Lancet:终末期慢性肾病患者的HCV感染有救了！

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Ⅳ或Ⅴ期慢性肾脏病人群比一般人群更易感染丙型肝炎病毒（HCV）。丙型肝炎病毒传播包括院内透析、输血（主要是过去）、移植（供体已被感染）。

透析中感染丙型肝炎病毒是引起患者死亡的巨大独立危险因素。而透析患者对干扰素和利巴韦林（PEG）的持续病毒应答（SVR）率很低，在35%左右，同时其耐受性差。不幸的是，Ⅳ或Ⅴ期的慢性肾病几乎被所有抗病毒药物的临床控制试验排除在外。

David Roth和他的同事在柳叶刀上报道了有3期研究的C-SURFER的第一个结果。他们招募了235名Ⅳ或Ⅴ期慢性肾脏病患者，其同时被HCV基因1型感染，患有慢性丙型肝炎（1型基因型：透析患者中最常见的被感染型），其中76%例血液透析，6%例肝硬化，80%例慢性丙型肝炎患者。患者被随机分配到两组：立即治疗组111例，延迟治疗组113例，每日一次口服结合grazoprevir（一种干扰素）100mg和elbasvir（立韦巴林）50mg，共12周。此外，有11例患者分配到一个密集的药代动力学组。

David Roth和他的同事发现立即治疗组，无论是否做了强化药代动力学研究（n = 122）：12周的持续病毒反应（SVR12）为99%（95% CI 95.3–100.0）。由此可见，治愈Ⅳ或Ⅴ期慢性肾脏病感染丙型肝炎病毒（至少对基因型1）的手段出现了。耐受性方面的研究也令人印象深刻：没有因为副作用而撤出的案例。

利用grazoprevir和elbasvir将治愈很大一部分感染HCV的Ⅳ或Ⅴ期慢性肾病病人。另外，是时候消灭存在于透析装置中的丙型肝炎病毒了。通过这种预防和治疗相结合治愈方式是最佳的方式，而不只是通过治疗实现治愈。这种基本有效的血液透析装置的应用，已经不能满足于期待已久的高活性抗丙型肝炎病毒药物的出现了。

来源：mdesci

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Grazoprevir plus elbasvir in treatment-naive and treatment-experienced patients with hepatitis C virus genotype 1 infection and stage 4–5 chronic kidney disease (the C-SURFER study): a combination phase 3 study

Dr David Roth, MDa, , , David R Nelson, MDb, Annette Bruchfeld, MDc, AnnMarie Liapakis, MDd, Marcelo Silva, MDe, Howard Monsour Jr, MDf, Paul Martin, MDg, Stanislas Pol, MDh, Maria-Carlota Londoño, MDi, Tarek Hassanein, MDj, Philippe J Zamor, MDk, Eli Zuckerman, MDl, Shuyan Wan, PhDm, Beth Jackson, MLASm, Bach-Yen Nguyen, MDm, Michael Robertson, MDm, Eliav Barr, MDm, Janice Wahl, MDm, Wayne Greaves, MDm

Background
Chronic hepatitis C virus (HCV) infection in patients with stage 4–5 chronic kidney disease increases the risk of death and renal graft failure, yet patients with hepatitis C and chronic kidney disease have few treatment options. This study assesses an all-oral, ribavirin-free regimen in patients with HCV genotype 1 infection and stage 4–5 chronic kidney disease.

Methods
In this phase 3 randomised study of safety and observational study of efficacy, patients with HCV genotype 1 infection and chronic kidney disease (stage 4–5 with or without haemodialysis dependence) were randomly assigned to receive grazoprevir (100 mg, NS3/4A protease inhibitor) and elbasvir (50 mg, NS5A inhibitor; immediate treatment group) or placebo (deferred treatment group) once daily for 12 weeks. Randomisation was done centrally with an interactive voice response system. An additional cohort of patients who were not randomised received the same regimen open-label and underwent intensive pharmacokinetic sampling. The primary efficacy outcome was a non-randomised comparison of sustained virological response at 12 weeks (SVR12) after the end of therapy for the combined immediate treatment group and the pharmacokinetic population with a historical control. The primary safety outcome was a randomised comparison between the immediate treatment group and the deferred treatment group. After 4 weeks of follow-up (study week 16), unmasking occurred and patients in the deferred treatment group received grazoprevir and elbasvir. The primary efficacy hypothesis was tested at a two-sided significance level (type I error) of 0·05 using an exact test for a binomial proportion. Safety event rates were compared between immediate treatment and deferred treatment groups using the stratified Miettinen and Nurminen method with baseline dialysis status as the strata. The study is registered at ClinicalTrials.gov, number NCT02092350.

Findings
224 patients were randomly assigned to the immediate treatment group with grazoprevir and elbasvir (n=111) or the deferred treatment group (n=113), and 11 were assigned to the intensive pharmacokinetic population. Overall, 179 (76%) were haemodialysis-dependent, 122 (52%) had HCV genotype 1a infection, 189 (80%) were HCV treatment-naive, 14 (6%) were cirrhotic, and 108 (46%) were African American. Of the 122 patients receiving grazoprevir and elbasvir, six were excluded from the primary efficacy analysis for non-virological reasons (death, lost-to-follow-up [n=2], non-compliance, patient withdrawal, and withdrawal by physician for violent behaviour). No patients in the combined immediate treatment group and intensive pharmacokinetic population and five (4%) in the deferred treatment group discontinued because of an adverse event. Most common adverse events were headache, nausea, and fatigue, occurring at similar frequencies in patients receiving active and placebo drugs. SVR12 in the combined immediate treatment group and intensive pharmacokinetic population was 99% (95% CI 95·3–100·0; 115/116), with one relapse 12 weeks after end of treatment when compared with a historical control of 45%, based on meta-analyses of interferon-based regimens used in clinical trials of patients infected with HCV who are on haemodialysis.

Interpretation
Once-daily grazoprevir and elbasvir for 12 weeks had a low rate of adverse events and was effective in patients infected with HCV genotype 1 and stage 4–5 chronic kidney disease.

http://www.sciencedirect.com/sci ... i/S0140673615003499