Investigating Myosteatosis in Steatotic Liver Diseases

NCT06514300 | Enrolling By Invitation

• 1 other identifier: ST-IR-01 - MYO-SLD
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• correlation between muscle mass and fat content and liver histological features of SLD

  muscle mass and fat content will be assessed by magnetic resonance imaging and spectroscopy. Liver phenotype will be histologically assessed by 3 blinded pathologists and computer-assisted morphometry.

  MRI and liver biopsy are performed at Day 1

Secondary Outcomes (2)

• liver molecular mechanisms involved in myosteatosis pathogenesis

  liver samples are collected during the biopsy

• impact of muscle fat content on muscle function

  muscle function tests are performed 1-week after the biopsy/MRI (Day 7)

Study Arms (3)

MASLD patients

patients presenting with liver steatosis and at least one cardiometabolic criteria.

ALD patients

patients presenting with liver steatosis secondary to an excessive consumption of alcoholic beverages and with no cardiometabolic criteria.

MetALD patients

patients presenting with liver steatosis, at least one cardiometabolic criteria and an excessive consumption of alcohol beverages.

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Cliniques universitaires Saint-Luc- Université Catholique de Louvain: lead
• Fonds National de la Recherche Scientifique: collaborator
• Concerted Research Action: collaborator

Study Sites (1)

Cliniques universitaires Saint-Luc

Brussels, 1200, Belgium

Location

Related Publications (8)

• 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.

  PMID: 36818816 BACKGROUND

• 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.

  PMID: 18682312 BACKGROUND

• 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.

  PMID: 34255003 BACKGROUND

• 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.

  PMID: 37364790 BACKGROUND

• 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.

  PMID: 34355155 BACKGROUND

• 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.

  PMID: 33865909 BACKGROUND

• 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.

  PMID: 38322420 BACKGROUND

• Henin G, Goffaux A, Declerck S, Andre-Dumont S, Pendeville E, Valet M, Lejeune T, Dahlqvist G, Loumaye A, Schnabl B, Starkel P, Lanthier N. Non-Cirrhotic Steatotic Liver Disease is Associated With Impaired Muscle Function: A Cross-Sectional Study. JCSM Commun. 2025 Jul-Dec;8(2):e70012. doi: 10.1002/rco2.70012. Epub 2025 Oct 7.

  PMID: 41127673 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

* liver biopsy * serum/plasma samples * urine samples

Study Officials

• Nicolas Lanthier, MD, PhD

  Cliniques universitaires Saint-Luc- Université Catholique de Louvain

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2024
• First Posted: July 23, 2024
• Study Start: June 22, 2020
• Primary Completion: August 1, 2024
• Study Completion: August 1, 2024
• Last Updated: July 23, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)