Associations of muscle mass and grip strength with severe NAFLD: a prospective study of 333,295 UK Biobank participants

Background & Aim: Cross-sectional studies have shown lower muscle mass and strength as risk factors for non-alcoholic fatty liver disease (NAFLD). However, the evidence from prospective studies is limited. This study examined both the strength and pattern of the associations between these two physical capability markers and severe NAFLD in the UK Biobank study. Methods: 333,295 participants were included in this prospective study. Grip strength was measured using a Jamar J00105 hydraulic hand dynamometer, and the Janssen equation was used to estimate skeletal muscle mass by bioimpedance. Muscle mass was adjusted for body weight and all exposures were sex-standardised. Associations of muscle mass and strength with severe NAFLD (defined as hospital admission or death) were first investigated by tertile of each exposure using Cox proportional hazard models. Nonlinear associations were investigated using penalised cubic splines fitted in the Cox proportional hazard models. Results: After a median follow-up of 10 years (IQR: 9.3 to 10.7 years), 3,311 individuals were diagnosed with severe NAFLD (3,277 hospitalisations and 34 deaths). Compared with the lowest tertile of muscle mass, the risk of NAFLD was lower in the middle (HR: 0.76 [95% CI: 0.70 to 0.83] and the highest tertile (HR: 0.46 [95% CI: 0.40 to 0.52]). Tertiles of grip strength showed a similar pattern. Nonlinearity was only identified for muscle mass (p<0.001). One lower tertile of grip strength and muscle mass accounted for 17.7%% and 33.1%% of diagnosed severe cases, respectively. Conclusions: Lower muscle mass and grip strength were associated with higher risk of developing severe NAFLD. Interventions to improve physical capability may be protective, but this needs to be investigated in appropriately designed trials