Relationship between relative skeletal muscle mass and nonalcoholic fatty liver disease: a systematic review and meta-analysis

Abstract

Background and Aim Nonalcoholic fatty liver disease (NAFLD) has gradually become one of the most common chronic liver diseases in the world. More and more evidence shows that low skeletal muscle mass index (SMI) may play a role in the development of NAFLD. Our aim was to quantify the association between SMI, sarcopenia and the presence and severity of NAFLD. Methods We systematically searched English relevant studies from PubMed, Embase, the Web of Science and the Cochrane Library updated to December 20th, 2018. Studies in which SMI was compared between NAFLD cases and controls were included. So were studies concerning the odds ratio (OR) of NAFLD, non-alcoholic steatohepatitis (NASH) and significant fibrosis in sarcopenia patients. Pooled weighted mean differences and ORs were calculated. Results Of the 1331 retrieved studies, 19 articles were included. SMI level in NAFLD patients was 1.77 (95% CI 1.15, 2.39) lower than that in normal controls. We also found a significantly higher occurrence risk of NAFLD (OR = 1.33, 95% CI 1.20 to 1.48), NASH (OR = 2.42, 95% CI 1.27 to 3.57) and NAFLD-related significant fibrosis (OR = 1.56, 95% CI 1.34, 1.78) in sarcopenia subjects. Conclusions SMI level in patients with NAFLD was lower than healthy people, and patients with sarcopenia have higher occurrence risk of NAFLD, as well as its advanced stages including NASH or NAFLD-related significant fibrosis. Further well-designed prospective studies are required to strengthen the arguments.

Relative Skeletal Muscle Mass Is an Important Factor in Non-Alcoholic Fatty Liver Disease in Non-Obese Children and Adolescents

“…The association between the SMM and NAFLD observed here is consistent with previous studies. Several cross-sectional studies found that sarcopenia is closely linked to the presence and severity of NAFLD [ 5 , 10 , 11 , 12 , 13 , 20 ], and a longitudinal study showed that increasing SMM overtime was beneficial for either preventing or resolving NAFLD [ 16 ]. However, so far, studies have been limited to adults, most of whom were obese, because sarcopenia was originally described in elderly individuals [ 9 ], and a clear association has been reported to exist between sarcopenia and obesity [ 21 ].…”

“…Evidence of a link between low SMM and insulin resistance has been gathered over the recent years, but the exact pathophysiology remains to be fully investigated [ 11 , 16 , 20 , 23 ]. The underlying mechanism is thought to be complex [ 5 , 10 , 11 , 16 ], and the hypotheses currently being discussed can be summarized as follows: First, considering that skeletal muscle is the major insulin-mediated glucose utilizing organ, a reduction in SMM may cause insulin resistance, which is one of the primary causes of NAFLD [ 10 , 12 , 24 , 25 ]. As a result of insulin resistance, a combination of increased free fatty acids and decreased lipid beta-oxidation in the liver may lead to the accumulation of triglycerides in the liver [ 16 , 24 ].…”

“…Third, low SMM promotes physical disability and increases obesity, creating a vicious cycle leading to liver steatosis [ 16 ]. Fourth, The intracellular oxidative stress, one of the pathophysiology of sarcopenia, causes chronic low-grade inflammation with increased concentrations of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) [ 30 , 31 , 32 ] and theses cytokines may trigger to stress responses in hepatocytes, leading to TNF-α-mediated liver damage [ 12 , 30 ]. Fifth, low vitamin D levels are being presented as a new potential pathophysiological mechanism, as vitamin D has been reported to play a major role in maintaining muscle function, and in recent years, it has been considered a factor associated with both sarcopenia and NAFLD [ 33 , 34 ].…”

“…It is known to promote insulin resistance, leading to the development of metabolic syndrome and diabetes [ 10 , 11 ]. Although the exact mechanism between the sarcopenia and NAFLD has yet to be fully identified, several studies showed that sarcopenia was significantly associated with an increased risk of having NAFLD, and even the severity of NAFLD based on abdominal sonography grading appears to be associated with sarcopenia, regardless of visceral fatness and other metabolic confounders [ 10 , 11 , 12 , 13 , 14 , 15 ]. Another seven-year longitudinal study showed that increases in relative SMM over time might lead to benefits, either by preventing the development of NAFLD or by the resolution of existing NAFLD [ 16 ].…”

Sarcopenia: an emerging risk factor for non-alcoholic fatty liver disease

“…Sarcopenia is significantly associated with an increased risk of NAFLD among the general population, and of significant liver fibrosis among subjects with NAFLD [3]. In the current issue of Hepatology International, Cai et al performed a meta-analysis of 19 studies [4] and found that the skeletal muscle index (SMI) in subjects with NAFLD was 1.77 times [95% confidence interval (CI) 1.15-2.39] lower than that in normal controls. They also reported significantly increased risks of NAFLD [odds ratio (OR) 1.33; 95% CI 1.20-1.48], NASH (OR 2.42; 95% CI 1.27-3.57), and NAFLD-related significant fibrosis (OR 1.56; 95% CI 1.34-1.78) in sarcopenic individuals compared with non-sarcopenic subjects.…”