Kileng Hege, Kjellin Midori, Akaberi Dario, Bergfors Assar, Duberg Ann-Sofi, Wesslén Lars, Danielsson Astrid, Gangsøy Kristiansen Magnhild, Gutteberg Tore, Goll Rasmus, Lannergård Anders, Lennerstrand Johan
a Department of Clinical Medicine, Gastroenterology and Nutrition Research Group , UiT The Arctic University of Norway , Tromsø , Norway.
b Department of Medicine , University Hospital of North Norway , Tromsø , Norway.
Scand J Gastroenterol. 2018 Oct-Nov;53(10-11):1347-1353. doi: 10.1080/00365521.2018.1511824. Epub 2018 Nov 5.
Resistance-associated substitutions (RASs) may impair treatment response to direct-acting antivirals (DAA) in hepatitis C virus (HCV) treatment. We investigated the effects of baseline NS3-RASs (Q80K and R155K) and clinically relevant NS5A-RASs in patients with HCV genotype (GT) 1a infection on treatment outcome, with or without resistance-based DAA-treatment. This multi-center study was carried out between 2014 and 2016.
PATIENTS/METHODS: Treatment in the intervention group (n = 92) was tailored to baseline resistance. Detection of NS3-RAS led to an NS5A-inhibitor-based regimen and detection of NS5A-RAS to a protease-inhibitor regimen. Patients without baseline RAS in the intervention group and all patients in the control group (n = 101) received recommended standard DAA-treatment.
The sustained virologic response rates (SVR) in the intervention and control groups were 97.8% (90/92) and 93.1% (94/101), respectively (p = .174). A trend toward higher SVR-rate in cirrhotic patients (p = .058) was noticed in the intervention group compared to the control group with SVR-rates 97.5% (39/40) and 83.3% (35/42), respectively. All patients with baseline NS3 (Q80K/R155K) or NS5A-RASs in the intervention group achieved SVR with personalized resistance-based treatment. In the control group, five patients with Q80K or R155K at baseline were treated with simeprevir + sofosbuvir and treatment failed in two of them. Furthermore, one of three patients who failed ledipasvir + sofosbuvir treatment had NS5A-RASs at baseline.
In line with the findings of the OPTIMIST-2 trial for Q80K and the EASL-guidelines 2016 for NS5A-RASs, baseline RASs appeared to have an impact on treatment outcome albeit a statistical significance was not observed in this low-prevalence population.
在丙型肝炎病毒（HCV）治疗中，耐药相关替代位点（RASs）可能会削弱对直接抗病毒药物（DAA）的治疗反应。我们研究了HCV基因1a型（GT1a）感染患者中基线NS3-RASs（Q80K和R155K）以及临床相关NS5A-RASs对治疗结果的影响，无论是否采用基于耐药性的DAA治疗。这项多中心研究于2014年至2016年开展。
患者/方法：干预组（n = 92）的治疗根据基线耐药情况进行调整。检测到NS3-RAS会采用基于NS5A抑制剂的治疗方案，检测到NS5A-RAS则采用蛋白酶抑制剂治疗方案。干预组中无基线RAS的患者以及对照组（n = 101）的所有患者均接受推荐的标准DAA治疗。
干预组和对照组的持续病毒学应答率（SVR）分别为97.8%（90/92）和93.1%（94/101）（p = 0.174）。与对照组相比，干预组中肝硬化患者的SVR率有升高趋势（p = 0.058），干预组和对照组的SVR率分别为97.5%（39/40）和83.3%（35/42）。干预组中所有基线存在NS3（Q80K/R155K）或NS5A-RASs的患者通过个性化的基于耐药性的治疗均实现了SVR。在对照组中，5例基线存在Q80K或R155K的患者接受了simeprevir + sofosbuvir治疗，其中2例治疗失败。此外，在接受ledipasvir + sofosbuvir治疗失败的3例患者中，有1例基线存在NS5A-RASs。
与OPTIMIST - 2试验中关于Q80K的研究结果以及2016年欧洲肝脏研究学会（EASL）指南中关于NS5A-RASs的研究结果一致，尽管在这个低流行率人群中未观察到统计学意义，但基线RASs似乎对治疗结果有影响。
