Paradoxical hepcidin–iron dysregulation in primary sclerosing cholangitis
Petr Kordac, Milan Hajek, Monika Cahova, Mojmir Hlavaty, Petr Sedivy, Monika Dezortova, Dita Pajuelo, Kamila Balusikova, Jan Brezina, Pavel DrastichBackground
Primary sclerosing cholangitis (PSC) is a chronic, progressive liver disease characterised by biliary inflammation. Its exact aetiology remains unclear. This study aimed to use a combination of diagnostic methods and blood analysis to better understand the metabolic changes accompanying PSC.
Methods
PSC patients (n = 60) and healthy controls (n = 60) were evaluated by magnetic resonance imaging and spectroscopy (hepatic fat and iron content), ultrasonography, standard blood analysis expanded with markers of iron metabolism, and colonoscopy.
Results
PSC patients exhibited significant liver fibrosis and elevated liver enzymes. Serum hepcidin was increased ( p < 0.01), but PSC patients did not show any markers of anaemia. Serum iron concentration and transferrin saturation were increased compared with healthy controls ( p < 0.0001 and p < 0.001, respectively) but did not reach levels seen in hemochromatosis. In contrast, the liver iron content was lower in PSC patients ( p < 0.0001).
Conclusion
PSC patients demonstrated an atypical pattern of iron metabolism: elevated circulating iron and depleted liver iron stores despite increased hepcidin levels. This paradox suggests a disruption of hepcidin-mediated iron regulation, potentially sustaining a proinflammatory environment. Further investigation is warranted to clarify underlying mechanisms and therapeutic implications.
Trial Registration
Clinical Trials I.D.: