{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:26:14Z","timestamp":1788395174345,"version":"build-2803163510"},"reference-count":47,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Fujian Provincial Natural Science Foundation of China","award":["2023J011690"],"award-info":[{"award-number":["2023J011690"]}]},{"name":"Major Project of Guangzhou National Laboratory","award":["GZNL2024A02003"],"award-info":[{"award-number":["GZNL2024A02003"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2026,6,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Fluconazole is key for pulmonary cryptococcosis (PC), but its hepatotoxicity (HT) risk is unclear. This study characterized fluconazole-induced liver injury in HIV-negative PC patients and explored its mechanism. We integrated clinical cohort analysis (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 123), network toxicology, molecular docking, and transcriptomics. HT incidence was 23.6%, predominantly cholestatic (55.2%). Immunocompromised status independently increased HT risk (aRR = 2.67,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.004). Baseline ALT &gt;16.5 U\/L was the best predictor (AUC = 0.69) among liver enzymes, which showed modest discriminatory value. A model combining liver enzymes, immune status, and comedications achieved superior prediction (AUC = 0.76). Mechanistically, AKT1, ERBB2, and KDR were identified as potential core targets. Transcriptomics confirmed their significant downregulation in general cholestasis models, and molecular docking demonstrated favorable affinity binding with fluconazole (strongest for KDR: \u22126.5 kcal\/mol). In conclusion, baseline liver enzymes and immune status are critical risk factors for fluconazole-induced HT, and fluconazole-induced cholestatic injury may involve the dysregulation of signaling pathways centered on AKT1, ERBB2, and KDR, suggesting potential targets for monitoring.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01976-25","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T10:00:21Z","timestamp":1776679221000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Fluconazole-induced liver injury in patients with pulmonary cryptococcosis: a comprehensive study integrating clinical cohort analysis, network toxicology, molecular docking, and 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