OBJECTIVE:: Chronic blood transfusion therapy reduces clinical events in children with sickle cell anemia but increases risk for an iron-related liver injury. Liver biopsy is the gold standard technique for quantifying liver iron content (LIC) and evaluating liver pathology. Ferritin, liver enzymes, and R2* magnetic resonance imaging of the liver are obtained as surrogate markers. In this study we compared surrogate markers with the gold standard, liver biopsy, in assessing liver histology. METHODS:: We conducted a retrospective review of 259 liver biopsies in 109 children with sickle cell anemia on chronic transfusion therapy and chelation therapy during a 9-year period at a single center. Liver pathology was compared with LIC, ferritin, and alanine aminotransferase. RESULTS:: Ferritin correlates with LIC (râ€Š=â€Š0.74, Pâ€Š< â€Š0.001), although there is a broad range of ferritin values for a given LIC. Furthermore, patients with a high LIC (≥7 mg Fe/g dry weight) demonstrated significantly higher ferritin as compared to the patients with lower LIC <7 (Pâ€Š<â€Š0.001). Periportal/portal inflammation also showed a significant relation. There was no significance when comparing ferritin and lobular inflammation or ferritin and alanine aminotransferase. When evaluating LIC in relation to fibrosis, the present study revealed that there was only a significant correlation with severe fibrosis (Fâ€Š=â€Š36, Pâ€ Š<â€Š0.001). CONCLUSIONS:: The results suggest that although correlations exist among ferritin and LIC and severe fibrosis and LIC, caution should be taken when they are used in isolation. Liver biopsy provides important pathologic information that cannot be obtained through surrogate markers. © 2014 by European Society.