| Title: |
Severe hypophosphatemia induced by excessive production of FGF23 in acute hepatitis: from bedside to bench. |
| Authors: |
Hamroun, Aghiles, Boukrout, Nihad, Cauffiez, Christelle, Fellah, Sandy, Hauwaert, Cynthia Van der, Pottier, Nicolas, Mentaverri, Romuald, Zaworski, Jeremy, Gnemmi, Viviane, Gibier, Jean-Baptiste, Letavernier, Emmanuel, Louvet, Alexandre, Provôt, François, Lenain, Rémi, Maanaoui, Mehdi, Glowacki, François, Lionet, Arnaud |
| Source: |
Clinical Kidney Journal; Nov2024, Vol. 17 Issue 11, p1-11, 11p |
| Subject Terms: |
HEPATIC fibrosis, FIBROBLAST growth factors, GENE expression, CIRRHOSIS of the liver, IN situ hybridization |
| Abstract: |
Background Although hepatic production of FGF23 has been suggested in chronic settings, there are no data indicating hypophosphatemia resulting from acute hepatic FGF23 production. Based on two clinical observations of profound hypophosphatemia in the setting of acute hepatitis, our study investigates the hypothesis of acute FGF23 liver expression. Methods Retrospective analyses were conducted to estimate FGF23 liver expression both qualitatively (in situ hybridization) and quantitatively (relative FGF23 gene expression and protein production) on histological specimens of human and murine acute hepatitis livers, compared with controls of hepatic fibrosis or healthy liver. Results The index clinical case involves acute alcoholic hepatitis complicated by profound hypophosphatemia due to phosphate diabetes, revealing a major production of both FGF23 C-terminal fraction (cFGF23) and bio-intact form (iFGF23, 39 751 RU/mL, N: 21–91; and 228.6 pg/mL, N: 22.7–93.1, respectively). A second case of acute hepatitis related to erythrocytic protoporphyria also exhibited comparable abnormalities. In both cases, no other cause of renal phosphate wasting was identified, and the hydroelectrolytic disorders disappeared in parallel with normalization of the liver balance and FGF23 levels. Histological data of acute hepatitis compared with cirrhosis and healthy liver confirmed our hypothesis of hepatic FGF23 overproduction. Furthermore, mouse models showed a significant increase in FGF23 mRNA relative liver expression in acute hepatitis and a moderate increase in cirrhosis, compared with healthy liver (respectively 60.55 ± 16.75 and 3.70 ± 0.87 vs 1.00 ± 0.65, both P < .05). These findings were also confirmed at the protein level. Conclusion This translational study raises the hypothesis of renal phosphate wasting induced by excessive hepatic production of FGF23 in case of acute hepatitis. [ABSTRACT FROM AUTHOR] |
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| Database: |
Complementary Index |
