Serum hyaluronic acid and procollagen type III N-terminal peptide as predictive biomarkers for iron overload-induced liver fibrosis in hemoglobinopathies

Background. Iron overload, a common complication of hemoglobinopathies such as sickle cell disease (SCD) and beta thalassemia major (BTM), drives liver fibrosis. Therefore, noninvasive biomarkers for early detection are critical. Hyaluronic acid (HA) and procollagen III N-terminal peptide (PIIINP) are potential biomarkers; however, their diagnostic utility in iron overload-induced liver fibrosis remains underexplored. Objective. To evaluate the diagnostic performance of serum HA and PIIINP levels as biomarkers for iron overload-induced liver fibrosis in patients with SCD and BTM. Materials and methods. This case-control study included 42 patients with SCD, 40 with BTM, and 50 healthy controls (40 were age-matched with BTM). Serum HA and PIIINP levels were measured via ELISA. Ferritin, liver enzyme, and renal function markers were analyzed using automated analyzers. Results. HA and PIIINP levels were significantly elevated in SCD (HA: 85.29±13.37 ng/mL; PIIINP: 4.44±1.2 ng/mL) and BTM patients (HA: 88.06±13.69 ng/mL; PIIINP: 4.67±1.53 ng/mL) compared to controls (HA: ~43 ng/mL; PIIINP: ~3.1 ng/mL; p<0.001). HA demonstrated superior diagnostic performance (AUC: 99% in BTM and 98% in SCD; sensitivity: 99% in BTM and 97% in SCD; specificity: 96% in BTM and 94% in SCD; cut-off: >57.8 ng/mL in BTM and >56.4 ng/mL in SCD) to PIIINP (AUC: 78% in BTM and 80% in SCD; sensitivity: 73% in BTM and 76% in SCD; specificity: 88% in BTM and 80% in SCD; cut-off: >4.1 ng/mL in BTM and >3.7 ng/mL in SCD). Conclusions. HA and PIIINP are promising noninvasive biomarkers for detecting iron overload-induced liver fibrosis in hemoglobinopathies, with HA showing superior diagnostic accuracy.