Solving the mystery of persistent isolated aspartate aminotransferase elevation: Macro-AST as a decisive diagnostic consideration

Background Persistent isolated elevation of aspartate aminotransferase (AST) often poses a diagnostic challenge. Macro-AST, though underrecognized, is a benign cause that may avoid unnecessary investigations. Aim To characterize the clinical and laboratory features of macro-AST in Chinese adults and to describe our experience with the PEG precipitation method in identifying this condition. Methods Clinical data from patients presenting with persistent isolated AST elevation at Beijing Ditan Hospital, Capital Medical University, between February and August 2025 were analyzed. All patients underwent comprehensive laboratory tests (including routine biochemistry, muscle enzymes and autoantibodies), imaging studies (abdominal ultrasound and transient elastography), and liver biopsy. After excluding other definitive diseases, macro-AST was confirmed using the PEG precipitation method. Sera from one healthy control and one disease control (with chronic active hepatitis B) were also collected. Results Three patients (2 female, 1 male) were confirmed with macro-AST. Immunological evaluation revealed heterogeneous serological features among the three patients, including positive autoantibodies and variably elevated immunoglobulin levels in a subset of cases. The persistent isolated AST elevation was not adequately explained by any histological finding. Following PEG precipitation, the AST recovery rate was considerably lower in macro-AST patients (mean 9.71% ± 6.29%; individual values: 2.02%, 17.42%, and 9.68%) than in the healthy control (88.10%) and the disease control with chronic active hepatitis B (59.63%), while PPA% was markedly higher in macro-AST patients (mean 90.29% ± 6.28%; individual values: 97.97%, 82.58%, and 90.32%) than in the healthy control (11.90%) and the disease control (40.37%). Conclusion Macro-AST should be considered in cases of persistent isolated AST elevation with unremarkable workup. Testing for macro-AST by PEG precipitation should be considered before proceeding to invasive procedures such as liver biopsy. In this study, the PEG precipitation method proved to be a practical adjunctive tool for identifying macro-AST, although its reliability and diagnostic accuracy in a wider population remain to be confirmed.