FibroScan-aspartate transaminase: A superior non-invasive model for diagnosing high-risk metabolic dysfunction-associated steatohepatitis

Table 1 Histopathological scoring of liver in the overall population, n (%)

NAS and fibrosis stage	Overall population (n = 279)	High-risk MASH group (n = 93)	Non-high-risk MASH group (n = 186)
NAS
0-3	52.0 (18.6)	0.0 (0.0)	52.0 (28.0)
≥ 4	227.0 (81.4)	93.0 (100.0)	134.0 (72.0)
Fibrosis stage
F0	11.0 (3.9)	0.0 (0.0)	11.0 (5.9)
F1	169.0 (60.6)	0.0 (0.0)	169.0 (90.9)
F2	65.0 (23.3)	61.0 (65.6)	4.0 (2.2)
F3	25.0 (9.0)	24.0 (25.8)	1.0 (0.5)
F4	9.0 (3.2)	8.0 (8.6)	1.0 (0.5)

NAS: Non-alcoholic fatty liver disease activity score; MASH: Metabolic dysfunction-associated steatohepatitis.

Table 2 Histopathological scoring of liver in the subgroup population, n (%)

NAS and fibrosis stage	Subgroup population (n = 117)	High-risk MASH group (n = 52)	Non-high-risk MASH group (n = 65)
NAS
0-3	23.0 (19.7)	0.0 (0.0)	23.0 (35.4)
≥ 4	94.0 (80.3)	52.0 (100.0)	42.0 (64.6)
Fibrosis stage
F0	2.0 (1.7)	0.0 (0.0)	2.0 (3.1)
F1	58.0 (49.6)	0.0 (0.0)	58.0 (89.2)
F2	34.0 (29.1)	31.0 (59.6)	3.0 (4.6)
F3	15.0 (12.8)	14.0 (26.9)	1.0 (1.5)
F4	8.0 (6.8)	7.0 (13.5)	1.0 (1.5)

NAS: Non-alcoholic fatty liver disease activity score; MASH: Metabolic dysfunction-associated steatohepatitis.

Table 3 Clinical characteristics of 279 patients with metabolic dysfunction-associated steatotic liver disease

Project	Overall population (n = 279)	High-risk MASH group (n = 93)	Non-high-risk MASH group (n = 186)	P value
Demographics
Male	126 (45.2)	28 (30.1)	98 (52.7)	< 0.05
Age (yr)	41.0 (30.0, 53.0)	48.0 (36.5, 57.0)	38.0 (29.0, 50.0)	< 0.05
BMI (kg/m2)	26.8 ± 3.4	27.3 ± 3.2	26.5 ± 3.6	0.26
Metabolic disease
Dysglycemia	187 (67.0)	72 (77.4)	115 (61.8)	< 0.05
Hypertension	72 (25.8)	32 (34.4)	40 (21.5)	< 0.05
Hyperlipidemia	37 (13.3)	18 (19.4)	19 (10.2)	< 0.05
Hypertriglyceridemia	150 (53.8)	44 (47.3)	106 (57.0)	0.13
Low HDL-C	202 (72.4)	73 (78.5)	129 (69.4)	0.11
Serologic indicators
TC (mmol/L)	4.9 ± 1.0	4.9 ± 1.0	4.9 ± 1.0	0.51
TG (mmol/L)	1.8 (1.3, 2.7)	1.7 (1.1, 2.3)	1.9 (1.3, 2.8)	0.08
HDL-C (mmol/L)	1.0 (0.9, 1.2)	1.1 (0.9, 1.2)	1.0 (0.9, 1.2)	0.70
LDL-C (mmol/L)	3.0 ± 0.8	2.9 ± 0.9	3.0 ± 0.8	0.75
Fasting blood glucose (mmol/L)	5.9 (5.4, 6.7)	6.3 (5.6, 7.2)	5.7 (5.3, 6.4)	< 0.05
PLT (× 109/L)	222.8 ± 66.1	205.6 ± 68.4	231.4 ± 63.3	< 0.05
ALT (U/L)	90.6 (55.7, 145.5)	99.1 (55.9, 148.8)	86.0 (55.2, 139.0)	0.28
AST (U/L)	50.1 (31.4, 81.2)	65.0 (37.7, 107.5)	43.8 (29.9, 62.4)	< 0.05
ALP (U/L)	82.0 (65.8, 98.5)	83.1 (69.5, 98.9)	79.9 (64.7, 98.4)	0.36
GGT (U/L)	63.5 (38.8, 103.1)	71.5 (45.7, 103.0)	60.4 (35.9, 105.6)	0.09
TBIL (μmol/L)	12.3 (9.4, 16.5)	13.0 (10.0, 17.5)	11.7 (9.1, 15.9)	0.08
ALB (g/L)	46.1 (43.0, 48.9)	44.8 (42.1, 48.0)	46.7 (43.7, 49.4)	< 0.05
HGB (g/L)	144.0 (134.0, 156.0)	141.3 (132.0, 153.0)	146.0 (134.9, 158.0)	0.07
Apolipoprotein A1 (g/L)	1.3 (1.2, 1.5)	1.4 (1.2, 1.5)	1.3 (1.2, 1.5)	< 0.05
Apolipoprotein B (g/L)	1.0 (0.8, 1.1)	0.9 (0.7, 1.2)	1.0 (0.8, 1.1)	0.95
Cr (μmol/L)	61.5 (52.4, 73.0)	56.9 (50.9, 67.3)	63.0 (53.0, 74.1)	< 0.05
Urea (mmol/L)	4.5 (3.8, 5.4)	4.5 (3.7, 5.4)	4.5 (3.8, 5.2)	0.97
Uric acid (μmol/L)	367.0 (301.0, 433.0)	369.0 (282.8, 443.0)	363.5 (304.0, 425.9)	0.67
eGFR (mL/min)	110.6 (100.6, 120.2)	108.0 (98.5, 114.9)	114.0 (105.0, 124.0)	< 0.05
PT (s)	11.3 (10.7, 11.9)	11.6 (11.1, 12.3)	11.2 (10.6, 11.7)	< 0.05
Non-invasive models
FIB-4	0.9 (0.6, 1.6)	1.4 (1.0, 2.8)	0.8 (0.6, 1.2)	< 0.05
APRI	0.6 (0.4, 1.0)	0.9 (0.5, 1.5)	0.5 (0.3, 0.8)	< 0.05
Forns index	4.2 (3.0, 5.6)	5.0 (3.7, 6.3)	3.9 (2.7, 4.9)	< 0.05
ARR	0.6 (0.5, 0.7)	0.6 (0.5, 0.9)	0.5 (0.4, 0.7)	< 0.05
S index	0.1 (0.1, 0.3)	0.2 (0.1, 0.3)	0.1 (0.1, 0.2)	< 0.05
GPR	0.7 (0.4, 1.2)	0.8 (0.5, 1.3)	0.6 (0.3, 1.0)	< 0.05

