S5855 Macro-AST: Recognizing a Rare Cause of Liver Enzyme Elevation

Introduction: Macro-aspartate aminotransferase (AST) is a rare, benign phenomenon that presents a diagnostic challenge due to persistently elevated AST levels in the absence of underlying liver disease. It results from the formation of a high molecular weight complex between AST and serum proteins, most commonly immunoglobulins, which hinders renal clearance and leads to falsely elevated serum AST. This phenomenon can mimic hepatocellular injury, often prompting extensive work up. Recognition of macro-AST is essential, as misinterpretation can lead to unnecessary and invasive diagnostic evaluations. We present a case that highlights this phenomenon. Case Description/Methods: A 54-year-old woman with a history of hyperlipidemia and Gilbert’s syndrome was referred for persistent elevation of AST, peaking at 299 U/L. Other liver-associated enzymes, including ALT, alkaline phosphatase, gamma-glutamyl transferase, and international normalized ratio, were within normal limits. Total bilirubin was mildly elevated to 1–2 mg/dL, predominantly indirect, consistent with known Gilbert’s syndrome. A comprehensive workup 2 years prior -including viral, autoimmune, and metabolic panels; hepatic imaging; liver biopsy; and assessment for muscle pathology- was unrevealing. Given the isolated, chronic AST elevation with no clinical evidence of liver disease, macro-AST was suspected. Polyethylene glycol (PEG) precipitation testing revealed pre-PEG AST of 281 U/L and post-PEG AST of 5 U/L, confirming the presence of macro-AST. Discussion: Macro-AST is an underrecognized cause of isolated AST elevation. While generally benign, its misinterpretation as hepatocellular etiology often leads to extensive and invasive diagnostic work up. PEG precipitation testing is the most accessible method for diagnosis, demonstrating high sensitivity and specificity. Alternative methods include ultracentrifugation and gel filtration chromatography—the current diagnostic gold standards—though they are less widely available. Emerging approaches, such as refrigerated sample storage at 4°C, have shown inconsistent utility. Clinicians should consider macro-AST in patients with isolated AST elevation, particularly when other investigations are normal, to avoid unnecessary interventions.