12 周无利巴韦林的索非布韦和非结构蛋白 5A 抑制剂方案足以治疗肝移植后丙型肝炎复发。

12 Weeks of a Ribavirin-Free Sofosbuvir and Nonstructural Protein 5A Inhibitor Regimen Is Enough to Treat Recurrence of Hepatitis C After Liver Transplantation.

机构信息

Hepatology and Liver Transplant Unit, Pontchaillou University Hospital, Rennes, France.

Hepatobiliary Center, AP-HP Paul Brousse Hospital, Villejuif, France.

出版信息

Hepatology. 2018 Oct;68(4):1277-1287. doi: 10.1002/hep.29918.

DOI:10.1002/hep.29918

PMID:29633389

Abstract

UNLABELLED

Sofosbuvir (SOF) combined with nonstructural protein 5A (NS5A) inhibitors has demonstrated its efficacy in treating a recurrence of hepatitis C virus (HCV) after liver transplantation (LT). However, the duration of treatment and need for ribavirin (RBV) remain unclear in this population. Our aim was to determine whether LT recipients could be treated with an SOF + NS5A inhibitor-based regimen without RBV for 12 weeks post-LT. Between October 2013 and December 2015, 699 LT recipients experiencing an HCV recurrence were enrolled in the multicenter ANRS CO23 CUPILT cohort. We selected patients receiving SOF and NS5A inhibitor ± RBV and followed for at least 12 weeks after treatment discontinuation. The primary efficacy endpoint was a sustained virological response 12 weeks after the end of treatment (SVR12). Among these 699 patients, 512 fulfilled the inclusion criteria. Their main characteristics were: 70.1% genotype 1, 18.2% genotype 3, 21.1% cirrhosis, and 34.4% previously treated patients. We identified four groups of patients according to their treatment and duration: SOF + NS5A without RBV for 12 (156 patients) or 24 (239 patients) weeks; SOF + NS5A + RBV for 12 (47 patients) or 24 (70 patients) weeks. SVR12 values reached 94.9%, 97.9%, 95.7%, and 92.9%, respectively (P = 0.14). Only 20 patients experienced a treatment failure. Under multivariate analysis, factors such as fibrosis stage, previous treatment, HCV genotype, and baseline HCV viral load did not influence SVR12 rates in the four groups (P = 0.21). Hematological adverse events (AEs) were more common in the RBV group: anemia (P < 0.0001) and blood transfusion (P = 0.0001).

CONCLUSION

SOF + NS5A inhibitors without RBV for 12 weeks constituted reliable therapy for recurrent HCV post-LT with an excellent SVR12 whatever the fibrosis stage, HCV genotype, and previous HCV treatment. (Hepatology 2018; 00:000-000).

摘要

目的

确定肝移植（LT）后，是否可以使用 SOF+NS5A 抑制剂方案，无利巴韦林（RBV），治疗 LT 后 12 周内的 HCV 复发。

方法

在 2013 年 10 月至 2015 年 12 月期间，ANRS CO23 CUPILT 多中心队列纳入了 699 例 HCV 复发的 LT 受者。我们选择了接受 SOF 和 NS5A 抑制剂±RBV 治疗且至少在治疗结束后 12 周时随访的患者。主要疗效终点是治疗结束后 12 周的持续病毒学应答（SVR12）。

结果

699 例患者中，512 例符合纳入标准。主要特征包括：基因型 1 占 70.1%、基因型 3 占 18.2%、肝硬化占 21.1%、既往治疗患者占 34.4%。根据治疗和疗程，我们将患者分为四组：SOF+NS5A 无 RBV 治疗 12（156 例）或 24（239 例）周；SOF+NS5A+RBV 治疗 12（47 例）或 24（70 例）周。SVR12 值分别达到 94.9%、97.9%、95.7%和 92.9%（P = 0.14）。仅有 20 例患者治疗失败。多因素分析显示，纤维化分期、既往治疗、HCV 基因型和基线 HCV 病毒载量等因素对四组 SVR12 率无影响（P = 0.21）。RBV 组更常见血液学不良事件（AE）：贫血（P < 0.0001）和输血（P = 0.0001）。