Joon Ho Moon, Won Kim, Bo Kyung Koo, and Nam H. Cho, on behalf of the Innovative Target Exploration of NAFLD (ITEN) consortium. Gut and Liver 2022;16:433-42. https://doi.org/10.5009/gnl210167

Background: We investigated the association between muscle strength and the prevalence of advanced fibrosis among individuals with non‐alcoholic fatty liver disease (NAFLD) using a nationwide cross‐sectional survey.Methods: Individuals, 20 to 79 years of age, from the Korean National Health and Nutrition Examination Surveys (KNHANES) from 2014 to 2016 were selected (N = 14 861), with sample weights applied. Muscle strength was quantified as the handgrip strength divided by the body mass index (BMI); low muscle strength (LMS) was defined as the lowest quartile (Q₁) of the handgrip strength/BMI for our sample population. NAFLD was defined as hepatic steatosis index >36. Advanced fibrosis was defined as a fibrosis‐4 index score ≥1.30 (Fibrosis_FIB4).Results: The mean age of the study population was 45.6 ± 0.2 years, and 42.4% were male. As muscle strength increased, the mean BMI and age decreased accordingly, and the proportions of diabetes, dyslipidaemia, hypertension, and obesity decreased significantly (P < 0.001 for all). In a crude analysis, the LMS was associated with an increased prevalence of NAFLD (odds ratio [OR] 3.62, 95% confidence interval [CI] 3.25–4.03, P < 0.001), which remained significant even after adjustment for age, sex, obesity, insulin resistance, diabetes, hypertension, dyslipidaemia, and high‐sensitivity C‐reactive protein (OR 1.66, 95% CI 1.28–2.16, P < 0.001). In this logistic regression model, the prevalence of NAFLD decreased by 24% with each quartile increment in muscle strength (OR 0.76, 95% CI 0.68–0.85, P < 0.001). Among individuals with NAFLD (n = 2092), LMS was significantly associated with the presence of advanced fibrosis (Fibrosis_FIB4) independently of age, sex, obesity, diabetes, hypertension, dyslipidaemia, and high‐sensitivity C‐reactive protein (OR 1.66, 95% CI 1.01–2.49, P = 0.015), which lost its statistical significance after additional adjustment for insulin resistance.Conclusions: Low muscle strength is independently associated with NAFLD. The significant association between LMS and advanced fibrosis in NAFLD may be mediated through insulin resistance.

Background: Sarcopenia is an independent risk factor not only for advanced‐stage non‐alcoholic fatty liver disease (NAFLD) but also for mortality. We investigated the association of sarcopenia and/or NAFLD with mortality among the Korean general population.Methods: Individuals aged 35–75 years without any history of cancer, ischaemic heart disease, ischaemic stroke, or secondary causes of chronic liver disease were selected from the Korean National Health and Nutrition Examination Surveys from 2008 to 2015. Their mortality data until December 2018 were retrieved from the National Death Registry. NAFLD and sarcopenia were defined by hepatic steatosis index and appendicular skeletal muscle mass divided by body mass index (BMI), respectively.Results: A total of 28 060 subjects were analysed [mean age, 50.6 (standard error, 0.1) years, 48.2 (0.3) % men]; the median follow‐up duration was of 6.8 (interquartile range, 4.8, 8.4) years. NAFLD predicted mortality after adjustment for age, sex, BMI, hypertension, dyslipidaemia, and smoking (HR 1.32, 95% CI 1.03–1.70), but this prediction lost its statistical significance after additional adjustment for diabetes mellitus. In contrast, NAFLD with advanced fibrosis independently increased the risk of mortality after adjustment for all covariates (HR 1.68, 95% CI 1.02–2.79). Stratified analysis revealed that NAFLD and sarcopenia additively increased the risk of mortality as an ordinal scale (HR 1.46, 95% CI 1.18–1.81, P for trend = 0.001). The coexistence of NAFLD and sarcopenia increased the risk of mortality by almost twice as much, even after adjustment for advanced fibrosis (HR 2.18, 95% CI 1.38–3.44).Conclusions: Concurrent NAFLD and sarcopenia conferred a two‐fold higher risk of mortality. The observation that NAFLD and sarcopenia additively increase mortality suggests that risk stratification would be helpful in predicting mortality among those with metabolic derangement.