非酒精性脂肪性肝病(NAFLD)：危险因素、发病机制和治疗综述

Non-Alcoholic Fatty Liver Disease (NAFLD): A Review of Risk Factors, Pathogenesis, and Treatment

摘要: 非酒精性脂肪性肝病(Non-Alcoholic Fatty Liver Disease, NAFLD)是世界范围内最常见的慢性肝病，其全球患病率估计高达35%，已成为一个重大的公共卫生问题。NAFLD包括单纯性脂肪肝，脂肪性肝炎(NASH)，以及潜在的肝硬化和肝癌。NAFLD与胰岛素抵抗、肥胖、肠道微生物失调和遗传危险因素密切相关。肥胖的流行和2型糖尿病患者的增多极大地促进了NAFLD负担的增加。NAFLD的发病机制、确定治疗靶点和推进药物开发方面取得了稳步进展，但仍存在重大挑战，尚未有药物被批准用于该疾病。一旦诊断确定，减肥、饮食调整和治疗潜在代谢综合征仍然是治疗的主要内容。指南建议在特定患者中使用吡格列酮和维生素E。本文综述了NAFLD和NASH的发病机制及危险因素，为治疗策略的发展和有用的诊断工具提供见解。

Abstract: Non-alcoholic fatty liver disease (NAFLD) represents the most prevalent chronic liver disorder globally, with an estimated worldwide prevalence reaching 35%, emerging as a significant public health issue. The disease spectrum encompasses a continuum from simple hepatic steatosis to non-alcoholic steatohepatitis (NASH), which may progress to advanced fibrosis, cirrhosis, and hepatocellular carcinoma. NAFLD pathogenesis is strongly linked to insulin resistance, obesity, gut microbiome dysbiosis, and genetic susceptibility factors. The escalating epidemics of obesity and type 2 diabetes have substantially contributed to the increasing disease burden of NAFLD. While considerable progress has been achieved in elucidating NAFLD pathogenesis, identifying potential therapeutic targets, and advancing pharmaceutical development, no pharmacologic agents have received regulatory approval for NAFLD treatment. Current management strategies emphasize lifestyle modifications, including weight reduction and dietary interventions, along with treatment of associated metabolic comorbidities. Guideline-based recommendations support the judicious use of pioglitazone and vitamin E in selected patient populations. This review comprehensively examines the pathogenic mechanisms and risk factors underlying NAFLD and NASH, providing insights to inform the development of targeted therapeutic strategies and improved diagnostic modalities.