A Pilot Randomised Study of the Metabolic and Histological Effects of Exercise in Non-alcoholic Steatohepatitis

Aims: Type 2 diabetes is a risk factor for the development and progression of non-alcoholic fatty liver disease (NAFLD). Lifestyle intervention is the principal treatment for NAFLD however the effects of exercise alone on the histological and metabolic severity of NAFLD are unclear. This study assessed the effects of 6 months exercise training and diet-induced weight loss on insulin resistance and liver histologyin overweight patients with NAFLD. Methods: 21 patients were randomised to circuit exercise (EX) training (60 minx3/week) or dietary induced weight loss (DIWL) (-500 kcal/d). Insulin sensitivity (euglycaemic-hyperinsulinemic clamp with tracer), adiposity (CT scan) and histology (liver biopsy) were assessed at 0 and 6 months. Results: Weight decreased by 9.7 +/- 4.6% (-6.7 +/- 6.3 kg p=0.02) with DIWL but was unchanged after EX. Both groups equivalently reduced visceral fat (DIWL -22 +/- 24% p=0.06 and EX - 18 +/- 18% p<0.05) while only EX increased lean mass (+3% p<0.01). DIWL markedly reduced steatosis (73 +/- 36% to 23 +/- 32%, p<0.05) and NAFLD activity score NAS (median (range) 5 (1-7) to 1 (0-5), p<0.05). After EX, there was no change in steatosis or NAS. A decrease in steatosis was associated with weight loss (r(s) = 0.82, p<0.0001). An improvement in fibrosis was associated with a decrease in steatosis (r(s) = 0.64, p=0.02). Small improvements in fasting hepatic insulin resistance were similar in both groups while changes in muscle insulin resistance were not significant. Conclusions: Circuit exercise is safe and efficacious for improving cardiometabolic risk factors in patients with NAFLD, however this dose of circuit training, without concomitant weight loss, was insufficient for histological improvements in NAFLD. The pilot study outcomes should stimulate further development of different exercise protocols (type, frequency and intensity) to address disease-specific conditions in those with severe insulin resistance.