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Sarcopenia from mechanism to diagnosis and treatment in liver disease
Open accessAbstract
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. These include survival, quality of life, development of other complications and post liver transplantation survival. Radiological image analysis is currently utilized 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 has recently gained attention as a possible mediator of the liver-muscle axis. 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 transforming growth factor beta superfamily member) and an increased phosphorylation of eukaryotic initiation factor 2α. In addition, mitochondrial dysfunction, increased reactive oxygen species that decrease protein synthesis and increased autophagy mediated proteolysis, also play a role. 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.
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“Finally, malnutrition [105], frailty [106, 107] and especially sarcopenia [108, 109, 110, 111] have become increasingly important in patients with advanced chronic liver disease and should be evaluated and treated in each patient.”
From Current treatment of non‐alcoholic fatty liver disease (2022) · cites this paper as [108]
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Metadata
- Authors
- Dasarathy, S., & Merli, M.
- Affiliations
- Cleveland Clinic (US)
- Sapienza University of Rome (IT)
- Corresponding author
- Dasarathy, Srinivasan
- Venue
- Journal of Hepatology
- Publisher
- Elsevier BV
- Published
- 2016-12
- Volume
- 65
- Issue
- 6
- Pages
- 1232-1244
- ISSN
- 0168-8278 (ISSN-L)
- PMC
- PMC5116259
- OpenAlex
- W2507464717
- Cited by
- 608
- References
- 147
- Citations by year
- 2026: 48 · 2025: 56 · 2024: 60 · 2023: 86 · 2022: 64 · 2021: 73 · 2020: 63 · 2019: 66 · 2018: 50 · 2017: 38 · 2016: 3
- FWCI
- 6.14
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Hepatology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion, other-oa)
- Funders
- National Institutes of Health (5r01dk083414-05, 4u01aa021893-05, DK83414, AA021893, UO1 AA021893)
- National Institute on Alcohol Abuse and Alcoholism (R21AA022742, U01-AA021893, P50AA024333)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK-083414, U01DK061732)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nutrition and Health in Aging
- Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
- Health Sciences › Nursing › Nutrition and Dietetics › Clinical Nutrition and Gastroenterology
- Keywords
- sarcopenia, liver cirrhosis, hyperammonemia, myostatin, eIF2α phosphorylation, leucine, glutamine, mitochondrial dysfunction, reactive oxygen species, autophagy, endotoxemia, gut microbiota, muscle fatigue, exercise training, protein supplementation, malnutrition, anabolic resistance
- MeSH terms
- Ketoglutaric Acids, Liver Diseases, Quality of Life, Muscle, Skeletal, Sarcopenia
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