Peeters, Michael, Schenk, Julie, De Somer, Thomas, Roskams, Tania, Locus, Tatjana, Klamer, Sofieke, Subissi, Lorenzo, Suin, Vanessa, Delwaide, Jean, Stärkel, Peter, De Maeght, Stéphane, Willems, Philippe, Colle, Isabelle, Van Hoof, Marc, Van Acker, Jos, Van Steenkiste, Christophe, Moreno, Christophe, Janssens, Filip, Reynders, Marijke, Steverlynck, Matthias, Verlinden, Wim, Lasser, Luc, de Galocsy, Chantal, Geerts, Anja, Maus, Jeroen, Gallant, Marie, Van Outryve, Steven, Marot, Astrid, Reynaert, Hendrik, Decaestecker, Jochen, Bottieau, Emmanuel, Schreiber, Jonas, Mulkay, Jean-Pierre, de Goeij, Sébastien, Salame, Mikhaël, Dooremont, Diederik, Dastis, Sergio Negrín, Boes, Juul, Nijs, Jochen, Beyls, Jan, Hens, Niel, Nevens, Frederik, Van Gucht, Steven, Vanwolleghem, Thomas, Belgian Association for the Study of the Liver, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service de gastro-entérologie, Belgian Association for the Study of the Liver, Locus, Tatjana/0000-0003-1357-8090, Peeters, Michael/0000-0002-0775-7888, Reynaert, Hendrik/0000-0002-2701-5777, Vanwolleghem, Thomas/0000-0002-0572-8741, Peeters , Michael, SCHENK, Julie, De Somer, Thomas, Roskams, Tania, Locus, Tatjana, Klamer, Sofieke, Subissi, Lorenzo, Suin, Vanessa, Delwaide, Jean, Starkel, Peter, De Maeght, Stephane, Willems, Philippe, Colle, Isabelle, Van Hoof, Marc, Van Acker, Jos, Van Steenkiste, Christophe, Moreno, Christophe, Janssens, Filip, Reynders , Marijke, Steverlynck, Matthias, Verlinden, Wim, Lasser, Luc, de Galocsy, Chantal, Geerts, Anja, Maus, Jeroen, Gallant, Marie, Van Outryve, Steven, Marot, Astrid, Reynaert, Hendrik, Decaestecker, Jochen, Bottieau, Emmanuel, Schreiber, Jonas, Mulkay, Jean-Pierre, de Goeij, Sebastien, Salame, Mikhael, Dooremont, Diederik, Dastis, Sergio Negrin, Boes, Juul, Nijs , Jochen, Beyls, Jan, HENS, Niel, Nevens, Frederik, Van Gucht, Steven, Vanwolleghem, Thomas, Gastroenterology, Faculty of Medicine and Pharmacy, Basic (bio-) Medical Sciences, Laboratory of Molecullar and Cellular Therapy, and Liver Cell Biology
Background & Aims: HEV genotype (gt) 3 infections are prevalent in high-income countries and display a wide spectrum of clinical presentations. Host - but not viral - factors are reported to be associated with worse clinical outcomes.Methods: Demographic, clinical, and biochemical data laboratory-confirmed HEV infections (by PCR and/or a combination of IgM and IgG serology) at the Belgian National Reference Centre between January 2010 and June 2018 were collected using stand-ardised case report forms. Genotyping was based on HEV open reading frame 2 sequences. Serum CXCL10 levels were measured by a magnetic bead-based assay. H&E staining was performed on liver biopsies.Results: A total of 274 HEV-infected individuals were included. Subtype assignment was possible for 179/218 viraemic cases, confirming gt3 as dominant with an almost equal representation of clades abchijklm and efg. An increased hospitalisation rate and higher peak serum levels of alanine aminotransferase, bilirubin, and alkaline phosphatase were found in clade efg-infected in-dividuals in univariate analyses. In multivariable analyses, clade efg infections remained more strongly associated with severe disease presentation than any of the previously identified host risk factors, being associated with a 2.1-fold higher risk of hos-pitalisation (95% CI 1.1-4.4, p = 0.034) and a 68.2% higher peak of bilirubin levels (95% CI 13.3-149.9, p = 0.010), independently of other factors included in the model. In addition, acute clade efg infections were characterised by higher serum CXCL10 levels (p = 0.0005) and a more pronounced liver necro-inflammatory activity (p = 0.022). Conclusions: In symptomatic HEV gt3 infections, clade efg is associated with a more severe disease presentation, higher serum CXCL10 levels, and liver necro-inflammatory activity, irrespective of known host risk factors.Clinical Trial Registration: The protocol was submitted to clinicaltrials.gov (NCT04670419).