Sickle Cell Hepatopathy

Sickle cell disease is a hemoglobinopathy characterized by a mutation of the beta-globin chain caused by glutamic acid substituted by valine at the sixth codon, which results in the formation of the mutant sickle cell hemoglobin (HbS) allele ßs. This substitution decreases the solubility of HbS when deoxygenated, causing sickle erythrocytes that lead to intravascular occlusion, resulting in both acute and chronic complications. Acute complications commonly include acute chest syndrome, strokes, acute anemia due to sequestration or aplastic crisis, hepatic crisis, acute cholecystitis, and priapism. Chronic complications include chronic kidney disease, cholelithiasis, transfusion-related viral hepatitis, pulmonary hypertension, avascular necrosis, and thrombosis, to name a few. Heterozygous individuals for the ßs allele carry the sickle cell trait and do not have sickle cell disease. However, individuals who are homozygous for the ßs allele have sickle cell anemia. The gene is found in African countries, India, the Caribbean, and Central and South America. In the United States, 1 in every 360 African American newborns has sickle cell disease. Sickle cell hepatopathy is an umbrella term encompassing both acute and chronic liver complications associated with sickle cell disease. Acute manifestations include sickle hepatic crisis, acute intrahepatic cholestasis, and hepatic sequestration. Chronic liver involvement may arise from repeated vaso-occlusive injury, iron overload from chronic transfusions, viral hepatitis, and bile duct abnormalities such as sickle cell cholangiopathy. Sickle-cell hepatopathy has an incidence of 10% to 40% of patients with sickle cell disease. Sickle-related liver disease accounts for about 7% of all sickle-related deaths.