{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T23:16:15Z","timestamp":1789168575935,"version":"build-2803163510"},"reference-count":37,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Intern Med"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Liver cirrhosis (LC) is frequently complicated by adrenal dysfunction; however, whether cirrhosis drives the coordinated, pathway\u2010specific reprogramming of cortisol metabolism remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>We aimed to characterize axis\u2010specific alterations in cortisol metabolism in patients with LC, those with adrenal insufficiency (AI), and controls using integrated serum and salivary steroid profiling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This prospective study included adults with LC (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a033) and control participants without cirrhosis who underwent cosyntropin\u2010stimulation test following transsphenoidal surgery for a nonfunctioning pituitary adenoma (controls,\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a027; AI,\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a010). Serum and saliva samples were collected at baseline, 30 and 60\u00a0min after stimulation and profiled for 26 serum and 12 salivary steroids through liquid chromatography\u2013tandem mass spectrometry. Multivariate models were constructed to identify cirrhosis\u2010associated steroid features, and their associations with disease severity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      LC was characterized by axis\u2010specific steroid remodeling, including suppressed 11\u03b2\u2010hydroxysteroid dehydrogenase 1 and A\u2010ring reduction activity with the 20\u03b1\u2010reduction pathway activation. Representative changes included a lower peak cortisol\u2010to\u2010cortisone ratio and reduced tetrahydrocortisone\u2010to\u2010cortisone ratio, alongside increased 20\u03b1\u2010reduced metabolites (all\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.001). This pattern was distinct from that in AI, in which steroid production and downstream metabolites were uniformly reduced. Iterative model refinement identified a parsimonious seven\u2010steroid signature that discriminated patients with LC from controls. Within the LC cohort, the steroid signature correlated with the Child\u2013Pugh score.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>LC is associated with coordinated, axis\u2010specific cortisol metabolic reprogramming, which is mechanistically distinct from AI. Integrated steroid profiling may provide mechanistic insight into altered glucocorticoid metabolism in cirrhosis and its relationship to disease severity\n.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/joim.70149","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T09:20:11Z","timestamp":1786699211000},"page":"513-527","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Liver cirrhosis is associated with altered glucocorticoid metabolism related to disease severity"],"prefix":"10.1111","volume":"300","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1462-5071","authenticated-orcid":false,"given":"Soyeon","family":"Park","sequence":"first","affiliation":[{"name":"Center for Advanced Biomolecular Recognition Korea Institute of Science and Technology  Seoul Republic of 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