(c) 2022 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. This study is a retrospective analysis of routinely collected data, within the Belgian National Reference Centre (NRC) programme funded by the National Institute for Health and Disability Insurance (RIZIV-INAMI, Belgium). TV is supported by a senior clinical investigator grant of the Research Foundation Flanders (FWO) (number 18B2821N, Belgium). JS and NH acknowledge funding from the European Research Council (ERC) Horizon 2020 research and innovation program (grant agreement 682540 — TransMID, European Union). The funding sources did not have any role in study design, in the collection, analysis, and interpretation of data, in the manuscript writing, or in the decision to submit the paper for publication. We thank Harry Dalton for helpful discussions on the national data collection and clinical outcome analysis and Christophe Conrad for his help in collecting patients data. The authors also especially thank all physicians from the following centres who participated in the study: Algemeen Ziekenhuis Alma, Eeklo; Algemeen Medisch Laboratorium, Antwerpen; Algemeen Stedelijk Ziekenhuis, Aalst; Algemeen Ziekenhuis Delta, Roeselare; Algemeen Ziekenhuis Delta, Torhout; Algemeen Ziekenhuis Nikolaas, Sint-Niklaas; Algemeen Ziekenhuis Sint-Elisabeth, Zottegem; Algemeen Ziekenhuis, Turnhout; Centre Hospitalier Universitaire Brugmann, Brussels; Centre Hospitalier de l’Ardenne, Libramont; Hôpital de Braine-l’Alleud-Waterloo, Braine-l’Alleud; Hôpital Delta, Brussels; Centre Hospitalier de Mouscron, Mouscron; Centre Hospitalier Régional Haute Senne, Soignies; Centre Hospitalier Epicura, Hornu; Centre Hospitalier Universitaire de Liège, Liège; Centre Hospitalier de la Wallonie Picarde, Tournai; Clinique CHC, Waremme; Grand Hôpital de Charleroi, Charleroi; Gasthuiszusters Antwerpen, Antwerpen; Hôpital Princesse Paola, Marche-en-Famenne; Hôpital Iris Sud, Brussels; Instituut voor Tropische Geneeskunde, Antwerpen; Hôpital de Jolimont, La Louvière; Centre Hospitalier de Jolimont, Lobbes; Centre Hospitalier de Jolimont, Nivelles; Centre Hospitalier de Jolimont, Tubize; Eurofins Labo Van Poucke, Kortrijk; Medisch Labo Medina, Dendermonde; Algemeen Ziekenhuis Maria Middelares, Gent; Ziekenhuis Netwerk Antwerpen Middelheim, Antwerpen; Cliniques Universitaires Saint-Luc, Brussels; Centre Hospitalier Universitaire UCL, Dinant; Centre Hospitalier Universitaire UCL, Namur; Centre Hospitalier Universitaire de MontGodinne, Yvoir; Clinique Saint-Luc, Bouge; Clinique Notre-Dame de Grâce, Gosselies; Sint-Andriesziekenhuis, Tielt; Algemeen Ziekenhuis West, Veurne; Algemeen Ziekenhuis Sint Blasius, Dendermonde; Algemeen Ziekenhuis SintJan, Brugge; Klinik Sankt-Joseph, Sankt-Vith; Algemeen Ziekenhuis SintLucas, Gent; Algemeen Ziekenhuis Sint-Maarten, Mechelen; Centre Hospitalier Universitaire Saint-Pierre, Brussels; Sint-Trudo Ziekenhuis, Sint-Truiden; Centre Hospitalier Universitaire Tivoli, La Louvière; Hôpital Erasme – Cliniques Universitaires de Bruxelles, Brussels; Universitair Ziekenhuis Antwerpen, Antwerpen; Universitair Ziekenhuis Gent, Gent; Cassiman David, Laleman Wim, Van Malenstein Hannah, Verslype Chris and Van der Merwe Schalk from Universitair Ziekenhuis Leuven, Leuven; Virga Jesse Ziekenhuis, Hasselt; Universitair Ziekenhuis Brussel, Brussels; Jan Yperman Ziekenhuis, Ieper.