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Title: | Viral clade is associated with severity of symptomatic genotype 3 hepatitis E virus infections in Belgium, 2010-2018 | Authors: | 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 |
Issue Date: | 2023 | Publisher: | ELSEVIER | Source: | JOURNAL OF HEPATOLOGY, 78 (1) , p. 67 -77 | Abstract: | 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. | Notes: | Vanwolleghem, T (corresponding author), Univ Hosp Antwerp, Gastroenterol & Hepatol, Drie Eikenstr 655, B-2650 Edegem, Belgium.; Van Gucht, S (corresponding author), Sciensano, Natl Reference Ctr Hepatitis Viruses, Infect Dis Humans, Viral Dis, Rue Juliette Wytsman 14, B-1050 Ixelles, Belgium. Steven.VanGucht@sciensano.be; Thomas.Vanwolleghem@uza.be |
Keywords: | Hepatitis E virus;Clade;Risk factor;Severity;Pathogenicity;CXCL10 | Document URI: | http://hdl.handle.net/1942/39819 | ISSN: | 0168-8278 | e-ISSN: | 1600-0641 | DOI: | 10.1016/j.jhep.2022.08.033 | ISI #: | 000923633900008 | Rights: | 2022 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. | Category: | A1 | Type: | Journal Contribution |
Appears in Collections: | Research publications |
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Microsoft Word - Manuscript-Cleaned_Post_Reviewing_2_Rebuttal2.docx.pdf | Peer-reviewed author version | 19.89 MB | Adobe PDF | View/Open |
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