代谢相关脂肪性肝病的机制、流行病学与诊断策略

Mechanisms, Epidemiology and Diagnostic Strategies of Metabolic Dysfunction-Associated Fatty Liver Disease

摘要: 代谢相关脂肪性肝病(MAFLD)已成为全球第一大慢性肝病，也是我国公共卫生领域面临的重要挑战，其高患病率、年轻化趋势及向肝纤维化、肝硬化甚至肝细胞癌(HCC)的进展风险，带来沉重的医疗经济负担。本文从病理生理机制、流行病学特征及临床诊断方式三方面展开系统阐述：发病机制上，传统“两次打击”理论已逐步被脂肪毒性、胰岛素抵抗(IR)主导的病理过程取代，且遗传易感性(如PNPLA3基因变异)及下游分子通路调控成为核心研究方向，外周脂肪储存能力缺陷引发的脂质异位沉积是疾病起始关键；流行特征呈现显著的地区、性别、年龄与种族异质性，全球平均患病率达25%~30%，我国成人患病率超过29%且呈“北高南低、城高乡低”分布，育龄期女性受雌激素保护患病风险较低，绝经后快速攀升，儿童青少年患病率增长显著，东亚人群存在低BMI下高易感性的独特特征；临床诊断中，肝穿刺活检为诊断金标准，但因有创性限制了其应用，超声为基层初筛主要手段，磁共振质子密度脂肪分数(MRI-PDFF)是无创定量评估的最优技术，机器学习模型则为疾病筛查与风险分层提供了前沿工具，但其临床转化仍面临泛化能力、可解释性与监管验证等挑战。本文通过梳理MAFLD的核心研究进展，为该病的临床防治策略制定与后续研究方向提供参考依据。

Abstract: Metabolic dysfunction-associated fatty liver disease (MAFLD) has become the most prevalent chronic liver disease worldwide and also poses a major challenge to public health in China. Its high prevalence, younger onset trend, and progressive risk towards liver fibrosis, cirrhosis, and even hepatocellular carcinoma (HCC) impose a heavy medical and economic burden. This paper systematically reviews the pathophysiological mechanisms, epidemiological characteristics, and clinical diagnostic approaches of MAFLD. In terms of pathogenesis, the traditional “two-hit” hypothesis has been gradually replaced by pathophysiological processes dominated by lipotoxicity and insulin resistance (IR). Genetic susceptibility (e.g., PNPLA3 gene variants) and the regulation of downstream molecular pathways have become core research directions. Defective peripheral fat storage capacity leading to ectopic lipid deposition is a key initiating event of the disease. Epidemiologically, MAFLD shows significant heterogeneity across regions, genders, ages, and ethnicities. The global average prevalence is 25%~30%, while the prevalence among Chinese adults exceeds 29%, with a distribution characterized by “higher in the north than in the south, higher in urban than in rural areas”. Women of childbearing age have a lower risk due to estrogen protection, but the risk rises rapidly after menopause. The prevalence in children and adolescents has increased markedly. East Asian populations exhibit a unique feature of high susceptibility even at a low BMI. In clinical diagnosis, liver biopsy remains the gold standard but is limited by its invasiveness. Ultrasound is the main tool for primary screening. Magnetic resonance imaging‑proton density fat fraction (MRI‑PDFF) is the optimal noninvasive technique for quantitative evaluation. Machine learning models provide cutting‑edge tools for disease screening and risk stratification, yet their clinical translation still faces challenges including generalizability, interpretability, and regulatory validation. By summarizing the key research advances in MAFLD, this paper provides a reference for the formulation of clinical prevention and treatment strategies and future research directions.