The Utility of Noninvasive serologic markers in the management of early allograft rejection in liver transplantation recipients

Background. Early allograft rejection after orthotopic liver transplantation (OLT) currently requires a biopsy for diagnosis. Alpha- glutathione S-transferase (α-GST) and Pi-glutathione S-transferase (Pi-GST) are potential noninvasive markers of hepatocyte and biliary epithelial cell injury. Our aim was to determine the utility of noninvasive serologic markers in the management of early hepatic allograft rejection. Methods. Forty-four of 52 consecutive adult patients undergoing primary OLT at the University of Florida were included in the study. All had protocol liver biopsies between days 6 and 8 after OLT. Serum α-GST and plasma Pi-GST were determined using a sandwich enzyme immunoassay (Biotrin International, Dublin, Ireland). All biopsy specimens were retrospectively reviewed and scored for rejection and cholestasis. Results. The biopsy specimens were scored for rejection as moderate to severe in 14 patients (group 1) or none to mild in 30 patients (group 2). Group 1 had statistically higher mean levels than group 2 for α- GST on days 6, 7, and 9; alanine aminotransferase on days 6 and 9; aspartate aminotransferase (AST) on days 6 and 7; alkaline phosphate (AP) on days 3 through 7, 9, and 10; and γ-glutamyl transferase on day 3. No differences between groups were seen with Pi-GST or total bilirubin. Between days 6 and 8, the following values were found more frequently in group 1 than group 2: α-GST level >15 ng/ml (11/14 vs. 14/30; P<0.01); AST >100 U/L (8/14 vs. 2/30; P=0.002); and AP >120 U/L (14/14 vs. 17/30). Combining AP with either α-GST or AST led to improved detection of rejection over any single marker alone. In the first week after the initiation of rejection treatment, α-GST was the only marker that accurately predicted response. Conclusion. Serum α- GST may be useful in the management of early hepatic allograft rejection. A combination of noninvasive markers may be beneficial to diagnose early hepatic allograft rejection.