Diagnostic Accuracy and Prognostic Value of the Dual GFAP/UCH-L1 Test in Patients Presenting to the Emergency Department with Mild Traumatic Brain Injury

BACKGROUND: Excessive use of head computed tomography (CT) in mild traumatic brain injury (TBI) increases radiation exposure and contributes to emergency department crowding. Blood biomarkers glial fibrillary acid protein (GFAP) and ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) may improve risk stratification and guide clinical decision-making. We evaluated the diagnostic accuracy and prognostic value of a dual GFAP/UCH-L1 test, GFAP, and UCH-L1-individually and jointly-for detecting acute intracranial injury and predicting mortality. METHODS: We conducted a retrospective observational study at a tertiary hospital from March 10, 2023, to March 31, 2025. Adult patients presenting within 12 h of mild TBI (Glasgow Coma Scale score 13 to 15) with available serum GFAP and UCH-L1 measurements were included. Biomarker concentrations were measured on the Alinity i. Dual GFAP/UCH-L1 test positivity was defined as GFAP ≥35 pg/mL and/or UCH-L1 ≥400 pg/mL. The primary outcome was acute intracranial injury on head CT. Diagnostic performance was assessed using CT as the reference standard. Secondary outcomes were 30- and 90-day mortality. RESULTS: A total of 2932 patients were included (median age 83 years; 57% women). Intracranial injury was identified in 230 patients (7.8%). The dual GFAP/UCH-L1 test showed high sensitivity (97.4%) and negative predictive value (98.6%). GFAP demonstrated better discrimination (area under the receiver operating characteristic [ROC] curve [AUC] 0.768) than UCH-L1 (AUC 0.642) and GFAP + UCH-L1 (0.742). In multivariable analysis, dual GFAP/UCH-L1 test positivity (odds ratio [OR] 7.28) independently predicted intracranial injury. UCH-L1 was associated with 30 day (hazard ratio [HR] 1.00028) and 90-day mortality (HR 1.00022). CONCLUSIONS: The dual GFAP/UCH-L1 test provides strong rule-out accuracy for acute intracranial injury, while UCH-L1 offers meaningful prognostic information. Biomarker guided assessment may reduce unnecessary CT use and support early risk stratification in emergency care.