Soluble Urokinase Plasminogen Activator Receptor is Associated With Progressive Liver Fibrosis in Hepatitis C Infection

Background: Progressive liver fibrosis is the main predictor of disease outcome in chronic hepatitis C viral (HCV) infection. Although the importance of the coagulation cascade has been suggested in liver fibrogenesis, the role of the fibrinolytic pathway is yet unclear. Goal: We evaluated the association of serum levels of the fibrinolysis-associated soluble urokinase plasminogen activator receptor (suPAR) with the severity of liver fibrosis in HCV infection. Study: suPAR serum levels were assessed in 146 chronically HCV-infected patients of 2 independent cohorts (64 subjects in the screening cohort, 82 in the validation cohort) by enzyme-linked immunosorbent assay and correlated with biopsy-proven histologic stage of liver fibrosis and noninvasive liver fibrosis markers (aspartate transaminase to platelets ratio index score, transient elastography). Results: suPAR serum levels were strongly associated with the histologic stage of liver fibrosis in both cohorts (P < 0.0001). Although mean suPAR levels in patients with F1 and F2 fibrosis were not different from healthy control subjects, they were significantly increased at higher stages of liver fibrosis (F3 and F4, P < 0.0001). suPAR values had a high diagnostic specificity and sensitivity to differentiate mild/moderate fibrosis (F1/F2) from severe fibrosis (F3/F4) with an area under curve of 0.774 (P = 0.0001) and for the differentiation of noncirrhosis from cirrhosis (F1/F2/F3 vs. F4, area under curve 0.791, P = 0.0001). SuPAR serum levels were also strongly correlated to the noninvasive fibrosis markers aspartate transaminase to platelets ratio index score (r = 0.52) and transient elastography (r = 0.44, both P < 0.0001). Conclusions: Serum suPAR levels were robust markers of liver fibrosis in 2 cohorts with a comparable diagnostic accuracy for prediction of severe liver fibrosis as established noninvasive marker.