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慢性丙型肝炎患者中对直接作用抗病毒药物耐药性的出现:一项真实世界研究。

Emergence of resistance against direct acting antivirals in chronic HCV patients: A real-world study.

作者信息

Majid Abdul, Khan Sanaullah, Siraj Sami, Haleem Sumbal, Ul Haq Najib, Ullah Riaz, Ali Essam A, Mustafa Adeela, Hussain Hidayat, Sohaib Muhammad

机构信息

Department of Zoology, Kohat University of Science and Technology, Kohat, Pakistan.

Department of Zoology, University of Peshawar, Pakistan.

出版信息

Saudi J Biol Sci. 2022 Apr;29(4):2613-2619. doi: 10.1016/j.sjbs.2021.12.044. Epub 2021 Dec 24.

Abstract

Interferon/Ribavirin therapy has been replaced by Direct Acting Antivirals (DAAs) due to emergence of Resistance Associated Variants (RAVs) and decrease Sustain Virologic Response (SVR). Current study investigated treatment response of Sofosbuvir and Ribavirin in chronic HCV patients. Total 256 HCV patients with genotype 1a, 2 and 3a received sofosbuvir/ribavirin according to international standards. HCV RNA presence in serum was used as marker for end treatment response (ETR) and sustain virologic response after 24 weeks of treatment (SVR24) in each case. Response to treatment with SOF + RBV was found statistically significant among different HCV genotypes (GT) as out of 47 HCV GT1 patients 42(89.36%) resulted into good ETR but 4(9.52%) of these relapsed and 5(10.63%) led into virologic failure. 5(100%) HCV GT2 patients resulted into SVR24 whereas, out of 204 HCV GT3 patients 194(95.69%) achieved good ETR however, 8(4.12%) of these relapsed and 10(4.90%) resulted in to virologic failure. Efficacy of therapy was found non-significant in treatment naïve and treatment experienced patients as in this study out of 145 treatment naïve patients 139(95.86%) achieved good ETR where 4(2.87%) relapsed while 6(4.13%) led into virologic break through on the other hand among 111 treatment experienced patients 102(91.89%) resulted into good ETR but 8(7.84%) relapsed whereas 9(8.10%) lead into virologic failure. Current study also propose that various liver and spleen complications/liver cirrhosis are related to response of HCV patients to SOF + RBV therapy whereas, variables like old age, gender is not compromising treatment response to DAAs therapy. Various mild side effects encountered by patients during treatment were fatigue, insomnia, headache, nausea, burning body, diarrhea, cough. Overall, this study reported 89.45% efficacy of SOF + RBV regime in chronic HCV Pakistani patients. Current study suggests hunting for possible reasons of resistance so that SOF + RBV therapy may not share the same fortune as previous therapies in near future.

摘要

由于耐药相关变异体(RAVs)的出现以及持续病毒学应答(SVR)的降低,干扰素/利巴韦林疗法已被直接抗病毒药物(DAAs)所取代。当前研究调查了索磷布韦和利巴韦林在慢性丙型肝炎患者中的治疗反应。共有256例基因型为1a、2和3a的丙型肝炎患者按照国际标准接受了索磷布韦/利巴韦林治疗。血清中丙型肝炎病毒RNA的存在被用作每种情况下治疗结束反应(ETR)和治疗24周后持续病毒学应答(SVR24)的标志物。在不同的丙型肝炎病毒基因型(GT)中,索磷布韦+利巴韦林治疗的反应具有统计学意义,在47例丙型肝炎GT1患者中,42例(89.36%)获得了良好的ETR,但其中4例(9.52%)复发,5例(10.63%)导致病毒学失败。5例(100%)丙型肝炎GT2患者获得了SVR24,而在204例丙型肝炎GT3患者中,194例(95.69%)获得了良好的ETR,然而,其中8例(4.12%)复发,10例(4.90%)导致病毒学失败。在初治和经治患者中,治疗效果无显著差异,在本研究中,145例初治患者中有139例(95.86%)获得了良好的ETR,其中4例(2.87%)复发,6例(4.13%)导致病毒学突破;另一方面,在111例经治患者中,102例(91.89%)获得了良好的ETR,但8例(7.84%)复发,9例(8.10%)导致病毒学失败。当前研究还提出,各种肝脏和脾脏并发症/肝硬化与丙型肝炎患者对索磷布韦+利巴韦林治疗的反应有关,而年龄、性别等变量并不影响对DAAs治疗的反应。患者在治疗期间遇到的各种轻微副作用包括疲劳、失眠、头痛、恶心、身体发热、腹泻和咳嗽。总体而言,本研究报告了索磷布韦+利巴韦林方案在巴基斯坦慢性丙型肝炎患者中的疗效为89.45%。当前研究建议寻找耐药的可能原因,以便索磷布韦+利巴韦林疗法在不久的将来不会与以前的疗法有相同的命运。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5d1/9072881/bd0b28ee8fa5/gr1.jpg

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