Hepatitis E virus infection and rejection in kidney transplant recipients

Paul Wasuwanich; Pokket Sirisreetreerux; Thammasin Ingviya; Edward S Kraus; Daniel C Brennan; Paul K Sue; Annette M Jackson; Kiyoko Oshima; Benjamin Philosophe; Robert A Montgomery; Wikrom Karnsakul

doi:10.1016/j.trim.2021.101517

Hepatitis E virus infection and rejection in kidney transplant recipients

Transpl Immunol. 2022 Feb:70:101517. doi: 10.1016/j.trim.2021.101517. Epub 2021 Dec 17.

Authors

Affiliations

¹ Division of Pediatric Gastroenterology, Nutrition, and Hepatology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
² Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
³ Department of Environmental Health Sciences, Johns Hopkins University, Baltimore, MD, USA; Department of Family and Preventive Medicine, Prince of Songkla University, Songkhla, Thailand.
⁴ Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁵ Division of Pediatric Infectious Diseases, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁶ Departments of Surgery and Immunology, Duke University, Durham, NC, USA.
⁷ Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁸ Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁹ Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA; NYU Langone Transplant Institute, New York University Langone Health, New York, NY, USA.
¹⁰ Division of Pediatric Gastroenterology, Nutrition, and Hepatology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: wkarnsa1@jhmi.edu.

PMID: 34923120
DOI: 10.1016/j.trim.2021.101517

Abstract

Background: Hepatitis E virus (HEV) infection has been associated with immune-mediated kidney diseases in developing countries. However, its relationship with kidney transplant outcomes has never been studied. We investigated the association between HEV infection and kidney graft rejection among kidney transplant recipients (KTRs).

Methods: We conducted a matched cohort and longitudinal study utilizing banked sera following kidney transplantation during 1988-2012. Studies with evidence of post-transplantation HEV infection were identified by positive ELISA tests (anti-HEV IgM or anti-HEV IgG seroconversion) or positive HEV PCR and matched to KTR controls with negative HEV ELISA and PCR tests in a 1:5 ratio by age, sex, crossmatch status, immunosuppression era, and time of HEV testing. Outcome data collected included time to first kidney graft rejection, transaminases, and glomerular filtration rates. Log-ranked test was used to analyze survival.

Results: Of 271 KTRs, 9 (3%) had evidence of post-transplantation HEV infection and were compared to 45 negative, matched controls. Median age at transplantation was 46 years. Kidney graft rejection was reported in 8 (89%) of cases and 21 (47%) of controls. Median time to first episode of kidney graft rejection was 17.4 months in cases and 30.8 months in controls (p = 0.029), with a higher hazard of developing kidney graft rejection in cases (HR = 3.23, 95% CI: 1.19-8.79). Lower mean glomerular filtration rates over time were observed in cases (35 mL/min/1.73m²) versus controls (42.4 mL/min/1.73m²) but did not reach significance (p = 0.24).

Conclusion: Subjects with evidence of post-transplantation HEV infection demonstrated earlier kidney graft rejection compared to controls.

Keywords: Glomerular filtration rate; Preventive medicine; Public health; Survival analysis; Transplantation.

MeSH terms

Graft Rejection
Hepatitis E virus* / genetics
Hepatitis E* / epidemiology
Humans
Kidney Transplantation*
Longitudinal Studies
RNA, Viral
Transplant Recipients

Substances

RNA, Viral