Fabrizi Fabrizio, Lampertico Pietro, Messa Piergiorgio
Divisione Nefrologia, Ospedale Maggiore e Fondazione IRCCS, Milano, Italia.
Divisione Gastroenterologia, Ospedale Maggiore e Fondazione IRCCS, e Università degli Studi di Milano, Italia.
G Ital Nefrol. 2018 Sep;35(5).
Hepatitis C virus infection is still common among patients with chronic kidney disease, particularly within Dialysis Units all over the world. Although the full extent of HCV transmission in dialysis units is unknown, outbreaks of HCV infection continue to occur all over the world. Evidence has been accumulated in the last decade suggesting that HCV plays consistent activity at hepatic and extra-hepatic level. A recent systematic review of the medical literature with a meta-analysis of clinical studies retrieved 15 longitudinal studies (n=2,299,134 patients) ; we found a significant relationship between anti-HCV positive serologic status and higher frequency of CKD; the summary estimate for adjusted hazard risk with HCV across the surveys, 1.54 (95% CI, 1.26; 1.87) (P<0.0001). The advent of direct-acting antiviral agents has revolutionized the therapy of HCV, including patients with advanced chronic kidney disease. Two regimens based on DAAs have been recently approved for the antiviral therapy of HCV in patients with CKD stage 4/5: elbasvir/grazoprevir and glecaprevir/pibrentasvir. Such regimens have been provided with high efficacy and safety, according to the results given by C-SURFER and EXPEDITION-4, respectively. Sofosbuvir, a non-structural 5B polymerase inhibitor, is the backbone of many anti-HCV drug regimens, and has significant renal excretion. As a result, the use of sofosbuvir is not recommended in patients with an eGFR <30 mL/min/1.73m². In summary, recent studies have shown that several combinations of DAAs are currently available for CKD patients, including those with CKD stage 4/5. These drugs have reported high efficacy and satisfactory tolerability, regardless of HCV genotype or renal impairment. We need to improve the screening for HCV and the access to DAAs in patients with CKD stage 4/5.
丙型肝炎病毒感染在慢性肾脏病患者中仍然很常见,尤其是在世界各地的透析单位中。尽管透析单位中丙型肝炎病毒传播的全部情况尚不清楚,但全球仍不断有丙型肝炎病毒感染的暴发。在过去十年中积累的证据表明,丙型肝炎病毒在肝脏和肝外水平发挥持续作用。最近一项对医学文献的系统综述及临床研究的荟萃分析检索到15项纵向研究(n = 2,299,134例患者);我们发现抗丙型肝炎病毒阳性血清学状态与慢性肾脏病较高的发生率之间存在显著关系;在各项调查中,丙型肝炎病毒调整后危险风险的汇总估计值为1.54(95%可信区间,1.26;1.87)(P<0.0001)。直接抗病毒药物的出现彻底改变了丙型肝炎病毒的治疗方法,包括晚期慢性肾脏病患者。最近有两种基于直接抗病毒药物的方案被批准用于4/5期慢性肾脏病患者的丙型肝炎病毒抗病毒治疗:艾尔巴韦/格拉瑞韦和格卡瑞韦/哌仑他韦。根据C-SURFER和EXPEDITION-4分别给出的结果,此类方案具有高疗效和安全性。索磷布韦是一种非结构5B聚合酶抑制剂,是许多抗丙型肝炎病毒药物方案的核心药物,且有显著的经肾排泄。因此,不建议估算肾小球滤过率<30 ml/min/1.73m²的患者使用索磷布韦。总之,最近的研究表明,目前有几种直接抗病毒药物组合可用于慢性肾脏病患者,包括4/5期慢性肾脏病患者。无论丙型肝炎病毒基因型或肾功能损害情况如何,这些药物均显示出高疗效和令人满意的耐受性。我们需要改进对4/5期慢性肾脏病患者的丙型肝炎病毒筛查及直接抗病毒药物的可及性。