Infectious Diseases Unit, Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.
Imam Abdulrahman Bin Faisal University, College of Applied Studies and Community Service, Department of marketing, KSA.
New Microbiol. 2021 Jan;44(1):12-18. Epub 2020 Dec 16.
Currently, treatment of chronic hepatitis C is based on a combination of direct-acting antiviral agents (DAAs) which achieve HCV clearance in more than 95% of patients. Despite this high rate of cure, treatment failures can occur in about 3-5% of treated patients. Resistance associated substitutions (RAS) are commonly detected after virological failure, although their role in real-life DAA failures is still debated. This study aimed to evaluate in real-life DAA-failing patients the prevalence of clinically relevant RASs for the different DAA classes and to identify possible predictors. Fifty consecutive HCV-infected patients who experienced a virological failure to a DAA-containing regimen were included in the study. Direct sequencing of HCV regions involved in DAA resistance (NS3, NS5A and NS5B) was performed with Sanger-based homemade protocols. The presence of mutations in the NS3 and NS5A regions was statistically associated with regimens containing protease inhibitors (p<0.0032) and NS5A inhibitors (p<0.0006), respectively. On the contrary, for the NS5B region, the known mutations associated with the NS5B RNA polymerase inhibitors were detected in treated HCV patients, although there was no statistical significance (p>0.5). A significant correlation was found between the presence of RASs and advanced fibrosis/cirrhosis, but not with age, sex and viral load. Our study demonstrates a high frequency of RASs in patients with DAA failure, thus highlighting the usefulness of genotypic tests in this setting. The identification of RASs may guide the choice of the most appropriate drugs for HCV re-treatment.
目前，慢性丙型肝炎的治疗基于直接作用抗病毒药物（DAAs）的联合治疗，该治疗方案在超过 95%的患者中实现了 HCV 清除。尽管治愈率如此之高，但在约 3-5%的治疗患者中仍会发生治疗失败。尽管在现实生活中的 DAA 失败中仍存在争议，但在病毒学失败后通常会检测到与耐药相关的替代（RAS）。本研究旨在评估现实生活中 DAA 失败患者中不同 DAA 类别的临床相关 RAS 的流行率，并确定可能的预测因素。本研究纳入了 50 例因 DAA 方案治疗而发生病毒学失败的 HCV 感染患者。使用基于 Sanger 的自制方案对 HCV 耐药相关区域（NS3、NS5A 和 NS5B）进行直接测序。NS3 和 NS5A 区域的突变的存在与包含蛋白酶抑制剂（p<0.0032）和 NS5A 抑制剂（p<0.0006）的方案分别具有统计学相关性。相反，对于 NS5B 区域，尽管没有统计学意义（p>0.5），但在接受治疗的 HCV 患者中检测到与 NS5B RNA 聚合酶抑制剂相关的已知突变。在存在 RAS 的情况下，发现 RAS 与晚期纤维化/肝硬化显著相关，但与年龄、性别和病毒载量无关。本研究表明，在 DAA 治疗失败的患者中，RAS 的出现频率很高，因此突出了在这种情况下进行基因分型检测的有用性。RAS 的鉴定可能有助于指导 HCV 再治疗的最适药物选择。
