Soluble urokinase plasminogen activator receptor is a marker for severity of liver fibrosis in hepatitis C infection

Aims: The plasminogen activator system and its receptors have been implicated in different immune mechanism and serum levels of the soluble urokinase plasminogen activator receptor (suPAR) are elevated in infectious and immune mediated diseases. However, while the importance of the coagulation cascade has been suggested in liver fibrogenesis due to viral heatitis, the role of the fibrinolytic pathway remains unclear. We evaluated the association of serum levels of suPAR with established parameters of liver fibrosis in two independent HCV infected cohorts.

Patients and methods: 146 patients with chronic HCV infection were included into the study (64 subjects in the screening cohort from Aachen, 82 in the validation cohort from Berlin). The diagnosis was based on a positive anti-HCV test and a positive HCV-RNA. Chronic liver diseases apart from HCV or an alcohol intake of more than 40g/day were excluded by standard procedures. Stage of fibrosis was assessed by liver biopsy and platelets counts and serum AST levels were determined to calculate the APRI-Score. In the Berlin cohort patients underwent transient elastography (Fibroscan®) at the time of liver biopsy. Serum levels of suPAR levels were quantified by ELISA.

Results: Serum levels of suPAR were significantly associated with the histological fibrosis score in both cohorts. While the mean suPAR levels in patients with F1 and F2 fibrosis were not different from healthy control subjects, there was a significant increase in suPAR serum concentration at higher stages of liver fibrosis (F3 and F4, P<0.0001). suPAR values had a high diagnostic specificity and sensitivity to differentiate between fibrosis stages F1/F2 and F3/F4 with an AUC of 0.774 (P=0.0001) and for the differentiation of F1/F2/F3 versus F4 (AUC 0.791, P=0.0001). Furthermore, suPAR concentrations were strongly correlated with the values of transient elastography (r=0.52, P<0.0001) and the APRI score (r=0.44, P<0.0001).

Conclusion: Serum suPAR levels were robust markers of liver fibrosis in two cohorts with a comparable diagnostic accuracy for prediction of severe liver fibrosis as established non-invasive marker. They might therefore be analyzed head to head or in combination with these parameters in forthcoming studies.