Circulating soluble urokinase plasminogen activator is elevated in patients with chronic liver disease, discriminates stage and aetiology of cirrhosis and predicts prognosis

Abstract

Inflammation is a major factor for the progression of chronic liver diseases. Interactions between urokinase plasminogen activator (uPA) and its receptor (uPAR) have been functionally linked to hepatic inflammation and fibrosis in mice. High serum concentrations of soluble uPAR (suPAR) are suggested to reflect activated immune cells. We evaluated suPAR serum levels as a diagnostic and prognostic biomarker in patients with chronic liver diseases. Prospective, cross-sectional cohort study of 159 patients with chronic liver diseases (61 without, 98 with established cirrhosis) and 43 healthy controls. Transplant-free survival was monitored for up to 3years. Soluble urokinase plasminogen activator serum concentrations were significantly elevated in patients with chronic liver diseases compared with controls. Cirrhotic patients displayed higher levels than non-cirrhotics, closely depending on stage of fibrosis or cirrhosis. suPAR levels had high diagnostic power to identify established cirrhosis in chronic liver diseases. Circulating suPAR closely correlated with liver function, fibrosis markers, but also with systemic inflammation and renal function. A distinct suPAR elevation was noticed in patients with alcoholic aetiology of liver disease. suPAR identified alcoholic origin more precisely compared with classical indicators of alcoholism (mean corpuscular volume, gamma glutamyl transpeptidase). Strikingly, elevated suPAR levels were identified as a strong predictor of mortality or need for transplantation. suPAR levels >9ng/ml indicated adverse prognosis (sensitivity: 70.7%, specificity: 77.8%, relative risk: 8.5; 95% confidence interval: 3.5-20.3). Serum suPAR is a potential novel biomarker for the diagnosis of cirrhosis, identification of alcoholic origin and for determining prognosis in patients with chronic liver disease.