Department of Hepatology and Gastroenterology, Aarhus University Hospital , Aarhus, Denmark.
Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney , Sydney, Australia.
Expert Rev Gastroenterol Hepatol. 2021 Jan;15(1):51-64. doi: 10.1080/17474124.2020.1817740. Epub 2020 Sep 17.
Metabolic associated fatty liver disease (MAFLD) is a new nomenclature for fatty liver replacing nonalcoholic fatty liver disease (NAFLD). MAFLD has emerged as the leading cause of liver-related morbidity and mortality with increasing incidence due to its close association with the global epidemic of obesity and type 2 diabetes mellitus. Macrophages play a key role in MAFLD development and progression of steatohepatitis and fibrosis. Therefore, targeting macrophages may be a new therapeutic approach for MAFLD and MAFLD with steatohepatitis.
We provide a comprehensive review of the significant role of macrophages in MAFLD. Further, we evaluate the current status of lifestyle interventions and pharmacological treatments with a focus on effects mediated through direct or indirect targeting of macrophages.
Targeting macrophages holds promise as a treatment option for the management of MAFLD and steatohepatitis. Improved stratification of patients according to MAFLD phenotype would contribute to more adequate design enhancing the yield of clinical trials ultimately leading to personalized medicine for patients with MAFLD. Furthermore, reflecting the multifactorial pathogenesis of MAFLD, combination therapies based on the various pathophysiological driver events including as pertinent to this review, macrophage recruitment, polarization and action, present an intriguing target for future investigation.
代谢相关脂肪性肝病(MAFLD)是一种新的命名法,用于替代非酒精性脂肪性肝病(NAFLD)的脂肪肝。由于其与肥胖症和 2 型糖尿病的全球流行密切相关,MAFLD 的发病率不断增加,已成为导致肝相关发病率和死亡率的主要原因。巨噬细胞在 MAFLD 发展、脂肪性肝炎和纤维化进展中起着关键作用。因此,针对巨噬细胞可能是 MAFLD 和 MAFLD 合并脂肪性肝炎的一种新的治疗方法。
我们全面回顾了巨噬细胞在 MAFLD 中的重要作用。此外,我们评估了生活方式干预和药物治疗的现状,重点是通过直接或间接靶向巨噬细胞来介导的效果。
针对巨噬细胞可能成为治疗 MAFLD 和脂肪性肝炎的一种选择。根据 MAFLD 表型对患者进行更好的分层,将有助于更充分地设计临床试验,最终为 MAFLD 患者提供个性化治疗。此外,反映 MAFLD 的多因素发病机制,包括本综述中提到的与巨噬细胞募集、极化和作用相关的各种病理生理驱动事件的联合治疗,为未来的研究提供了一个有趣的目标。