Muscle fat content is strongly associated with NASH: A longitudinal study in patients with morbid obesity.

Background & Aims: Studies exploring the relationship between muscle fat content and non-alcoholic fatty liver disease (NAFLD) are scarce. Herein, we aimed to evaluate the association of muscle mass and fatty infiltration with biopsy-assessed NAFLD in patients with obesity.
Methods: At inclusion (n = 184) and 12 months after a dietary intervention (n = 15) or bariatric surgery (n = 24), we evaluated NAFLD by liver biopsy, and skeletal muscle mass index (SMI) by CT (CT-SMI) or bioelectrical impedance analysis (BIA-SMI). We developed an index to evaluate absolute fat content in muscle (skeletal muscle fat index [SMFI]) from CT-based psoas muscle density (SMFI _Psoas ).
Results: Muscle mass was higher in patients with NAFLD than in those without (CT-SMI 56.8 ± 9.9 vs. 47.4 ± 6.5 cm ² /m ² , p <0.0001). There was no association between sarcopenia and non-alcoholic steatohepatitis (NASH). SMFI _Psoas was higher in NASH ≥F2 and early NASH F0-1 than in NAFL (78.5 ± 23.6 and 73.1 ± 15.6 vs. 61.2 ± 12.6, p <0.001). A 1-point change in the score for any of the individual cardinal NASH features (i.e. steatosis, inflammation or ballooning) was associated with an increase in SMFI _Psoas (all p <0.05). The association between SMFI _Psoas and NASH was highly significant even after adjustment for multiple confounders (all p <0.025). After intervention (n = 39), NASH improvement, defined by NAFLD activity score <3 or a 2-point score reduction, was achieved in more than 75% of patients (n = 25 or n = 27, respectively) that had pre-established NASH at inclusion (n = 32) and was associated with a significant decrease in SMFI _Psoas (p <0.001). Strikingly, all patients who had ≥11% reduction in SMFI _Psoas achieved NASH improvement (14/14, p <0.05).
Conclusions: Muscle fat content, but not muscle mass, is strongly and independently associated with NASH. All individuals who achieved a ≥11% decrease in SMFI _Psoas after intervention improved their NASH. These data indicate that muscle fatty infiltration could be a potential marker for (and perhaps a pathophysiological contributor to) NASH.
Lay Summary: The fat content in skeletal muscles is highly reflective of the severity of non-alcoholic fatty liver disease (NAFLD) in patients with morbid obesity. In particular, muscle fat content is strongly associated with non-alcoholic steatohepatitis (NASH) and decreases upon NASH improvement. These data indicate that muscle fatty infiltration could be a marker and possible pathophysiological contributor to NASH.
Competing Interests: Conflict of interest The authors declare that they have no conflict of interest in relation to this work to disclose. Please refer to the accompanying ICMJE disclosure forms for further details.
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