Noninvasive biomarkers in non-alcoholic fatty liver disease: Current status and a glimpse of the future

Table 1 Biomarkers for the diagnosis of nonalcoholic steatohepatitis (vs simple steatosis)

Biomarkers	Study description	Results	Ref.
Simple markers	Adults: 97 obese patients undergoing bariatric surgery, 35 had NASH	Algorithm using AST and presence of T2DM, AUC of 0.82 for prediction of NASH	[55]
	Adults: 80 NAFLD; 39 SS, 41 NASH	Score using age, gender, AST, BMI, Hyaluronic acid, AST: ALT ratio. AUROC for NASH of 0.76	[56]
	Adults: 200 patients undergoing bariatric surgery. 64 had NASH	AUROC for NASH: 0.8 using a score composed of Hypertension, Diabetes, AST > 27, ALT > 27, Sleep apnoea, non-black race	[53]
	Adults: 80 NAFLD; 39 SS, 41 NASH	Score using age, gender, AST, BMI, Hyaluronic acid, AST: ALT ratio. AUROC for NASH of 0.76	[56]
Inflammation	Adults: 57 NASH, 17 SS, 10 controls	AUROC NASH with HOMA-IR and Adiponectin/Leptin ratio: 0.82	[32]
	Adults: 26 NASH, 19 SS; 38 obese, 12 controls	TNF-α, IL8, Age, ALT higher in NAFLD; TNF-α predictor	[27]
	Adults: 20 NAFLD, 30 obese	Insulin resistance, ferritin, glutathione peroxidase, higher in NAFLD than obese	[23]
	Adults: 80 NASH, 29 simple steatosis	Lower Adiponectin, higher TNF-α, higher IR in NASH vs controls	[30]
		Lower Adiponectin, higher HOMA-IR in NASH vs SS
	Paediatric: 36 training and 36 validation NAFLD	AUROC for Adiponectin/HOMA-IR as predictors of NASH: 0.79 AUROC for NASH using TNF-α was 0.91, Leptin: 0.8 combined: 0.96	[29]
	Adults: 23 NASH, 21 SS, 18 controls	IL6 and TNF-α, TNFR1 higher in those with NASH vs rest TNF-α, CCL2/MCP-1 higher and Adiponectin lower in NASH	[35]
	Adults: 22 SS, 25 NASH, 30 controls		[28]
	Adults: 28 NAFLD, 33 controls, 30 obese	Resistin linked to NAFLD severity, but not adiponectin, leptin or IR	[33]
	Paediatric: 59 NAFLD	RBP-4 levels inverse relationship with NASH	[57]
Algorithms
NASH test	257 patients (17% NASH) and 383 controls	AUROC 0.79 for NASH. 13 variables: Age, Sex, Weight Height, TG, cholesterol, α2-macroglobulin, ApoA1, Haptoglobin, AST, ALT, γGT, bilirubin	[58]
NASH Diagnostics	Adults: 101 NAFLD, 69 test, (32% NASH) 32 validation	AUROC 0.91 for prediction of NASH. Sensitivity 96%, specificity70% with combination of CK18-M65, CK18-M30, resistin and adiponectin	[44]
NAFIC score	Adult Japanese patients with NAFLD	AUROC for NASH in test group 0.85. AUROC for NASH in validation group 0.78. Variables: Ferritin, fasting insulin, type IV collagen S	[59]
	177 test group (95 NASH), 442 validation group
Nice model	Adults: 454 obese, 310 test, 154 validation	Model: AUROC for prediction of NASH 0.88 in test and 0.83 in validation set Algorithm: CK18-M30, ALT, presence of MS Combination of Insulin resistance, Hypertension and ALT gives sensitivity of 80% and specificity of 89% in prediction of NASH	[60]
HAIR	Adults: 105 obese patients undergoing bariatric surgery, including 26 with NASH		[50]

BMI: Body mass index; AUROC: Area under the curve; NASH: Nonalcoholic steatohepatitis NAFLD: Nonalcoholic fatty liver disease; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; TNF-α: Tumor necrosis factor-α; CK: Cytokeratin; IL: Interleukin; HOMA-IR: Homeostasis model assessment-insulin resistance; TG: Triglycerides.