Investigating Myosteatosis in Steatotic Liver Diseases

MYO-SLD : a Prospective Study to Determine the Phenotype of Muscle Fat Accumulation in a Cohort of Patients With SLD as to Confirm the Association Between Muscle Composition and Texture and the Phenotype of Liver Disease

Steatotic liver diseases (SLD) are the most common chronic liver diseases worldwide. SLD are defined by an excessive liver lipid content (steatosis) of more than 5% of the total liver weight and includes 3 clinical entities : metabolic dysfunction-associated steatotic liver disease (MASLD), alcohol-related liver disease (ALD) and a mixed entity combining the two settings referred as MetALD. SLD are associated to extra-hepatic complications such as cardiovascular diseases, insulin resistance or muscle changes. Among the latter, myosteatosis, defined by an excessive muscle fat content, has been reported as a muscle change in MASLD occuring even in non-cirrhotic stages. Investigators will explore these muscle changes in SLD patients according to the severity of the underneath liver disease.

This project investigates the correlation between liver and muscle phenotypes assessed in a cohort of all 3 SLD subgroups (MASLD, ALD and MetALD). If a severe form of SLD is suspected based on a severely increased liver elasticity, assessed by transient elastography, participants undergo a liver biopsy, liver and muscle magnetic resonance imaging. Eating habits and physical activity level are recorded using the 24 hour-recall and international physical activity questionnaire. Psychological disorders are also screened using dedicated questionnaires.

Inclusion Criteria:

• Age between18 to 75 years
• Presence of hepatic steatosis, suggested by a controlled attenuation parameter (CAP) ≥ 252 dB/m on elastometry and elevated transaminases (ALT ≥ 25 or 33 IU/L in women or men respectively)
• Presence of overweight (BMI > 25 kg/m²), obesity (BMI > 30 kg/m²), metabolic syndrome, prediabetes or type 2 diabetes. Metabolic syndrome is defined by int ernational Diabetes Federation as follows : waist circumference ≥ 94/80cm for men/women with ≥ 2 other criteria: arterial pressure ≥ 130/85 mmHg or treatment for hypertension, fasting glucose ≥ 130/85 mmHg or treatment for hypertension, serum triglycerides > 150 mg/dl or treatment for dyslipidemia, HDL cholesterol < 40/50 mg/dl for men/women or treatment for dyslipidemia.

Exclusion Criteria:

• Liver disease from other causes (alcohol, active viral chronic hepatitis B or C, Wilson's disease, autoimmune hepatitis, alpha1-anti-trypsin deficiency,...)
• Heavy consumption of alcoholic beverages, i.e. > 140 g or 210 g of ethanol in women or men respectively).
• Intravenous drug use
• HbA1C > 10%
• Decompensated cirrhosis (presence of ascites, bilirubin level > 1.2 mg/dL in a patient without Gilbert's syndrome, albumin level < 35 g/L)
• Pregnancy
• Use of drugs that may cause steatosis (methotrexate, amiodarone, tamoxifen, oral corticosteroids) currently or in the last 3 months
• Change in treatment of hyperglycaemia (dose or medication) in the last 3 months
• Change in body weight >5% in the last 3 months
• Active cancer
• End stage renal disease or dialysis
• Type 1 diabetes or secondary diabetes
• Digestive malabsorption
• Untreated thyroid disease
• Taking a treatment under study or approved for NASH (semaglutide, lanifibranor, obeticholic acid).
• Musculoskeletal disorders, neuromuscular or inflammatory diseases such as connective tissue diseases, myositis and vasculitis that have musculoskeletal manifestations.