Spotlight on Impactful Research: Relationship Between Relative Skeletal Muscle Mass and Nonalcoholic Fatty Liver Disease: A 7‐Year Longitudinal Study

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Abbreviations

HSI

hepatic steatosis index

NAFLD

nonalcoholic fatty liver disease

SMI

skeletal muscle index

Nonalcoholic fatty liver disease (NAFLD) has largely been considered as the hepatic manifestation of the metabolic syndrome. Accordingly, NAFLD has mostly been viewed in the context of obesity and excess visceral adipose tissue. Treatments have focused on medical weight loss. Recently, the impact of diminished skeletal muscle on NAFLD has been examined. Threshold loss of skeletal muscle, termed sarcopenia, was found to be a risk factor for the presence1 and severity2 of NAFLD. However, these studies were limited by a cross‐sectional design. Therefore, it was not possible to assess whether sarcopenia led to a higher incidence of NAFLD or whether increasing skeletal muscle could result in resolution of NAFLD. A population‐based, longitudinal study was recently published3 examining the relationship between changes in skeletal muscle and NAFLD, defined by clinical models.

The described study3 divided participants into NAFLD present and NAFLD absent cohorts. In one arm, the investigators examined changes in skeletal muscle with incident NAFLD (n = 10,534). In the second arm, the study investigators examined the effect of changes in skeletal muscle on the resolution of NAFLD (n = 2631). There were important aspects of the study design to consider. The changes in skeletal muscle were examined by serial bioelectrical impendence analysis measured 1 year apart. Skeletal muscle was quantified as the skeletal muscle index (SMI), which measures appendicular skeletal muscle mass adjusted for body weight. This is notable because the authors refer to skeletal muscle mass when they are measuring weight‐adjusted appendicular skeletal mass. The presence of NAFLD was based on a clinical model, the hepatic steatosis index (HSI), that uses aminotransferases, diabetes, gender, and body mass index to assess for the presence of NAFLD.4 The HSI was assessed annually, up to 7 years. Once again, the authors refer to NAFLD, whereas “suspected NAFLD” may be a more appropriate term. The outcomes examined were incident NAFLD in the cohort without steatosis and NAFLD resolution in the cohort with steatosis.

Overall, the study population was relatively lean with a mean body mass index of 24 kg/m². Nineteen percent of participants had suspected NAFLD at baseline. Fifteen percent of those without NAFLD experienced development of NAFLD during follow‐up. Those in the greatest tertile of SMI change over 1 year had a lower risk for incident NAFLD compared with the lowest tertile of SMI change. In the cohort with existing NAFLD, only 3% had resolution. Those in the highest tertile of SMI were more likely to have resolution over follow‐up. In addition, the highest tertile of SMI change had a greater chance of NAFLD resolution compared with the lowest tertile. A succinct summary of the results was that increased SMI was protective against incident NAFLD and associated with NAFLD resolution. The results were similar when changes in SMI over 1 year were examined. Those with increased SMI over 1 year were less likely to experience NAFLD and more likely to experience resolution of existing NAFLD. The clinical implications of the results would be that increasing skeletal muscle may decrease the future risk for NAFLD and promote resolution of existing NAFLD. This could lead clinicians to recommend exercise, such as resistance exercise, with the goal of increasing muscle mass to persons at risk for NAFLD or with NAFLD already present.

There are three major limitations in the study to consider. The most significant is the reliance on a clinical model to define NAFLD. One study, cited by the authors, found that changes in HSI were weakly correlated with changes in liver fat measured by proton magnetic resonance spectroscopy.5 Models for NAFLD have been designed and validated in cross‐sectional studies, and the longitudinal use of these markers, which include fixed components such as gender, requires further investigation. The second limitation is the use of SMI to measure changes in skeletal muscle mass. The index measures the amount of appendicular skeletal mass adjusted to total body mass. When measured longitudinally, changes in fat mass without changes in skeletal muscle could alter SMI. For instance, if a person gains fat mass alone over 1 year, his or her HSI would increase and the SMI would decrease without any change in skeletal muscle. Lastly, the population was exclusively Korean, had low amounts of steatosis, and was relatively lean. Whether these results would be seen in a different population, especially with higher rates of obesity, is not known.

Despite the limitations, multiple studies have now found an association between low muscle mass and fatty liver disease. Behavioral factors, such as diet and exercise, are viewed as both risk factors and therapeutic targets in NAFLD. There is growing evidence that sarcopenia is an independent risk factor for NAFLD. Physical inactivity is another recognized risk factor for NAFLD. A therapeutic target to treat NAFLD could include one to increase skeletal muscle. However, the intensity, type, and duration of exercise best suited to treat NAFLD are not known.6 The current article presents an area of expanding research and clinical interest. A recent review found that both aerobic and resistance training could reduce hepatic steatosis.7 What is not known currently is whether exercise should be individualized to patients based on body composition. At the current time, there are at minimum increasing data to suggest that adding resistance training with a goal of increasing skeletal muscle mass should be considered as part of a comprehensive strategy to reduce hepatic steatosis.