Muscular alterations, cognitive deficit, movement disorders and risk of falls in cirrhotic patients: an observational, perspective and translational study in experimental models of liver disease and sarcopenia.

Anno
2021
Proponente Manuela Merli - Professore Ordinario
Sottosettore ERC del proponente del progetto
LS4_8
Componenti gruppo di ricerca
Componente Categoria
Laura Barberi Dottorando/Assegnista/Specializzando componente non strutturato del gruppo di ricerca / PhD/Assegnista/Specializzando member non structured of the research group
Oliviero Riggio Componenti strutturati del gruppo di ricerca / Structured participants in the research project
Frida Leonetti Componenti strutturati del gruppo di ricerca / Structured participants in the research project
Mariano Serrao Componenti strutturati del gruppo di ricerca / Structured participants in the research project
Lorenzo Ridola Componenti strutturati del gruppo di ricerca / Structured participants in the research project
Abstract

Sarcopenia is a frequent complication in the natural history of cirrhosis caused by inadequate energy intake, rapid transition to a fasting state, alterations in energy substrates utilization, impairment of protein synthesis and increased muscle catabolism. Hepatic encephalopathy (HE), a syndrome of brain dysfunction caused by liver failure and/or portal-systemic shunting , is also frequent in cirrhotic patients . HE is related to a series of relevant outcomes both for patients and for caregivers: further decompensation, mortality, low quality of life, high risk of falls , having a relevant impact on patient's social life and healthcare services.
The relationship between muscle alteration and cognitive impairment in cirrhosis is actually under debate. Therefore, it appears intriguing and interesting to investigate the interaction between minimal HE, assessed by psychometric tests and also using a series of biomedical instruments able to study movement alterations, and impairment of muscle mass and function evaluated by imaging and a physical performance battery test. An experimental study to investigate the liver muscle axis in these patients will also be performed on cultured human mioblast. Two clinical units and one experimental unit will carry on the project aimed to study:
-kinematic and kinetic parameters in subjects with and without MHE;
the correlation between kinematic and kinetic alterations, indexes of dynamic stability, with muscle mass and/or performance ;
-the ability of kinematic and kinetic parameters vs parameters of muscle mass and/or performance in identifying cirrhotic subjects at risk of falls, OHE-development, hospitalization, death during 6 months follow up;
-whether liver-derived exosomes, isolated from plasma samples of cirrhotic patients with MHE, or with sarcopenia, or with altered kinematic and kinetic parameters could vehicle, to skeletal muscle, microRNAs able to induce or contribute to muscle alterations.

ERC
LS4_8, LS4_5, LS7_3
Keywords:
EPATOLOGIA, NEUROLOGIA, METABOLISMO, BIOLOGIA CELLULARE

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