• Alexander Koch, Henning W Zimmermann, Nikolaus Gassler, Christoph Jochum, Ralf Weiskirchen, Jan Bruensing, Lukas Buendgens, Hanna Dückers, Tony Bruns, Guido Gerken, Ulf P Neumann, David H Adams, Christian Trautwein, Ali Canbay, and Frank Tacke.
• Department of Medicine III, RWTH-University Hospital Aachen, Aachen, Germany.
• Liver Int. 2014 Oct 1; 34 (9): 1330-9.

Background & AimsAcute liver failure (ALF) is a life-threatening condition with a high mortality rate. The expression of urokinase plasminogen activator receptor (uPAR, CD87) and release of its shedded receptor into serum as soluble uPAR (suPAR) have been closely related to immune activation and prognosis in systemic inflammation and cirrhosis. We now aimed at investigating the clinical relevance and cellular source of uPAR and circulating suPAR in ALF.MethodsSerum suPAR concentrations were measured in 48 ALF patients and 62 healthy controls from a German liver transplantation centre. Hepatic immune cell subsets and uPAR expression were studied by FACS, qPCR and immunohistochemistry.ResultsCirculating suPAR levels were significantly increased in ALF patients, independent from the underlying aetiology, in comparison to controls. Serum suPAR concentrations were closely correlated with parameters reflecting liver cell injury, decreased liver function and the model of end-stage liver disease (MELD) score in ALF patients. By immunohistochemistry from explanted livers, ALF was associated with distinct immune cell accumulation and strong up-regulation of intrahepatic uPAR mRNA expression. CD87 (uPAR) expression was specifically detected on intrahepatic 'non-classical' monocytes (CD14(+) CD16(+) ), NKT and CD56(dim) NK cells isolated from human liver, but not on parenchymal or other non-parenchymal hepatic cell types. Membrane-bound uPAR was rapidly cleaved from monocytes upon inflammatory stimulation by lipopolysaccharide (LPS) and partially by co-cultured lymphocytes.ConclusionsSimilar to its prognostic properties in patients with sepsis or cirrhosis, intrahepatic uPAR activation and serum suPAR concentrations might serve as an interesting biomarker in ALF.© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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