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Ballestri et al. Metab Target Organ Damage 2023;3:1 https://dx.doi.org/10.20517/mtod.2022.23 Page 5 of 22

Table 1. Indirect biomarkers of liver fibrosis

Author Cut-offs AUROC
Biomarker Equation
(ref.) for F3/F4 *
AST: ALT ratio (AAR) Williams AST (IU/L)/ALT (IU/l) < 0.8 to rule -
[36]
et al. out
> 1.0 to rule
in**
9
Forns index Forns 7.811-3.131 ln [platelet count (×10 /L)] + 0.781 ln [GGT (IU/L)] + 3.467 ln [age (years)]-0.014 [cholesterol (mg/dl)] < 4.2 to rule 0.81
[37]
et al. out
> 6.9 to rule
¶
in
9
AST-to-platelet ratio Wai AST (IU/L)/(ULN)/platelet count (×10 /L) × 100 ≤ 0.5 to rule 0.88
[38]
index (APRI) score et al. out
> 1.5 to rule
¶
in
2
BARD score Harrison Weighted sum of BMI ≥ 28 kg/m , 1 point ≥ 2 points to 0.81
[39]
et al. AST/ALT ratio ≥ 0.8, 2 points rule in
Diabetes present, 1 point
9
Fibrosis-4 index (FIB- Sterling Age × AST (IU/L)/platelet count (×10 /L) × √ALT (IU/l) < 1.45 to 0.765
[40]
4) et al. rule out
> 3.25 to
rule in
2 9
NAFLD fibrosis score Angulo -1.675 + 0.037 × age (years) + 0.094 × BMI (Kg/m ) + 1.13 × IFG or T2D (yes = 1; no = 0 =) + 0.99 × AST/ALT ratio - 0.013 × platelet count (×10 /L)- < -1.45 (< 0.82
[41]
(NFS) et al. 0.66 × albumin (g/dL) 65 years)
< 0.12 (> 65
years) to
rule out^
≥ 0.67 to
rule in
9
GGT-to-platelet ratio Lemoine GGT/ULN of GGT/platelet count (10 /L) ×100 > 0.32 to 0.76-
[43]
(GPR) et al. rule in 0.93°
Hepamet fibrosis Ampuero 1/[1 + e (5.390-0.986 (if Age 45-64 years) - 1.719 (if Age ≥ 65 years) + 0.875 (if Male sex) - 0.896 (if AST 35-69 IU/L) - 2.126 (if AST ≥ 70 IU/L) - < 0.12 to 0.84
[44]
score (HFS) et al. 0.027 (if Albumin 4-4.49 g/dL) - 0.897 (if Albumin < 4 g/dL) - 0.899 (if HOMA 2-3.99 with no DM) -1.497 (if HOMA ≥ 4 with no DM) - 2.184 (if DM) rule out
- 0.882 (if Platelets 155-219 × 1000/µL) - 2.233 (if Platelets < 155 × 1000/µL))] > 0.47 to
rule in

AUROC: Area under the receiver operating characteristics; AST: aspartate aminotransferase; ALT: alanine aminotransferase; BMI: body mass index; DM: diabetes mellitus; IFG impaired fasting glucose; HOMA:
homeostasis model assessment; IU: international units; GGT: gamma-glutamyl transpeptidase; T2D: type 2 diabetes; ULN: upper limit of normal; -: not available; *AUROC values for validation sets; **Original cut-off
¶ [42]
developed for cirrhosis (F4); Original cut-off developed for significant fibrosis (F2 to F4); ^age-related cut-off, according to McPherson et al. ; °two validation cohorts.

markers (NFS; FIB4; Fibrotest; FibroMeter), vibration-controlled transient elastography (VCTE), and the combinatory elasto-blood test FibroMeterVCTE. The

authors found that the AUROCs were significantly lower among type 2 diabetes (T2D) patients, mainly owing to decreased specificity. The reasons underlying