Plasma FSTL-1 as a non-invasive diagnostic biomarker for patients with advanced liver fibrosis

Objective: Reliable novel non-invasive biomarkers for the diagnosis of advanced liver fibrosis are urgently needed in clinical practice. We aimed to investigate the accuracy of plasma Follistatin-like protein 1 (FSTL-1) in the diagnosis of advanced liver fibrosis in chronic liver diseases. Design: We collected cross-sectional clinical data for a Derivation Cohort (n=86) and a Validation Cohort (n=431), totaling 517 subjects with the liver biopsy. Advanced liver fibrosis was defined by the METAVIR pathological score (F≥3). Dual cut-off values for diagnosis were explored. Results: In the Derivation Cohort, plasma FSTL-1 levels were significantly elevated in patients with advanced liver fibrosis, with an area under the receiver operating characteristic curve (AUROC) of 0.83 (95% confidence interval [CI], 0.74-0.92). In the Validation Cohort, plasma FSTL-1 maintained good diagnostic performance, with an AUROC of 0.88 (95% CI, 0.83-0.92). Plasma FSTL-1 levels were significantly associated with individual histological features of METAVIR scoring system, including interface hepatitis, lobular necrosis, and hepatocellular ballooning ( p <0.0001). A cut-off value≤0.43 ng/mL was the optimal rule-out threshold, with a sensitivity of 84.62% (95%CI 76.46%-90.30%) and a specificity of 79.51% (95%CI 74.81%-83.53%), while≥0.50 ng/mL was the best rule-in threshold, with a specificity of 86.41% (95%CI 81.06%-90.43%) and a sensitivity of 70.67% (95%CI 64.41%-76.23%). Conclusion: Plasma FSTL-1 has high diagnostic accuracy and could potentially reduce the need for liver biopsy in identifying patients with advanced liver fibrosis.