All data are presented as n (%) or mean ± SD or M (P25, P75). MASH: Metabolic dysfunction-associated steatohepatitis; BMI: Body mass index; HDL-C: High density lipoprotein cholesterol; TC: Total cholesterol; TG: Triglycerides; LDL-C: Low density lipoprotein cholesterol; PLT: Platelets; ALT: Alanine transaminase; AST: Aspartate transaminase; ALP: Alkaline phosphatase; GGT: Gamma-glutamyl transferase; TBIL: Total bilirubin; ALB: Albumin; HGB: Hemoglobin; Cr: Creatinine; eGFR: Estimated glomerular filtration rate; PT: Prothrombin time; FIB-4: Fibrosis-4; APRI: Aspartate transaminase to platelet ratio index; ARR: Aspartate transaminase to alanine transaminase ratio; GPR: Gamma-glutamyl transpeptidase to platelet ratio.

Table 4 Characteristics of seven non-invasive models in the subgroup population

Non-invasive models	Subgroup population (n = 117)	High-risk MASH group (n = 52)	Non-high-risk MASH group (n = 65)	P value
FAST	0.5 (0.3, 0.7)	0.6 (0.5, 0.8)	0.3 (0.2, 0.5)	< 0.05
FIB-4	1.0 (0.6, 1.6)	1.4 (0.9, 2.6)	0.7 (0.5, 1.2)	< 0.05
APRI	0.5 (0.3, 1.0)	0.7 (0.5, 1.2)	0.4 (0.2, 0.7)	< 0.05
Forns index	4.4 ± 1.9	5.1 ± 1.9	3.9 ± 1.7	< 0.05
ARR	0.6 (0.5, 0.8)	0.7 (0.5, 0.9)	0.5 (0.4, 0.7)	< 0.05
S index	0.1 (0.1, 0.2)	0.2 (0.1, 0.3)	0.1 (0.1, 0.2)	0.51
GPR	0.7 (0.5, 1.2)	0.7 (0.5, 1.2)	0.7 (0.4, 1.2)	0.81

MASH: Metabolic dysfunction-associated steatohepatitis; FAST: FibroScan-aspartate transaminase; FIB-4: Fibrosis-4; APRI: Aspartate transaminase to platelet ratio index; ARR: Aspartate transaminase to alanine transaminase ratio; GPR: Gamma-glutamyl transpeptidase to platelet ratio.

