From the Guidelines
Muscle loss in liver cirrhosis, known as sarcopenia, occurs due to multiple factors related to liver dysfunction, including altered protein metabolism, impaired hepatic ammonia clearance, and metabolic disturbances, as highlighted in the 2021 practice guidance by the American Association for the Study of Liver Diseases 1. The primary mechanisms of muscle loss in liver cirrhosis include:
- Reduced protein synthesis: The liver's impaired ability to produce proteins leads to decreased muscle protein production.
- Increased protein breakdown: Cirrhosis causes elevated levels of inflammatory cytokines, which promote muscle protein breakdown.
- Metabolic disturbances: Altered glucose metabolism and insulin resistance contribute to muscle wasting.
- Malnutrition: Poor appetite, malabsorption, and dietary restrictions often lead to inadequate nutrient intake.
- Reduced physical activity: Fatigue and complications of cirrhosis often result in decreased physical activity, further promoting muscle loss.
- Hormonal imbalances: Reduced testosterone levels and growth hormone resistance contribute to muscle atrophy. To address muscle loss in cirrhosis patients:
- Ensure adequate protein intake (1.2-1.5 g/kg/day) through diet or supplements, as recommended by the EASL clinical practice guidelines on nutrition in chronic liver disease 1.
- Encourage regular physical activity, including resistance exercises, as tolerated, to improve muscle mass and function, as suggested by the EASL clinical practice guidelines on nutrition in chronic liver disease 1 and the KASL clinical practice guidelines for liver cirrhosis 1.
- Treat underlying nutritional deficiencies (e.g., vitamin D, zinc) to support muscle health.
- Consider branched-chain amino acid supplementation (0.25 g/kg/day) to support muscle protein synthesis.
- Manage complications of cirrhosis that may contribute to muscle loss, such as hepatic encephalopathy and ascites. The most recent and highest quality study, the 2024 EASL-EASD-EASO clinical practice guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD) 1, recommends a high-protein diet and a late-evening snack for adults with sarcopenia, sarcopenic obesity, or decompensated cirrhosis, and emphasizes the importance of maintaining muscle mass and reducing the risk of sarcopenia.
From the Research
Pathophysiology of Muscle Loss in Liver Cirrhosis
The pathophysiology of muscle loss in liver cirrhosis is complex and multifactorial. Key factors contributing to muscle loss include:
- Poor nutritional intake 2
- Protein catabolism 3
- Physical inactivity 2
- Hyperammonemia, which is the best-studied mediator of the liver-muscle axis 3
- Impaired skeletal muscle protein synthesis and increased proteolysis via autophagy 3
- Increased expression of myostatin 3
- Impaired mitochondrial function and tricarboxylic acid cycle intermediates 3
Consequences of Muscle Loss
Muscle loss in liver cirrhosis has significant consequences, including:
- Increased mortality 4, 5, 6
- Increased risk of sepsis-related mortality 6
- Increased risk of development of other complications of cirrhosis, such as hepatic encephalopathy 4
- Worsened post-liver transplant outcomes 3
- Decreased quality of life 3, 2
Assessment and Management
Assessment of muscle loss in liver cirrhosis can be done using cross-sectional imaging studies, such as computed tomography (CT) scan or magnetic resonance imaging (MRI) 5. Management of muscle loss includes: