Sickle cell hepatopathy
Authors: Subhas Banerjee, Charles Owen, Sanjiv Chopra
Journal: Hepatology (2001)

Sickle cell hepatopathy encompasses a range of hepatic pathology arising from a wide variety of insults to the liver in patients with sickle cell disease.It occurs predominantly in patients with homozygous sickle cell anemia, and to a lesser extent in patients with sickle cell trait, Hb SC disease and Hb S ␤ thalassemia.The hepatic disease may primarily be caused by the sickling process, but more commonly arises as a consequence of the multiple transfusions that these patients require in their lifetime.The term multitransfusion hepatopathy may therefore be more appropriate for these latter patients.The direct manifestations of sickle cell disease in the liver relate predominantly to vascular occlusion with acute ischemia, sequestration, and cholestasis, although chronic cholestatic syndromes have also been described.The main hepatic complications of multiple transfusions include acute and chronic infection with hepatitis B and C and iron overload.A further potential consequence of the chronic hemolysis is the development of pigment stones, with consequent cholecystitis and acute and chronic biliary obstruction from choledocholithiasis.Unfortunately, much of the literature on sickle cell hepatopathy lacks depth, because there are few sizeable or controlled studies, and most studies provide only incomplete information regarding coexisting chronic infection with hepatitis B or C, hepatic iron deposition, and chronic biliary obstruction from choledocholithiasis.It is therefore difficult to evaluate the contributing effects of these various insults in the final pathologic and clinical picture in these patients.As will be discussed subsequently, sickle cell anemia may lead to several unique liver syndromes (Table 1). CLINICAL SYNDROMESHomozygous sickle cell anemia affects 1 in 600 African American babies, and sickle cell trait affects 8% to 10% of the black population. 1 Few American studies have sought to establish the incidence of liver disease in this population.In an autopsy study on 70 patients with sickle cell anemia, sickle C disease, and sickle thalassemia, hepatomegaly was noted in 91% of patients, indicating that some form of liver involvement is relatively common. 2bnormal liver function tests are common in patients with sickle cell anemia, even in the absence of liver disease.Raised bilirubin levels, predominantly unconjugated, are universal in sickle cell patients due to chronic hemolysis.Total bilirubin concentrations are usually less than 6 mg/dL.Johnson et al. found that 72 of 100 patients with sickle cell anemia had an isolated elevation of bilirubin, with no other clinical or laboratory evidence of liver disease. 3Bilirubin levels correlate with lactic dehydrogenase levels, 3 suggesting that variable levels found in patients are related to the degree of hemolysis and/or ineffective erythropoiesis rather than to disorders of bilirubin transport or processing.Hemolysis also raises plasma aspartate transaminase (AST) levels, which therefore also correlate with lactic dehydrogenase levels. 3Plasma alanine transaminase (ALT) levels therefore more accurately reflect hepatocyte injury in sickle cell patients.Elevations in the serum alkaline phosphatase are commonly seen in patients with sickle cell anemia, particularly during pain crises.However, studies suggest that bone alkaline phosphatase is the major enzyme fraction contributing to this increase. 4,5 ACUTE SYNDROMESPatients with sickle cell disease may present with an acute syndrome characterized by right upper quadrant abdominal pain and jaundice.The differential diagnosis includes acute sickle hepatic crises, sickle cell intrahepatic cholestasis, acute viral hepatitis, cholecystitis, and choledocholithiasis with common bile duct obstruction.These can usually be differentiated by a careful history, liver function tests, serologic tests for viral hepatitis, and hepatobiliary imaging studies. Acute Sickle Hepatic Crisis Hepatic Sequestration Crisis/Reverse SequestrationIn patients with sickle cell anemia, the usual site of massive sequestration of red blood cells is in the pulmonary vasculature, and before the advent of hyposplenism, the spleen.Hepatic sequestration may also occur, usually presenting with