Metabolic (dysfunction)-associated fatty liver disease (MAFLD) affects up to a third of the global population; its burden has grown in parallel with rising rates of type 2 diabetes mellitus and obesity. MAFLD increases the risk of end-stage liver disease, hepatocellular carcinoma, death and liver transplantation and has extrahepatic consequences, including cardiometabolic disease and cancers. Although typically associated with obesity, there is accumulating evidence that not all people with overweight or obesity develop fatty liver disease. On the other hand, a considerable proportion of patients with MAFLD are of normal weight, indicating the importance of metabolic health in the pathogenesis of the disease regardless of body mass index. The clinical profile, natural history and pathophysiology of patients with so-called lean MAFLD are not well characterized. In this Review, we provide epidemiological data on this group of patients and consider overall metabolic health and metabolic adaptation as a framework to best explain the pathogenesis of MAFLD and its heterogeneity in individuals of normal weight and in those who are above normal weight. This framework provides a conceptual schema for interrogating the MAFLD phenotype in individuals of normal weight that can translate to novel approaches for diagnosis and patient care.

代谢（功能障碍）相关的脂肪肝病（MAFLD）影响全球多达三分之一的人口；随着 2 型糖尿病和肥胖症发病率的上升，其负担也在增加。MAFLD 会增加终末期肝病、肝细胞癌、死亡和肝移植的风险，并具有肝外后果，包括心脏代谢疾病和癌症。尽管通常与肥胖有关，但越来越多的证据表明，并非所有超重或肥胖的人都会患上脂肪肝。另一方面，相当比例的 MAFLD 患者体重正常，这表明无论体重指数如何，代谢健康在疾病发病机制中的重要性。临床概况，所谓的瘦 MAFLD 患者的自然病史和病理生理学特征尚未得到很好的表征。在这篇综述中，我们提供了这组患者的流行病学数据，并将整体代谢健康和代谢适应作为一个框架，以最好地解释 MAFLD 的发病机制及其在正常体重个体和高于正常体重个体中的异质性。该框架提供了一个概念模式，用于询问体重正常的个体的 MAFLD 表型，可以转化为诊断和患者护理的新方法。我们提供了这组患者的流行病学数据，并将整体代谢健康和代谢适应作为一个框架，以最好地解释 MAFLD 的发病机制及其在正常体重个体和高于正常体重个体中的异质性。该框架提供了一个概念模式，用于询问体重正常的个体的 MAFLD 表型，可以转化为诊断和患者护理的新方法。我们提供了这组患者的流行病学数据，并将整体代谢健康和代谢适应作为一个框架，以最好地解释 MAFLD 的发病机制及其在正常体重个体和高于正常体重个体中的异质性。该框架提供了一个概念模式，用于询问体重正常的个体的 MAFLD 表型，可以转化为诊断和患者护理的新方法。