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The biomarker suPAR and gastroenterology

The following factors are associated with an elevated suPAR level:

    • Cirrhosis1,2,5
    • Alcoholic liver disease3
    • Excessive alcohol consumption3
    • Nonalcoholic fatty liver disease4
    • Acute liver failure6,8
    • Alcoholic pancreatitis7
    • Poor prognosis1-5,7

In addition, an elevated suPAR level is associated with future incidence of:

    • Hepatocellular carcinoma8

Inflammation plays a key role in the development of chronic hepatic diseases, and as suPAR is a marker of the degree of inflammation, the diagnostic and prognostic value of suPAR in hepatic diseases has been studied.

The suPAR level is significantly higher in patients with cirrhosis compared to healthy controls1,2. In a study of 159 patients with chronic hepatic diseases, including 98 patients with cirrhosis, the diagnostic ability of suPAR in identifying cirrhosis was good, and suPAR was a strong predictor of mortality or need of transplantation. A cutoff level >9 ng/mL predicted a poor prognosis with a sensitivity and specificity of 70.7% and 77.8%, respectively, as well as a relative risk of 8.5 (3.5-20.3)1.

The suPAR level is higher in patients with alcoholic etiology and correlates positively with fibrosis1,3,4. In addition, the suPAR level is higher in individuals with excessive alcohol consumption compared to healthy individuals3.

In patients with decompensated cirrhosis, the suPAR level is significantly higher (median 12.9 ng/mL) than in patients with compensated cirrhosis (8.9 ng/mL), and suPAR is associated with 28-day mortality5.

In patients with spontaneous bacterial peritonitis, an elevated suPAR level in ascites fluid was found, and the level was associated with severity and prognosis5.

“It has become clear that suPAR is a very strong prognostic marker, exceeding the prognostic value of all other routinely measured biomarkers in our hospital.”

Prof. Ove Andersen,
MD, PhD, DmSc, Copenhagen University Hospital Hvidovre, Denmark
suPAR News Vol. 3, June 2020

In a small study of patients with acute liver failure, a high median suPAR level of 13.2 ng/mL was found. Similarly, a strong correlation between suPAR and declining liver function (increasing AST/ALT and INR), independently of the etiology, was found6.

A study of 104 patients shows that the suPAR level on admission was superior to CRP, hematocrit, and creatinine as a prognostic marker of the severity of acute alcoholic pancreatitis. Using a cut-off value of 5 ng/mL, the sensitivity and specificity for predicting moderate or serious pancreatitis were 79% and 78%, respectively. The suPAR level was significantly associated with severity: Mild and moderate/serious: 4.2 ng/mL vs. 6.2 ng/mL, respectively7.

1. Zimmerman HW, Koch A, Seidler S et al. Circulating soluble urokinase plasminogen activator is elevated in patients with chronic liver disease, discriminates stage and etiology of cirrhosis and predicts prognosis. Liver Int. 2012 Mar;32(3):500-509.
2. Wiese S, Mortensen C, Gøtze JO. Cardiac and proinflammatory markes predict prognosis in cirrhosis. Liver Int. 2014 Jul;34(6):e19-30.
3. Tuomi, Heidi, et al. “Serum soluble urokinase plasminogen activator receptor in alcoholics: Relation to liver disease severity, fibrogenesis, and alcohol use.” J Gastroenterolo Hepatic 2014 Dec;29(12): 1991-1995.
4. Sjöwall C, Martinsson K, Cardell K et al. Soluble urokinase plasminogen activator receptor levels are associated with severity of fibrosis in nonalcoholic fatty liver disease. Trails Res. 2015 Jun;165(6):658.666.
5. Zimmermann HW, Reuken PA, Koch A, et al. Soluble urokinase plasminogen activator receptor is compartmentally regulated in decompensated cirrhosis and indicates immune activation and short-term mortality. J Intern Med 2013; 274: 86–100 Koch A, Zimmerman H, Gassler N et al. Clinical relevance and cellular source of elevated soluble urokinase plasminogen activator receptor in acute liver failure. Liver int. 2014 Oct;34(9):1330-1339.
6. Nikkola, A., Aittoniemi, J. J., Huttunen, R., Sand, J., & Laukkarinen,J. (2015). Mo1351 Systemic Levels of Soluble Urokinase-Type Plasminogen Activator Receptor (suPAR) Predict the Severity of Acute Alcohol Pancreatitis. Gastroenterology, 148(4), S-680.
7. Chounta, A. et al. Serum soluble urokinase plasminogen activator receptor as a screening test for the early diagnosis of hepatocellular carcinoma. Liver Int. 35, 601–607 (2015)
8. Loosen SH et al, Serum levels of soluble urokinase plasminogen activator receptor (suPAR) predict outcome after resection of colorectal liver metastases. Oncotarget. 2018 5;9(43):27027-27038.

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