Serum growth differentiation factor 15: A novel biomarker for diagnostic and prognostic prediction in biliary atresia

Growth differentiation factor 15 (GDF15), a stress-responsive cytokine, is a diagnostic biomarker of mitochondrial diseases. Given our previous finding that hepatocellular mitochondrial viability is crucial for native liver survival (NLS) in patients with biliary atresia (BA), this study investigated whether GDF15 could function as a biomarker for liver injury, diagnosis, and prognosis in BA.

Using immunofluorescence, the proportion of GDF15-positive hepatocytes were determined in liver specimens obtained at treatment initiation from BA, other infantile cholestatic diseases (IC), and choledochal cysts or hepatoblastoma having normal livers (NL). Its correlation with hepatic fibrosis severity, jaundice clearance (JC) achievement, and NLS was evaluated in BA. Using ELISA, serum GDF15 levels were measured in patients with BA, IC, and age-matched healthy controls and correlated with the proportion of GDF15-positive hepatocytes and liver biochemical parameters at diagnosis.

The GDF15-positive hepatocyte proportion was higher in BA (n = 54) than in IC (n = 22) or NL (n = 16) (p < 0.001). This proportion was also higher in BA without JC (p < 0.01) or NLS (p < 0.05) and correlated with fibrosis severity (p < 0.001). Serum GDF15 levels were higher in BA (n = 11) than in IC (n = 9) (cutoff = 680.4 pg/mL; sensitivity = 80%, specificity = 82%) and controls (n = 40) (p < 0.001), and significantly correlated with GDF15-positive hepatocyte proportion (p < 0.001) and with total and direct bilirubin, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase (all p < 0.05), while showing inverse correlations with platelet count (p < 0.01).

GDF15 is a reliable indicator of hepatic dysfunction and a diagnostic and prognostic biomarker of BA.

Ⅱ.