Prognostic biomarkers for predicting decompensation in alcoholic and non-alcoholic patients with compensated cirrhosis: a systematic review and meta-analysis
Baktikulova K. Kurmangaliyeva S. Kurmangaliyev K. Tissin K. Mussin N.M. Tamadon A.
2025Frontiers Media SA
Frontiers in Medicine
2025#12
Background: 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. Methods: 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 I2 and Cochrane Q tests. Subgroup analyses explored biomarker performance by etiology and type (inflammatory, functional, and structural). Results: 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 = 7.39 [4.90, 11.15]) and spleen size (HR = 5.79 [2.00, 16.80]) were strong predictors, alongside functional markers such as bilirubin (HR = 4.27 [2.93, 6.22]) and MELD score (HR = 1.13 [1.07, 1.20]). In alcoholic cirrhosis, inflammatory biomarkers, particularly extracellular vesicles (HR = 5.09 [2.01, 12.86]) and keratin-18 (HR = 1.77 [1.14, 2.75]), showed superior predictive value. Interleukin-6 was predictive across both etiologies (HR = 1.31 [1.00, 1.71]). Heterogeneity was substantial (I2 > 50%) for most biomarkers, reflecting population and methodological variability. Publication bias was low based on funnel plots and Egger’s test. Conclusion: 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. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251076849 Copyright
biomarkers , cirrhosis prognosis , disease , humans , progression liver
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Department of Microbiology, Virology and Immunology, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan
Department of Surgery No. 2, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan
Department of Natural Sciences, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan
Department of Microbiology
Department of Surgery No. 2
Department of Natural Sciences
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