Impact of fibroblast growth factor 23 (FGF23) for the pathogenesis of decompensated liver cirrhosis

• Applicant: Professor Dr. Christian Lange
• Subject Area: Gastroenterology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 559832542

Systemic inflammation has been recognized as an important determinant of the progression of liver cirrhosis, in particular in the development of organ failures and acute-on-chronic liver failure. Fibroblast Growth Factor 23 (FGF23) is a cytokine of the FGF19-family, playing an important role in the regulation of phosphate and vitamin D homeostasis. In addition, FGF23 impacts on inflammatory processes, for example by modulating migration of neutrophil granulocytes or induction of acute-phase-proteins in the liver. Two different forms of FGF23 exist: intact FGF23, which is bioactive and mediates the above-mentioned functions of FGF23, and a cleaved form of FGF23 (C-terminal FGF23, Cter-FGF23), which plays a recently discovered role in iron metabolism by suppressing inflammation-induced hepcidin-secretion in the liver. Hence, FGF23 could have pleiotropic effects in the pathogenesis of decompensated cirrhosis and ACLF, as well as in anaemia of patients with cirrhosis. The role of intact FGF23 and Cter-FGF23 for the pathogenesis of cirrhosis, ACLF and anaemia shall therefore be investigated in human samples with liver cirrhosis, in organoids as well as in two animal models of acute-on-chronic liver injury (carbontetrachloride (CCl4)- and ethanol-induced chronic liver injury, in combination with sterile systemic inflammation vs. infection).

• DFG Programme: Research Grants