Sarcopenia from mechanism to diagnosis and treatment in liver disease.
Sarcopenia from mechanism to diagnosis and treatment in liver disease.
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DOI：
10.1016/j.jhep.2016.07.040
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发表时间：
2016-12
影响因子：
25.7
通讯作者：
Merli M
中科院分区：
文献类型：
--
作者：
Dasarathy S;Merli M
肌肉减少症或骨骼肌质量损失是营养不良的主要组成部分，并且是肝硬化中的常见并发症，其对临床结果（包括存活率、生活质量、其他并发症的发展和肝移植后存活率）产生不利影响。放射学图像分析目前用于诊断肝硬化中的肌肉减少症。营养补充和体力活动用于对抗肌肉减少症，但并不总是有效的，因为潜在的分子和代谢异常持续存在或不受这些治疗的影响。尽管食物摄入的改变、高代谢、氨基酸谱的改变、内毒素血症、加速饥饿和活动性降低都可能导致肝硬化中的肌肉减少症，但高氨血症作为肝-肌肉轴的可能介质最近引起了人们的注意。α-酮戊二酸的分解，亮氨酸交换谷氨酰胺的转运增加，亮氨酸的信号传导受损，肌生长抑制素的表达增加，TGFβ超家族成员和真核起始因子2α磷酸化增加、线粒体功能障碍、减少蛋白质合成的活性氧增加和自噬介导的蛋白质水解增加。这些分子和代谢改变可能导致肝硬化患者的合成代谢抵抗和对营养补充的反应不足。中枢和骨骼肌疲劳导致运动能力和反应受损。使用低产氨潜力的蛋白质、富含亮氨酸的氨基酸补充剂、长期降氨策略以及阻力和耐力运动的组合来增加肌肉质量和功能可以针对肌肉中的分子异常。针对内毒素血症和肠道微生物组的策略需要进一步评估。
Sarcopenia or loss of skeletal muscle mass is the major component of malnutrition and is a frequent complication in cirrhosis that adversely affects clinical outcomes including survival, quality of life, development of other complications and post liver transplantation survival. Radiological image analysis is currently used to diagnose sarcopenia in cirrhosis. Nutrient supplementation and physical activity are used to counter sarcopenia but have not been consistently effective because the underlying molecular and metabolic abnormalities persist or are not influenced by these treatments. Even though alterations in food intake, hypermetabolism, alterations in amino acid profiles, endotoxemia, accelerated starvation and decreased mobility may all contribute to sarcopenia in cirrhosis, hyperammonemia as a possible mediator of the liver-muscle axis has recently gained attention Increased muscle ammonia causes: cataplerosis of α-ketoglutarate, increased transport of leucine in exchange for glutamine, impaired signaling by leucine, increased expression of myostatin, a TGFβ superfamily member and an increased phosphorylation of eukaryotic initiation factor 2α, mitochondrial dysfunction, increased reactive oxygen species that decrease protein synthesis and increased autophagy mediated proteolysis. These molecular and metabolic alterations may contribute to the anabolic resistance and inadequate response to nutrient supplementation in cirrhosis. Central and skeletal muscle fatigue contributes to impaired exercise capacity and responses. Use of proteins with low ammoniagenic potential, leucine enriched amino acid supplementation, long term ammonia lowering strategies and a combination of resistance and endurance exercise to increase muscle mass and function may target the molecular abnormalities in the muscle. Strategies targeting endotoxemia and the gut microbiome need further evaluation.