The Tip of the Iceberg: A Rare Cause of Acute Liver Failure

Case Presentation:

A 53 year-old man with a history of sickle cell trait and stroke presented with subacute, progressively worsening generalized abdominal pain and distension. He had recently been diagnosed with cirrhosis due to autoimmune hepatitis at an outside hospital. Physical examination was notable for scleral icterus and a nontender, moderately distended abdomen with bulging flanks.

Initial testing showed bilirubin 28mg/dL (direct: 19mg/dL), ALT 35U/L, AST 78U/L, ALK 206IU/L, hemoglobin 11mg/dL, and INR 2.2. He was diagnosed with autoimmune hemolytic anemia with LDH 756U/L, haptoglobin 17mg/dL, and Coombs positive. Diagnostic paracentesis showed no infection. CT abdomen showed cirrhosis, ascites, and splenic and renal infarcts. Broad work-up for cirrhosis was significant only for a weakly positive anti-smooth muscle antibody. He was treated with prednisone for autoimmune hepatitis. He failed to improve, with ongoing hemolysis and pain. Bilirubin rose to 41mg/dL. Hemoglobin electrophoresis showed hemoglobin S 51% and hemoglobin C 46%, consistent with hemoglobin SC disease. Liver biopsy showed septal fibrosis and dilated sinusoids filled with sickled erythrocytes. He received several exchange transfusions with initial improvement and was referred for liver transplant. Unfortunately, his condition deteriorated and he died.

Discussion:

Acute liver failure is commonly seen by the hospitalist. This case illustrates a rare cause of acute cholestatic liver failure and several cognitive heuristics that led to errors, delaying accurate diagnosis and treatment.

This patient was ultimately diagnosed with hemoglobin SC disease, a milder form of homozygous hemoglobin SS sickle cell disease (SCD). SCD can cause several forms of both acute and chronic liver disease. A rare, life-threatening complication of SCD is acute vascular occlusion leading to sequestration and intrahepatic cholestasis, characterized by hyperbilirubinemia and high mortality. Treatment of acute liver failure due to SCD is challenging. Exchange transfusion to keep the combined hemoglobin S and C level <30% can be used. Liver transplantation is a final option though outcomes data are sparse and liver failure can recur.

The diagnosis was delayed in this case due to several cognitive errors, including blind obedience and availability and anchoring heuristics. Blind obedience led to relying on the diagnosis of sickle cell trait though the patient had many clinical signs of SCD, such as history of stroke, splenic autoinfarction, and nephropathy. Autoimmune hemolytic anemia was diagnosed, rather than SCD, by availability heuristic. Anchoring led clinicians to fail to explore other causes of liver failure after autoimmune hepatitis was diagnosed.

Conclusions:

Hemoglobin SC disease with acute cholestasis is a rare cause of liver failure. SCD should be considered on the differential diagnosis for acute cholestatic liver failure. Cognitive heuristics can lead to errors in clinical reasoning.