Soriano Vincent, Labarga Pablo, de Mendoza Carmen, Fernández-Montero José V, Esposito Isabella, Benítez-Gutiérrez Laura, Peña José M, Barreiro Pablo
a Infectious Diseases Unit , La Paz University Hospital , Madrid 28046 , Spain.
b Department of Internal Medicine , La Luz Clinic , Madrid 28035 , Spain.
Expert Opin Pharmacother. 2016;17(2):217-29. doi: 10.1517/14656566.2016.1112790. Epub 2015 Nov 23.
Chronic hepatitis C virus (HCV) infection has become a curable disease. More than 90% sustained virologic response rates have been obtained with 8-24 weeks of treatment with distinct combinations of direct-acting antivirals (DAA) in most registration trials. However, outcomes in real-world patients tend to be lower and treatment of special patient populations is often challenging.
We address the treatment of chronic hepatitis C with DAA in major special patient populations, such as HIV-positive persons, transplant recipients, patients with advanced cirrhosis, renal insufficiency, hepatitis B or D coinfection, injection drug users (IDUs) and prior DAA failures.
Drug interactions between DAA and medications given to persons with HIV infection or transplant recipients can result in treatment failure and adverse events. Severe organ dysfunction as in kidney insufficiency or decompensated cirrhosis may lead to DAA overexposure and toxicities. Dysfunctional social circumstances and behavior are associated to poor drug adherence and increased risk for HCV re-infection in active IDUs. Finally, DAA response might be impaired by viral interference in patients with hepatitis B or D coinfection or drug resistance in HCV either at baseline or after prior DAA failures.
慢性丙型肝炎病毒(HCV)感染已成为一种可治愈的疾病。在大多数注册试验中,使用不同组合的直接作用抗病毒药物(DAA)进行8至24周的治疗,已获得超过90%的持续病毒学应答率。然而,现实世界中患者的治疗效果往往较低,特殊患者群体的治疗通常具有挑战性。
我们探讨了在主要特殊患者群体中使用DAA治疗慢性丙型肝炎的情况,这些群体包括HIV阳性者、移植受者、晚期肝硬化患者、肾功能不全患者、乙肝或丁肝合并感染患者、注射吸毒者(IDU)以及既往DAA治疗失败者。
DAA与给予HIV感染者或移植受者的药物之间的药物相互作用可能导致治疗失败和不良事件。如肾功能不全或失代偿期肝硬化等严重器官功能障碍可能导致DAA暴露过量和毒性反应。功能失调的社会环境和行为与药物依从性差以及活跃的注射吸毒者中HCV再感染风险增加有关。最后,在乙肝或丁肝合并感染患者中,病毒干扰或在基线时或既往DAA治疗失败后HCV产生耐药性,可能会损害DAA的应答效果。