Non-invasive blood biomarkers for assessment of liver fibrosis in metabolic dysfunction-associated steatotic liver disease

Table 1 Serum biomakers for the assessment of fibrosis in metabolic dysfunction-associated steatotic liver disease

Serum biomaker	Components	Interpretation	Strength of recommendation
AST-to-ALT ratio[25,26]	ALT, ALT	Advanced fibrosis > 1.0	One star
AST-to-platelet ratio index[27-33]	AST, platelet count	Rules out fibrosis < 0.5	Two stars
		Significant fibrosis >1.0
Fibrosis-4[29,33-38]	Age, platelet count, AST, and ALT	Rules out fibrosis < 1.3	Three stars
		Advanced fibrosis > 2.671
NAFLD fibrosis score[22,28,39-44]	Body mass index, age	Rules out fibrosis < -1.455	Three stars
	AST/ALT ratio, platelet count, albumin, hyperglycemia	Advanced fibrosis > 0.675
BARD score[28,45-48]	BMI > 28 kg/m2, AST/ALT ratio > 0.8, diabetes	Low risk for advanced fibrosis 0-1	Two stars
		High risk for advanced fibrosis 0-1
Hepascore fibrosis score[32,49-51]	Age, diabetes, sex, AST, albumin, platelet count, HOMA-IR	Significant fibrosis > 0.50	Two stars
		Advanced fibrosis > 0.65
N-terminal PRO-C3[52-58]	Reflect true synthesis of type III collagen	Advanced fibrosis >25 U/L	Two stars
ADAPT[55]	Age, diabetes status, PRO-C3, and thrombocyte count	Rules out advanced fibrosis ≤ 6.3287	Three stars
		Advanced fibrosis > 9.8
Mac-2 binding protein glycosylation isomer[59-65]	A glycoprotein expressed by activated hepatic stellate cells	Advanced fibrosis > 0.71 COI	Two stars
Enhanced liver fibrosis score[22,28,43,66-68]	PIIINP, HA, TIMP-1	Rules out fibrosis < 7.7	Three stars
		Advanced fibrosis > 9.8
FibroTest[22,69,70]	GGT, total bilirubin	Rules out fibrosis < 0.3	Three stars
	α2-macroglobulin
	Apolipoprotein A-I	Advanced fibrosis > 0.7
	Haptoglobin, cholinesterase
FibroMeter[21,22,71-73]	Age, weight, AST, ALT, platelet count, blood glucose, and ferritin	Rules out fibrosis < 0.31	Three stars
		Advanced fibrosis > 0.45
Agile 3+ score[74,75]	LSM, platelets, AST, ALT, diabetes status, sex, and age	Rules out fibrosis < 0.351	Three stars
		Advanced fibrosis > 0.679

¹The cutoff value of fibrosis-4 for individuals ≥ 65 years old is adjusted to 2.0.

The strength of recommendation reflects the graded evidence level supporting whether primary risk assessment or secondary risk assessment using serum biomarkers is recommended in clinical practice for patients with metabolic dysfunction-associated steatotic liver disease. The highest strength of recommendation is designated as three stars. AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; NAFLD: Non-alcoholic fatty liver disease; BMI: Body mass index; HOMA-IR: Homeostatic model assessment of insulin resistance; PRO-C3: Propeptide of type 3 collagen; ADAPT: Age, diabetes status, propeptide of type 3 collagen, and thrombocyte; COI: Cot-off index; PIIINP: N-terminal propeptide of type III procollagen; HA: Hyaluronic acid; TIMP-1: Tissue inhibitor of metalloproteinase 1; GGT: Gamma-glutamyl transferase; LSM: Liver stiffness measurement.