Impact of sarcopenia on the progression of nonalcoholic fatty liver disease: a frequently forgotten association

The development of sarcopenia in patients with chronic liver disease has been recognized as a predictor of poor outcome. Sarcopenia, or the progressive loss of skeletal muscle mass begins to manifest in the early stages of chronic liver disease and worsens with progression to advanced liver disease with a prevalence approaching 60% in patients with end-stage liver disease (1). Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide with a disease spectrum ranging from relatively static isolated nonalcoholic fatty liver (NAFL) to progressive nonalcoholic steatohepatitis (NASH), which can lead to advanced fibrosis and cirrhosis. Although a majority of patients with NASH are obese, not all individuals with obesity develop NASH (2). Furthermore, NASH has been diagnosed with a relatively lower frequency in non-obese individuals (2). Recent cross-sectional studies have linked sarcopenia with both NAFLD and NASH as well as significant fibrosis beyond what is explained by obesity (3-6), though the cross-sectional design of these studies precludes a conclusion of temporal association. The interaction between muscle homeostasis and NAFLD is an intriguing concept due to the role of skeletal muscle in energy metabolism. Koo et al. reported an increasing prevalence of sarcopenia with the progression from without NAFLD (8.7%) to NAFLD (17.9%), and then to NASH (35%) (4). In addition, sarcopenia was associated with greater degrees of steatosis and fibrosis, with 46% of individuals with sarcopenia having significant fibrosis compared to 25% of those without sarcopenia (4). Sarcopenia was associated with a 2.5-fold higher risk of NASH and significant fibrosis in those with NAFLD, independent of obesity and insulin resistance (4). Limited longitudinal data have supported the cross-sectional observations. More recently, Kim et al. reported a 7-year longitudinal cohort study examining the relationship between skeletal muscle mass and NAFLD defined by hepatic steatosis index (7). Approximately, 15% of subjects without NAFLD at baseline developed incident NAFLD during the 7-year observation, with the highest tertile of skeletal muscle mass inversely associated with the incidence of NAFLD compared to the lowest tertile after adjusting for several known risk factors. Among subjects with NAFLD at baseline, the highest tertile of skeletal muscle mass was associated with resolution of NAFLD