A dynamic association between myosteatosis and liver stiffness: Results from a prospective interventional study in obese patients

Maxime Nachit; Nicolas Lanthier; Julie Rodriguez; Audrey M Neyrinck; Patrice D Cani; Laure B Bindels; Sophie Hiel; Barbara D Pachikian; Pierre Trefois; Jean-Paul Thissen; Nathalie M Delzenne

doi:10.1016/j.jhepr.2021.100323

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.

Authors

Maxime Nachit^{1

2}, Nicolas Lanthier^{1

3}, Julie Rodriguez⁴, Audrey M Neyrinck⁴, Patrice D Cani^{4

5}, Laure B Bindels⁴, Sophie Hiel⁴, Barbara D Pachikian⁶, Pierre Trefois⁷, Jean-Paul Thissen^{8

9}, Nathalie M Delzenne⁴

Affiliations

¹ Laboratory of Hepato-Gastroenterology, Institut de Recherche Expérimentale et Clinique, UCLouvain, Université catholique de Louvain, Brussels, Belgium.
² Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.
³ Service d'Hépato-Gastroentérologie, Cliniques universitaires Saint-Luc, UCLouvain, Université catholique de Louvain, Brussels, Belgium.
⁴ Metabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Université catholique de Louvain, Brussels, Belgium.
⁵ WELBIO - Walloon Excellence in Life Sciences and BIOtechnology, UCLouvain, Université catholique de Louvain, Brussels, Belgium.
⁶ Centre d'Investigation Clinique en Nutrition, UCLouvain, Université catholique de Louvain, Louvain-La-Neuve, Belgium.
⁷ Medical Imaging Department, Cliniques universitaires St-Luc, UCLouvain, Université catholique de Louvain, Brussels, Belgium.
⁸ Pole of Endocrinology, Diabetes and Nutrition, Institut de Recherche Expérimentale et Clinique, UCLouvain, Université catholique de Louvain, Brussels, Belgium.
⁹ Service d'Endocrinologie, diabétologie et nutrition, Cliniques universitaires Saint-Luc, UCLouvain, Université catholique de Louvain, Brussels, Belgium.

Abstract

Background & aims: Retrospective cross-sectional studies linked sarcopenia and myosteatosis with metabolic dysfunction-associated fatty liver disease (MAFLD). Here, we wanted to clarify the dynamic relationship between sarcopenia, myosteatosis, and MAFLD.

Methods: A cohort of 48 obese patients was randomised for a dietary intervention consisting of 16 g/day of inulin (prebiotic) or maltodextrin (placebo) supplementation. Before and after the intervention, we evaluated liver steatosis and stiffness with transient elastography (TE); we assessed skeletal muscle index (SMI) and skeletal muscle fat index (SMFI) (a surrogate for absolute fat content in muscle) using computed tomography (CT) and bioelectrical impedance analysis (BIA).

Results: At baseline, sarcopenia was uncommon in patients with MAFLD (4/48, 8.3%). SMFI was higher in patients with high liver stiffness than in those with low liver stiffness (640.6 ± 114.3 cm²/ Hounsfield unit [HU] vs. 507.9 ± 103.0 cm²/HU, p = 0.001). In multivariate analysis, SMFI was robustly associated with liver stiffness even when adjusted for multiple confounders (binary logistic regression, p <0.05). After intervention, patients with inulin supplementation lost weight, but this was not associated with a decrease in liver stiffness. Remarkably, upon intervention (being inulin or maltodextrin), patients who lowered their SMFI, but not those who increased SMI, had a 12.7% decrease in liver stiffness (before = 6.36 ± 2.15 vs. after = 5.55 ± 1.97 kPa, p = 0.04).

Conclusions: Myosteatosis, but not sarcopenia, is strongly and independently associated with liver stiffness in obese patients with MAFLD. After intervention, patients in which the degree of myosteatosis decreased reduced their liver stiffness, irrespective of body weight loss or prebiotic treatment. The potential contribution of myosteatosis to liver disease progression should be investigated.

Clinical trials registration number: NCT03852069.

Lay summary: The fat content in skeletal muscles (or myosteatosis) is strongly associated with liver stiffness in obese patients with MAFLD. After a dietary intervention, patients in which the degree of myosteatosis decreased also reduced their liver stiffness. The potential contribution of myosteatosis to liver disease progression should be investigated.

Keywords: ALM, appendicular lean mass; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BIA, bioelectrical impedance analysis; BMI, body mass index; CAP, controlled attenuation parameter; CT scan; CT, computed tomography; CTDIvol, volume CT dose index; DEXA, dual-energy X-ray absorptiometry; DLP, dose–length product; FFM, fat-free mass; HT, hypertension; HU, Hounsfield unit; HbA1c, haemoglobin A1c; ITF, inulin-type fructans; L3, third lumbar level; Liver; M0, baseline; M3, end of the 3-month intervention; MAFL, metabolic associated fatty liver; MAFLD, metabolic dysfunction-associated fatty liver disease; MRI, magnetic resonance imaging; Muscle fat; Myosteatosis; NASH, non-alcoholic steatohepatitis; PMI, psoas muscle index; SMD, skeletal muscle density; SMDpsoas, psoas muscle density; SMFI, skeletal muscle fat index; SMFIpsoas, psoas fat index; SMI, skeletal muscle index; SMIbw, SMI scaled on body weight; SMIht2, SMI scaled on height squared; Sarcopenia; TE, transient elastography; γGT, γ-glutamyl transferase.

Associated data

ClinicalTrials.gov/NCT03852069