Diagnostic Test Accuracy of Serum Glutamate Dehydrogenase (GLDH) for Drug-Induced Liver Injury: A Meta-Analysis

Drug-induced liver injury (DILI) remains an important clinical and regulatory challenge because commonly used liver injury biomarkers may lack sufficient tissue specificity. Alanine aminotransferase (ALT), the standard biochemical marker, may be elevated in both hepatic and non-hepatic injury, limiting its ability to distinguish hepatocellular damage from skeletal muscle injury. Serum glutamate dehydrogenase (GLDH), a hepatocyte-enriched mitochondrial enzyme, has been proposed as a more tissue-specific biomarker of hepatocellular injury. The objective of this study was to systematically determine the pooled sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), and diagnostic odds ratio of serum GLDH for DILI; to construct a summary receiver operating characteristic (SROC) curve; and to assess the certainty of evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE) for diagnostic test accuracy. Systematic searches of major electronic databases were conducted from inception to December 2024. Studies reporting the sensitivity and specificity of serum GLDH for DILI in adults using a valid reference standard were included. Two reviewers independently screened studies, extracted data, and assessed study quality using Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). Bivariate random-effects meta-analysis using the Reitsma model was performed in R (R Foundation for Statistical Computing, Vienna, Austria). Certainty of evidence was assessed using GRADE for diagnostic test accuracy. Six studies, including 1,617 participants, comprising 595 DILI cases and 1,022 controls, were included. Pooled sensitivity was 0.87 (95% CI 0.80-0.92), and pooled specificity was 0.86 (95% CI 0.81-0.90). Pooled LR+ was 6.30 (95% CI 4.30-9.23), and pooled LR- was 0.15 (95% CI 0.10-0.24). The SROC curve demonstrated excellent overall discrimination. Sensitivity analysis excluding two case-control studies with high spectrum bias yielded consistent estimates. The certainty of evidence was low for sensitivity and very low for specificity, mainly because of spectrum bias in two studies and indirectness related to the control population in one study. Serum GLDH demonstrates good diagnostic accuracy for identifying DILI across the included studies, with a pooled sensitivity of 87% and specificity of 86%. These findings support GLDH as a complementary biomarker to ALT, particularly in clinical contexts where hepatocyte-specific injury needs to be distinguished from non-hepatic causes of aminotransferase elevation. Further high-quality prospective studies are needed to evaluate GLDH alongside ALT in real-time diagnostic and clinical decision-making settings.