Data_Sheet_2_Impact of Sarcopenia on the Severity of the Liver Damage in Patients With Non-alcoholic Fatty Liver Disease.docx

An extensive body of the literature shows a strong interrelationship between the pathogenic pathways of non-alcoholic fatty liver disease (NAFLD) and sarcopenia through the muscle-liver-adipose tissue axis. NAFLD is one of the leading causes of chronic liver diseases (CLD) affecting more than one-quarter of the general population worldwide. The disease severity spectrum ranges from simple steatosis to non-alcoholic steatohepatitis (NASH), cirrhosis, and its complications: end-stage chronic liver disease and hepatocellular carcinoma. Sarcopenia, defined as a progressive loss of the skeletal muscle mass, reduces physical performances, is associated with metabolic dysfunction and, possibly, has a causative role in NAFLD pathogenesis. Muscle mass is a key determinant of the whole-body insulin-mediated glucose metabolism and impacts fatty liver oxidation and energy homeostasis. These mechanisms drive the accumulation of ectopic fat both in the liver (steatosis, fatty liver) and in the muscle (myosteatosis). Myosteatosis rather than the muscle mass per se, seems to be closely associated with the severity of the liver injury. Sarcopenic obesity is a recently described entity which associates both sarcopenia and obesity and may trigger worse clinical outcomes including hepatic fibrosis progression and musculoskeletal disabilities. Furthermore, the muscle-liver-adipose tissue axis has a pivotal role in changes of the body composition, resulting in a distinct clinical phenotype that enables the identification of the “sarcopenic NAFLD phenotype.” This review aims to bring some light into the complex relationship between sarcopenia and NAFLD and critically discuss the key mechanisms linking NAFLD to sarcopenia, as well as some of the clinical consequences associated with the coexistence of these two entities: the impact of body composition phenotypes on muscle morphology, the concept of sarcopenic obesity, the relationship between sarcopenia and the severity of the liver damage and finally, the future directions and the existing gaps in the knowledge.

大量文献表明，非酒精性脂肪性肝病（non-alcoholic fatty liver disease, NAFLD）与肌肉减少症（sarcopenia）之间通过肌肉-肝脏-脂肪组织轴存在紧密的致病通路关联。非酒精性脂肪性肝病（NAFLD）是慢性肝病（chronic liver diseases, CLD）的主要病因之一，影响全球超过四分之一的普通人群。该病的严重程度谱范围从单纯性脂肪变性到非酒精性脂肪性肝炎（non-alcoholic steatohepatitis, NASH）、肝硬化及其并发症：终末期慢性肝病与肝细胞癌。肌肉减少症（sarcopenia）被定义为骨骼肌量进行性丧失，可降低躯体运动能力，与代谢功能障碍相关，且可能在NAFLD的发病机制中发挥致病作用。骨骼肌量是全身胰岛素介导葡萄糖代谢的关键决定因素，同时影响肝脏脂肪氧化与能量稳态。上述机制可促进异位脂肪在肝脏（脂肪变性，即脂肪肝）与肌肉（肌内脂肪沉积，myosteatosis）中蓄积。似乎肌内脂肪沉积（myosteatosis）而非骨骼肌量本身，与肝损伤严重程度密切相关。肌肉减少性肥胖（sarcopenic obesity）是近年来被定义的一种疾病表型，同时兼具肌肉减少症与肥胖特征，可能引发更差的临床结局，包括肝纤维化进展与肌肉骨骼功能障碍。此外，肌肉-肝脏-脂肪组织轴在机体组成改变中发挥关键作用，由此形成独特的临床表型，可用于识别"肌肉减少性NAFLD表型（sarcopenic NAFLD phenotype）"。本综述旨在阐明肌肉减少症与NAFLD之间的复杂关联，批判性探讨二者之间的关键致病机制，以及这两种疾病共存时的部分临床结局：包括机体组成表型对肌肉形态的影响、肌肉减少性肥胖的概念、肌肉减少症与肝损伤严重程度的关联，最后还将展望未来研究方向与当前尚存的知识空白。