Relation of Liver Siderosis to Liver Fibrosis in Hemodialysis Patients with Severe Hyperferritinemia Secondary to High Doses of Intravenous Iron Supplementation

Published:September 27, 2022DOI:
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      Aggressive iron substitution in hemodialysis (HD) patients leads to iron overload. The association between liver siderosis and fibrosis is still debatable. We studied the association of liver siderosis with liver fibrosis in HD patients. Furthermore, we studied the performance of liver stiffness measurements in identifying advanced liver fibrosis. We investigated the performance of biochemical indicators of iron status in identifying advanced liver fibrosis.

      Patients and methods

      Fifty-five HD patients (average hemodialysis duration 6±2 years) with hyperferritinemia secondary to intravenous iron supplementation (weakly iron dose 252.7 ± 63 mg; median blood transfusions 3 [2-5]) were recruited. The liver fibrosis grade was determined with FibroScan, APRI, and Fib-4 index. Liver iron concentration (LIC) was estimated with MRI. Iron parameters and liver function biochemical indicators were also assessed.


      The median serum ferritin and TSAT were 3531 μg/l and 77%, respectively. 34.5%, 20%, and 45.5% of the patients showed mild, moderate, or severe liver siderosis, respectively. All patients with severe liver siderosis showed advanced liver fibrosis. Patients with severe liver siderosis and advanced liver stiffness showed higher serum iron, TSAT, AST, ALT, serum bilirubin, APRI, and Fib-4 index scores than those with mild liver siderosis. Serum iron and TSAT showed good utility in identifying advanced liver fibrosis determined with FibroScan, APRI, and Fib-4 index. Liver stiffness exhibited good utility in identifying advanced liver fibrosis diagnosed with APRI and Fib-4 index.


      High weekly intravenous iron dose associated with severe hyperferritinemia, high serum iron, and TSAT might lead to severe liver siderosis and concomitant liver fibrosis in HD patients. Serum iron and TSAT, Fibroscan, Fib-4 and APRI scores might offer non-invasive tools for identifying advanced liver fibrosis in those patients.



      ALP (alkaline phosphatase), ALT (alanine aminotransferase), APRI (Aspartate aminotransferase-to-platelet ratio index), AST (aspartate aminotransferase), BALP (bone alkaline phosphatase), CKD (chronic kidney disease), ESKD (end-stage kidney disease), Fib-4 (fibrosis-4 index), HD (hemodialysis), kPa (kilopascal), LSM (liver stiffness measurement), TIBC (total iron binding capacity), TSAT (transferrin saturation)