Department II of Internal Medicine and Center for Molecular Medicine Cologne, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany.
Faculty of Medicine, University Hospital of Cologne, Institute of Virology, University of Cologne, Cologne, Germany.
Immun Inflamm Dis. 2021 Jun;9(2):513-520. doi: 10.1002/iid3.411. Epub 2021 Feb 8.
Recently, chronic hepatitis E virus (HEV) infections gained increasing attention as a possible cause for elevated liver enzymes of unknown origin and liver cirrhosis in solid organ transplant recipients. Reduction of immunosuppressive therapy and/or use of antiviral drug ribavirin have been established as possible treatment strategies.
The efficacy of dose reduction of mycophenolic acid (MPA) and ribavirin therapy was retrospectively analyzed in eight renal transplant patients of our outpatient clinic who were diagnosed with HEV infection by detection of specific antibodies (immunoglobulin M and immunoglobulin G) and/or positive RNA in blood and stool. In four patients serial HEV viral loads in blood were measured.
Only one patient reached HEV clearance after reduction of immunosuppressive therapy (predominantly reduction of MPA daily dose) alone, whereas six patients were treated with ribavirin after reduction of immunosuppressive therapy due to persistent virus replication. Four of six patients reached HEV clearance after 3 months of ribavirin therapy. HEV clearance was observed after 34-42 days. Two patients, both treated with rituximab within the last 12 months before diagnosis of HEV infection, needed prolonged ribavirin therapy due to persistent viral replication.
Reduction of daily dose of MPA therapy alone in transplant patients with chronic HEV infection may not be sufficient to control viral replication. HEV clearance under ribavirin therapy shows interindividual variability. Therefore, serial viral monitoring may be useful to personalize treatment duration. Rituximab therapy is a risk factor for complicated-to-treat chronic HEV infection.
最近,慢性戊型肝炎病毒(HEV)感染作为导致实体器官移植受者不明原因肝酶升高和肝硬化的可能原因引起了越来越多的关注。减少免疫抑制治疗和/或使用抗病毒药物利巴韦林已被确立为可能的治疗策略。
我们对门诊的 8 例肾移植患者进行了回顾性分析,这些患者通过检测特异性抗体(免疫球蛋白 M 和免疫球蛋白 G)和/或血液和粪便中的 RNA 阳性,诊断为 HEV 感染。4 例患者连续测量了血液中的 HEV 病毒载量。
仅 1 例患者在单独减少免疫抑制治疗(主要是减少吗替麦考酚酯每日剂量)后达到 HEV 清除,而 6 例患者由于持续病毒复制而在减少免疫抑制治疗后接受利巴韦林治疗。6 例患者中有 4 例在接受利巴韦林治疗 3 个月后达到 HEV 清除。HEV 清除发生在 34-42 天后。由于持续的病毒复制,2 例患者在诊断为 HEV 感染前的 12 个月内均接受过利妥昔单抗治疗,需要延长利巴韦林治疗。
慢性 HEV 感染的移植患者单独减少吗替麦考酚酯的日剂量治疗可能不足以控制病毒复制。利巴韦林治疗下的 HEV 清除具有个体间的变异性。因此,连续的病毒监测可能有助于确定治疗时间。利妥昔单抗治疗是慢性 HEV 感染治疗困难的一个危险因素。