Clinical approaches to non-alcoholic fatty liver disease

Table 1 Summary of lifestyle intervention studies: diet and/or physical activity

Ref.	Population, Study Design	Intervention	Results
[71]	n = 96, 12-mo intervention on adults with hepatic steatosis and type 2 diabetes	Combination of moderate caloric restriction (1200-1800 kcal/d) and increased moderate physical activity (175 min per week)	Significant decreases in BMI, weight, waist circumference, percent body fat and A1C
[72]	n = 50, longitudinal study with lifestyle intervention in NAFLD adults	10 concealing sessions with a dietitian, and moderate intensity activity 3 h/wk	Significantly decreased body fat and liver fat and increased fitness. NAFLD at baseline resolved in 20 participants
[68]	n = 28, randomized control trial adults with elevated ALT or AST, BMI of 25-40	Combination of diet (1000-1500/d), exercise (10000 steps per day and 200 min/wk of moderate physical activity) and behavior modification	Weight in intervention group decreased by 9.3%, significant improvement of NASH. > 7% weight loss significantly improved steatosis
[73]	n = 152, randomized intervention of adults with elevated liver enzymes, central obesity and metabolic risk factors	Randomized to moderate (6 sessions/10 wk) or low-intensity (3 sessions/4 wk) or control. Physical activity 150 min/wk and low saturated fat and process food diet (1700-2400 kcal/d)	Moderate intensity – improvement in all risk factors, greater reduction in liver enzymes and weight loss than low-intensity
[74]	n = 19, 8 wk exercise intervention in NAFLD adults	8 wk (3 × wk) of resistance exercise (n = 11) vs control (n = 8)	13% reduction in liver lipid. Lipid oxidation, glucose and IR improved. No effect on weight or body fat

BMI: Body mass index; NAFLD: Non-alcoholic fatty liver disease; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; NASH: Nonalcoholic steatohepatitis; IR: Insulin resistance.

Table 2 Summary of medication intervention studies

Ref.	Population, Study Design	Intervention	Results
[79]	n = 15, open label study with histologically confirmed NAFLD adults	All patients received 20 mg/kg per day of metformin for 48 wk	In the initial 3 mo there was improvement in ALT and AST levels and insulin sensitivity, after 3 mo no further improvement noted
[80]	n = 57 24-mo observational study with NAFLD or NASH overweight and obese children	Metformin was progressively titrated from 250-500 mg tid at weekly intervals and patients were given a hypocaloric or isocaloric diet and recommended to engage in 45 min/d of physical activity (n = 57) compared to control group (n = 30) with the same diet and physical activity recommendations	ALT significantly improved with decreasing body weight. NAS score decreased in both groups, no significant changes in fibrosis
[85]	n = 63, randomized, double-blind placebo – controlled in NASH adults	32 patients were given rosiglitazone (4 mg/d for 1 mo then 8 mg/d for 11 mo) vs placebo (n = 31)	Improved steatosis and normalized transaminase, only ½ responded. Improvement of insulin sensitivity
[86]	n = 47, randomized control study in adults with impaired glucose tolerance or type 2 diabetes with NASH	6 mo of hypocaloric diet and 45 mg (n = 26) of pioglitazone vs 6 mo of hypocaloric diet (n = 21)	Diet and pioglitazone improved glucose tolerance and normalized ALT. Histologic features of NASH improved, no significant reduction in fibrosis
[87]	n = 13 patient cohort with NASH adults	All were treated with 30 mg/d of pioglitazone for 48 wk, than followed up 48 wk after stopping pioglitazone.	Stopping pioglitazone increased ALT, decreased adiponectin, worsened insulin sensitivity and increased hepatic fat, no change in fibrosis
[89]	n = 247, randomization of adults with NASH without diabetes	96 wk of either 30 mg pioglitazone (n = 80), vitamin E (800 IU/d) (n = 84) or placebo (n = 83)	Vitamin E significantly improved NASH. AST and ALT significantly improved in vitamin E and pioglitazone groups, and reduction in hepatic steatosis with no improvement in fibrosis score.
[90]	n = 45 prospective, double-blind randomized, placebo controlled trial in NASH adults	Received vitamin E and C (1000 IU and 1000 mg) (n = 23) or placebo for 6 mo (n = 22) additionally patients received weight loss counselling and encouraged to follow a low fat diet	Vitamin treatment significantly improved fibrosis score

NAFLD: Non-alcoholic fatty liver disease; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; tid: Three times a day; NASH: Nonalcoholic steatohepatitis.