Porcine-derived pancreatic enzyme replacement therapy may be linked to chronic hepatitis E virus infection in cystic fibrosis lung transplant recipients

Christina S Thornton; Barbara J Waddell; Stephen E Congly; Julianna Svishchuk; Ranjani Somayaji; Linda Fatovich; Debra Isaac; Karen Doucette; Kevin Fonseca; Steven J Drews; Jamie Borlang; Carla Osiowy; Michael D Parkins

doi:10.1136/gutjnl-2023-330602

Porcine-derived pancreatic enzyme replacement therapy may be linked to chronic hepatitis E virus infection in cystic fibrosis lung transplant recipients

Gut. 2024 Apr 15:gutjnl-2023-330602. doi: 10.1136/gutjnl-2023-330602. Online ahead of print.

Authors

Christina S Thornton^{1

2}, Barbara J Waddell², Stephen E Congly¹, Julianna Svishchuk², Ranjani Somayaji^{1

2}, Linda Fatovich¹, Debra Isaac¹, Karen Doucette³, Kevin Fonseca⁴, Steven J Drews^{5

6}, Jamie Borlang⁷, Carla Osiowy⁷, Michael D Parkins^{8

2}

Affiliations

¹ Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
² Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada.
³ Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
⁴ Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, Alberta, Canada.
⁵ Canadian Blood Services, Edmonton, Alberta, Canada.
⁶ Department of Laboratory Medicine & Pathology, University of Alberta, Edmonton, Alberta, Canada.
⁷ Public Health Agency of Canada, Winnipeg, Manitoba, Canada.
⁸ Department of Medicine, University of Calgary, Calgary, Alberta, Canada mdparkin@ucalgary.ca.

PMID: 38621922
DOI: 10.1136/gutjnl-2023-330602

Abstract

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.

Keywords: cystic fibrosis; hepatitis E; immunodeficiency; pancreatic disease; pancreatic enzymes.