{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T10:49:43Z","timestamp":1793875783092,"version":"4.7.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T00:00:00Z","timestamp":1771891200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Acute-on-chronic liver failure is a fatal syndrome involving sudden hepatic deterioration in patients with chronic liver disease, resulting in high short-term mortality. The intrahepatic molecular mechanisms that drive disease progression are poorly understood, partly due to limited access to human liver tissues.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>Transcriptomic profiling of liver tissues from patients with hepatitis B virus-related acute-on-chronic liver failure and a corresponding murine model was performed. Comparative analyses were conducted across disease stages to delineate the dynamic immune and metabolic trajectories.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Result<\/jats:title>\n                    <jats:p>The analysis uncovered a conserved immune-metabolic dysregulation during disease progression. In both patients and mice, immune activation-characterized by monocyte and macrophage infiltration and altered cytokine signaling-coincided with progressive metabolic failure, including the suppression of mitochondrial functions. The murine model further demonstrated a transition from an early stage of hyperinflammation to a later stage of immune exhaustion. Moreover, several monocyte and macrophage-associated genes were identified as conserved markers that correlate with disease severity, highlighting their potential as biomarkers or therapeutic targets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study defines a conserved immune-metabolic interplay during the progression of hepatitis B virus-related acute-on-chronic liver failure and validates the murine model\u2019s accuracy for studying the disease\u2019s terminal stage. The identified dysregulation of immune cells and metabolic pathways presents actionable targets for developing stage-specific therapies intended to disrupt the disease\u2019s vicious immune-metabolic cycle.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1702689","type":"journal-article","created":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T06:45:56Z","timestamp":1771915556000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Cross-species hepatic transcriptomics identify conserved immune-metabolic reprogramming in acute-on-chronic liver failure progression"],"prefix":"10.3389","volume":"17","author":[{"given":"Panyu","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]},{"name":"Key Laboratory for Translational Research and Innovative Therapeutics of 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