Objective: To evaluate the real-world efficacy and safety of sofosbuvir and velpatasvir (SOF/VEL) tablets in the treatment of Chinese patients with chronic HCV infection. Methods: An open-label, single-center, prospective clinical study was conducted in a county in northern China. A total of 299 cases were enrolled. Of these, 161 cases with chronic hepatitis C and 73 cases with compensated cirrhosis received SOF/VEL for 12 weeks. 65 cases with decompensated cirrhosis received SOF/VEL combined with ribavirin for 12 weeks (22 cases) or SOF/VEL for 24 weeks (43 cases). Virological indicators, liver and renal function indexes, and liver stiffness measurement were detected at baseline, the fourth week of treatment, the end of treatment, and the 12-weeks of follow-up. Adverse reactions and laboratory abnormalities were observed during the course of treatment . The primary endpoint was undetectable rate of HCV RNA (SVR12) at 12 weeks of follow-up with the use of modified intention-to-treat (mITT) approach. Measurement data between two groups were compared using t-test. One Way ANOVA was used for comparison between multiple groups. Enumeration data were analyzed by chi-square test or Fisher's exact test. Results: 291 cases had completed treatment. HCV RNA was undetectable after 12 weeks of follow-up, and the SVR12 rate was 97.3% (95% confidence interval: 95.4%-99.3%). Among them, 97.4% of genotype 1b, 96.4% of genotype 2a, and 100% of those with undetected genotype achieved SVR12. The SVR12 rates in patients with chronic hepatitis C, compensated and decompensated liver cirrhosis were 98.1%, 98.6% and 93.8%, respectively. An improvement in alanine aminotransferase, aspartate aminotransferase and other liver biochemical indicators accompanied with virological clearance and reduced liver stiffness measurement was observed in patients with compensated cirrhosis, with statistically significant difference. There was no significant abnormality in renal function before and after treatment. The most common adverse reactions were fatigue, headache, epigastric discomfort and mild diarrhea. The overall adverse reactions were mild. One patient died of decompensated liver cirrhosis combined with massive upper gastrointestinal bleeding, which was unrelated to antiviral treatment. Four patients discontinued treatment prematurely due to adverse events. Relapse was occurred in four cases, and drug-resistance related mutations were detected in three cases. Conclusion: Sofosbuvir and velpatasvir tablets in Chinese HCV-infected patients with different genotypes, different clinical stages or previously treated with pegylated interferon combined with ribavirin resulted in higher SVR12, indicating that the treatment safety profile is good.
目的： 评价索磷布韦维帕他韦片（SOF/VEL）治疗中国慢性HCV感染者真实世界中的有效性和安全性。 方法： 在中国北方某县开展一项开放标签、单中心、前瞻性临床研究，共入组299例患者，其中慢性丙型肝炎患者161例，代偿期肝硬化73例，给予SOF/VEL12周方案治疗；失代偿期肝硬化患者65例，给予SOF/VEL加利巴韦林12周（22例）或SOF/VEL24周（43例）方案治疗。在基线、治疗第4周、治疗结束、随访12周时分别检测病毒学指标、肝功能、肾功能、肝脏弹性检测等。观察治疗过程中的不良反应与实验室异常。采用调整后意向性分析（mITT），主要研究终点是随访12周时HCV RNA检测不到率（SVR12）。计量资料两组比较采用t检验，多组间比较采用One Way ANOVA方差分析。计数资料采用χ2检验或Fisher精确检验。 结果： 291例患者在完成治疗并随访12周时HCV RNA检测不到，SVR12率为97.3%（95%可信区间：95.4%～99.3%）。其中基因1b型97.4%、基因2a型96.4%，基因型未检出者100%获SVR12。慢性丙型肝炎、肝硬化代偿期、失代偿期患者SVR12率分别为98.1%、98.6%和93.8%。伴随病毒学清除，可见丙氨酸转氨酶、天冬氨酸转氨酶等肝脏生化学指标好转，代偿期肝硬化患者可见肝脏硬度值下降，差异均有统计学意义。治疗前后未见显著肾功能异常。最常见不良反应是疲乏、头痛、上腹不适和轻度腹泻，总体不良反应轻微。病死1例，为肝硬化失代偿期合并上消化道大量出血，与抗病毒治疗无关。因不良反应提前中止治疗4例；复发4例，其中3例检测到耐药相关变异。 结论： 索磷布韦维帕他韦片治疗不同基因型、不同临床阶段或既往聚乙二醇干扰素联合利巴韦林治疗史的中国HCV感染者均可获高SVR12，治疗安全性良好。.