Cited by 608Nutrition and Health in AgingLiver Disease and TransplantationClinical Nutrition and Gastroenterology

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Sarcopenia from mechanism to diagnosis and treatment in liver disease

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Dasarathy, Srinivasan, Merli, Manuela·2016·Journal of Hepatology

DOI 10.1016/j.jhep.2016.07.040PMC PMC5116259

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Abstract

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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Authors: Dasarathy, S., & Merli, M.
Affiliations: Cleveland Clinic (US)
Sapienza University of Rome (IT)
Corresponding author: Dasarathy, Srinivasan
ORCID: Dasarathy, Srinivasan
Merli, Manuela
Venue: Journal of Hepatology
Publisher: Elsevier BV
Published: 2016-12
Volume: 65
Issue: 6
Pages: 1232-1244
ISSN: 0168-8278 (ISSN-L)
DOI: 10.1016/j.jhep.2016.07.040
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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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Sarcopenia from mechanism to diagnosis and treatment in liver disease

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