박소연 (한국과학기술연구원, 한양대학교)

최만호 (한국과학기술연구원)

박소연 (한국과학기술연구원, 한양대학교)

박민정 (고려대학교 의과대학)

박승신 (서울대학교 의과대학)

이준석 (한양대학교)

조은주 (서울대학교 의과대학)

김정희 (서울대학교 의과대학)

최만호 (한국과학기술연구원)

Liver cirrhosis is frequently complicated by adrenal dysfunction; however, whether cirrhosis drives the coordinated, pathway-specific reprogramming of cortisol metabolism remains unclear.  This study aimed to characterize cortisol metabolic reprogramming in liver cirrhosis using serum and salivary steroid profiles evaluated by LC-MS and to evaluate its clinical significance.  Patients with liver cirrhosis (n = 33), control subjects (n = 27), and patients with adrenal insufficiency (n = 10) were enrolled and underwent a cosyntropin stimulation test.  Serum and saliva samples were collected at baseline and at 30 and 60 minutes post-stimulation and profiled for 26 serum and 12 salivary steroids using LC-MS.  Patients with liver cirrhosis exhibited a distinct steroid metabolic profile characterized by reduced 11β-hydroxysteroid dehydrogenase activity and A-ring reduction, and enhanced 20α-reduction, indicating extensive cortisol metabolic reprogramming.  Based on these metabolic alterations, a seven-steroid signature was established, demonstrating excellent diagnostic performance for liver cirrhosis (AUROC = 0.992, 95% CI: 0.970–1.000). In addition, the steroid signature was significantly associated with the Child–Pugh score and independently predicted hepatic decompensation (hazard ratio = 4.06, p < 0.05).  The proposed steroid panel may provide a promising diagnostic assay, assessment of disease severity, and prediction of clinical outcomes in patients with liver cirrhosis.

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