Pancreatic enzyme replacement therapy as a possible source of hepatitis E virus (HEV) infections – Canadian study with patients after lung transplantation for cystic fibrosis
Thornton CS, Gut. 2024;73(10):1702-1711
Immunosuppression after organ transplantation is a risk factor for chronic courses of HEV infection. In this Canadian study, phylogenetic analyzes of HEV isolates from chronically infected transplant recipients (n = 3) and HEV isolates found in 44% of the pancreatic enzyme preparations examined suggest that the porcine derived-pancreatic enzyme preparations could be a possible source of infection.
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, the authors sought to understand its epidemiology and potential drivers.
Design: All pwCF post-transplant attending the 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 2-fold higher seropositivity relative risk and this was 4 times higher than the Canadian average. Only 3 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. 91% 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: Persons with cystic fibrosis (pwCF) had disproportionate rates of hepatitis E virus (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 pancreatic enzyme replacement therapy are required.