Current guidelines for the management of non-alcoholic fatty liver disease: A systematic review with comparative analysis

Table 1 Diagnostic criteria for non-alcoholic fatty liver disease according to the various guidelines

	EASL	NICE	Asia-Pacific	AISF	AASLD
Required criteria	Steatosis in > 5% of hepatocytes by either imaging or histology	Excessive fat in the liver	Hepatic steatosis by either imaging or histology	Hepatic steatosis on either imaging or histology	Evidence of hepatic steatosis either by imaging or histology
	No other causes of steatosis	No other causes of steatosis	No other causes of steatosis	No other causes of steatosis	No other causes of steatosis
	Insulin resistance	No significant alcohol consumption	No significant alcohol consumption	No significant alcohol consumption	No significant alcohol consumption
					No coexisting chronic liver disease
Alcohol consumption threshold (men)	30 g/d	30 g/d	2 standard drink/d	30 g/d	21 standard drink/wk
			140 g/wk		294 g/wk
Alcohol consumption threshold (women)	20 g/d	20 g/d	1 standard drink/d	20 g/d	14 standard drink/wk
			70 g/wk		196 g/wk

EASL: European Association for the Study of the Liver; NICE: National Institute for Health and Care Excellence; AISF: Italian Association for the study of the Liver; AASLD: American Association for the Study of Liver Diseases; MRI: Magnetic resonance imaging.

Table 2 Comparative analysis of the recommendations regarding the screening for non-alcoholic fatty liver disease

	EASL	NICE	Asia-Pacific	AISF	AASLD
Systematic screening	No	No	No	No	No
Screening in high-risk groups	Yes	Yes	Yes	Not mentioned	No1
	Obesity	Obesity	Obesity
	Metabolic syndrome	Type II Diabetes	Type II Diabetes
	Abnormal liver enzymes
Screening modality	Yes liver enzymes	No liver enzymes	No liver enzymes
		Yes ultrasonography	Yes ultrasonography
			Yes transient elastography

¹"Active surveillance" (but not screening) suggested for patients with type II diabetes mellitus. EASL: European Association for the Study of the Liver; NICE: National Institute for Health and Care Excellence; AISF: Italian Association for the Study of the Liver; AASLD: American Association for the Study of Liver Diseases.

Table 3 Comparison of recommendations about non-invasive evaluation of fibrosis and follow up strategies

	EASL	NICE	Asia-Pacific	AISF	AASLD
Non-invasive evaluation	NFS and FIB-4 upon diagnosis. If inconclusive, perform transient elastography	ELF blood test	Combination of serum tests and imaging tools (no specification about the preferred tests)	NFS + FIB-4 upon diagnosis. If inconclusive, perform transient elastography	NFS, FIB-4 and transient elastography (or MRE) upon diagnosis
Follow up	Negative markers > reassess every 2 yr; Fibrosis or abnormal liver enzymes > reassess every year; Cirrhosis-> surveillance every 6 mo	Negative ELF test, > reassess every 3 yr; Positive ELF test > liver biopsy	No information provided	Negative markers > reassess every 2 yr; Fibrosis or abnormal liver enzymes > reassess every year; Cirrhosis > surveillance every 6 mo	No information provided

EASL: European Association for the Study of the Liver; NICE: National Institute for Health and Care Excellence; AISF: Italian Association for the study of the Liver; AASLD: American Association for the Study of Liver Diseases; NFS: NAFLD fibrosis score; FIB-4: Fibrosis-4; ELF: Enhanced Liver Fibrosis; MRE: Magnetic resonance elastography.

Table 4 Guidance statements about lifestyle interventions

	EASL	NICE	Asia-Pacific	AISF	AASLD
Dietary restrictions	500-1000 kcal deficit; weight loss of 500-1000 g/wk with a 7%-10% total weight loss	Main recommendations on diet of NICE’s obesity and preventing excess weight gain guidelines	500-1000 kcal deficit	1200-1600 kcal/d; fat-low (< 30% of total calories); carbohydrate-low (< 50% of total calories)	500-1000 kcal deficit
Physical activity	Aerobic and resistance training (150-200 min/wk in 3-5 sessions)	Main recommendation of on physical activity of NICE’s obesity and preventing excess weight gain guidelines	Aerobic and resistance training	Aerobic and resistance training	Aerobic and resistance training (> 150 min/wk)
Gold standard diet	Low-to-moderate fat and moderate-to-high carbohydrate intake	No specific suggestions	All, excluding very low-calorie diets	Mediterranean diet	No specific suggestions
	Low-carbohydrate ketogenic diets or high-protein
	Mediterranean diet

EASL: European Association for the Study of the Liver; NICE: National Institute for Health and Care Excellence; AISF: Italian Association for the Study of the Liver; AASLD: American Association for the Study of Liver Diseases.

Table 5 Recommendations about pharmacological treatment of non-alcoholic fatty liver disease

	EASL	NICE	ASIA-PACIFIC	AISF	AASLD
Metformin	Insufficient evidence	Not beneficial	Not beneficial	Not mentioned	Not beneficial
Vitamin E	Insufficient evidence	Consider use regardless of diabetes	Not beneficial	Insufficient evidence	Consider use in non-diabetic, biopsy-proven NASH
PPAR-gamma agonists	Consider use in selected diabetic patients	Consider pioglitazone in adults regardless of diabetes	Insufficient evidence in Asian	Insufficient evidence, potentially useful	Pioglitazone indicated in biopsy-proven NASH (regardless of diabetes)
PUFA	Not beneficial	Insufficient evidence	Not beneficial	Not mentioned	Not beneficial
Pentoxifylline	Insufficient evidence	Not mentioned	Not beneficial	Not mentioned	Not mentioned
GLP-1 analogues	Insufficient evidence, potentially useful	Insufficient evidence	Insufficient evidence in Asian patients	Insufficient evidence, potentially useful	Insufficient evidence
UDCA	Not beneficial	Not beneficial	Not mentioned	Not mentioned	Not beneficial
Obetycolic acid	Scarce evidence	Not mentioned	waiting for ongoing RCT results	Waiting for ongoing RCT results	Insufficient evidence
Silymarin	Not mentioned	Not mentioned	insufficient evidence, potentially useful	Not mentioned	Not mentioned
Statins	Safe but not beneficial	Safe but not beneficial	Safe but not beneficial	Safe but not beneficial	Safe but not beneficial

EASL: European Association for the Study of the Liver; NICE: National Institute for Health and Care Excellence; AISF: Italian Association for the Study of the Liver; AASLD: American Association for the Study of Liver Diseases; PPAR: Peroxisome proliferator-activated receptors; PUFA: Poly-unsaturated fatty acids; GLP-1: Glucagon-like peptide-1.