1）和未知（N=1）。