Hepatology Department, Université Paris Descartes, Cochin hospital, APHP, Paris, France.
INSERM U1223 and Center for Translational Science, Institut Pasteur, Paris, France.
Liver Int. 2018 Feb;38 Suppl 1:28-33. doi: 10.1111/liv.13626.
BACKGROUND & AIMS: The recommended combination of pangenotypic direct-acting antivirals (DAAs) for the treatment of hepatitis C virus (HCV) associates the co-formulation of 2 or 3 second-generation DAAs. In the so-called "special populations" defined as patients with chronic kidney disease (CKD), HCV/HIV co-infection, HCV/HBV co-infection and an unsuccessful previous DAA regimen, these combinations have a high antiviral potency (sustained virologic response (SVR) > 95%), fair tolerance and a reduced pill burden.
We have taken into account the scientific evidence on the treatment of "special populations", in particular from the RUBY 1-2 trials, EXPEDITION 2-4 study, C-WORTHY trial, ASTRAL 5, POLARIS 1-4 studies, MAGELLAN 1 and REVENGE study.
CKD and HCV/HIV co-infection are not predictors of a non-viral response. The glecaprevir/pibentrasvir (Maviret) combination appears to be the first-line therapy for CKD patients while the sofosbuvir/vlpatasvir/voxaliprevir (Sovesi) combination is the first-line option for DAAs failures. Both are effective in patients with HIV-or HBV-HCV co-infection and should be chosen according to the potential drug-drug interaction profile.
The notion of "special populations" is no longer pertinent with pangenotypic DAAs combinations. International guidelines recommend treating all infected patients and the next challenge is not the therapeutic choice, but to improve the limitations for screening and access to care in HCV infection.
推荐使用泛基因型直接作用抗病毒药物(DAA)联合治疗丙型肝炎病毒(HCV),包含两种或三种第二代 DAA 的联合治疗方案。在定义为慢性肾脏病(CKD)、HCV/HIV 合并感染、HCV/HBV 合并感染和既往 DAA 方案失败的“特殊人群”中,这些组合具有很高的抗病毒效力(持续病毒学应答(SVR)>95%)、良好的耐受性和降低的药物负担。
我们考虑了治疗“特殊人群”的科学证据,特别是 RUBY 1-2 试验、EXPEDITION 2-4 研究、C-WORTHY 试验、ASTRAL 5、POLARIS 1-4 研究、MAGELLAN 1 和 REVENGE 研究。
CKD 和 HCV/HIV 合并感染不是非病毒应答的预测因素。格卡瑞韦/哌仑他韦(Maviret)联合治疗方案似乎是 CKD 患者的一线治疗选择,而索非布韦/维帕他韦/伏西瑞韦(Sovesi)联合治疗方案是 DAA 失败的首选方案。两者在 HIV 或 HBV-HCV 合并感染患者中均有效,应根据潜在的药物相互作用特征选择。
泛基因型 DAA 联合治疗方案的“特殊人群”概念已不再适用。国际指南建议治疗所有感染患者,下一个挑战不是治疗选择,而是改善 HCV 感染的筛查和获得治疗的限制。