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Macrophage markers soluble CD163 and soluble mannose receptor are associated with liver injury in patients with paracetamol overdose

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Version 2 2020-02-26, 13:16
Version 1 2019-05-08, 16:30
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posted on 2020-02-26, 13:16 authored by Cecilie Brøckner Siggaard, Konstantin Kazankov, Sidsel Rødgaard-Hansen, Holger J. Møller, Mhairi C. Donnelly, Kenneth J. Simpson, Henning Grønbaek

The macrophage activation markers, soluble CD163 (sCD163) and soluble mannose receptor (sMR), are associated with liver disease severity and prognosis. We aimed to investigate macrophage activation reflected by sMR and sCD163 in patients with mild and severe paracetamol (PCM) intoxication and effects of antidote treatment in patients and healthy controls. We measured sMR and sCD163 levels by in-house enzyme-linked immunosorbent assays in two independent prospective cohorts of PCM overdosed patients: 49 patients with early mild PCM overdose from Aarhus University Hospital and 30 patients with severe acute liver injury included at the Royal Infirmary of Edinburgh. Furthermore, we investigated sMR and sCD163 in 14 healthy controls during N-acetylcysteine treatment. Within the mild PCM cohort, patients with elevated alanine transaminase on admission had significantly higher levels of sCD163 compared with patients with normal alanine transaminase (2.92[2.00–5.75] versus 1.29[1.02–1.69] mg/L, p = .009), whereas sMR showed no significant difference. In patients with acute liver injury, both markers were markedly higher compared to the mild PCM cohort (sCD163: 10.73[5.79–14.62] versus 1.34[1.06–1.96], p < .001; sMR: 0.80[0.63–1.14] versus 0.18[0.14–0.25], p < .001). Antidote treatment significantly reduced sCD163 levels in both PCM overdosed patients and healthy controls. In conclusion, macrophage activation assessed by the levels of sMR and sCD163 is associated with the degree of liver injury in patients with PCM intoxication and is ameliorated by antidote treatment, suggesting macrophage involvement in PCM-induced liver injury.

Trial registration:ClinicalTrials.gov identifier: NCT03679442.

Funding

This work was supported by the NOVO Nordisk Foundation (Grant no. R159-A13267) and Savvaerksejer Jeppe Juhl og hustru Ovita Juhls Mindelegat (Grant no. 2013-1). Both have been granted personally to Henning Grønbaek. Holger Jon Møller received funding from Medical sciences, Danish Council for Independent Research (Grant no. TRAIN 10-092797). Furthermore, Henning Grønbaek has received research grants from Abbvie and Intercept. Konstantin Kazankov has received lecture fees from Norgine.

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    Scandinavian Journal of Gastroenterology

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