Serum Alpha-1 Antitrypsin as a Prognostic Biomarker in Idiopathic Sudden Sensorineural Hearing Loss: A Pilot Longitudinal Study

Idiopathic sudden sensorineural hearing loss (ISSNHL) carries an uncertain prognosis, and no validated serum biomarker currently guides treatment decisions. This prospective pilot study examined whether serum Alpha-1 Antitrypsin (A1AT), a hepatically synthesized anti-inflammatory protease inhibitor, predicts audiological recovery following corticosteroid treatment and whether its longitudinal trajectory reflects treatment response. Thirteen adults with confirmed ISSNHL received a standardized 14-day oral corticosteroid course, with escalation to intratympanic steroids or hyperbaric oxygen for insufficient responders. Serum A1AT and audiometric assessments using the individual pure-tone average (iPTA, 500–8000 Hz) were obtained at diagnosis (T0), one month (T1), and three months post-treatment (T2). Significant overall hearing improvement was confirmed across timepoints (Friedman χ² = 10.706, p = .005). Baseline A1AT predicted iPTA improvement at T1 (Spearman ρ = 0.808, p < .001) and at T2 (ρ = 0.791, p = .001). Responders by Modified Siegel criteria had a mean baseline A1AT of 165.0 mg/dL versus 131.5 mg/dL in non-responders (Mann-Whitney U = 1.0, p = .019). The cumulative change in A1AT from T0 to T2 was negatively correlated with hearing recovery (ρ = −0.797, p = .001): patients whose A1AT declined showed greater improvement, while all four patients with rising A1AT showed no recovery. Baseline A1AT was unrelated to hearing loss severity at diagnosis (ρ = 0.049, p = .873). These findings support A1AT as both a baseline prognostic marker and a dynamic indicator of cochlear anti-inflammatory response in ISSNHL.