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

•This is the first European cohort study exploring both grip strength and muscle mass associations with NAFLD. •Lower muscle mass and grip strength were associated with a higher risk of incident NAFLD. •One lower tertile of grip strength and muscle mass accounted for 17.7% and 33.1% of diagnosed incident cases, respectively. Background & Aims Cross-sectional studies have reported that lower muscle mass and strength are 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 2 physical capability markers and severe NAFLD using data from the UK Biobank study. Methods A total of 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 bioelectrical impedance. 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. Non-linear 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 had severe NAFLD (3,277 hospitalisations and 34 deaths). Compared with the lowest tertile of muscle mass, the risk of severe NAFLD was lower in the middle (hazard ratio 0.76; 95% CI 0.70–0.83) and the highest tertile (hazard ratio 0.46; 95% CI 0.40–0.52). Tertiles of grip strength showed a similar pattern. Non-linearity was only identified for muscle mass (p <0.001). Being on the lower tertile of grip strength and muscle mass accounted for 17.7% and 33.1% of severe NAFLD 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. Lay summary Lower muscle mass – both quantity and quality – were associated with a higher risk of severe non-alcoholic fatty liver disease. Therefore, improving muscle mass might be a protective factor against this increasing public health problem. Cross-sectional studies have reported that lower muscle mass and strength are 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 2 physical capability markers and severe NAFLD using data from the UK Biobank study. A total of 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 bioelectrical impedance. 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. Non-linear associations were investigated using penalised cubic splines fitted in the Cox proportional hazard models. After a median follow-up of 10 years (IQR 9.3 to 10.7 years), 3,311 individuals had severe NAFLD (3,277 hospitalisations and 34 deaths). Compared with the lowest tertile of muscle mass, the risk of severe NAFLD was lower in the middle (hazard ratio 0.76; 95% CI 0.70–0.83) and the highest tertile (hazard ratio 0.46; 95% CI 0.40–0.52). Tertiles of grip strength showed a similar pattern. Non-linearity was only identified for muscle mass (p <0.001). Being on the lower tertile of grip strength and muscle mass accounted for 17.7% and 33.1% of severe NAFLD cases, respectively. 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.