Background

The investigation of muscle quality is important to understand underlying muscle health and pathology in disease states, such as End Stage Liver Disease (ESLD). Myosteatosis, i.e., fat infiltration into skeletal muscle, is a key indicator of muscle quality and may negatively affect muscle function. Previous studies have shown that myosteatosis occurs in patients with non-alcoholic fatty liver disease¹. However, most studies involving patients with ESLD have typically assessed myosteatosis in L3/L4 muscle groups^2,3. Thus, an in-depth investigation of myosteatosis in the lower limbs of patients with ESLD, and in particular the quadriceps, remains to be completed.

Aims and objectives

The primary aim was to investigate whether quadriceps intermuscular adipose tissue (IMAT) differs between patients with ESLD and healthy age/sex-matched controls (HC), and whether IMAT differs based on anatomical location and/or quadriceps muscle head. A secondary aim was to explore the impact of IMAT on muscle function.

Methods

33 patients with ESLD (55.0±10.5 years) and 17 HC (49.6±15.4 years) participated in this observational study. Quadriceps IMAT was estimated at 20,40,50,60 and 80% of muscle length (distal = 0%) via Magnetic Resonance Imaging (MRI) Dixon technique. Vastus lateralis, vastus medialis, vastus intermedius, and rectus femoris IMAT was also calculated at 50% of muscle length. Bioelectrical impedance analysis and maximal knee extensor isokinetic assessments were also completed to assess body composition and muscle strength respectively. Finally, wrist worn accelerometers were worn for up to 14 days  to  assess habitual physical activity.  The study was approved by the Health Research Authority – West Midlands Solihull (REC reference: 18/WM/0167) and was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. ClinicalTrials.gov identifier: NCT04734496.

Results

Two-way ANOVA showed a main effect of anatomical location (P<0.0001) and condition (p<0.0001), in addition to a significant interaction (i.e., location x condition) (P<0.01) for quadriceps IMAT. Šidák’s post hoc comparison showed quadriceps IMAT was greater in ESLD at all anatomical locations compared to HC. Similarly, when comparing individual quadricep muscles, two-way ANOVA showed a main effect for muscle (P<0.0001) and condition (P<0.0001) with a significant interaction (i.e., muscle x condition) (P<0.01). Šidák’s multiple comparisons revealed significant differences between quadriceps muscles in ESLD but not HC. Pearson r correlation showed significant positive correlations between quadriceps IMAT (at 50% muscle length) and BMI (r=0.62, P<0.0001, n=50), body fat percentage (r=0.65, P<0.0001, n=50) and age (r=0.36, P<0.01, n=50). In addition, negative correlations existed between quadriceps IMAT and both maximal knee extensor strength (r=-0.50, P<0.001, n=50) and habitual physical activity (r=-0.51, P<0.001, n=42).

Conclusions

Quadriceps IMAT is greater in patients with ESLD compared to HC, irrespective of the anatomical location or muscle analysed. Correlations suggest that quadriceps IMAT is positively associated with overall body fat percentage and BMI, and negatively associated with physical activity. Importantly, quadriceps IMAT may negatively impact muscle function and strength.