Case Presentation: A 40-year-old man presented with complaints of right upper abdominal pain and malaise. He reported no fevers, chills, or change in pain with food intake. He has a history of Sickle Cell Disease (HgbSS) and cholelithiasis. Physical examination revealed icteric sclera and tenderness to palpation in the right upper quadrant.
Labwork returned with a total bilirubin level of 58 mg/dL, direct bilirubin level of 36 mg/dL, AST 187 units/L, ALT 61 units/L, alkaline phosphatase 303 units/L, BUN of 17 mg/dL, Creatinine of 2.6 mg/dL. PT and INR were elevated at 16 seconds and 1.6, respectively. White blood cell count was elevated at 15 x 103/microL. Hemoglobin was 8.0 g/dL, above patient baseline. Reticulocyte index was 9.2% and LDH was elevated at 709 units/L. Peripheral smear revealed 1+ sickle cells. Hepatitis serologies were non-reactive.
Abdominal ultrasound noted cholelithiasis without findings suggestive of cholecystitis. Ultrasound and subsequent MRCP showed no biliary ductal dilatation ANA, Anti-Smooth Muscle Antibodies and Anti-Microsomal Antibodies were negative.
The patient was diagnosed with intrahepatic cholestasis and was treated with an urgent exchange blood transfusion. Hemoglobin electrophoresis improved following exchange to HgbS < 30%. Both his renal and liver dysfunction demonstrated improvement following exchange and the patient was discharged home.
Discussion: Sickle Cell Disease is a widely prevalent inherited disorder of hemoglobin with a high mortality rate due to its multi organ complications. Hepatic manifestations of the disease, broadly referred to as sickle hepatopathy, can vary in severity as well as chronicity at presentation. Implicated culprits include gallstone disease, acute hepatic crisis, hepatic sequestration crisis, and acute viral hepatitis as a consequence of recent transfusion.
Intrahepatic cholestasis (SCIC) has also emerged as a rare but often fatal form of sickle cell liver disease. Clinically, SCIC is defined as extreme conjugated hyperbilirubinemia, coagulopathy, and acute right upper abdominal pain from acute hepatomegaly. Chronic sickling within the sinusoids of the liver leads to hepatic dysfunction. Over time, progressive hypoxia and ischemia cause ballooning hepatocytes. Due to its infrequent presentation, the management of patients with SCIC is not clear. Multiple case reports, however, have demonstrated improvement in patient outcomes with exchange blood transfusions (EBT). Concomitant renal dysfunction, as seen here, has also been observed and represents a poor prognostic factor. Although the pathophysiology of this dysfunction remains unclear, EBT has been shown in these trials to facilitate renal recovery as well.
Conclusions: Sickle cell crises can lead to significant morbidity and mortality if not diagnosed quickly. Recognition of SCIC can lead to prompt treatment including exchange transfusion to prevent multi-organ damage.