Glecaprevir and Pibrentasvir in Patients with HCV and Severe Renal Impairment
Glecaprevir and Pibrentasvir in Patients with HCV and Severe Renal Impairment
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DOI：
10.1056/nejmoa1704053
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发表时间：
2017-10-12
影响因子：
158.5
通讯作者：
Mensa, Federico J.
中科院分区：
文献类型：
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作者：
Gane, Edward;Lawitz, Eric;Mensa, Federico J.
慢性丙型肝炎病毒（HCV）感染在慢性肾脏疾病患者中比那些没有这种疾病的患者更普遍。同时感染HCV的慢性肾脏病患者进展为终末期肾脏病的风险高于未感染HCV的慢性肾脏病患者。HCV感染和晚期慢性肾脏病患者的治疗选择有限。METHODS我们进行了一项多中心、开放标签、3期试验，以评估NS 3/4A蛋白酶抑制剂glecaprevir和NS 5A抑制剂pibentasvir联合治疗12周的HCV基因型为1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、1或6例感染，并且还患有代偿性肝病（伴或不伴肝硬化）伴严重肾损害、依赖透析或两者兼有。患者患有4期或5期慢性肾脏疾病，既往未接受过HCV感染治疗，或既往接受过干扰素或聚乙二醇干扰素、利巴韦林、索非布韦或这些药物的联合治疗。主要终点是治疗结束后12周的持续病毒学应答。在104例入组试验的患者中，52%为基因型1感染，16%为基因型2感染，11%为基因型3感染，19%为基因型4感染，2%为基因型5或6感染。持续病毒学应答率为98%（104例患者中有102例; 95%置信区间为95 - 100）。治疗期间没有患者出现病毒学失败，治疗结束后也没有患者出现病毒学复发。至少10%的患者报告的不良事件为瘙痒、疲乏和恶心。24%的患者报告了严重不良事件。四名患者停止试验治疗过早，因为不良事件，其中三名患者有持续的病毒学respons. CONCLUSIONSTtreatment与glecaprevir和pibentasvir为12周导致持续的病毒学应答率高，在4期或5期慢性肾脏疾病和HCV感染的患者。
BACKGROUNDChronic hepatitis C virus (HCV) infection is more prevalent among patients who have chronic kidney disease than among those who do not have the disease. Patients with chronic kidney disease who also have HCV infection are at higher risk for progression to end-stage renal disease than those who have chronic kidney disease without HCV infection. Patients with both HCV infection and advanced chronic kidney disease have limited treatment options.METHODSWe conducted a multicenter, open-label, phase 3 trial to evaluate the efficacy and safety of treatment with the combination of the NS3/4A protease inhibitor glecaprevir and the NS5A inhibitor pibrentasvir for 12 weeks in adults who had HCV genotype 1, 2, 3, 4, 5, or 6 infection and also had compensated liver disease (with or without cirrhosis) with severe renal impairment, dependence on dialysis, or both. Patients had stage 4 or 5 chronic kidney disease and either had received no previous treatment for HCV infection or had received previous treatment with interferon or pegylated interferon, ribavirin, sofosbuvir, or a combination of these medications. The primary end point was a sustained virologic response 12 weeks after the end of treatment.RESULTSAmong the 104 patients enrolled in the trial, 52% had genotype 1 infection, 16% had genotype 2 infection, 11% had genotype 3 infection, 19% had genotype 4 infection, and 2% had genotype 5 or 6 infection. The sustained virologic response rate was 98% (102 of 104 patients; 95% confidence interval, 95 to 100). No patients had virologic failure during treatment, and no patients had a virologic relapse after the end of treatment. Adverse events that were reported in at least 10% of the patients were pruritus, fatigue, and nausea. Serious adverse events were reported in 24% of the patients. Four patients discontinued the trial treatment prematurely because of adverse events; three of these patients had a sustained virologic response.CONCLUSIONSTreatment with glecaprevir and pibrentasvir for 12 weeks resulted in a high rate of sustained virologic response in patients with stage 4 or 5 chronic kidney disease and HCV infection.