S5503 Macro-AST: A Rare but Benign Cause of Persistent Isolated AST Elevation

Introduction: Macro-aspartate aminotransferase (macro-AST) is a benign phenomenon caused by the formation of high-molecular-weight complexes, typically between aspartate aminotransferase (AST) and immunoglobulins, that results in isolated serum AST elevation without evidence of actual liver or muscle injury. Despite normal findings on other liver tests and the absence of symptoms, unrecognized macro-AST may trigger extensive, sometimes invasive, diagnostic evaluations. We report a case of a 65-year-old woman with persistently elevated AST, which was confirmed as macro-AST via polyethylene glycol (PEG) precipitation. Case Description/Methods: A 65-year-old woman with a history of chronic obstructive pulmonary disease (COPD) and xerophthalmia was referred for evaluation of persistently elevated AST levels. For 4 years, her AST remained elevated (139 U/L), while her alanine aminotransferase, alkaline phosphatase, and bilirubin levels were normal. She reported minimal alcohol use, a long history of smoking, and limited physical activity due to COPD. Abdominal computed tomography and ultrasound showed no hepatic lesions and normal hepatobiliary anatomy. Viral and autoimmune hepatitis markers were negative. ANA was positive at a titer of 1:160, and the rheumatoid factor was within normal limits. Immunoglobulins, C-reactive protein, erythrocyte sedimentation rate, ceruloplasmin, alpha-1 antitrypsin, ferritin, iron panel, thyroid-stimulating hormone test, and monospot tests were also normal. Sjögren’s syndrome testing was negative. Absent joint symptoms ruled out autoimmune arthritis. Due to persistent isolated AST elevation, macro-AST testing via PEG precipitation was performed, confirming the diagnosis, with AST dropping to 17 U/L post-precipitation. Discussion: Macro-AST results from immune-complex formation between AST and immunoglobulins, producing a high-molecular-weight enzyme that remains in circulation without causing actual tissue injury. It is a benign and often underrecognized cause of isolated AST elevation. In asymptomatic patients with persistently elevated AST and otherwise unremarkable workups, macro-AST should be considered early to avoid extensive and invasive evaluations, including liver biopsy. While diagnostic methods such as gel filtration chromatography and ultracentrifugation are available, they are costly and not routinely accessible. PEG precipitation remains the preferred method because it is easy to use, cost-effective, and widely accessible. Greater awareness among clinicians and laboratory professionals about this condition can help minimize unnecessary tests and lower overall healthcare expenses.