Muscle fat content is associated with the presence of steatotic liver disease, muscle function impairment and insulin resistance

Introduction: Decreased skeletal muscle density is associated with metabolic dysfunction-associated steatohepatitis (MASH) in subjects with severe obesity. However, reliable data on muscle fat content and its related consequences are lacking in the general MASLD population and in alcohol-related liver disease (ALD). Aim: To investigate the muscle phenotype (mass and intramuscular fat) by magnetic resonance imaging in relation to muscle function and liver disease severity, histologically assessed in a large cohort of patients with SLD. Methods: Patients with a steatotic liver disease (SLD) were prospectively recruited from hepatology and diabetology outpatient clinics and the alcohol withdrawal unit. Patients underwent liver/skeletal muscles MRI (3.0 T, GE Healthcare®). If fibrotic SLD was suspected based on increased liver stiffness (transient elastography) (≥ 7.8 kPa),a liver biopsy was performed on that same day. Controls were recruited based on the absence of SLD on transient elastography and underwent the same MRI protocol. Liver fat content and stiffness were further measured by proton density fat fraction (PDFF) and magnetic resonance elastography (MRE). Muscle mass was estimated using the height-normalized skeletal muscle index (SMI) at the third lumbar vertebra. Intramuscular fat content from paravertebral (psoas and erector) and right leg muscles was measured using PDFF. Liver biopsies were histologically scored using the SAF score first by two local pathologists and revised by two international ones to reach consensus. Muscle function was assessed using the Liver Frailty Index (LFI) combining handgrip strength, balance and sit-to-stand tests. Insulin resistance was assessed in non-diabetic participants using the homeostasis model assessment for insulin resistance (HOMA-IR). Type 2 diabetes was defined by the daily intake of hypoglycemic drugs. Intergroup comparisons were systematically performed by gender, analyzing men and women separately to account for the physiological effects of gender on muscle phenotype. Results: 92 participants with SLD (54 MASLD, 38 ALD) and 10 controls were included out of 118 screened participants between March 2021 and August 2024. Control and SLD groups were comparable for age (median age: 43 for controls, 57 for MASLD, 51 for ALD – p = 0.140). Type 2 diabetes was more prevalent in the MASLD group (33%) than in control (0%) and ALD (8%) groups (p < 0.0001). SLD groups did not differ in terms of liver stiffness assessed by transient elastography and magnetic resonance elastography. Steatosis was graded as 2-3 in 54% of the SLD cohort. Ballooning was graded as 0 in 50%, 1 in 23% and 2 in 27%. Fibrosis was graded as ≥ 2 in 63% of the SLD cohort. Mean muscle fat content and mass, across all examined muscles, were significantly higher in the 2 SLD groups compared to controls for both sexes (mean SMI (cm²/m²): 36.0 in control, 58.6 in MASLD, 47.7 in ALD – p < 0.001). Muscle fat content, mass and function was similar in MASLD and ALD groups in spite of clear metabolic differences. Participants with a SLD and a mean paravertebral muscles fat content above 30% consistently had an impaired muscle function (sit-to-stand, handgrip strength test and LFI) compared to participants with low (>30%) muscle fat but comparable age and BMI (p > 0.05). The association hods true in men and in women. Insulin resistance assessed by the HOMA-IR positively correlated to mean leg fat content in MASLD (r = 0.45, p = 0.017) and in ALD (r = 0.47, p = 0.005). Conclusions: Muscle fat content as assessed using accurate quantitative MRI technique, is increased in the presence of SLD, whether MASLD or ALD, in a large prospective cohort. This observation supports grouping MASLD and ALD into a common entity related to muscle changes, with myosteatosis being associated with impaired muscle function and insulin resistance.

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Henin, G., Nachit, M., André-Dumont, S., Goffaux, A., Declerck, S., Gouw, A., Sempoux Christine, Baldin, P., Henry, P., Duchêne, G., Trefois, P., Danse, E., Reyngoudt, H., Marty, B., Loumaye, A., Starkel, P., Leclercq, I., & Lanthier, N. (2026). Muscle fat content is associated with the presence of steatotic liver disease, muscle function impairment and insulin resistance. Acta Gastro-Enterologica Belgica, 89(1), Y03. https://hdl.handle.net/2078.5/271984 (Original work published 2026)