Association of Nonalcoholic Fatty Liver Disease With Relative Skeletal Muscle Mass: A Public Health Perspective

The recently published article by Kim et al. strongly suggests that nonalcoholic fatty liver disease (NAFLD) is a major public health problem in ethnically disparate populations in the postgenomic era.(1) Clinical studies with stringent inclusion/exclusion criteria for enrollment of eligible subjects from well-defined patient population subsets are warranted to provide meaningful insights into cost-effective management of NAFLD; observational/cross-sectional/longitudinal/gene-epidemiology studies with large sample sizes would be beneficial in reducing the increasing burden of NAFLD among patients of varying genetic landscapes.(2) A major strength in this 7-year longitudinal study with an impressive sample size (12,624 subjects without baseline NAFLD, 2,943 subjects with baseline NAFLD) is the stratified/subgroup analysis in patient cohorts with relevant statistical adjustments for clinical covariates/parameters and subsequent association(s) of clinically diagnosed NAFLD with skeletal muscle mass; written informed consent is a core tenet of bioethics in good-practice research, and NAFLD cases in follow-up timeline-based studies should be succinctly informed of the rationale of ethical participation in research by devoting quality time in organizing effective patient-interaction awareness lectures/one-to-one interviews/counseling sessions. It was interesting to observe a total number of 10,534 subjects without baseline NAFLD and 2,631 subjects with baseline NAFLD in robust Cox-proportional hazard analysis for reliable assessment of changes in relative skeletal muscle mass over a year; clinical diagnosis was accurate wherein symptomatic NAFLD subjects were defined by hepatic steatosis index (a previously validated NAFLD prediction model), and relative skeletal muscle mass was presented using the skeletal muscle mass index/diagnostic measure of body weight–adjusted appendicular skeletal muscle mass, determined by sophisticated bioelectrical impedance analysis. The findings revealed that 1,864 (14.8%) out of 12,624 subjects without baseline NAFLD developed NAFLD during the 7-year follow-up period, thereby suggesting that increases in relative skeletal muscle mass over time may lead to benefits either in development of NAFLD or resolution of existing NAFLD. I wish to add that the statistical data appear bias-free and accurate with appreciable statistical power so as to draw definitive conclusions; further replicative studies with participation of age-matched, healthy, disease-free controls of the same ethnicity as NAFLD cases are warranted for a cost-effective, strategic public health research model. Therapeutic targeting of metabolic/ biochemical signaling pathways, especially transmembrane receptors, lipid mediators/second messengers, and drug-metabolizing enzymes/membrane transporters coupled with computed tomography/magnetic resonance imaging and/or pharmacogenetics may be clinically efficacious in demystifying the underlying cellular/molecular/immunobiological mechanisms in NAFLD pathogenesis and development of predictive/ prognostic biomarkers in NAFLD management.