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

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.

Quality control of total carbon dioxide (CO2) in serum or plasma using the Abbott Architect is affected by environmental pCO2 concentrations.

Introduction: Total CO2, or bicarbonate, is a parameter in clinical chemistry often applied to assess the metabolic status of a patient. This article discusses the observations and interventions during an episode of assay instability on an Abbott Architect routine chemistry analyser.Results: The Levey-Jennings plot of QC data showed a circadian pattern, having an overestimation of total CO2 during periods of high personnel attendance. A qualitative analysis revealed a correlation between atmospheric CO2 in the lab environment and the acquired total CO2 value in a quality control sample. Assessment of total CO2 is hence influenced by the equilibrium between atmospheric CO2, dissolved CO2 and bicarbonate. The effect is more pronounced on samples containing low concentrations of total CO2. The bias related to environmental CO2 is also noticeable on patient samples, patient means between periods with high and low atmospheric CO2 levels differed by 2 mmol/L.Discussion: Passive ventilation of the laboratory environment is proven insufficient during weather conditions in which the lab is not exposed to wind. Consistent reduction of atmospheric CO2 could only be guaranteed with an active ventilation infrastructure. Systematic closure of analyser lids also reduced analyser variance.Conclusion: The lab environment is an important source of parameter variance. Both environmental and infrastructural aspects must be considered when assessing the potential cause of the instability.