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Resistance-associated substitutions (RASs) to HCV direct-acting antivirals (DAAs) at baseline of treatment in thalassemia patients: a referral center study.

地中海贫血患者治疗基线时HCV直接作用抗病毒药物 (DAAs) 的耐药相关替代 (RASs): 一项转诊中心研究。

  • 影响因子:2.16
  • DOI:10.1007/s00705-020-04728-x
  • 作者列表:"Safarnezhad Tameshkel F","Karbalaie Niya MH","Zamani F","Motamed N","Ajdarkosh H","Vafaeimanesh J","Khoonsari M","Sohrabi MR","Aten S","Azarkeivan A","Eslami MS","Perumal D","Maadi M","Ghanbari B","Keyvani H
  • 发表时间:2020-10-01
Abstract

:Patients with thalassemia major are at high risk of hepatitis C through blood transfusion from donors infected by hepatitis C virus (HCV). The use of direct-acting antiviral (DAA) therapy against such HCV infections has increased in different populations. However, resistant viral variants can affect treatment outcomes, and therefore improved surveillance strategies are needed. Accordingly, we aimed to evaluate resistance-associated substitutions (RASs) to HCV DAAs at the baseline of treatment in thalassemia patients in a referral center. Out of 89 thalassemia patients who suffered from HCV infection and were referred to our center between 2016 and 2017, 43 underwent further analysis of the HCV nonstructural proteins NS5A and NS5B using polymerase chain reaction (PCR) sequencing methods. Unique primers were designed using bioinformatics software for separate detection of HCV subtypes 1a, 3a, and 1b. Detection of RASs was performed based on previously published literature. Statistical analysis was carried out using SPSS version 19. The participants, 60.4% (26/43) of whom were male, had a mean age ± standard deviation (SD) of 33.0 ± 5.0 years. HCV subtype 1a was found in 27 cases, 3a in 13, and 1b in three. In HCV subtype 1a there were 163 mutations in NS5A and 212 mutations in NS5B. The frequency of RASs was 20.9% (8 RASs in 9 patients), including M28V and H58P in subtype 1a, L28M, R30Q, C316N, and C316S in subtype 1b, and S24F in subtype 3a. Statistically, the subtype 1b and a higher mutation rate in NS5A were associated with RASs (p-value < 0.05). The emergence of natural RASs to HCV DAAs serves as a warning of the risk of drug resistance in response to the broad usage of antivirals. However, relapses in these DAA-treated HCV-infected thalassemia patients are rarely reported. Our findings indicate that the prevalence of RASs prevalence at baseline was 20.9% in these patients, and this calls for extrapolation to a larger population study, as highlighted in other studies, with larger sample sizes, high-throughput methods, and follow-up in order to fully evaluate treatment outcomes in RASs-detected individuals. Optimized therapeutic strategies, particularly in complex, difficult-to-cure patients, can effectively prevent DAA treatment failure as a result of selection for RASs.

摘要

: 重型地中海贫血患者通过丙型肝炎病毒 (HCV) 感染的献血者输血,是丙型肝炎的高危人群。针对此类HCV感染的直接作用抗病毒 (DAA) 疗法的使用在不同人群中增加。然而,耐药病毒变体可能影响治疗结果,因此需要改进监测策略。因此,我们旨在评估转诊中心地中海贫血患者治疗基线时对HCV daa的耐药相关替代 (RASs)。在2016年至2017年期间被转诊至本中心的89例患有HCV感染的地中海贫血患者中,43例使用聚合酶链反应 (PCR) 测序方法对HCV非结构蛋白NS5A和NS5B进行了进一步分析。使用生物信息学软件设计独特的引物,用于单独检测HCV亚型1a、3a和1b。基于先前发表的文献进行RASs的检测。使用SPSS版本19进行统计分析。参与者中60.4% 名 (26/43) 为男性,平均年龄 ± ± 标准差 (SD) 为33.0 ± ± 5.0岁。HCV亚型1a型27例,3a型13例,1b型3例。在HCV亚型1a中,NS5A中有163个突变,NS5B中有212个突变。RASs的频率为20.9% (9例患者中8例RASs),包括亚型1a中的M28V和H58P,亚型1b中的L28M、R30Q、C316N和C316S,亚型3a中的S24F。统计学上,NS5A中的亚型1b和更高的突变率与RASs相关 (p-值   <0.05)。针对HCV daa的天然RASs的出现作为响应于抗病毒药物的广泛使用的耐药性风险的警告。然而,在这些DAA治疗的HCV感染的地中海贫血患者中复发的报道很少。我们的研究结果表明,在这些患者中,基线RASs患病率为20.9%,这需要推断为更大的人群研究,正如其他研究中强调的那样,具有更大的样本量,高通量方法,和随访,以便充分评估RASs检测个体的治疗结果。优化的治疗策略,特别是在复杂、难以治愈的患者中,可以有效地防止由于RASs的选择而导致的DAA治疗失败。

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