Acierno Carlo, Barletta Fannia, Caturano Alfredo, Nevola Riccardo, Sasso Ferdinando Carlo, Adinolfi Luigi Elio, Rinaldi Luca
Department of Infectious Diseases, San Carlo Hospital, 85100 Potenza, Italy.
Department of Anesthesiology and Intensive Care, San Carlo Hospital, 85100 Potenza, Italy.
Nutrients. 2025 Jul 5;17(13):2229. doi: 10.3390/nu17132229.
Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the leading cause of chronic liver disease worldwide, driven by the global epidemics of obesity, type 2 diabetes, and metabolic syndrome. In this evolving nosological landscape, alcohol consumption-traditionally excluded from the diagnostic criteria of non-alcoholic fatty liver disease (NAFLD)-has regained central clinical importance. The recently defined MetALD phenotype acknowledges the co-existence of metabolic dysfunction and a significant alcohol intake, highlighting the synergistic nature of their pathogenic interactions. This narrative review provides a comprehensive analysis of the biochemical, mitochondrial, immunometabolic, and nutritional mechanisms through which alcohol exacerbates liver injury in MASLD. Central to this interaction is cytochrome P450 2E1 (CYP2E1), whose induction by both ethanol and insulin resistance enhances oxidative stress, lipid peroxidation, and fibrogenesis. Alcohol also promotes mitochondrial dysfunction, intestinal barrier disruption, and micronutrient depletion, thereby aggravating metabolic and inflammatory derangements. Furthermore, alcohol contributes to sarcopenia and insulin resistance, establishing a bidirectional link between hepatic and muscular impairment. While some observational studies have suggested a cardiometabolic benefit of a moderate alcohol intake, emerging evidence challenges the safety of any threshold in patients with MASLD. Accordingly, current international guidelines recommend alcohol restriction or abstinence in all individuals with steatotic liver disease and metabolic risk. The review concludes by proposing an integrative clinical model and a visual cascade framework for the assessment and management of alcohol consumption in MASLD, integrating counseling, non-invasive fibrosis screening, and personalized lifestyle interventions. Future research should aim to define safe thresholds, validate MetALD-specific biomarkers, and explore the efficacy of multidisciplinary interventions targeting both metabolic and alcohol-related liver injury.
代谢功能障碍相关脂肪性肝病（MASLD）已成为全球慢性肝病的主要原因，这是由肥胖、2型糖尿病和代谢综合征的全球流行所驱动的。在这一不断演变的疾病分类格局中，饮酒——传统上被排除在非酒精性脂肪性肝病（NAFLD）诊断标准之外——已重新获得核心临床重要性。最近定义的酒精性脂肪性肝病（MetALD）表型承认代谢功能障碍和大量饮酒并存，突出了它们致病相互作用的协同性质。这篇叙述性综述全面分析了酒精在MASLD中加重肝损伤的生化、线粒体、免疫代谢和营养机制。这种相互作用的核心是细胞色素P450 2E1（CYP2E1），乙醇和胰岛素抵抗均可诱导其表达，从而增强氧化应激、脂质过氧化和纤维化形成。酒精还会促进线粒体功能障碍、肠道屏障破坏和微量营养素缺乏，从而加剧代谢和炎症紊乱。此外，酒精会导致肌肉减少症和胰岛素抵抗，在肝脏和肌肉损伤之间建立双向联系。虽然一些观察性研究表明适度饮酒对心脏代谢有益，但新出现的证据对MASLD患者任何饮酒阈值的安全性提出了挑战。因此，当前国际指南建议所有患有脂肪性肝病和代谢风险的个体限制饮酒或戒酒。综述最后提出了一个综合临床模型和一个可视化级联框架，用于评估和管理MASLD患者的饮酒情况，整合咨询、非侵入性纤维化筛查和个性化生活方式干预。未来的研究应旨在确定安全阈值，验证MetALD特异性生物标志物，并探索针对代谢和酒精相关肝损伤的多学科干预措施的疗效。
