Gallacher Jennifer, Taha Yusri, da Silva Filipe Ana, Ijaz Samreen, McPherson Stuart
Viral Hepatitis Service, The Newcastle upon Tyne Hospitals NHS Foundation Trust, United Kingdom.
Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.
IDCases. 2023 Mar 6;32:e01741. doi: 10.1016/j.idcr.2023.e01741. eCollection 2023.
Persistent Hepatitis E Virus infection (HEV) is a rare but increasingly recognised condition in immunocompromised individuals. Untreated, this infection can rapidly progress to cirrhosis. Ribavirin is recommended as the first line treatment and the majority achieve sustained viral clearance. However, treatment options are limited for those who fail ribavirin. We report a case of a patients with ribavirin-refractory persistent HEV who responded to ledipasvir/sofosbuvir and ribavirin treatment. This patients had failed 2 course of ribavirin and 1 course of PEG-Interferon and ribavirin and he was known to harbour ribavirin-associated mutations (G1634R, D1384G and K1383N) in the RNA dependent RNA polymerase. He was treated with ledipasvir/sofosbuvir (LDV/SOF; Harvoni 90/400 mg) and ribavirin (R) 400 mg twice daily for 32 weeks. At treatment initiation his HEV RNA was 1.1 × 10 IU/ML and reduced to 1.8 × 10 IU/ML and 43 IU/ML at one and four weeks of treatment, respectively, becoming not detected in blood and stool by week eight. His blood HEV RNA remained undetectable for seven months after treatment completion. Unfortunately, at eight months post-treatment, his blood HEV RNA became detectable at a low level (35 IU/ML). His stool HEV RNA was also detectable at 620 IU/ML consistent with a late relapse. He restarted LDV/SOF+R and by week four of treatment HEV RNA was not detected in blood and stool. He remains on treatment. In conclusion, this is the first report demonstrating the antiviral activity of LDV/SOF+R in the treatment of persistent HEV infection.
持续性戊型肝炎病毒（HEV）感染在免疫功能低下个体中较为罕见，但越来越受到关注。未经治疗，这种感染可迅速发展为肝硬化。利巴韦林被推荐作为一线治疗药物，大多数患者可实现病毒持续清除。然而，对于利巴韦林治疗失败的患者，治疗选择有限。我们报告了一例利巴韦林难治性持续性HEV感染患者，该患者对来迪派韦/索磷布韦和利巴韦林治疗有反应。该患者接受了2个疗程的利巴韦林治疗以及1个疗程的聚乙二醇干扰素和利巴韦林治疗均失败，且已知其RNA依赖RNA聚合酶中存在与利巴韦林相关的突变（G1634R、D1384G和K1383N）。他接受了来迪派韦/索磷布韦（LDV/SOF；Harvoni 90/400 mg）和利巴韦林（R）每日两次、每次400 mg的治疗，持续32周。治疗开始时，他的HEV RNA为1.1×10 IU/ML，在治疗1周和4周时分别降至1.8×10 IU/ML和43 IU/ML，到第8周时血液和粪便中均未检测到。治疗完成后7个月，他的血液HEV RNA仍未检测到。不幸的是，治疗后8个月，他的血液HEV RNA在低水平（35 IU/ML）时再次被检测到。他的粪便HEV RNA也在620 IU/ML时被检测到，符合晚期复发。他重新开始LDV/SOF+R治疗，治疗至第4周时血液和粪便中均未检测到HEV RNA。他仍在接受治疗。总之，这是第一份证明LDV/SOF+R在治疗持续性HEV感染中具有抗病毒活性的报告。
