Department of Virology, National Reference Center for Viral Hepatitis B, C and D, Hôpital Henri Mondor (AP-HP), Université Paris-Est, Créteil, France.
Team "Viruses, Hepatology, Cancer", Institut Mondor de Recherche Biomédicale, INSERM U955, Université Paris-Est, Créteil, France.
Hepatology. 2023 Aug 1;78(2):607-620. doi: 10.1097/HEP.0000000000000379. Epub 2023 Apr 1.
Suboptimal rates of sustained virological response have been reported in patients infected with an "unusual," non-1a/1b HCV genotype 1 subtype. The objectives of this study were to assess the proportion of non-1a/1b genotype 1 subtypes in a population of HCV-infected patients who failed to achieve sustained virological response after first-line direct-acting antiviral treatment, to virologically characterize their failures and to assess their outcomes on retreatment.
Samples addressed between January 2015 and December 2021 to the French National Reference Center for Viral Hepatitis B, C, and D were prospectively analyzed by means of Sanger and deep sequencing. Among 640 failures, 47 (7.3%) occurred in patients infected with an "unusual" genotype 1 subtype. Samples were available in 43 of them; 92.5% of these patients were born in Africa. Our results show the presence at baseline and at treatment failure of NS3 protease and/or NS5A polymorphisms conferring inherent reduced susceptibility to direct-acting antivirals in these patients, together with the presence at failure of additional resistance-associated substitutions not naturally present as dominant species, but jointly selected by first-line therapy.
Patients infected with "unusual" HCV genotype 1 subtypes are over-represented among direct-acting antiviral treatment failures. Most of them were born and likely infected in sub-Saharan Africa. "Unusual" HCV genotype 1 subtypes naturally carry polymorphisms that confer reduced susceptibility to the drugs currently used to cure hepatitis C, in particular the NS5A inhibitors. Retreatment with sofosbuvir plus an NS3 protease and an NS5A inhibitor is generally efficacious.
在感染“非典型”非 1a/1b 丙型肝炎病毒 (HCV) 1 型亚型的患者中，持续病毒学应答率较低。本研究的目的是评估未能在一线直接作用抗病毒治疗后达到持续病毒学应答的 HCV 感染患者中非 1a/1b 1 型亚型的比例，对其失败的病毒学特征进行描述，并评估其再治疗的结局。
2015 年 1 月至 2021 年 12 月，法国国家乙型肝炎、丙型肝炎和丁型肝炎病毒参考中心前瞻性地对 addressed 样本进行了 Sanger 和深度测序分析。在 640 例失败中，47 例（7.3%）发生在感染“非典型”1 型亚型的患者中。其中 43 例样本可用；这些患者中有 92.5%出生于非洲。我们的结果显示，在基线和治疗失败时，这些患者的 NS3 蛋白酶和/或 NS5A 多态性赋予了对直接作用抗病毒药物的固有低敏感性，此外，在失败时还存在非自然存在的、但由一线治疗共同选择的额外耐药相关替代物。
在直接作用抗病毒治疗失败的患者中，“非典型”HCV 1 型亚型感染患者的比例过高。他们大多出生并可能在撒哈拉以南非洲感染。“非典型”HCV 1 型亚型天然携带赋予对目前用于治疗丙型肝炎的药物（特别是 NS5A 抑制剂）低敏感性的多态性。索磷布韦联合 NS3 蛋白酶和 NS5A 抑制剂的再治疗通常是有效的。
