Schmitt Annika, Günther Rainer, Mauss Stefan, Boeker Klaus H W, Buggisch Peter, Hillenbrand Heribert, John Christine, Klinker Hartwig, Pathil Anita, Simon Karl-Georg, Serfert Yvonne, Niederau Claus, Vermehren Johannes, Wedemeyer Heiner, Sarrazin Christoph
St. Josefs-Hospital, Wiesbaden.
Universitätsklinikum Schleswig-Holstein (UKSH), Campus Kiel, Kiel.
Z Gastroenterol. 2020 Apr;58(4):341-351. doi: 10.1055/a-1068-3056. Epub 2020 Feb 10.
Virologic failure to approved combinations of direct antiviral agents (DAA) in patients with chronic hepatitis C virus (HCV) infection is rare. Mostly it involves difficult to treat patients with advanced liver disease and prior interferon-experience. Before approval of VOX/VEL/SOF, a restricted number of patients received rescue treatment, and the choice of DAA combinations for re-treatment were selected on an individual basis. In the present analysis, patient characteristics and rescue-regimens after virologic failure mainly based on first generation DAAs are described.
Data were obtained from the German Hepatitis C-Registry (DHC-R), which is a national multicenter real-world cohort currently including about 16 500 patients recruited by more than 250 centers. The present analysis is based on 6683 patients who initiated a DAA therapy and for whom follow-up data (per-protocol analysis) were available.
Among the patients, 188 (2.8 %) experienced a virologic relapse. Compared to SVR-patients, relapse patients were significantly more often male (77.7 % versus 56.9 %, respectively, p < 0.001), showed cirrhosis significantly more (48.4 % versus 28.1 %, respectively, p < 0.001) and a prior interferon-containing therapy (46.3 % versus 39.0 %, respectively, p = 0.049). The majority of patients who relapsed were infected with genotype 1 (47.4 %) followed by genotype 3 (29.8 %), and 95 relapse patients started DAA re-treatment. Characteristics of patients with rescue-treatment are similar to these of patients with relapse after initial DAA treatment. Thirty-one of 39 patients with complete follow-up data achieved SVR (79.5 %), and 8 patients had a relapse again (20.5 %). Patients who received rescue treatment including a new DAA class according to guidelines, except patients who received VOX/VEL/SOF, showed higher SVR rates than the entire group (21/25, 84 %). All patients who received VOX/VEL/SOF achieved SVR (n = 4, 100 %).
Patients with failure with DAA combination therapies are a difficult but urgent to treat population with the frequent presence of cirrhosis and prior treatment failure with interferon-based therapies. Rescue therapy with inclusion of a new DAA class leads to high SVR rates, but multiple targeted therapy with VOX/VEL/SOF seems to be most effective.
在慢性丙型肝炎病毒（HCV）感染患者中，经批准的直接抗病毒药物（DAA）联合治疗出现病毒学失败的情况很少见。大多数情况涉及难以治疗的晚期肝病患者以及有过干扰素治疗经历的患者。在VOX/VEL/SOF获批之前，接受挽救治疗的患者数量有限，重新治疗时DAA联合方案的选择是个体化的。在本分析中，描述了病毒学失败后基于第一代DAA的患者特征和挽救方案。
数据来自德国丙型肝炎注册中心（DHC-R），这是一个全国性的多中心真实世界队列，目前包括由250多个中心招募的约16500名患者。本分析基于6683例开始DAA治疗且有随访数据（符合方案分析）的患者。
在这些患者中，188例（2.8%）出现病毒学复发。与实现持续病毒学应答（SVR）的患者相比，复发患者男性比例显著更高（分别为77.7%和56.9%，p<0.001），肝硬化患者比例显著更高（分别为48.4%和28.1%，p<0.001），且有过含干扰素治疗经历的患者比例更高（分别为46.3%和39.0%，p=0.049）。大多数复发患者感染的是1型基因型（47.4%），其次是3型基因型（29.8%），95例复发患者开始了DAA重新治疗。接受挽救治疗患者的特征与初始DAA治疗后复发患者的特征相似。39例有完整随访数据的患者中有31例实现了SVR（79.5%），8例再次复发（20.5%）。接受包括指南中新型DAA类药物的挽救治疗的患者，除接受VOX/VEL/SOF的患者外，SVR率高于整个组（21/25，84%）。所有接受VOX/VEL/SOF的患者均实现了SVR（n=4，100%）。
DAA联合治疗失败的患者是一个治疗困难但急需治疗的群体，他们经常伴有肝硬化且既往基于干扰素的治疗失败。包含新型DAA类药物的挽救治疗可导致较高的SVR率，但使用VOX/VEL/SOF进行多靶点治疗似乎最有效。
