Clinica Medica "A. Murri", Department of Precision and Regenerative Medicine and Ionian Area (DiMePre-J), University of Bari "Aldo Moro", 70124 Bari, Italy.
Aboca S.p.a. Società Agricola, 52037 Sansepolcro, Italy.
Int J Mol Sci. 2024 May 22;25(11):5640. doi: 10.3390/ijms25115640.
The epidemiological burden of liver steatosis associated with metabolic diseases is continuously growing worldwide and in all age classes. This condition generates possible progression of liver damage (i.e., inflammation, fibrosis, cirrhosis, hepatocellular carcinoma) but also independently increases the risk of cardio-metabolic diseases and cancer. In recent years, the terminological evolution from "nonalcoholic fatty liver disease" (NAFLD) to "metabolic dysfunction-associated fatty liver disease" (MAFLD) and, finally, "metabolic dysfunction-associated steatotic liver disease" (MASLD) has been paralleled by increased knowledge of mechanisms linking local (i.e., hepatic) and systemic pathogenic pathways. As a consequence, the need for an appropriate classification of individual phenotypes has been oriented to the investigation of innovative therapeutic tools. Besides the well-known role for lifestyle change, a number of pharmacological approaches have been explored, ranging from antidiabetic drugs to agonists acting on the gut-liver axis and at a systemic level (mainly farnesoid X receptor (FXR) agonists, PPAR agonists, thyroid hormone receptor agonists), anti-fibrotic and anti-inflammatory agents. The intrinsically complex pathophysiological history of MASLD makes the selection of a single effective treatment a major challenge, so far. In this evolving scenario, the cooperation between different stakeholders (including subjects at risk, health professionals, and pharmaceutical industries) could significantly improve the management of disease and the implementation of primary and secondary prevention measures. The high healthcare burden associated with MASLD makes the search for new, effective, and safe drugs a major pressing need, together with an accurate characterization of individual phenotypes. Recent and promising advances indicate that we may soon enter the era of precise and personalized therapy for MASLD/MASH.
与代谢性疾病相关的肝脂肪变性的流行病学负担在全球范围内和所有年龄组中都在不断增加。这种情况可能导致肝损伤的进展（即炎症、纤维化、肝硬化、肝细胞癌），但也独立增加了心血管代谢疾病和癌症的风险。近年来，从“非酒精性脂肪性肝病”（NAFLD）到“代谢功能障碍相关脂肪性肝病”（MAFLD），最后到“代谢功能障碍相关脂肪性肝病”（MASLD）的术语演变，伴随着对局部（即肝）和系统致病途径之间联系的机制的认识不断增加。因此，需要对个体表型进行适当的分类，以研究创新的治疗工具。除了生活方式改变的众所周知的作用外，还探索了许多药理方法，从抗糖尿病药物到作用于肠道-肝脏轴和全身水平的激动剂（主要是法尼醇 X 受体（FXR）激动剂、PPAR 激动剂、甲状腺激素受体激动剂）、抗纤维化和抗炎药物。MASLD 复杂的内在病理生理学历史使得迄今为止选择单一有效的治疗方法成为一项重大挑战。在这种不断发展的情况下，不同利益相关者（包括有风险的个体、卫生专业人员和制药行业）之间的合作可以显著改善疾病的管理和初级和二级预防措施的实施。与 MASLD 相关的高医疗保健负担使得寻找新的、有效的、安全的药物成为一个主要的紧迫需求，同时还需要对个体表型进行准确的特征描述。最近有希望的进展表明，我们可能很快将进入 MASLD/MASH 精确和个体化治疗的时代。
