The Utility of Retinol-Binding Protein 4 in Predicting Liver Fibrosis in Chronic Hepatitis C Patients in Response to Direct-Acting Antivirals

Background: Hepatic fibrosis grading is crucial for chronic hepatitis C (CHC) patients in monitoring liver disease progression and antiviral treatment indication. Retinol-binding protein 4 (RBP4), an adipokine secreted by adipocytes and hepatocytes, has variable levels in health and disease. Purpose: To comparatively evaluate RBP4 serum levels in predicting liver fibrosis in CHC versus fibroscan, noninvasive fibrosis, and inflammatory indices. Patients and Methods: Cohort study included 50 naive non-obese CHC patients and 20 age-, sex- and body mass index-matched healthy subjects. Fibroscan, RBP4, and noninvasive fibrosis as APRI, CDS, FIB-4, GUCI, Lok index indices based on serological markers, and inflammatory indices as platelet to lymphocyte ratio (PLR) and liver regeneration markers as; alpha-fetoprotein (AFP) and APRI, were evaluated in response to direct-acting antivirals (DAAs). Results: RBP4 was significantly lower in patients than in controls (P=0.0001) and progressively decreased with the increase in fibrosis grade (F0-F=41.42+/-3.08), (F2=39.32+/-1.43), (F3-F4= 35.31+/-0.5), (P=0.0001). Liver function, stiffness, and RBP4 significantly improved after treatment (P=0.0001). RBP4 negatively correlated with viral load (r=-0.78, p=0.0001), fibroscan fibrosis grade (r=-0.52, p=0.0001), AFP (r=-0.63, p=0.0001), and positively correlated with platelet (r=0.424, p=0.0001), and white cell count (r=0.298, p=0.002). RBP4 at a cutoff value <40.55 ng/mL might predict significant fibrosis (90.48% sensitivity, 62.5% specificity, AUROC=0.811, 95% CI=67.5-90.0) and at a cutoff value <35.9 ng/mL could predict advanced fibrosis (100% sensitivity, 100% specificity, AUROC =1.0, 95% CI=0.929-1). Conclusion: RBP4 showed excellent accuracy, sensitivity, specificity, PPV, and NPV. RBP4 has a superior diagnostic performance in predicting advanced fibrosis grads in CHC patients and hence can replace expensive invasive procedures.