Michels Fernanda Bellini Lunardi, Amaral Ana Cristina de Castro, Carvalho-Filho Roberto José de, Vieira Gustavo de Almeida, Souza Ana Lucia da Silva, Ferraz Maria Lucia Gomes
Universidade Federal de São Paulo (UNIFESP), Disciplina de Gastroenterologia, São Paulo, SP, Brasil.
Arq Gastroenterol. 2020 Jan-Mar;57(1):45-49. doi: 10.1590/S0004-2803.202000000-09.
Direct-acting antivirals have revolutionized hepatitis C treatment, also for patients with chronic kidney disease (CKD), but some controversy exists regarding the use of sofosbuvir (SOF) in patients with glomerular filtration rate (GFR) <30 mL/min.
To evaluate the efficacy and safety of these regimens for hepatitis C treatment of patients with CKD and after renal transplantation, as well as the impact of SOF on renal function in non-dialysis patients.
All patients with hepatitis C and CKD or renal transplant treated with direct-acting antivirals at a referral center in Brazil between January 2016 and August 2017 were included. Efficacy was evaluated based on viral load (HCV RNA) and a sustained virological response (SVR) consisting of undetectable RNA 12 and/or 24 weeks after the end of treatment (SVR12 and SVR24) was defined as cure. Safety was determined by adverse events and ribavirin, when combined, was administered in escalating doses to all patients with GFR <60 mL/min. The impact of SOF on renal function was determined by the measurement of baseline creatinine during and after the end of treatment and its increase was evaluated using the Acute Kidney Injury Network (AKIN) classification.
A total of 241 patients (52.7% females) with a mean age of 60.72±10.47 years were included. The combination of SOF+daclatasvir was the predominant regimen in 75.6% of cases and anemia was present in 28% of patients who used ribavirin (P=0.04). The SVR12 and SVR24 rates were 99.3% and 97.1%, respectively. The treatment was well tolerated and there were no major clinically relevant adverse events, with the most prevalent being asthenia (57.7%), itching (41.1%), headache (40.7%), and irritability (40.2%). Among conservatively treated and renal transplant patients, oscillations of creatinine levels (AKIN I) were observed in 12.5% of cases during treatment and persisted in only 8.5% after the end of treatment. Of these, 2.0% had an initial GFR <30 mL/min and this percentage decreased to 1.1% after SOF use. Only 0.5% and 1.6% of the patients progressed to AKIN II and AKIN III elevation, respectively.
The direct-acting antivirals were safe and efficacious in CKD patients treated with SOF-containing regimens, with the observation of high SVR rates, good tolerability and few severe adverse events. The combination with ribavirin increased the risk of anemia and the administration of escalating doses seems to be useful in patients with GFR <60 mL/min. In patients with GFR <30 mL/min, SOF had no significant renal impact, with serum creatinine returning to levels close to baseline after treatment.
直接作用抗病毒药物彻底改变了丙型肝炎的治疗方式，对慢性肾脏病（CKD）患者亦是如此，但对于肾小球滤过率（GFR）<30 mL/分钟的患者使用索磷布韦（SOF）仍存在一些争议。
评估这些方案对CKD患者及肾移植后丙型肝炎治疗的疗效和安全性，以及SOF对非透析患者肾功能的影响。
纳入2016年1月至2017年8月在巴西一家转诊中心接受直接作用抗病毒药物治疗的所有丙型肝炎合并CKD或肾移植患者。根据病毒载量（HCV RNA）评估疗效，治疗结束后12周和/或24周RNA检测不到（SVR12和SVR24）组成的持续病毒学应答（SVR）定义为治愈。通过不良事件确定安全性，对于所有GFR<60 mL/分钟的患者，联合使用利巴韦林时采用递增剂量给药。通过治疗期间和治疗结束后测量基线肌酐来确定SOF对肾功能的影响，并使用急性肾损伤网络（AKIN）分类评估肌酐升高情况。
共纳入241例患者（52.7%为女性），平均年龄60.72±10.47岁。75.6%的病例中SOF+达卡他韦联合方案占主导，使用利巴韦林的患者中有28%出现贫血（P=0.04）。SVR12和SVR24率分别为99.3%和97.1%。治疗耐受性良好，未出现重大临床相关不良事件，最常见的是乏力（57.7%）、瘙痒（41.1%）、头痛（40.7%）和易怒（40.2%）。在保守治疗和肾移植患者中，治疗期间12.5%的病例观察到肌酐水平波动（AKIN I），治疗结束后仅8.5%持续存在。其中，2.0%的患者初始GFR<30 mL/分钟，使用SOF后该比例降至1.1%。分别仅有0.5%和1.6%的患者进展为AKIN II和AKIN III升高。
直接作用抗病毒药物在接受含SOF方案治疗的CKD患者中安全有效，观察到高SVR率、良好耐受性和极少严重不良事件。与利巴韦林联合增加了贫血风险，递增剂量给药似乎对GFR<60 mL/分钟的患者有用。在GFR<30 mL/分钟的患者中，SOF对肾功能无显著影响，治疗后血清肌酐恢复至接近基线水平。
