• Armin Karamian, Hana Farzaneh, Masoud Khoshnoodi, Nazanin Maleki, Saurabh Rohatgi, Jeremy N Ford, and Javier M Romero.
• School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. karamian.armin91@gmail.com.
• Eur J Trauma Emerg Surg. 2025 Jan 24; 51 (1): 6868.

PurposeTraumatic brain injury (TBI) is a leading cause of death and disability worldwide. In recent years, blood biomarkers including glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) have shown a promising ability to detect head CT abnormalities following TBI. This review aims to combine the existing research on GFAP and UCH-L1 biomarkers and examine how well they can predict abnormal CT results after mild TBI.MethodsOur study protocol was registered in PROSPERO (CRD42024556264). PubMed, Google Scholar, and Cochrane electronic databases were searched. We reviewed 37 full-text articles for eligibility and included 14 in our systematic review and meta-analysis.ResultsThirteen studies reported data for GFAP. The optimal cutoff of GFAP was 65.1 pg/mL with a sensitivity of 76% (95% CI 37 ̶ 95) and a specificity of 74% (95% CI 39 ̶ 93). In patients with GCS 13 ̶ 15 the optimal cutoff was 68.5 pg/mL, showing a sensitivity of 75% (95% CI 17 ̶ 98), and a specificity of 73% (95% CI 20 ̶ 97). Seven studies provided data on UCH-L1. The optimal cutoff was 225 pg/mL, with a sensitivity of 86% (95% CI 50 ̶ 97) and a specificity of 51% (95% CI 19 ̶ 83). In patients with GCS 13 ̶ 15, the optimal cutoff was 237.7 pg/mL, with a sensitivity of 89% (95% CI 74 ̶ 96), and a specificity of 36% (95% CI 29 ̶ 44). Modeling the diagnostic performance of GFAP showed that in adult patients with GCS 13-15 for ruling out CT abnormalities, at the threshold of 4 pg/mL, the optimal diagnostic accuracy was achieved with a sensitivity of 98% (95% CI 94-99) and (negative predictive value) NPV of 97%. For UCH-L1, the optimal diagnostic accuracy for ruling out intracranial abnormalities in adults with GCS 13-15 was achieved at the threshold of 64 pg/mL, with a sensitivity of 99% (95% CI 92-100) and NPV of 99%.ConclusionPresent results suggest that GFAP and UCH-L1 have the clinical potential for screening mild TBI patients for intracranial abnormalities on head CT scans.© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.

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