Duerr Michael, Liefeldt Lutz, Friedersdorff Frank, Choi Mira, Öllinger Robert, Hofmann Jörg, Budde Klemens, Schrezenmeier Eva, Halleck Fabian
Department of Nephrology and Intensive Medical Care, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany.
Department of Urology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany.
J Clin Med. 2020 Dec 29;10(1):89. doi: 10.3390/jcm10010089.
Transplant candidates are facing incremental mortality risks on the waiting list. Here, we report a novel strategy to expand the donor pool by including hepatitis C seropositive (HCV+) donors. We investigated a pre-exposure prophylactic (PrEP) treatment with direct-acting antivirals (DAA) to allow transplantation for HCV seronegative (HCV-) kidney transplant recipients (KTR) with the aim to prevent HCV infection post transplantation. In this prospective trial, a pan-genotypic PrEP with daclatasvir and sofosbuvir once daily for 12 week was administered at transplantation. The primary endpoint sustained virological negativity (SVN) 12 weeks after the end of PrEP. Seven patients received a transplantation from four HCV+ donors. Accumulated waiting time was 70 ± 31.3 months already. Of note, study subjects underwent transplantation 24.7 ± 16.1 days after given consent. All KTR developed excellent graft function without any rejection episodes. One patient died with a functioning graft due to sepsis 13 months after transplantation. PrEP demonstrated efficacy with no signs of HCV transmission with excellent tolerability. Two out of four HCV+ donors were viremic at the time of explantation. Interestingly, KTR developed HCV antibodies also from non viramic donors. The acceptance of HCV+ donor was safe and reduced waiting time under the protection of PrEP DAA in kidney transplantation.
移植候选者在等待名单上面临着不断增加的死亡风险。在此,我们报告一种通过纳入丙型肝炎血清学阳性(HCV+)供体来扩大供体库的新策略。我们研究了一种使用直接作用抗病毒药物(DAA)的暴露前预防(PrEP)治疗方法,以使丙型肝炎血清学阴性(HCV-)的肾移植受者(KTR)能够接受移植,目的是预防移植后丙型肝炎感染。在这项前瞻性试验中,在移植时给予泛基因型的PrEP,即每日一次服用达卡他韦和索磷布韦,持续12周。主要终点是PrEP结束后12周的持续病毒学阴性(SVN)。7名患者接受了来自4名HCV+供体的移植。累积等待时间已经达到70±31.3个月。值得注意的是,研究对象在获得同意后24.7±16.1天接受了移植。所有KTR的移植肾功能良好,没有任何排斥反应。1例患者在移植后13个月因败血症死亡,移植肾功能正常。PrEP显示出疗效,没有丙型肝炎传播的迹象,耐受性良好。4名HCV+供体中有2名在器官切除时存在病毒血症。有趣的是,KTR也从非病毒血症供体那里产生了丙型肝炎抗体。在PrEP DAA的保护下,接受HCV+供体进行肾移植是安全的,并且缩短了等待时间。