Biomaterial Database

Viral clade is associated with severity of symptomatic genotype 3 hepatitis E virus infections in Belgium, 2010-2018. 2023

Michael Peeters, and Julie Schenk, and Thomas De Somer, and Tania Roskams, and Tatjana Locus, and Sofieke Klamer, and Lorenzo Subissi, and Vanessa Suin, and Jean Delwaide, and Peter Stärkel, and Stéphane De Maeght, and Philippe Willems, and Isabelle Colle, and Marc Van Hoof, and Jos Van Acker, and Christophe Van Steenkiste, and Christophe Moreno, and Filip Janssens, and Marijke Reynders, and Matthias Steverlynck, and Wim Verlinden, and Luc Lasser, and Chantal de Galocsy, and Anja Geerts, and Jeroen Maus, and Marie Gallant, and Steven Van Outryve, and Astrid Marot, and Hendrik Reynaert, and Jochen Decaestecker, and Emmanuel Bottieau, and Jonas Schreiber, and Jean-Pierre Mulkay, and Sébastien de Goeij, and Mikhaël Salame, and Diederik Dooremont, and Sergio Negrín Dastis, and Juul Boes, and Jochen Nijs, and Jan Beyls, and Niel Hens, and Frederik Nevens, and Steven Van Gucht, and Thomas Vanwolleghem, and

Sciensano, Infectious Diseases in Humans, Viral Diseases, National Reference Centre of Hepatitis Viruses, Brussels, Belgium.

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. 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. 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). 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. The protocol was submitted to clinicaltrials.gov (NCT04670419). 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.

UI	MeSH Term	Description	Entries
D010802	Phylogeny	The relationships of groups of organisms as reflected by their genetic makeup.	Community Phylogenetics,Molecular Phylogenetics,Phylogenetic Analyses,Phylogenetic Analysis,Phylogenetic Clustering,Phylogenetic Comparative Analysis,Phylogenetic Comparative Methods,Phylogenetic Distance,Phylogenetic Generalized Least Squares,Phylogenetic Groups,Phylogenetic Incongruence,Phylogenetic Inference,Phylogenetic Networks,Phylogenetic Reconstruction,Phylogenetic Relatedness,Phylogenetic Relationships,Phylogenetic Signal,Phylogenetic Structure,Phylogenetic Tree,Phylogenetic Trees,Phylogenomics,Analyse, Phylogenetic,Analysis, Phylogenetic,Analysis, Phylogenetic Comparative,Clustering, Phylogenetic,Community Phylogenetic,Comparative Analysis, Phylogenetic,Comparative Method, Phylogenetic,Distance, Phylogenetic,Group, Phylogenetic,Incongruence, Phylogenetic,Inference, Phylogenetic,Method, Phylogenetic Comparative,Molecular Phylogenetic,Network, Phylogenetic,Phylogenetic Analyse,Phylogenetic Clusterings,Phylogenetic Comparative Analyses,Phylogenetic Comparative Method,Phylogenetic Distances,Phylogenetic Group,Phylogenetic Incongruences,Phylogenetic Inferences,Phylogenetic Network,Phylogenetic Reconstructions,Phylogenetic Relatednesses,Phylogenetic Relationship,Phylogenetic Signals,Phylogenetic Structures,Phylogenetic, Community,Phylogenetic, Molecular,Phylogenies,Phylogenomic,Reconstruction, Phylogenetic,Relatedness, Phylogenetic,Relationship, Phylogenetic,Signal, Phylogenetic,Structure, Phylogenetic,Tree, Phylogenetic
D005838	Genotype	The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.	Genogroup,Genogroups,Genotypes
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000078985	Clinical Trial Protocols as Topic	Works about the written descriptions of a clinical study. It contains the study's objectives, design, and methods including subject target and/or enrollment criteria. It may also present relevant scientific background and statistical information.
D000328	Adult	A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available.	Adults
D001530	Belgium	A country in Western Europe, bordering the North Sea, between France and the Netherlands. The capital is Brussels.
D001663	Bilirubin	A bile pigment that is a degradation product of HEME.	Bilirubin IX alpha,Bilirubin, (15E)-Isomer,Bilirubin, (4E)-Isomer,Bilirubin, (4E,15E)-Isomer,Bilirubin, Calcium Salt,Bilirubin, Disodium Salt,Bilirubin, Monosodium Salt,Calcium Bilirubinate,Hematoidin,delta-Bilirubin,Bilirubinate, Calcium,Calcium Salt Bilirubin,Disodium Salt Bilirubin,Monosodium Salt Bilirubin,Salt Bilirubin, Calcium,delta Bilirubin
D012367	RNA, Viral	Ribonucleic acid that makes up the genetic material of viruses.	Viral RNA
D016751	Hepatitis E	Acute INFLAMMATION of the LIVER in humans; caused by HEPATITIS E VIRUS, a non-enveloped single-stranded RNA virus. Similar to HEPATITIS A, its incubation period is 15-60 days and is enterically transmitted, usually by fecal-oral transmission.	Enterically-Transmitted Non-A, Non-B Hepatitis,Epidemic Non-A, Non-B Hepatitis,Hepatitis, Viral, Non-A, Non-B, Enterically-Transmitted,Hepatitis, Water-Borne,ET-NANBH,Enterically Transmitted Non A, Non B Hepatitis,Epidemic Non A, Non B Hepatitis,Hepatitides, Water-Borne,Hepatitis, Water Borne,Water-Borne Hepatitides,Water-Borne Hepatitis
D016752	Hepatitis E virus	A positive-stranded RNA virus species, causing enterically-transmitted non-A, non-B hepatitis (HEPATITIS E).	Hepatitis E virus (strain Burma),Orthohepevirus A,Paslahepevirus,Paslahepevirus balayani,Paslahepeviruses