Kamar Nassim, Lhomme Sebastien, Abravanel Florence, Cointault Olivier, Esposito Laure, Cardeau-Desangles Isabelle, Del Bello Arnaud, Dörr Gaëlle, Lavayssière Laurence, Nogier Marie Béatrice, Guitard Joelle, Ribes David, Goin Anne Laure, Broué Pierre, Metsu David, Sauné Karine, Rostaing Lionel, Izopet Jacques
1 Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France. 2 INSERM U1043, IFR-BMT, CHU Purpan, Toulouse, France. 3 Université Paul Sabatier, Toulouse, France. 4 Laboratory of Virology, CHU Purpan, Toulouse, France. 5 Department of Thoracic Surgery and Lung Transplantation, CHU Rangueil-Larrey, Toulouse, France. 6 Pediatric Hepatology, Hôpital des enfants, Toulouse, France. 7 Laboratory of Toxicology, CHU Purpan, Toulouse, France.
Transplantation. 2015 Oct;99(10):2124-31. doi: 10.1097/TP.0000000000000850.
Ribavirin is efficient at treating chronic hepatitis E virus infection in solid-organ transplant patients. However, the early kinetics of viral replication under therapy and the impact of immunosuppressant regimens on viral replication are unknown: thus, determining the aim of our study.
Thirty-five patients with a solid-organ transplant and chronic hepatitis E virus infection were given ribavirin for 3 months. The hepatitis E virus (HEV) RNA concentrations were determined before treatment, at days 7, 15, and 21 and at months 1, 2, and 3 during therapy and after ribavirin cessation.
A sustained virological response (SVR) occurred in 63%. Decreased viral concentration within the first week post-ribavirin therapy was an independent predictive factor for SVR, and a decreased HEV concentration of 0.5 log copies/mL or greater had an 88% positive predictive value. No correlation between ribavirin trough level on day 7 or at month 2 with a virological response or an SVR was observed. Before therapy, HEV RNA concentration was significantly greater in patients receiving mechanistic target of rapamycin inhibitor-based immunosuppression compared to patients given calcineurin inhibitors. The use of mycophenolic acid did not impact on the response to ribavirin.
An early response to ribavirin can be used to define the optimal duration of therapy in the setting of HEV infection.
利巴韦林在治疗实体器官移植患者的慢性戊型肝炎病毒感染方面有效。然而，治疗期间病毒复制的早期动力学以及免疫抑制剂方案对病毒复制的影响尚不清楚，因此确定了我们的研究目的。
35例实体器官移植且患有慢性戊型肝炎病毒感染的患者接受了3个月的利巴韦林治疗。在治疗前、治疗第7天、15天和21天以及治疗期间和停用利巴韦林后的第1、2和3个月测定戊型肝炎病毒（HEV）RNA浓度。
63%的患者出现持续病毒学应答（SVR）。利巴韦林治疗后第一周内病毒浓度降低是SVR的独立预测因素，HEV浓度降低0.5 log拷贝/mL或更多具有88%的阳性预测值。未观察到第7天或第2个月的利巴韦林谷浓度与病毒学应答或SVR之间的相关性。治疗前，与接受钙调神经磷酸酶抑制剂的患者相比，接受基于雷帕霉素抑制剂的免疫抑制治疗的患者的HEV RNA浓度显著更高。霉酚酸的使用对利巴韦林的应答没有影响。
利巴韦林的早期应答可用于确定戊型肝炎病毒感染情况下的最佳治疗持续时间。
