Malnutrition and sarcopenia have been shown to impact morbidity and mortality in liver cirrhosis in retrospective studies in patients evaluated for liver transplantation. The first part of the study will examine, in a prospective multicenter investigation, the role of sarcopenia on 1 year mortality in a large national cohort of patients with liver cirrhosis of different origin and severity. Sarcopenia will be evaluated by imaging CT scan. The CT scan transverse L3 images will be analyzed centrally by two trained observers by SliceOmatic Software V4.2. Skeletal muscle will be identified and quantified by HU thresholds of -29 to +150. Patients will be classified as having sarcopenia using cut-off values proposed by Carey et al.
Patients will be followed for a 12 months period. Clinical, functional and biochemical evaluation will be performed during the study at different time points (3, 6, and 12 months). The occurrence of complications (ascites, hepatic encephalopathy, GI bleeding,..), episodes of hospitalization or any relevant clinical event will be recorded at each visit. The study has been approved by the Ethical Committee Review Board. A sample size of 277 patients has been planned.
The second part of the study will investigate liver-muscle crosstalk in an in vitro model of human skeletal muscle cells. Exosomes, that are small vesicles (40¿100 nm) possess the capability of `communicating¿ with neighboring or distant cells by fusing with the plasma membrane and delivering their cargo, including proteins, mRNAs, and miRNAs. Exosomes will be extracted from the plasma of patients with liver cirrhosis of different origin and severity. Nutritional status and sarcopenia will also be recorded. The in vitro model we¿ll allow us to evaluate whether liver-derived exosomes, and their miRNA cargo, can interfere with muscle cell proliferation and differentiation and with protein homeostasis inducing the sarcopenic process.