Clinical trial NCT06514300: Investigating Myosteatosis in Steatotic Liver Diseases
Official title: 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
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Alcohol-related Liver Disease
Metabolic Dysfunction Associated Steatotic Liver Disease
Steatotic Liver Disease of Mixed Origin (MetALD)
Steatotic Liver Diseases
Myosteatosis
Magnetic Resonance Imaging
Magnetic Resonance Spectroscopy
Liver Histology
Keywords: myosteatosis
steatotic liver disease
metabolic dysfunction-associated steatotic liver disease
alcohol-related liver disease
MetALD
magnetic resonance imaging
magnetic resonance spectroscopy
liver biopsy
Lead sponsor: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Sponsor class: OTHER
Collaborators: name: Fonds National de la Recherche Scientifique
name: Concerted Research Action
First posted: 2024-07-23
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: This study is intended for patients with steatotic liver diseases SLD) characterized by an excessive liver lipid content higher than 5% (steatosis). SLD include 3 clinical entities with specific diagnostic criteria previously defined (Rinella MC, et al. J Hepatol. 2023) : metabolic dysfunction-associated steatotic liver disease, highly related to overweight, obesity and type 2 diabetes; alcohol-related liver disease, secondary to an excessive alcohol beverages consumption; and a third mixed entity combining both conditions called MetALD. All SLD patients will be recruited in this project to investigate if muscle phenotype is specifically related to one type of SLD.

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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 \&gt; 25 kg/m²), obesity (BMI \&gt; 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 \&gt; 150 mg/dl or treatment for dyslipidemia, HDL cholesterol \&lt; 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\&#39;s disease, autoimmune hepatitis, alpha1-anti-trypsin deficiency,...)
* Heavy consumption of alcoholic beverages, i.e. \&gt; 140 g or 210 g of ethanol in women or men respectively).
* Intravenous drug use
* HbA1C \&gt; 10%
* Decompensated cirrhosis (presence of ascites, bilirubin level \&gt; 1.2 mg/dL in a patient without Gilbert's syndrome, albumin level \&lt; 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 \&gt;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.

Primary outcomes:
measure: correlation between muscle mass and fat content and liver histological features of SLD
timeFrame: MRI and liver biopsy are performed at Day 1
Secondary outcomes:
measure: liver molecular mechanisms involved in myosteatosis pathogenesis
timeFrame: liver samples are collected during the biopsy
measure: impact of muscle fat content on muscle function
timeFrame: muscle function tests are performed 1-week after the biopsy/MRI (Day 7)
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Cliniques universitaires Saint-Luc
Study officials:
affiliation: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
name: Nicolas Lanthier, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Linge J, Nasr P, Sanyal AJ, Dahlqvist Leinhard O, Ekstedt M. Adverse muscle composition is a significant risk factor for all-cause mortality in NAFLD. JHEP Rep. 2022 Dec 24;5(3):100663. doi: 10.1016/j.jhepr.2022.100663. eCollection 2023 Mar.
citation: Ong JP, Pitts A, Younossi ZM. Increased overall mortality and liver-related mortality in non-alcoholic fatty liver disease. J Hepatol. 2008 Oct;49(4):608-12. doi: 10.1016/j.jhep.2008.06.018. Epub 2008 Jul 9.
citation: Singal AK, Mathurin P. Diagnosis and Treatment of Alcohol-Associated Liver Disease: A Review. JAMA. 2021 Jul 13;326(2):165-176. doi: 10.1001/jama.2021.7683.
citation: Rinella ME, Lazarus JV, Ratziu V, Francque SM, Sanyal AJ, Kanwal F, Romero D, Abdelmalek MF, Anstee QM, Arab JP, Arrese M, Bataller R, Beuers U, Boursier J, Bugianesi E, Byrne CD, Castro Narro GE, Chowdhury A, Cortez-Pinto H, Cryer DR, Cusi K, El-Kassas M, Klein S, Eskridge W, Fan J, Gawrieh S, Guy CD, Harrison SA, Kim SU, Koot BG, Korenjak M, Kowdley KV, Lacaille F, Loomba R, Mitchell-Thain R, Morgan TR, Powell EE, Roden M, Romero-Gomez M, Silva M, Singh SP, Sookoian SC, Spearman CW, Tiniakos D, Valenti L, Vos MB, Wong VW, Xanthakos S, Yilmaz Y, Younossi Z, Hobbs A, Villota-Rivas M, Newsome PN; NAFLD Nomenclature consensus group. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. J Hepatol. 2023 Dec;79(6):1542-1556. doi: 10.1016/j.jhep.2023.06.003. Epub 2023 Jun 24.
citation: Nachit M, Lanthier N, Rodriguez J, Neyrinck AM, Cani PD, Bindels LB, Hiel S, Pachikian BD, Trefois P, Thissen JP, Delzenne NM. A dynamic association between myosteatosis and liver stiffness: Results from a prospective interventional study in obese patients. JHEP Rep. 2021 Jun 15;3(4):100323. doi: 10.1016/j.jhepr.2021.100323. eCollection 2021 Aug.
citation: Nachit M, Kwanten WJ, Thissen JP, Op De Beeck B, Van Gaal L, Vonghia L, Verrijken A, Driessen A, Horsmans Y, Francque S, Leclercq IA. Muscle fat content is strongly associated with NASH: A longitudinal study in patients with morbid obesity. J Hepatol. 2021 Aug;75(2):292-301. doi: 10.1016/j.jhep.2021.02.037. Epub 2021 Apr 15.
citation: Henin G, Loumaye A, Leclercq IA, Lanthier N. Myosteatosis: Diagnosis, pathophysiology and consequences in metabolic dysfunction-associated steatotic liver disease. JHEP Rep. 2023 Nov 14;6(2):100963. doi: 10.1016/j.jhepr.2023.100963. eCollection 2024 Feb.