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Although this review uses the MASLD\u2010MASH\u2010fibrosis\/cirrhosis\u2010HCC sequence as a mechanistically informative model, the gut\u2010liver\u2010immune framework is also relevant, with important etiology\u2010specific differences, to alcohol\u2010associated liver disease (ALD), chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus (HCV) infection, and mixed\u2010etiology liver disease. Across these contexts, hepatocyte lipotoxicity or viral\/alcohol\u2010induced injury, mitochondrial stress, endotoxemia, altered bile\u2010acid signaling, fibrotic remodeling, and immune exhaustion progressively reshape the hepatic microenvironment toward tumor\u2010permissive inflammation and immune escape. We integrate transcriptomic, single\u2010cell, spatial, microbial, and metabolomic evidence to define stage\u2010 and etiology\u2010dependent immunometabolic states. Particular emphasis is placed on microbial metabolites, including short\u2010chain fatty acids, secondary bile acids, and tryptophan\u2010derived indoles, which engage host receptors such as FFAR2\/3, GPR109A, FXR, TGR5, AhR, and PXR to influence lipid metabolism, epithelial barrier integrity, cytokine programs, epigenetic remodeling, and antitumor surveillance. We further discuss how sex, baseline microbiome composition, hepatic zonation, and preclinical model selection influence disease trajectories and therapeutic responses. By focusing on the gut microbiota\u2010metabolism\u2010immunity axis, this review provides a systems\u2010level framework for biomarker discovery, risk stratification, precision nutrition, and rational combination therapies. Targeting the coordinated interplay among diet, microbiota, metabolism, immunity, and the hepatic spatial niche may help intercept chronic liver disease before malignant transformation and improve therapeutic responses in established HCC.<\/jats:p>","DOI":"10.1002\/advs.202523582","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T13:59:50Z","timestamp":1783691990000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Gut Microbiota, Immunity, and Metabolism in the Progression From Chronic Liver Disease to Hepatocellular Carcinoma"],"prefix":"10.1002","volume":"13","author":[{"given":"Yi","family":"Hu","sequence":"first","affiliation":[{"name":"Immunology Department School of Medicine Jinan University  Guangzhou Guangdong P. R. China"},{"name":"Key Laboratory of Viral Pathogenesis &amp; Infection Prevention and Control (Jinan University) Ministry of Education  Guangzhou P. R. 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