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The Liver in Sickle Cell Disease. ABSTRACT: Liver involvement is found in nearly 40% of children with sickle cell disease. The most frequent complication is cholelithiasis. The most severe complication is acute hepatic crisis, with symptoms ranging from increasing jaundice to multiple organ failure and death. The emergency and mostly efficient treatment is exchange transfusion. Chronic cholangiopathy is increasingly recognized, with autoimmune features in most cases, worsened by chronic ischemia. Transfusion-related iron overload is not yet a concern in children, and hepatotoxicity of iron chelators is rare. We propose recommendations to prevent, explore, and treat these complications. We emphasize the close collaboration required between hepatologists and specialists of sickle cell disease.