α-Glutathione S-Transferase: A New Biomarker for Liver Injury?

Background: Serum alanine and aspartate aminotransferases (ALT/AST) have been the gold standard for detection and quantification of liver injury for over 6 decades, but have relatively long half-lives (T1/2) (literature estimates approximately 17 and 47 h, respectively) and thus do not reflect immediate changes in liver injury or recovery. A new point-of-care immunoassay for α-glutathione S-transferase (α-GST) measures this cytosolic liver enzyme with a predicted T1/2 of 60-90 min based on preliminary studies and might enable earlier detection of improving or worsening liver injury than conventional enzyme testing. Methods: Serial serum samples collected daily from 31 patients enrolled in the Acute Liver Failure Study Group, with acetaminophen (APAP) toxicity, drug-induced liver injury, ischemic hepatopathy (IH), or autoimmune hepatitis were analyzed to determine α-GST using the Qualigen FastPack® α-GST Assay (Carlsbad), a chemiluminescent immunoassay using a paramagnetic particle matrix with an upper limit of normal of 11 ng/mL. AST and ALT values were obtained from the medical record and have an upper limit of normal of 40 IU/L. The T1/2 values for α-GST, AST, and ALT were calculated from the peak value for APAP and IH etiologies considered as single time point injuries, using an exponential trendline equation of the serial values. Results: Median α-GST for all etiologies were increased on day 1, returning to normal by day 3, whereas median AST and ALT values did not return to normal, even at day 7. The median T1/2 for α-GST, AST, and ALT were 6.4, 22.2, and 33.9 h, respectively. Conclusions: α-GST is a more responsive marker of liver injury/recovery, allowing for more rapid real-time assessment of improvement or worsening of liver disease.