Department of Internal Medicine, Division of Digestive Diseases and Nutrition, Rush University Medical Center, Chicago, IL 60612, USA.
Texas Liver Institute, University of Texas Health San Antonio, San Antonio, TX 78215, USA.
Viruses. 2023 Sep 29;15(10):2026. doi: 10.3390/v15102026.
A fixed-dose combination of sofosbuvir/velpatasvir (SOF/VEL) plus weight-based ribavirin (RBV) for 12 weeks is recommended for the treatment of patients with hepatitis C virus (HCV)-associated decompensated cirrhosis. However, large global studies, while confirming the effectiveness of SOF/VEL in a broad range of patients, often exclude these patients. This Phase 2, single-arm, open-label study in adult patients with HCV-associated decompensated cirrhosis in France and the USA aimed to provide further data on the safety and efficacy of SOF/VEL plus RBV for 12 weeks in this population. Patients were treated with a fixed-dose combination of SOF 400 mg/VEL 100 mg plus weight-based RBV once daily for 12 weeks. The inclusion criteria were chronic HCV infection (≥6 months), quantifiable HCV RNA at screening, Child-Turcotte-Pugh class B or C cirrhosis, and liver imaging within 6 months of Day 1 to exclude hepatocellular carcinoma. Among 32 patients who initiated treatment, 78.1% achieved sustained virologic response 12 weeks after the end of treatment (SVR12). Failure to achieve SVR12 was due to non-virologic reasons (investigator discretion, = 1; death, = 6). All 25 patients in the per-protocol population achieved SVR12 and all but one achieved sustained virologic response 24 weeks after the end of treatment. Adverse events (AEs) were as expected for a patient population with advanced liver disease. All Grade 3-4 and serious AEs and deaths were deemed unrelated to treatment. In patients with HCV-associated decompensated cirrhosis, SOF/VEL plus RBV achieved high SVR12 rates and was generally well tolerated.
索磷布韦/维帕他韦（SOF/VEL）固定剂量联合基于体重的利巴韦林（RBV）治疗 12 周，被推荐用于治疗丙型肝炎病毒（HCV）相关失代偿性肝硬化患者。然而，大型全球研究虽然证实了 SOF/VEL 在广泛患者人群中的有效性，但这些研究往往排除了这些患者。这项在法国和美国的丙型肝炎相关失代偿性肝硬化成年患者中进行的 2 期、单臂、开放性研究旨在提供更多关于 SOF/VEL 联合 RBV 治疗 12 周在该人群中的安全性和有效性的数据。患者接受 SOF 400 mg/VEL 100 mg 固定剂量联合每日一次基于体重的 RBV 治疗 12 周。纳入标准为慢性 HCV 感染（≥6 个月）、筛选时有可定量的 HCV RNA、Child-Turcotte-Pugh 分级 B 或 C 级肝硬化以及在第 1 天前 6 个月内进行肝脏成像以排除肝细胞癌。在开始治疗的 32 例患者中，78.1%在治疗结束后 12 周时达到持续病毒学应答 12 周（SVR12）。未能达到 SVR12 是由于非病毒学原因（研究者判断， = 1；死亡， = 6）。在符合方案人群中，所有 25 例患者均达到 SVR12，除 1 例患者外，所有患者在治疗结束后 24 周时均达到持续病毒学应答。不良事件（AE）与晚期肝病患者人群的预期相符。所有 3-4 级和严重 AE 及死亡均被认为与治疗无关。在 HCV 相关失代偿性肝硬化患者中，SOF/VEL 联合 RBV 可实现高 SVR12 率，且通常具有良好的耐受性。
