Serum Hepcidin Levels are Associated with Poor Outcomes of Patients with Severe Traumatic Brain Injury: A Two-Center Observational Analytical Study

Background: Severe traumatic brain injury (sTBI) is related to disturbances in iron metabolism, and hepcidin is involved in the regulation of this process. However, it is unclear about serum hepcidin levels after sTBI. In this study, serum hepcidin levels were detected for association with severity and worse outcomes of sTBI. Methods: In this two-center observational analytical study, age, gender, alcohol drinking, cigarette smoking, hypertension, diabetes mellites and hyperlipidemia were not significantly different between 154 patients with sTBI and 154 controls; and serum hepcidin levels were measured. The Glasgow Coma Scale (GCS) and Rotterdam computed tomography (CT) classification were used as severity metrics. Patients got 180-day follow-up by adopting the extended Glasgow Outcome Scale (GOSE), with score of 1– 4 signifying poor prognosis. The primary outcome was poor prognosis, and secondary outcomes included death, overall survival, and acute lung injury (ALI). Results were determined using multivariate approaches. Results: Serum hepcidin levels were markedly higher in patients than in controls. Serum hepcidin levels were linearly correlated with GCS scores, Rotterdam CT scores, GOSE scores, death risk, and possibilities of shorter overall survival, poor prognosis, and ALI, and were independently associated with preceding severity indicators and outcome variables. The results of regression analyses were robust, based on the E-value and sensitivity analyses. Serum hepcidin levels displayed analogous discrimination efficiency for death, poor prognosis, and ALI, compared to both GCS scores and Rotterdam CT scores. Moreover, ALI had a partial mediating effect on relationship between serum hepcidin levels, poor prognosis, and death. Conclusion: Substantially elevated serum hepcidin levels, in tight correlation with trauma severity, are closely associated with poor outcomes; and ALI partially deciphers links between serum hepcidin levels and clinical outcomes, indicating that serum hepcidin may be a prognostic surrogate of sTBI. Keywords: traumatic brain injury, hepcidin, severity, acute lung injury, outcome, biomarkers