Sandireddy Reddemma, Sakthivel Suganya, Gupta Priyanka, Behari Jatin, Tripathi Madhulika, Singh Brijesh Kumar
Cardiovascular and Metabolic Disorders Research Program, Duke-NUS Medical School, Singapore, Singapore.
Front Cell Dev Biol. 2024 Jul 16;12:1433857. doi: 10.3389/fcell.2024.1433857. eCollection 2024.
Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is the most common liver disorder worldwide, with an estimated global prevalence of more than 31%. Metabolic dysfunction-associated steatohepatitis (MASH), formerly known as non-alcoholic steatohepatitis (NASH), is a progressive form of MASLD characterized by hepatic steatosis, inflammation, and fibrosis. This review aims to provide a comprehensive analysis of the extrahepatic manifestations of MASH, focusing on chronic diseases related to the cardiovascular, muscular, and renal systems. A systematic review of published studies and literature was conducted to summarize the findings related to the systemic impacts of MASLD and MASH. The review focused on the association of MASLD and MASH with metabolic comorbidities, cardiovascular mortality, sarcopenia, and chronic kidney disease. Mechanistic insights into the concept of lipotoxic inflammatory "spill over" from the MASH-affected liver were also explored. MASLD and MASH are highly associated (50%-80%) with other metabolic comorbidities such as impaired insulin response, type 2 diabetes, dyslipidemia, hypertriglyceridemia, and hypertension. Furthermore, more than 90% of obese patients with type 2 diabetes have MASH. Data suggest that in middle-aged individuals (especially those aged 45-54), MASLD is an independent risk factor for cardiovascular mortality, sarcopenia, and chronic kidney disease. The concept of lipotoxic inflammatory "spill over" from the MASH-affected liver plays a crucial role in mediating the systemic pathological effects observed. Understanding the multifaceted impact of MASH on the heart, muscle, and kidney is crucial for early detection and risk stratification. This knowledge is also timely for implementing comprehensive disease management strategies addressing multi-organ involvement in MASH pathogenesis.
代谢功能障碍相关脂肪性肝病（MASLD），以前称为非酒精性脂肪性肝病（NAFLD），是全球最常见的肝脏疾病，全球估计患病率超过31%。代谢功能障碍相关脂肪性肝炎（MASH），以前称为非酒精性脂肪性肝炎（NASH），是MASLD的一种进展形式，其特征为肝脂肪变性、炎症和纤维化。本综述旨在全面分析MASH的肝外表现，重点关注与心血管、肌肉和肾脏系统相关的慢性疾病。我们对已发表的研究和文献进行了系统综述，以总结与MASLD和MASH的全身影响相关的研究结果。该综述重点关注MASLD和MASH与代谢合并症、心血管死亡率、肌肉减少症和慢性肾脏病的关联。我们还探讨了受MASH影响的肝脏中脂毒性炎症“溢出”概念的机制见解。MASLD和MASH与其他代谢合并症（如胰岛素反应受损、2型糖尿病、血脂异常、高甘油三酯血症和高血压）高度相关（50%-80%）。此外，超过90%的2型糖尿病肥胖患者患有MASH。数据表明，在中年个体（尤其是45-54岁的个体）中，MASLD是心血管死亡率、肌肉减少症和慢性肾脏病的独立危险因素。受MASH影响的肝脏中脂毒性炎症“溢出”的概念在介导所观察到的全身病理效应中起关键作用。了解MASH对心脏、肌肉和肾脏的多方面影响对于早期检测和风险分层至关重要。这些知识对于实施针对MASH发病机制中多器官受累的综合疾病管理策略也很及时。
