Division of Gastroenterology & Liver Unit, University of Alberta, Edmonton, AB T6G 2X8, Canada.
Ajmera Transplant Program, Department of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada.
Cells. 2022 Apr 4;11(7):1216. doi: 10.3390/cells11071216.
Myosteatosis, or pathological excess fat accumulation in muscle, has been widely defined as a lower mean skeletal muscle radiodensity on computed tomography (CT). It is reported in more than half of patients with cirrhosis, and preliminary studies have shown a possible association with reduced survival and increased risk of portal hypertension complications. Despite the clinical implications in cirrhosis, a standardized definition for myosteatosis has not yet been established. Currently, little data exist on the mechanisms by which excess lipid accumulates within the muscle in individuals with cirrhosis. Hyperammonemia may play an important role in the pathophysiology of myosteatosis in this setting. Insulin resistance, impaired mitochondrial oxidative phosphorylation, diminished lipid oxidation in muscle and age-related differentiation of muscle stem cells into adipocytes have been also been suggested as potential mechanisms contributing to myosteatosis. The metabolic consequence of ammonia-lowering treatments and omega-3 polyunsaturated fatty acids in reversing myosteatosis in cirrhosis remains uncertain. Factors including the population of interest, design and sample size, single/combined treatment, dosing and duration of treatment are important considerations for future trials aiming to prevent or treat myosteatosis in individuals with cirrhosis.
肌肉脂肪增多症，或肌肉内病理性脂肪过度堆积，通常被定义为 CT 下骨骼肌平均密度降低。超过一半的肝硬化患者存在这种情况，初步研究表明其可能与生存率降低和门静脉高压并发症风险增加有关。尽管在肝硬化中有重要的临床意义，但肌肉脂肪增多症还没有一个标准化的定义。目前，关于肝硬化个体肌肉内脂质堆积的机制的相关数据很少。高氨血症可能在这种情况下的肌肉脂肪增多症的病理生理学中发挥重要作用。胰岛素抵抗、线粒体氧化磷酸化受损、肌肉脂质氧化减少以及与年龄相关的肌肉干细胞向脂肪细胞分化也被认为是导致肌肉脂肪增多症的潜在机制。降低血氨治疗和 ω-3 多不饱和脂肪酸逆转肝硬化中肌肉脂肪增多症的代谢后果尚不确定。对于旨在预防或治疗肝硬化患者肌肉脂肪增多症的未来试验，感兴趣的人群、设计和样本量、单一/联合治疗、剂量和治疗持续时间等因素都需要重点考虑。
