Non-alcoholic fatty liver disease (NAFLD) has reached epidemic proportions, affecting an estimated one-quarter of the world’s adult population. Multiple organ systems have been implicated in the pathophysiology of NAFLD; however, the role of skeletal muscle has until recently been largely overlooked. A growing body of evidence places skeletal muscle—via its impact on insulin resistance and systemic inflammation—and the muscle-liver axis at the center of the NAFLD pathogenic cascade. Population-based studies suggest that sarcopenia is an effect-modifier across the NAFLD spectrum in that it is tightly linked to an increased risk of non-alcoholic fatty liver, non-alcoholic steatohepatitis (NASH), and advanced liver fibrosis, all independent of obesity and insulin resistance. Longitudinal studies suggest that increases in skeletal muscle mass over time may both reduce the incidence of NAFLD and improve preexisting NAFLD. Adverse muscle composition, comprising both low muscle volume and high muscle fat infiltration (myosteatosis), is highly prevalent in patients with NAFLD. The risk of functional disability conferred by low muscle volume in NAFLD is further exacerbated by the presence of myosteatosis, which is twice as common in NAFLD as in other chronic liver diseases. Crosstalk between muscle and liver is influenced by several factors, including obesity, physical inactivity, ectopic fat deposition, oxidative stress, and proinflammatory mediators. In this perspective review, we discuss key pathophysiological processes driving sarcopenia in NAFLD: anabolic resistance, insulin resistance, metabolic inflexibility and systemic inflammation. Interventions that modify muscle quantity (mass), muscle quality (fat), and physical function by simultaneously engaging multiple targets and pathways implicated in muscle-liver crosstalk may be required to address the multifactorial pathogenesis of NAFLD/NASH and provide effective and durable therapies.

Liver fibrosis stage strongly influences the hepatocyte-specific uptake of Gd-EOB-DTPA. Potentially the normalisation technique and K (Hep) will reduce patient and system bias, yielding a robust approach to non-invasive liver function determination.

Alterations in intramuscular ATP, PCr and fat content in FMS probably reflect a combination of inactivity related to pain and dysfunction of muscle mitochondria.

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Background Adverse muscle composition (MC) as measured by magnetic resonance imaging has previously been linked to poor function, comorbidity, and increased hospitalization. The aim of this study was to investigate if adverse MC predicts all‐cause mortality using data from UK Biobank. Methods There were 40 178 participants scanned using a 6 min magnetic resonance imaging protocol. Images were analysed for thigh fat‐tissue free muscle volume and muscle fat infiltration (MFI) using AMRA® Researcher (AMRA Medical, Linköping, Sweden). For each participant, a sex, weight, and height invariant muscle volume z‐score was calculated. Participants were partitioned into four MC groups: (i) normal MC, (ii) only low muscle volume [<25th percentile for muscle volume z‐score (population wide)], (iii) only high MFI [>75th percentile (population wide, sex‐specific)], and (iv) adverse MC (low muscle volume z‐score and high MFI). Association of MC groups with mortality was investigated using Cox proportional‐hazard modelling with normal MC as referent (unadjusted and adjusted for low hand grip strength, sex, age, body mass index, previous diagnosis of disease (cancer, type 2 diabetes and coronary heart disease), lifestyle, and socioeconomic factors (smoking, alcohol consumption, physical activity, and Townsend deprivation index). Results Muscle composition measurements were complete for 39 804 participants [52% female, mean (SD) age 64.2 (7.6) years and body mass index 26.4 (4.4) kg/m2]. Three hundred twenty‐eight deaths were recorded during a follow‐up period of 2.9 (1.4) years after imaging. At imaging, adverse MC was detected in 10.5% of participants. The risk of death from any cause in adverse MC compared with normal MC was 3.71 (95% confidence interval 2.81–4.91, P < 0.001). Only low muscle volume and only high MFI were independently associated with all‐cause mortality [1.58 (1.13–2.21), P = 0.007, and 2.02 (1.51–2.71), P < 0.001, respectively]. Adjustment of low hand grip strength [1.77 (1.28–2.44), P < 0.001] did not attenuate the associations with any of the MC groups. In the fully adjusted model, adverse MC and only high MFI remained significant (P < 0.001 and P = 0.020) while the association with only low muscle volume was attenuated to non‐significance (P = 0.560). The predictive performance of adverse MC [1.96 (1.42–2.71), P < 0.001] was comparable with that of previous cancer diagnosis [1.93 (1.47–2.53), P < 0.001] and smoking [1.71 (1.02–2.84), P = 0.040]. Low hand grip strength was borderline non‐significant [1.34 (0.96–1.88), P = 0.090]. Conclusions Adverse MC was a strong and independent predictor of all‐cause mortality. Sarcopenia guidelines can be strengthened by including cut‐offs for myosteatosis enabling detection of adverse MC.