Metabolism of iron in liver diseases in childhood

Objective: We aimed to specify the changes of iron metabolism in acute and chronic liver diseases, to determine iron accumulation in these patients, to investigate the correlation between iron metabolism and the present inflammation and whether iron accumulation in the liver in case of acute and chronic liver diseases plays a role in worsening of liver pathology accordingly.Material and Method: All the individuals diagnosed with acute and chronic liver disease who presented to Karadeniz Technical University, Faculty of Medicine, Department of Pediatrics, Division of Gastroenterology on 02/02/2009 to 01/09/2010 were included in the study group independently of age and gender. A total of 44 patients were included during a period of 1,5 years. 10 of these had acute hepatitis and 34 had chronic liver disease. The cases were examined in three groups: cases with acute hepatitis was classified as Group 1; cases who recovered 4 weeks after acute hepatitis were classified as Group 2 and cases with chronic liver disease were classified as Group 3.In patients in Group 1 and Group 3, hemogram, alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, albumin, gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), serum iron (SI), iron binding capacity (IBC), ferritin, C-reactive protein (CRP), coagulation tests (prothrombin time (PT)-activated partial thromboplastin time (aPTT)), hepatitis markers (Anti HCV IgM, anti HBs IgM, Anti HAV IgM, AntiHbC IgM), hepcidin, interleukin-6(IL-6), transforming growth factor-beta (TGF-ß), total oxidative status (TOS), total antioxidant status (TAS) tests were performed. TOS and TAS results were evaluated using oxidative stress index (OSI) which is obtained by TOS/TAS ratio. In patients in Group 2, AST-ALT, bilirubin, GGT, hepcidin, IL-6, TGF-ß, TOS, TAS, ferritin and serum iron were measured.To determine the severity of damage in the liver, Child-Pugh and PELD/MELD scoring was performed. Totally 25 liver biopsy specimens were examined. Iron staining, histopathological classification (fibrosis score) and liver dry iron weight were studied in liver specimens. Subjects who received erythrocyte transfusion or whole blood transfusion at least one month before the study and who did not sign informed consent form were excluded from the study. The data of the three groups were compared using SPSS 16.0 statistical program.Results: Ferritin, hepcidin, AST and ALT levels in Group 1 were statistically higher than Group 2 and Group 3 (p<0.05). Although mean hepcidin and ferritin levels in Group 3 were higher than Group 2, no difference was found to be statistically significant (p>0.05). A statistically significant difference was not found in IL-6, TAS, TOS, TGF-ß, CRP, OSI (TOS/TAS) levels between the three groups (p>0.05). While no correlation was found between hepcidin and ferritin and inflammatory markers (IL-6, TGF-ß, CRP) and between hepatic fat accumulation/fibrosis and iron staining, a positive correlation was found between hepcidin and ferritin and PELD (p<0.05).Conclusion: Hepcidin and ferritin have been found to be higher proportionally to liver inflammation in acute hepatitis. However, the fact that there is no positive correlation between hepcidin and ferritin, IL-6 and TGF-ß in acute hepatitis indicates that hepcidin increases independently of ferritin, IL-6 and TGF-ß. In patients with chronic liver disease, a non-statistical increase in hepcidin and ferritin levels compared to subjects who recovered was attributed to the heterogeneity of cases. The fact that the oxidant and antioxidant systems were not effected to a high degree in patients with acute and chronic liver disease suggested that the present inflammation was not severe enough to activate the oxidant system.