Physical activity as a treatment of non-alcoholic fatty liver disease: A systematic review

Table 2 Published study findings for the relationship between physical activity and nonalcoholic fatty liver disease (2010-2015)

Ref.	Population	Type of activity	Weight loss	Insulin resistance	Inflammation and	Liver	Liver fat	Liver	Conclusions
		intervention	(% Δ)	and lipids	oxidative stress	enzymes	by imaging	histology
Hallsworth et al[26]	NAFLD	Activity monitor	NA	NA	NA	NA	NA	NA	NAFLD = more sedentary time, less energy expenditure, and greater prevalence of DM than healthy controls
Gerber et al[14]	NAFLD, NAFLD + DM	Activity monitor	NA	NA	NA	NA	NA	NA	NAFLD = less PA time than non-NAFLD NAFLD + DM = lowest quartile of average PA as well as moderate-vigorous PA
Oh et al[33]	NAFLD	Acceleration	-1.9%	NA	↓ TNF-α, IL-6, leptin, IMCL ↑ adiponectin	Improved	Improved (US)	NA	Acceleration training results in significant improvement in IR, inflammation, liver enzymes, steatosis and quality of life
Kawaguchi et al[32]	NAFLD	Hybrid	-0.9%	↓ Insulin HOMA-IR	↓ IL-6	Improved	Improved (US)	NA	Hybrid training results in significant improvement in IR, inflammation, liver enzymes and steatosis
Kistler et al[34]	NASH, NAFLD	None (self-report)	NA	↓ Insulin and glucose (vigorous PA vs inactive)	No effect	No effect	NA	Vigorous PA = ↓ odds of NASH and fibrosis	Vigorous but not moderate or total exercise is associated with the severity of NAFLD
Haus et al[36]	NAFLD	Aerobic	0	↓ Glucose HOMA-IR	↑ Lipid PUI, adiponectin	NA	NA	Improved steatosis	Short-term aerobic exercise favorably alters hepatic lipid composition by increasing polyunsaturated lipids
Promrat et al[38]	NASH	Aerobic	-9.3%	↓ Glucose, insulin, HbA1C HOMA-IR (NS)	NA	Improved	NA	Improved NAS. No change in fibrosis	> 7% weight loss resulted in improvement in overall NAS, ballooning, steatosis, inflammation
Pugh et al[39]	NAFLD	Aerobic	0	No effect	No effect	Improved	No effect	NA	Aerobic exercise improves NO-mediated vasodilation in NAFLD
Pugh et al[40]	NAFLD	Aerobic	0	↓ Glucose	No effect	No effect	No effect	NA	Aerobic exercise improves flow mediated dilation in NAFLD
Sullivan et al[27]	NAFLD	Aerobic	0	No effect	No effect	Improved	Improved (H-MRS)	NA	Aerobic exercise without weight loss results in significant reduction in intrahepatic triglyceride content
Jin et al[23]	NAFLD	Aerobic	-3.9%	↓ Total cholesterol	NA	Improved	NA	Improved steatosis	Aerobic exercise results in decreased steatosis among living donors even in the absence of significant weight loss
Oh et al[28]	NAFLD	Aerobic	-13.3%	↓ HbA1C HOMA-IR, LDL, TG ↑ insulin, HDL	↓ TNF-α, IL-6, leptin, hsCRP, ferritin, TBARS ↑ adiponectin	Improved	Improved (US and Fibroscan)	NA	Diet with exercise exceeds diet alone in reducing steatosis, inflammation, insulin resistance
Sun et al[24]	NAFLD	Aerobic	-11.6%	↓ HOMA-IR, total cholesterol	No effect	Improved	NA	NA	Aerobic exercise results in decrease in ALT, insulin resistance, and the metabolic syndrome
Zelber-Sagi et al[30]	NAFLD	Resistance	-0.75%	↓ Total cholesterol	↓ Ferritin	No effect	Improved (US)	NA	Resistance exercise results in reduction in steatosis, abdominal adiposity, inflammation, cholesterol
Hallsworth et al[29]	NAFLD	Resistance	0	↓ HOMA-IR (NS)	↑ Fat oxidation	No effect	Improved (H-MRS)	NA	Resistance exercise results in a 13% relative reduction in intrahepatic lipids
Bacchi et al[43]	NAFLD + DM	Resistance vs aerobic	No	↓ HDL, TG, HbA1c ↑ clamp-measured insulin sensitivity	No effect	No effect	Improved (MRI)	NA	Both resistance and aerobic exercise result in improved steatosis, abdominal, and visceral fat content
Eckard et al[21]	NAFLD, NASH (88%)	Resistance and aerobic	-1.3%1	No effect	No effect	Improved	NA	Improved NAS in all groups	Lifestyle modification, even without weight loss, improves NAS
Oh et al[35]	NAFLD	Aerobic	10.4%2	↓ HOMA-IR, LDL, TG ↑ HDL	↓ TNF-α, IL-6, leptin, hsCRP, ferritin, TBARS ↑ adiponectin	Improved	Improved (US, fibroscan)	NA	Moderate to vigorous PA (> 250 min weekly) significantly reduces markers of IR, oxidative stress and fatty acid metabolism independent of weight reduction

¹Weight lost in the diet plus exercise arms, mild weight gain was seen in the moderate exercise alone arm;

²Average weight lost across all groups (range 6.4%-12.4%). ALT: Alanine aminotransferase; DM: Diabetes mellitus; H-MRS: Hydrogen-magnetic resonance spectroscopy; HbA1C: Glycosylated hemoglobin; HDL: High-density lipoprotein cholesterol; HOMA-IR: Insulin resistance by homeostasis model assessment; hsCRP: High sensitivity c-reactive protein; IL-6: Interleukin-6; IMCL: Intramyocellular lipids; LDL: Low-density lipoprotein cholesterol; NA: Not assessed; NAFLD: Nonalcoholic fatty liver disease; NASH: Nonalcoholic steatohepatitis; NO: Nitric oxide; NS: Not statistically significant; PA: Physical activity; PUI: Lipid polyunsaturated index; TBARS: Thiobarbituric acid reactive substances; TG: Triglycerides; TNF-α: Tumor necrosis factor alpha; US: Ultrasound.