Highlights
- •This is a study of clinical outcome, CXCL10 level, and viral phylogenetic analysis of 274 HEV infections in Belgium.
- •HEV gt3 clade is the strongest predictor for outcomes in symptomatic infections.
- •HEV gt3 clade efg is linked to higher hospitalisation rates, peak bilirubin levels, serum CXCL10 levels, and liver necro-inflammatory activity.
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.
Graphical abstract
Graphical Abstract
Keywords
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Article info
Publication history
Published online: September 05, 2022
Accepted:
August 19,
2022
Received in revised form:
July 29,
2022
Received:
December 3,
2021
Footnotes
Author names in bold designate shared co-first authorship
Identification
Copyright
© 2022 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
