Growth differentiation factor-15 as a non-invasive biomarker of liver fibrosis in sickle cell disease

Int J Hematol. 2025 Nov;122(5):637-646. doi: 10.1007/s12185-025-04035-8. Epub 2025 Jul 13.

Abstract

This study aimed to evaluate the relationship between growth differentiation factor-15 (GDF-15) levels and liver fibrosis in patients with sickle cell disease (SCD) and assess the diagnostic performance of GDF-15 as a non-invasive biomarker. Thirty patients with SCD were categorized into two groups based on fibrosis severity (≥ F2 vs. < F2) determined by Fibroscan, AST to Platelet Ratio Index (APRI) and FIB-4. GDF-15 levels were compared between groups, and independent predictors of GDF-15 were identified by multiple linear regression. Patients with significant liver fibrosis (≥ F2) had significantly higher GDF-15 levels. Multivariate linear regression revealed that GDF-15 concentration was independently associated with liver elastography values (β = 0.619, p = 0.002). The area under the curve for detecting significant fibrosis using GDF-15 as a diagnostic test was 0.835 (95% CI: 0.686-0.983, p = 0.002). A GDF-15 cut-off of 4200 pg/ml had a positive predictive value of 73.6%, a negative predictive value of 81.8%, sensitivity of 87.5% and specificity of 64.3%. In conclusion, GDF-15 is strongly associated with liver fibrosis in SCD and demonstrates high diagnostic accuracy as a non-invasive biomarker. Given its role in inflammation, oxidative stress, and iron metabolism, GDF-15 may serve as a valuable tool for early fibrosis detection and disease monitoring.

Keywords: Fibroscan; GDF-15; Liver fibrosis; Non-invasive diagnosis; Sickle cell disease.

MeSH terms

  • Adolescent
  • Adult
  • Anemia, Sickle Cell* / blood
  • Anemia, Sickle Cell* / complications
  • Biomarkers / blood
  • Elasticity Imaging Techniques
  • Female
  • Growth Differentiation Factor 15* / blood
  • Humans
  • Liver Cirrhosis* / blood
  • Liver Cirrhosis* / diagnosis
  • Liver Cirrhosis* / etiology
  • Male
  • Middle Aged
  • Young Adult

Substances

  • Growth Differentiation Factor 15
  • Biomarkers
  • GDF15 protein, human