Tavares Rita Chelly Felix, de Castro Amaral Feldner Ana Cristina, Pinho João Renato Rebello, de Mello Malta Fernanda, Carvalho-Filho Roberto José, Santana Rúbia Anita Ferraz, de Castro Vanessa Fusco Duarte, Dastoli Gregório Tadeu Fernando, Lima Juliana Custódio, Ferraz Maria Lucia Cardoso Gomes
Gastroenterology Division, Federal University of Sao Paulo, São Paulo, SP, Brazil,
Albert Einstein Diagnostic Medicine, Albert Einstein Hospital São Paulo, SP, Brazil.
Infect Drug Resist. 2018 Oct 25;11:1993-2000. doi: 10.2147/IDR.S169512. eCollection 2018.
Direct-acting antiviral agents (DAAs) permit the use of interferon (IFN)-free regimens to treat hepatitis C (HCV) in patients with chronic kidney disease (CKD) on hemo-dialysis (HD) or renal transplant (RTx) recipients, with excellent response rates and safety. However, the occurrence of basal or therapy-induced resistance-associated substitutions (RASs) to DAAs can result in treatment failure. The aim of this study was to estimate the prevalence of RASs to NS3A, NS5A and NS5B inhibitors, and particularly the Q80K polymorphism, in CKD patients on HD and RTx recipients infected with HCV.
HD and RTx patients infected with HCV-genotype 1 (GT1) were subjected to sequencing of the NS3, NS5A and NS5B regions.
Direct sequencing of NS3 protease, NS5A and NS5B was performed in 76 patients (HD, n=37; RTx, n=39). The overall prevalence of RASs was 38.2%, but only 5.3% of the patients had mutations in more than one region. Substitutions were detected in NS3A (17.8%), NS5A (21.9%) and NS5B (8.4%). Q80K was detected in 1.5 % of the patients. Highly inhibitory RASs were uncommon (L31M, 2.6%; L159+C316N, 2.6%). RASs were more prevalent in HCV-GT1a (42.9%) than in HCV-GT1b (32.4%), =0.35. RASs were detected in 52.4% of treatment-naive patients and 27.8% of peg-IFN/ribavirin-experienced patients (=0.12). The presence of RASs was associated with time of RTx (=0.01).
The Q80K polymorphism was uncommon in our sample of HD and RTx patients. Despite the high prevalence of naturally occurring RASs, most of the substitutions detected were associated with a low level of resistance to DAAs.
直接抗病毒药物（DAAs）使无干扰素方案可用于治疗接受血液透析（HD）的慢性肾脏病（CKD）患者或肾移植（RTx）受者中的丙型肝炎（HCV），疗效和安全性均佳。然而，对DAAs出现的基础或治疗诱导的耐药相关替代（RASs）可导致治疗失败。本研究的目的是评估HD和RTx受者中感染HCV的CKD患者对NS3A、NS5A和NS5B抑制剂的RASs流行率，尤其是Q80K多态性。
对感染HCV基因1型（GT1）的HD和RTx患者进行NS3、NS5A和NS5B区域测序。
对76例患者（HD患者37例，RTx患者39例）进行了NS3蛋白酶、NS5A和NS5B的直接测序。RASs的总体流行率为38.2%，但只有5.3%的患者在一个以上区域存在突变。在NS3A（17.8%）、NS5A（21.9%）和NS5B（8.4%）中检测到替代。1.5%的患者检测到Q80K。高抑制性RASs不常见（L31M，2.6%；L159+C316N，2.6%）。RASs在HCV-GT1a（42.9%）中比在HCV-GT1b（32.4%）中更普遍，P=0.35。在52.4%的初治患者和27.8%的接受聚乙二醇干扰素/利巴韦林治疗的患者中检测到RASs（P=0.12）。RASs的存在与RTx时间有关（P=0.01）。
在我们的HD和RTx患者样本中，Q80K多态性不常见。尽管自然发生的RASs流行率较高，但检测到的大多数替代与对DAAs的低水平耐药有关。
