Serum GFAP and UCH-L1 Levels for the Assessment of the Absence of Hemorrhagic Transformation: A Multicenter Prospective Cohort Study.

Background: Currently, validated biomarkers for assessing hemorrhagic transformation (HT) after intravenous thrombolysis (IVT) are lacking. We aimed to validate a test combining GFAP (glial fibrillary acidic protein) and UCH-L1 (ubiquitin C-terminal hydrolase-L1) to indicate the absence of HT after IVT.

Methods: We prospectively enrolled consecutive patients with stroke treated with IVT from 16 hospitals. Serum GFAP and UCH-L1 levels were measured 24 hours after IVT. Cases from 1 hospital were randomly assigned to the training (70%) and testing (30%) cohorts for internal validation. The external validation cohort included patients from the other 15 hospitals. Cutoff levels of GFAP and UCH-L1 for assessing the absence of HT were established in the training cohort and subjected to internal and external verification.

Results: A total of 1063 patients were included. Both GFAP and UCH-L1 levels were independently associated with HT, infarct volume, and 3-month outcome; levels lower than cutoff (12.6 and 63.1 pg/mL, respectively) excluded patients with HT with a negative predictive value of 98.31% (95% CI, 89.70%-99.91%) and detection sensitivity of 98.08% (95% CI, 88.42%-99.90%) in the training cohort. In the testing and validation cohorts, negative predictive value was 100% (95% CI, 75.93%-100%) and 100% (95% CI, 82.19%-100%), respectively, and the sensitivity was 100% (95% CI, 80.76%-100%) and 100% (95% CI, 77.08%-100%), respectively.

Conclusions: Serum GFAP and UCH-L1 levels exhibit high sensitivity and negative predictive value for indicating the absence of HT 24 hours after IVT, which supports their potential role in assessing patients' condition after IVT.