Mushtaq Saima, Mansoor Atika, Umar Muhammad, Khan Amjad, Siddiqi Saima, Manzoor Sobia
Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan.
Institute of Biomedical and Genetic Engineering, Islamabad, Pakistan.
J Med Virol. 2020 Dec;92(12):3475-3487. doi: 10.1002/jmv.25745. Epub 2020 Mar 13.
This study aims to evaluate the clinical effectiveness in terms of sustained virological response (SVR), predictors of SVR and safety of available second-generation generic direct-acting antivirals in Pakistani chronic hepatitis C patients. This is a retrospective study conducted in multiple centers of Pakistan from January 2015 to January 2019. The samples include patients infected with chronic hepatitis C virus, regardless of virus genotype, cirrhosis, or prior treatment. A total of 993 patients were included in the present study, with the majority receiving sofosbuvir with daclatasvir (95%), sofosbuvir with daclatasvir and ribavirin (4%), and sofosbuvir with ribavirin (1%). There were 96% cases of chronic hepatitis, 3% cases compensated cirrhosis, and 1% cases of decompensated cirrhosis. Genotype 3 (99.6%) was the most common genotype. Overall SVR after 12 weeks was 98% for all treatment regimens. High SVR12 was observed with sofosbuvir in combination with daclatasvir (98.5%), then sofosbuvir in combination with daclatasvir and ribavirin (90.2%) and sofosbuvir in combination with ribavirin (75%). SVR rates were high in chronic hepatitis C patients (98.2%) as compared with cirrhotic patients (92.1%) and it was high in treatment-naive (98.8%) then interferon experienced patients (90.1%). In multivariate binary logistic regression analysis, patients' education status, treatment strategy, viral load, and alanine aminotransferase had a statistically significant association with SVR at 12 weeks. No major adverse events occurred which required treatment discontinuation. Generic oral direct acting antiviralss (sofosbuvir with daclatasvir) achieved higher SVR12 rates and were well tolerated in this large real-world cohort of genotype 3 infected patients.
本研究旨在评估第二代通用型直接抗病毒药物对巴基斯坦慢性丙型肝炎患者的持续病毒学应答(SVR)的临床疗效、SVR的预测因素及安全性。这是一项于2015年1月至2019年1月在巴基斯坦多个中心进行的回顾性研究。样本包括感染慢性丙型肝炎病毒的患者,无论病毒基因型、是否患有肝硬化或既往治疗情况如何。本研究共纳入993例患者,其中大多数接受索磷布韦联合达卡他韦治疗(95%),索磷布韦联合达卡他韦及利巴韦林治疗(4%),索磷布韦联合利巴韦林治疗(1%)。慢性肝炎病例占96%,代偿期肝硬化病例占3%,失代偿期肝硬化病例占1%。基因型3(99.6%)是最常见的基因型。所有治疗方案12周后的总体SVR为98%。索磷布韦联合达卡他韦治疗的SVR12较高(98.5%),其次是索磷布韦联合达卡他韦及利巴韦林治疗(90.2%)和索磷布韦联合利巴韦林治疗(75%)。慢性丙型肝炎患者的SVR率(98.2%)高于肝硬化患者(92.1%),初治患者的SVR率(98.8%)高于曾接受干扰素治疗的患者(90.1%)。在多变量二元逻辑回归分析中,患者的教育程度、治疗策略、病毒载量和丙氨酸氨基转移酶与12周时的SVR有统计学显著关联。未发生需要停药治疗的重大不良事件。通用型口服直接抗病毒药物(索磷布韦联合达卡他韦)在这一大型基因型3感染患者的真实世界队列中实现了较高的SVR12率,且耐受性良好。