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

Abstract

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.

Keywords:

• APRI
• FIB-4
• GUCI
• noninvasive fibrosis indices
• platelet lymphocyte ratio
• transient elastography fibroscan

Acknowledgments

We acknowledge Alnoby AM for cooperative help in data analysis.

Disclosure

The authors have declared no potential conflicts of interest in this work.