A 75-year-old man is brought to the emergency department from home after being found unresponsive by his son. His medical history is significant for coronary artery disease with coronary stenting 2 years ago, diabetes mellitus, hypertension, and stroke. He was hospitalized 2 months ago with pneumonia and upper gastrointestinal bleeding, during which time he received intravenous antibiotics and a transfusion of 4 units of packed red blood cells. In the emergency department today, temperature is 39.1 C (102.4 F), blood pressure is 70/40 mm Hg, pulse is 120/min, respiratory rate is 32/min, and oxygen saturation is 79% on room air. Laboratory results are notable for leukocytosis but are otherwise unremarkable. Chest x-ray reveals a new right upper lobe infiltrate. He is treated with normal saline, antibiotics, vasopressors, and mechanical ventilation. The next day, laboratory analyses reveal the following:
Hemoglobin 9.5 mg/dL Leukocytes 15,000/mm3 Platelet 120,000/mm3 Sodium 137 mEq/L Potassium 4.1 mEq/L Chloride 100 mEq/L Bicarbonate 19 mEq/L Blood urea nitrogen 51 mg/dL Creatinine 2.1 mg/dL Bilirubin, total 1.2 mg/dL Aspartate aminotransferase 3,720 units/L Alanine aminotransferase 3,250 units/L Alkaline phosphatase 162 mEq/L
Which of the following most likely accounts for the abnormal liver function panel?
This patient presented with unresponsiveness, likely from septic shock (hypotension requiring vasopressors, respiratory failure requiring mechanical ventilation) in the setting of pneumonia (right upper lobe infiltrate, leukocytosis, fever). One day later, he developed elevations in the aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. This presentation is most consistent with ischemic hepatic injury, or shock liver.
The hallmark of ischemic hepatopathy is a rapid and significant increase in the transaminases with modest accompanying elevations in total bilirubin and alkaline phosphatase. AST and ALT levels peak at 25 to 250 times the upper limit of normal and can reach >10,000 U/L. This reflects diffuse liver injury due to hypotension; as a result of the liver's dual blood supply, diffuse injury is more common than focal infarction. In patients who survive the underlying cause of their hypotension (eg, septic shock, heart failure), liver enzymes typically return to normal within 1-2 weeks.
(Choice A) Acute viral hepatitis can lead to large AST and ALT elevations but is typically accompanied by significant hyperbilirubinemia, nausea, and vomiting. Although this patient recently received blood transfusions, donor blood screening has virtually eliminated the risk of blood transfusion–associated hepatitis C infection.
(Choice B) Alcoholic liver disease typically causes less dramatic increases in the transaminases compared to those seen in this patient. The AST/ALT ratio is usually ~2, and the AST is rarely >300 units/L.
(Choice C) Granulomatous disorders (eg, tuberculosis, sarcoidosis) rarely cause massive transaminase elevations. Chronic hepatic damage is occasionally associated.
(Choice E) Acalculous cholecystitis is a common complication of critical illness that arises due to gallbladder stasis. Patients have symptoms of biliary obstruction. Elevations of the alkaline phosphatase and total bilirubin levels are more significant than those of the transaminase levels.
(Choice F) Iron overload may cause chronic hepatic dysfunction with low-grade elevations in the AST and ALT. Transfusion of 4 units of packed red blood cells would be unlikely to cause iron overload.
(Choice G) Autoimmune hepatitis may cause large increases in the AST and ALT. However, young women are more commonly affected, and the associated serum bilirubin increases are typically more dramatic.
Educational objective:
Ischemic hepatic injury occurs in the setting of hypotension and manifests as acute, massive increases in the transaminases with milder associated increases in the total bilirubin and alkaline phosphatase. In patients who survive the inciting condition (eg, hypotension), liver enzymes typically return to normal within a few weeks.