Viral clade is associated with severity of symptomatic genotype 3 hepatitis E virus infections in Belgium, 2010-2018
Michael Peeters, Julie Schenk, Thomas De Somer, Tania Roskams, Tatjana Locus, Sofieke Klamer, Lorenzo Subissi, Vanessa Suin, Jean Delwaide, Peter Stärkel, Stéphane De Maeght, Philippe Willems, Isabelle Colle, Marc Van Hoof, Jos Van Acker, Christophe Van Steenkiste, Christophe Moreno, Filip Janssens, Marijke Reynders, Matthias Steverlynck, Wim Verlinden, Luc Lasser, Chantal de Galocsy, Anja Geerts, Jeroen Maus, Marie Gallant, Steven Van Outryve, Astrid Marot, Hendrik Reynaert, Jochen Decaestecker, Emmanuel Bottieau, Jonas Schreiber, Jean-Pierre Mulkay, Sébastien de Goeij, Mikhaël Salame, Diederik Dooremont, Sergio Negrín Dastis, Juul Boes, Jochen Nijs, Jan Beyls, Niel Hens, Frederik Nevens, Steven Van Gucht, Thomas Vanwolleghem, Belgian Association for the Study of the Liver, Michael Peeters, Julie Schenk, Thomas De Somer, Tania Roskams, Tatjana Locus, Sofieke Klamer, Lorenzo Subissi, Vanessa Suin, Jean Delwaide, Peter Stärkel, Stéphane De Maeght, Philippe Willems, Isabelle Colle, Marc Van Hoof, Jos Van Acker, Christophe Van Steenkiste, Christophe Moreno, Filip Janssens, Marijke Reynders, Matthias Steverlynck, Wim Verlinden, Luc Lasser, Chantal de Galocsy, Anja Geerts, Jeroen Maus, Marie Gallant, Steven Van Outryve, Astrid Marot, Hendrik Reynaert, Jochen Decaestecker, Emmanuel Bottieau, Jonas Schreiber, Jean-Pierre Mulkay, Sébastien de Goeij, Mikhaël Salame, Diederik Dooremont, Sergio Negrín Dastis, Juul Boes, Jochen Nijs, Jan Beyls, Niel Hens, Frederik Nevens, Steven Van Gucht, Thomas Vanwolleghem, Belgian Association for the Study of the Liver
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 standardised 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 individuals 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 hospitalisation (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).
Impact and implications: HEV genotype (gt) 3 infections display a wide spectrum of clinical presentations currently ascribed to host factors. Here we examined the role of viral factors on liver disease outcomes by combining viral phylogeny with clinical, biochemical, cytokine, and histological data from 274 Belgian adults infected with HEV presenting between 2010 and 2018. HEV gt 3 clade efg infections were associated with a more severe disease presentation, higher serum CXCL10 levels and liver necro-inflammatory activity, irrespective of known host risk factors. HEV gt3 clade-dependent clinical outcomes call for broad HEV gt3 subtyping in clinical practice and research to help identify those at higher risk for worse outcomes and to further unravel underlying virus-host interactions.
Keywords: CXCL10; Clade; Hepatitis E virus; Pathogenicity; Risk factor; Severity.
Copyright © 2022 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Source: PubMed