Isolated elevation of aspartate aminotransferase (AST) in an asymptomatic patient due to macro‐AST

Abstract

Background A rare and benign cause of isolated aspartate aminotransferase (AST) increase is due to the presence of macro aspartate aminotransferase (macro‐AST). Macro‐AST is not usually considered by clinicians, leading to a large number of unnecessary and even invasive tests before diagnosed. Most commonly used laboratory methods for detection of macro‐enzymes are precipitation with polyethylene glycol (PEG), ultracentrifugation and gel filtration chromatography (GFC). Methods We report a case of an asymptomatic patient with persistent isolated AST elevation. PEG precipitation and an alternative method based on the low stability of this macro‐enzyme were performed on the patient serum. Results Macro‐AST was early detected by the laboratory observing a significant decrease in AST concentrations when the serum is stored at 4ºC. Conclusions Macro‐AST detection based in this method can be very useful as screening, especially in those laboratories where other technologies are not available. Macro‐AST must be considered as cause of unexplained isolated AST elevations before prior investigations to avoid the consequent cost and potential harm to the patient. In our case, early detection of macro‐AST with this method avoided unnecessary treatment and invasive test such as liver biopsy.

A Case of Macroenzyme Aspartate Aminotransferase Mimicking Hepatic Injury

“…Precipitation in PEG removes the immunoglobulin component of the immune complex, allowing for dissociation of the enzymes and accurate measurement of their concentrations. There are limitations, including low sensitivity and the need for confirmatory testing [4,5]. In general, when a PEG precipitation test is performed the results are interpreted based upon the "PEG precipitable activity" (i.e., "% percent precipitable activity {PPA}") and the reference range differs for each type of macroenzyme [4].…”

“…The early detection of macroenzymes is clinically important as it can prevent the unnecessary utilization of healthcare resources and reduce the financial burden on the patient. A simple and economic means for detecting macroenzymes is through the use of polyethylene glycol precipitation testing [4,5]. This case highlights the importance of an accurate diagnosis in the evaluation of isolated aspartate aminotransferase levels.…”

“…Macroenzymes are formed by the aggregation of monomeric immunoglobulins with circulating enzymes, ultimately forming large multimers that are difficult to clear in the kidneys [1][2][3][4][5][6]. There are two different forms of macroenzymes, macroenzyme type I and macroenzyme type II.…”

Isolated elevated aspartate aminotransferase in an asymptomatic woman due to macro-aspartate aminotransferase: A case report

“…Macroenzymes are serum high molecular weight compounds formed by complexes of enzymes and their polymerization products. The enzymes are usually linked to immunoglobulins (mainly Ig G and Ig M) or other plasma components, which make their clearance slower and more difficult via urine, and ultimately lead to higher levels of their activity[3,5]. Macro-AST is one type of macroenzyme, which was first reported by Konttinen in 1978 in two healthy women[6].…”

“…For the study, we requested a new sample from the patient and used two serum samples from other patients with elevated AST as controls. We conducted the precipitation with PEG following a previously described method[3,4]. The activity of AST dropped sharply to 1.4 U/L after the process (Table 2).…”