Heterogeneity of non-alcoholic fatty liver disease: Implications for clinical practice and research activity

Table 1 Non-invasive tests of hepatic fibrosis and potential confounding factors

Biomarker panel	Parameters	Validation	Prognostic ability	Confounding factors/limitations
APRI	AST, platelet	Good	Fair	Large number of individuals fall in the indeterminate range
Fibrosis-4 index	Age, AST, ALT, platelet	Very good	Very good	Poor performance in patients aged ≤ 35 yr
				Low specificity in patients aged ≥ 65 yr
				Less sensitive in South Asian Population
NAFLD fibrosis score	Age, BMI, IFG or diabetes, AST, ALT, platelet, albumin	Very good	Good	Different cutoff values needed for younger or older participants
				Albumin may decrease in chronic illnesses, malnutrition, nephrotic syndrome and protein-losing enteropathy
				Less sensitive in South Asian Population
Enhanced liver fibrosis panel	PIIINP, HA, TIMP1	Good	Very good	PIIINP is increased in other fibrotic diseases or bone fracture
				TIMP1 is increased in cancer and inflammation
				Not as widely available as non-patented scores and more expensive
FibroMeter NAFLD	Age, weight, prothrombin index, ALT, AST, ferritin, fasting glucose	Fair	NA	Prothrombin index affected by anti-coagulants
				Ferritin is an acute phase protein
				Glucose is affected by anti-diabetic treatment
				More validation needed
NIS4	miR-34a-5p, α2-M, YKL-40, and glycated hemoglobin	Fair	NA	Not as widely available as non-patented scores and more expensive
				More validation is needed

ALT: Alanine aminotransferase; APRI: AST-to platelet ratio index; AST: Aspartate aminotransferase; BMI: Body mass index; HA: Hyaluronic acid; IFG: Impaired fasting glucose; α2-M: α2 macroglobulin; NA: Not applicable; NAFLD: Non-alcoholic fatty liver disease; PIIINP: Procollagen type III N-terminal peptide; PTI: Prothrombin index; TIMP-1: Tissue inhibitor of matrix metalloproteinase 1.