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

Background and Aims: Reliable novel noninvasive 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. Approach and Results: We collected cross-sectional clinical data for a derivation cohort (n = 86) and a validation cohort (n = 431), totaling 517 subjects with liver biopsy. Advanced liver fibrosis was defined by the METAVIR pathological score (F ≥3). Dual cutoff values for diagnosis were explored. In the derivation cohort, plasma FSTL-1 levels were significantly elevated in patients with advanced liver fibrosis, with an AUROC of 0.85 (95% CI, 0.75–0.96). 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 the METAVIR scoring system, including interface hepatitis, lobular necrosis, and hepatocellular ballooning ( p < 0.0001). A cutoff 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%). Conclusions: Plasma FSTL-1 has high diagnostic accuracy and could potentially reduce the need for liver biopsy in identifying patients with advanced liver fibrosis.