Evaluation of glutamate dehydrogenase (GLDH) as a diagnostic and prognostic marker in drug-induced liver injury

Introduction
Drug-induced liver injury (DILI) is a significant clinical event, associated with notable morbidity and mortality. The paucity of DILI diagnostic and/or prognostic biomarkers still represents an unmet need.

Aim
We aimed to evaluate the role of glutamate dehydrogenase (GLDH) as a diagnostic and prognostic marker in patients with DILI.

Material and methods
A case-control study was conducted on 40 acute DILI patients and 40 acute viral hepatitis patients, in addition to a healthy control group (20). Clinical and laboratory characteristics were evaluated including ELISA assay of GLDH, along with RUCAM score and liver biopsy whenever feasible. All cases were followed up for 6 months. Diclofenac was the most incriminated drug in DILI (40%). GLDH was higher in the DILI than control and acute viral hepatitis patients (18.5 ±10.4, 0.89 ±0.6, 1.5 ±1.2 U/l) respectively (p < 0.001). Moreover, it was strongly correlated with aminotransferases, alkaline phosphatase, prothrombin concentration (PC), and bilirubin. The GLDH level in hepatocellular injury was 24.5 ±4.4 U/l, while it was 1.5.5 ±0.6 U/l in mixed and 3.5 ±1.1 U/l in cholestatic injury (p < 0.001). The AUC for GLDH level was 0.936 (p < 0.001) at a cutoff of 2.1 U/l, where the sensitivity was 90%, specificity 85%, positive predictive value 91.08% and negative predictive value 83.31% in prediction of DILI. GLDH was higher in patients who died than those who survived (32.36 ±1.1 vs. 15.36 ±10.1 U/l, respectively) (p = 0.000). Multivariate analysis defined age, bilirubin, and GLDH as independent predictors of poor outcomes in DILI.

Conclusions
GLDH is a highly specific, simple, real-time, and inexpensive diagnostic and prognostic marker of DILI and shows potential to address this unmet need.