TY - JOUR
T1 - Circulating soluble urokinase plasminogen activator is elevated in patients with chronic liver disease, discriminates stage and aetiology of cirrhosis and predicts prognosis
AU - Zimmermann, Henning W.
AU - Koch, Alexander
AU - Seidler, Sebastian
AU - Trautwein, Christian
AU - Tacke, Frank
PY - 2012/3
Y1 - 2012/3
N2 - Background: 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. Aims: We evaluated suPAR serum levels as a diagnostic and prognostic biomarker in patients with chronic liver diseases. Methods: 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 3 years. Results: 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 >9 ng/ml indicated adverse prognosis (sensitivity: 70.7%, specificity: 77.8%, relative risk: 8.5; 95% confidence interval: 3.5-20.3). Conclusions: 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.
AB - Background: 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. Aims: We evaluated suPAR serum levels as a diagnostic and prognostic biomarker in patients with chronic liver diseases. Methods: 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 3 years. Results: 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 >9 ng/ml indicated adverse prognosis (sensitivity: 70.7%, specificity: 77.8%, relative risk: 8.5; 95% confidence interval: 3.5-20.3). Conclusions: 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.
KW - Chronic liver disease
KW - Cirrhosis
KW - Fibrosis
KW - Inflammation
KW - Mortality
KW - suPAR
UR - https://www.scopus.com/pages/publications/84856659379
U2 - 10.1111/j.1478-3231.2011.02665.x
DO - 10.1111/j.1478-3231.2011.02665.x
M3 - Article
C2 - 22098627
AN - SCOPUS:84856659379
SN - 1478-3223
VL - 32
SP - 500
EP - 509
JO - Liver International
JF - Liver International
IS - 3
ER -