Objectives In high-income countries hepatitis E virus (HEV) is an uncommonly diagnosed porcine-derived zoonoses. After identifying disproportionate chronic HEV infections in persons with cystic fibrosis (pwCF) postlung transplant, we sought to understand its epidemiology and potential drivers. Design All pwCF post-transplant attending our regional CF centre were screened for HEV. HEV prevalence was compared against non-transplanted pwCF and with all persons screened for suspected HEV infection from 2016 to 2022 in Alberta, Canada. Those with chronic HEV infection underwent genomic sequencing and phylogenetic analysis. Owing to their swine derivation, independently sourced pancreatic enzyme replacement therapy (PERT) capsules were screened for HEV. Results HEV seropositivity was similar between transplanted and non-transplanted pwCF (6/29 (21%) vs 16/83 (19%); p=0.89). Relative to all other Albertans investigated for HEV as a cause of hepatitis (n=115/1079, 10.7%), pwCF had a twofold higher seropositivity relative risk and this was four times higher than the Canadian average. Only three chronic HEV infection cases were identified in all of Alberta, all in CF lung transplant recipients (n=3/29, 10.3%). Phylogenetics confirmed cases were unrelated porcine-derived HEV genotype 3a. Ninety-one per cent of pwCF were taking PERT (median 8760 capsules/person/year). HEV RNA was detected by RT-qPCR in 44% (47/107) of PERT capsules, and sequences clustered with chronic HEV cases. Conclusion PwCF had disproportionate rates of HEV seropositivity, regardless of transplant status. Chronic HEV infection was evident only in CF transplant recipients. HEV may represent a significant risk for pwCF, particularly post-transplant. Studies to assess HEV incidence and prevalence in pwCF, and potential role of PERT are required. All data relevant to the study are included in the article or uploaded as supplementary information.

中文翻译：

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猪源胰酶替代疗法可能与囊性纤维化肺移植受者的慢性戊型肝炎病毒感染有关


目标 在高收入国家，戊型肝炎病毒 (HEV) 是一种罕见的猪源性人畜共患病。在确定肺移植后囊性纤维化 (pwCF) 患者中不成比例的慢性 HEV 感染后，我们试图了解其流行病学和潜在驱动因素。设计 所有前往我们区域 CF 中心的 pwCF 移植后均接受了 HEV 筛查。将 HEV 患病率与非移植 pwCF 以及 2016 年至 2022 年加拿大艾伯塔省所有疑似 HEV 感染者进行了比较。慢性 HEV 感染者接受了基因组测序和系统发育分析。由于源自猪，因此对独立来源的胰酶替代疗法 (PERT) 胶囊进行了 HEV 筛查。结果 移植和非移植 pwCF 之间的 HEV 血清阳性率相似（6/29 (21%) 与 16/83 (19%)；p=0.89）。相对于所有其他阿尔伯塔省调查的 HEV 作为肝炎原因的调查（n=115/1079，10.7%），pwCF 的血清阳性相对风险高出两倍，比加拿大平均水平高四倍。全阿尔伯塔省仅发现 3 例慢性 HEV 感染病例，全部为 CF 肺移植受者（n=3/29，10.3%）。系统发育学证实病例与猪源HEV基因型3a无关。 91% 的 pwCF 正在服用 PERT（中位数为 8760 粒胶囊/人/年）。通过 RT-qPCR 在 44% (47/107) 的 PERT 胶囊中检测到 HEV RNA，并且序列与慢性 HEV 病例聚集。结论 无论移植状态如何，PwCF 的 HEV 血清阳性率均不成比例。慢性 HEV 感染仅在 CF 移植受者中明显。 HEV 可能对 pwCF 构成重大风险，尤其是移植后。 需要进行研究来评估 pwCF 中 HEV 的发病率和患病率以及 PERT 的潜在作用。与研究相关的所有数据都包含在文章中或作为补充信息上传。