{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T06:09:28Z","timestamp":1791526168253,"version":"4.3.4"},"reference-count":64,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T00:00:00Z","timestamp":1756857600000},"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. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Hepatic decompensation is a critical turning point in the progression of compensated cirrhosis, with distinct pathophysiological trajectories in alcoholic and non-alcoholic etiologies. This systematic review and meta-analysis evaluates prognostic biomarkers for predicting decompensation in patients with compensated cirrhosis, emphasizing differences between alcoholic and non-alcoholic liver disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Following PRISMA 2020 guidelines, we systematically searched PubMed, Scopus, and Web of Science for peer-reviewed studies (up to April 2025) reporting hazard ratios (HRs) and 95% confidence intervals for biomarkers predicting decompensation in adults with compensated cirrhosis. Eligible studies included observational cohorts and control arms of RCTs, stratified by etiology (alcoholic vs. non-alcoholic). Data were pooled using random-effects models, with heterogeneity assessed via <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup> and Cochrane Q tests. Subgroup analyses explored biomarker performance by etiology and type (inflammatory, functional, and structural).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>From 691 records, 66 studies (Among these, 955 patients (2.6%) were alcoholic and 36,108 (97.4%) non-alcoholic, totaling 37,063 participants) were included. In non-alcoholic cirrhosis, structural biomarkers like portal vein diameter (HR\u202f=\u202f7.39 [4.90, 11.15]) and spleen size (HR\u202f=\u202f5.79 [2.00, 16.80]) were strong predictors, alongside functional markers such as bilirubin (HR\u202f=\u202f4.27 [2.93, 6.22]) and MELD score (HR\u202f=\u202f1.13 [1.07, 1.20]). In alcoholic cirrhosis, inflammatory biomarkers, particularly extracellular vesicles (HR\u202f=\u202f5.09 [2.01, 12.86]) and keratin-18 (HR\u202f=\u202f1.77 [1.14, 2.75]), showed superior predictive value. Interleukin-6 was predictive across both etiologies (HR\u202f=\u202f1.31 [1.00, 1.71]). Heterogeneity was substantial (<jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup> &amp;gt;\u202f50%) for most biomarkers, reflecting population and methodological variability. Publication bias was low based on funnel plots and Egger\u2019s test.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Etiology-specific biomarkers enhance prognostic accuracy in compensated cirrhosis. Structural and functional markers dominate in non-alcoholic cirrhosis, while inflammatory biomarkers are more predictive in alcoholic cirrhosis. Integrating these into personalized risk models could improve clinical management, though prospective validation is needed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Systematic Review Registration<\/jats:title><jats:p><jats:uri>https:\/\/www.crd.york.ac.uk\/PROSPERO\/view\/CRD420251076849<\/jats:uri><\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2025.1650124","type":"journal-article","created":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T05:36:44Z","timestamp":1756877804000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Prognostic biomarkers for predicting decompensation in alcoholic and non-alcoholic patients with compensated cirrhosis: a systematic review and meta-analysis"],"prefix":"10.3389","volume":"12","author":[{"given":"Kristina","family":"Baktikulova","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saulesh","family":"Kurmangaliyeva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kairat","family":"Kurmangaliyev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantin","family":"Tissin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadiar M.","family":"Mussin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amin","family":"Tamadon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,3]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1016\/j.jhep.2023.03.017","article-title":"Global burden of liver disease: 2023 update","volume":"79","author":"Devarbhavi","year":"2023","journal-title":"J Hepatol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1007\/s44337-024-00083-x","article-title":"Liver stiffness as a dynamic predictor of decompensation and mortality in alcohol-related liver disease","volume":"1","author":"Addissouky","year":"2024","journal-title":"Discover Medicine"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1186\/s12933-024-02434-5","article-title":"Metabolic 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