title: Molecular detection of hepatitis E virus (HEV) in liver biopsies after liver transplantation.
abstract: We aimed to determine the rate of hepatitis E virus (HEV) infection, a recently increasingly recognized disease in the Western world, in liver transplant patients by direct molecular testing of liver tissue. A RT-PCR assay was designed for detecting the HEV open reading frame (ORF) 2/3 gene region in formalin-fixed, paraffin-embedded tissues, and applied to all liver biopsies (n=683) taken 4 weeks or later from all patients (n=282) after liver transplantation of two large academic centers. HEV-RNA was detected in ten biopsies from four different patients (rate: 1%). Histology in early HEV infection was variable including cases with only few hepatocellular apoptoses, no or only minute inflammation. Hepatitis lasted for at least 6 months in 3/4 patients. Serologic testing for HEV-RNA in a subcohort (159 patients) was positive in five patients (rate: 3%), resulting in an overall HEV detection rate of 3% (8/282). In case both liver tissue and sera of a patient were available from the same time period, all cases tested positive in one material were also tested positive in the other material, respectively. All patients had de novo autochthonous infection with HEV genotype 3. Our data confirm that HEV infection is a relevant cause of liver injury after liver transplantation. Molecular testing for HEV in routinely processed transplant liver biopsies is powerful for evaluating patients with elevated transaminases of unknown origin. Histology of HEV infection under immunosuppression in the early phase is distinct from HEV infection in immunocompetent individuals.
authors.affiliation: 1] Institute of Virology, Technische Universität München/Helmholtz Zentrum München, Munich, Germany [2] German Center for Infection Research (DZIF), Munich and Heidelberg Sites, Braunschweig, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Protzer
authors.affiliation: Institute of Surgical Pathology, University Zurich, Zurich, Switzerland.
authors.forename: Friederike
authors.initials: F
authors.lastname: Böhm
authors.affiliation: Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Longerich
authors.affiliation: Institute of Virology, Technische Universität München/Helmholtz Zentrum München, Munich, Germany.
authors.forename: Judith
authors.initials: J
authors.lastname: Seebach
authors.affiliation: Department of Infectious Diseases, Virology, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Mojdeh
authors.initials: M
authors.lastname: Heidary Navid
authors.affiliation: Institute of Surgical Pathology, University Zurich, Zurich, Switzerland.
authors.forename: Juliane
authors.initials: J
authors.lastname: Friemel
authors.affiliation: Institute of Surgical Pathology, University Zurich, Zurich, Switzerland.
authors.forename: Ewerton
authors.initials: E
authors.lastname: Marques-Maggio
authors.affiliation: Institute of Surgical Pathology, University Zurich, Zurich, Switzerland.
authors.forename: Marion
authors.initials: M
authors.lastname: Bawohl
authors.affiliation: 1] Institute of Virology, Technische Universität München/Helmholtz Zentrum München, Munich, Germany [2] German Center for Infection Research (DZIF), Munich and Heidelberg Sites, Braunschweig, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Heikenwalder
authors.affiliation: 1] German Center for Infection Research (DZIF), Munich and Heidelberg Sites, Braunschweig, Germany [2] Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Schirmacher
authors.affiliation: Clinics of Visceral and Transplant Surgery, University of Zurich, Zurich, Switzerland.
authors.forename: Philipp
authors.initials: P
authors.lastname: Dutkowski
authors.affiliation: Clinics of Visceral and Transplant Surgery, University of Zurich, Zurich, Switzerland.
authors.forename: Pierre-Alain
authors.initials: PA
authors.lastname: Clavien
authors.affiliation: Department of General and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Schemmer
authors.affiliation: Department of Infectious Diseases, Virology, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Paul
authors.initials: P
authors.lastname: Schnitzler
authors.affiliation: Department of Gastroenterology, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gotthardt
authors.affiliation: Clinics of Hepatology and Gastroenterology, University of Zurich, Zurich, Switzerland.
authors.forename: Beat
authors.initials: B
authors.lastname: Müllhaupt
authors.affiliation: Institute of Surgical Pathology, University Zurich, Zurich, Switzerland.
authors.forename: Achim
authors.initials: A
authors.lastname: Weber
mesh_terms: D000328:Adult; D005260:Female; D016751:Hepatitis E / Q000175:diagnosis*; D016752:Hepatitis E virus / Q000302:isolation & purification*; D006801:Humans; D008099:Liver / Q000473:pathology / Q000601:surgery / Q000821:virology*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged