Evidence map›Paper›PMID 40575997›Full record

Trial reportLiver international : official journal of the International Association for the Study of the Liver2025

Extrahepatic Replication and Genomic Signatures of the Hepatitis E Virus in the Kidney.

Avista Wahid, Nele Meyer, Christine Wundes, Lucas Hüffner, Saskia Janshoff, Nicola Frericks, Martina Friesland, Katja Dinkelborg, Elmira Aliabadi, Fenja Laue and 19 more

Registry-linked trialAbstract readClinical Trial, Phase IIMulticenter Study
In one paragraph

Trial report in Liver international : official journal of the International Association for the Study of the Liver, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03282474 (HepNet Pilot Trial), which is not on this map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03282474 phase2completednot on this map

HepNet Pilot Trial: Multicenter Trial for the Treatment of Chronic Hepatitis E With Sofosbuvir (SofE)

TypeinterventionalSponsorHannover Medical SchoolRan2017 to 2019Enrolled10ConditionsHepatitis E, Hepatitis Chronic ViralArmsSofosbuvir
3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Extrahepatic Replication and Genomic Signatures of the Hepatitis E Virus in the Kidney.Liver international : official journal of the International Association for the Study of the Liver · 2025
    Trial
  2. Article
  3. Review
  4. Review
  5. Article
  6. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

29 authors.

Avista WahidInstitute for Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, a Joint Venture Between the Helmholtz Centre for Infection Research and the Hannover Medical School, Hannover, Germany.
Nele MeyerInstitute for Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, a Joint Venture Between the Helmholtz Centre for Infection Research and the Hannover Medical School, Hannover, Germany.
Christine WundesInstitute for Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, a Joint Venture Between the Helmholtz Centre for Infection Research and the Hannover Medical School, Hannover, Germany.
Lucas HüffnerInstitute for Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, a Joint Venture Between the Helmholtz Centre for Infection Research and the Hannover Medical School, Hannover, Germany.
Saskia JanshoffDepartment of Molecular and Medical Virology, Ruhr University Bochum, Germany.
Nicola FrericksDepartment of Molecular and Medical Virology, Ruhr University Bochum, Germany.
Martina FrieslandInstitute for Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, a Joint Venture Between the Helmholtz Centre for Infection Research and the Hannover Medical School, Hannover, Germany.
Katja DinkelborgInstitute for Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, a Joint Venture Between the Helmholtz Centre for Infection Research and the Hannover Medical School, Hannover, Germany.
Elmira AliabadiInstitute for Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, a Joint Venture Between the Helmholtz Centre for Infection Research and the Hannover Medical School, Hannover, Germany.
Fenja LaueInstitute for Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, a Joint Venture Between the Helmholtz Centre for Infection Research and the Hannover Medical School, Hannover, Germany.
Markus CornbergDepartment of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany.ORCID 0000-0002-9141-8001
Benjamin MaasoumyDepartment of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany.ORCID 0000-0002-3250-3177
Birgit BremerDepartment of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany.
Sven PischkeUniversity Medical Centre Hamburg-Eppendorf, Hamburg, Germany.ORCID 0000-0003-3370-3274
Tobias MüllerDepartment of Gastroenterology and Hepatology, Charité Campus Virchow-Klinikum (CVK), Berlin, Germany.ORCID 0000-0003-3426-5421
Julian Zur Schulze WieschUniversity Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
Julia BenckertDepartment of Gastroenterology and Hepatology, Charité Campus Virchow-Klinikum (CVK), Berlin, Germany.
Rainer G UlrichDZIF, Partner Site Hamburg-Lübeck-Borstel-Riems, Germany.
Svenja HardtkeGerman Center for Infection Research (DZIF), HepNet Study-House/German Liver Foundation, Hannover, Germany.
Petra DörgeDepartment of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany.
Florian VondranDZIF, Partner Site Hannover-Braunschweig, Germany.
Ansgar LohseUniversity Medical Centre Hamburg-Eppendorf, Hamburg, Germany.ORCID 0000-0002-8823-3129
Michael Peter MannsDepartment of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany.
Daniel TodtDepartment of Molecular and Medical Virology, Ruhr University Bochum, Germany.ORCID 0000-0002-3564-1014
Heiner WedemeyerDepartment of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany.ORCID 0000-0003-2906-0480
Thomas PietschmannInstitute for Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, a Joint Venture Between the Helmholtz Centre for Infection Research and the Hannover Medical School, Hannover, Germany.
Eike SteinmannDepartment of Molecular and Medical Virology, Ruhr University Bochum, Germany.
André GömerDepartment of Molecular and Medical Virology, Ruhr University Bochum, Germany.ORCID 0000-0002-4567-0441
Patrick BehrendtInstitute for Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, a Joint Venture Between the Helmholtz Centre for Infection Research and the Hannover Medical School, Hannover, Germany.ORCID 0000-0001-5750-4259

Funding

Deutsche ForschungsgemeinschaftDeutsches Zentrum für Infektionsforschung
6 · The paper itself

Abstract

introductionThe hepatitis E virus (HEV; species Paslahepevirus balayani) is a common human pathogenic and zoonotic virus that can cause both acute fulminant and chronic hepatitis. Despite its reputation as a hepatotropic virus, HEV infection is also associated with a number of extrahepatic diseases, including kidney disorders. However, the extent to which HEV replicates in kidney cells remains unclear. The present study aims to investigate the capacity of HEV to propagate in kidney cells in vitro and to assess whether HEV displays mutational signatures that correlate with compartmentalisation in vivo.

methodsWe use HEV cell culture models to study the replication cycle and the effect of antivirals in human kidney cell lines and primary cells. In addition, we identified patients with chronic HEV infection (n = 9) from which we then sequenced the viral RNA of urine, stools and plasma to analyse the viral sequence composition, to assess intra-host diversity and compartmentalisation (n = 2).

resultsA wide range of human kidney cell lines as well as primary cells supports viral entry, replication and propagation of HEV in vitro. Interestingly, the broad-spectrum antiviral ribavirin was less effective in inhibiting HEV replication in some kidney cells. Sequencing of HEV RNA-directed RNA polymerase coding region from plasma, stool and urine and subsequent phylogenetic analysis revealed diversification of HEV into tissue-specific viral subpopulations. In particular, the viruses derived from urine were found to be distinct from those derived from plasma and stool.

conclusionsIn conclusion, kidney cells support the propagation of HEV in vitro and exhibit reduced sensitivity to antiviral treatment. Furthermore, HEV patient-derived sequences demonstrated compartmentalisation into distinct clusters that correlated with sample source. Collectively, these data indicate the potential for extrahepatic replication of HEV, which may result in clinically significant disease or serve as a reservoir for patient relapse.

trial registrationHepNet-SofE study (NCT03282474).

Indexed as

Hepatitis EHepatitis E virusKidneyVirus ReplicationAntiviral AgentsCell LineGenome, ViralHumansRNA, ViralAntiviral AgentsRNA, Viralcompartmentalizationhepatitis Ekidney impairment

Identifiers

PMID40575997
PMCPMC12203452

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.