Department of Hepatology, Hôpital Henri Mondor, Université Paris-Est.
INSERM U955, Team "Viruses, Hepatology, Cancer", Institut Mondor de Recherche Biomédicale (IMRB).
Eur J Gastroenterol Hepatol. 2021 Dec 1;33(1S Suppl 1):e191-e196. doi: 10.1097/MEG.0000000000002003.
Patients with inherited blood disorders (IBLD) have a high risk of hepatitis C virus (HCV) infection. The aim of this work was to assess the efficacy and safety of HCV direct-acting antiviral (DAA)-based treatment in patients with IBLD and chronic HCV infection.
Twenty-seven patients (25 with sickle cell disease, 1 with β-thalassemia and 1 with hemoglobin D-Punjab), including 3 with compensated cirrhosis, were included. They were treated with sofosbuvir in combination with ribavirin, daclatasvir, ledipasvir, or velpatasvir or with grazoprevir/elbasvir for 8 or 12 weeks. In the case of treatment failure, in-vitro assessment of resistance-associated substitutions (RASs) and full-length genome sequence analysis by means of deep sequencing were performed.
Treatment was safe and well-tolerated and there were no drug discontinuations due to DAA-related adverse events. Twenty-five out of the 27 patients (93%) achieved sustained virological response 12 weeks post-treatment. One patient discontinued after 18 days due to adverse events unrelated to the antiviral treatment. One patient infected with 'unusual' genotype 2 subtype 2m relapsed. Subtype 2m naturally carries the NS5A L31M RAS. In a genotype 2a subgenomic replicon model, L31M increased daclatasvir effective concentration 50% (EC50) by 97-fold, but velpatasvir EC50 by only 3-fold, without altering the replication capacity. This patient was successfully retreated with sofosbuvir/velpatasvir for 12 weeks.
DAA-based regimens are well tolerated and highly efficacious in patients with chronic hepatitis C and IBLD in the real-world setting. Thus, DAA-based antiviral treatment should be prioritized in this thus far neglected population of HCV-infected patients.
遗传性血液疾病（IBLD）患者感染丙型肝炎病毒（HCV）的风险较高。本研究旨在评估以直接作用抗病毒药物（DAA）为基础的 HCV 治疗方案在 IBLD 合并慢性 HCV 感染患者中的疗效和安全性。
共纳入 27 例患者（25 例镰状细胞病、1 例β-地中海贫血和 1 例血红蛋白 D-Punjab 患者），其中 3 例为代偿性肝硬化，接受索非布韦联合利巴韦林、达卡他韦、来迪派韦或维帕他韦或格拉瑞韦/艾尔巴韦治疗 8 或 12 周。治疗失败时，进行耐药相关取代（RAS）的体外评估和采用深度测序进行全长基因组序列分析。
治疗安全且耐受良好，无因 DAA 相关不良事件而停药的情况。27 例患者中有 25 例（93%）在治疗结束后 12 周时达到持续病毒学应答。1 例患者因与抗病毒治疗无关的不良事件在 18 天后停药。1 例感染“罕见”基因型 2 亚型 2m 的患者复发。2m 亚型天然携带 NS5A L31M RAS。在基因型 2a 亚基因组复制子模型中，L31M 使达卡他韦 EC50 增加 97 倍，但使维帕他韦 EC50 仅增加 3 倍，而不改变复制能力。该患者成功地接受了 12 周的索非布韦/维帕他韦治疗。
在真实世界环境中，DAA 方案治疗慢性丙型肝炎和 IBLD 患者的耐受性良好，疗效高。因此，在迄今为止被忽视的 HCV 感染患者中，应优先考虑 DAA 为基础的抗病毒治疗。