Table 5 The comparison between the subgroup and the remaining population

Project	Subgroup population	Remaining population	P value
	(n = 117)	(n = 162)
Demographics
Male	49 (41.9)	77 (47.5)	0.35
Age (yr)	44.0 (32.0, 53.0)	40.0 (30.0, 53.3)	0.38
BMI (kg/m2)	26.4 ± 3.4	27.6 ± 3.4	0.08
Metabolic disease
Dysglycemia	80 (68.4)	107 (66.0)	0.68
Hypertension	33 (28.2)	39 (24.1)	0.44
Hyperlipidemia	21 (17.9)	16 (9.9)	0.05
Hypertriglyceridemia	69 (59.0)	81 (50.0)	0.14
Low HDL	89 (76.1)	113 (69.8)	0.24
Serologic indicators
TC (mmol/L)	5.0 ± 1.0	4.8 ± 1.0	0.19
TG (mmol/L)	2.0 (1.3, 2.9)	1.7 (1.3, 2.5)	0.46
HDL-C (mmol/L)	1.0 (0.9, 1.2)	1.0 (0.9, 1.2)	0.98
LDL-C (mmol/L)	3.0 ± 0.9	2.9 ± 0.8	0.43
Fasting blood glucose (mmol/L)	5.9 (5.5, 6.8)	5.8 (5.3, 6.7)	0.38
PLT (× 109/L)	229.2 ± 71.1	218.1 ± 62.0	0.17
ALT (U/L)	72.5 (46.0, 125.0)	100.1 (62.7, 152.6)	0.01
AST (U/L)	46.2 (29.8, 77.4)	52.5 (34.9, 83.1)	0.11
ALP (U/L)	77.6 (66.1, 98.1)	83.6 (65.6, 101.2)	0.49
GGT (U/L)	71.4 (43.5, 105.1)	58.6 (37.5, 103.2)	0.25
TBIL (μmol/L)	12.4 (9.5, 16.4)	12.3 (9.2, 16.7)	0.88
ALB (g/L)	46.6 (42.7, 49.0)	45.6 (43.1, 48.9)	0.41
HGB (g/L)	145.0 (136.0, 156.0)	143.5 (131.0, 156.1)	0.16
Apolipoprotein A1 (g/L)	1.4 (1.2, 1.5)	1.3 (1.1, 1.5)	0.22
Apolipoprotein B (g/L)	1.0 (0.8, 1.1)	0.9 (0.7, 1.1)	0.10
Cr (μmol/L)	61.5 (52.7, 71.3)	61.5 (52.0, 73.1)	0.93
Urea (mmol/L)	4.5 (3.8, 5.2)	4.7 (3.8, 5.4)	0.41
Uric acid (μmol/L)	369.0 (304.0, 436.5)	363.5 (296.0, 433.0)	0.64
eGFR (mL/min)	112.5 (103.4, 120.2)	107.0 (98.5, 119.5)	0.24
PT (s)	11.3 (10.7, 11.9)	11.3 (10.6, 11.9)	0.90
Non-invasive models
FIB-4	1.0 (0.6, 1.6)	0.9 (0.6, 1.6)	0.88
APRI	0.5 (0.3, 1.0)	0.6 (0.4, 1.0)	0.08
Forns index	4.4 (3.0, 5.6)	4.1 (3.0, 5.7)	0.74
ARR	0.6 (0.5, 0.8)	0.5 (0.4, 0.7)	0.06
S index	0.1 (0.1, 0.2)	0.1 (0.1, 0.3)	0.53
GPR	0.7 (0.5, 1.2)	0.7 (0.4, 1.2)	0.45

All data are presented as n (%) or mean ± SD or M (P25, P75). BMI: Body mass index; HDL-C: High density lipoprotein cholesterol; TC: Total cholesterol; TG: Triglycerides; LDL-C: Low density lipoprotein cholesterol; PLT: Platelets; ALT: Alanine transaminase; AST: Aspartate transaminase; ALP: Alkaline phosphatase; GGT: Gamma-glutamyl transferase; TBIL: Total bilirubin; ALB: Albumin; HGB: Hemoglobin; Cr: Creatinine; eGFR: Estimated glomerular filtration rate; PT: Prothrombin time; FIB-4: Fibrosis-4; APRI: Aspartate transaminase to platelet ratio index; ARR: Aspartate transaminase to alanine transaminase ratio; GPR: Gamma-glutamyl transpeptidase to platelet ratio.

Table 6 The evaluation of seven non-invasive models for diagnosing high-risk metabolic dysfunction associated steatohepatitis

Non-invasive models	High threshold criteria	Sensitivity (%)	Specificity (%)	PPV (%)	NPV (%)	AUROC (95%CI)	P value
Overall population
FIB-4	2.67	26.9	95.2	73.5	72.2	0.75 (0.69-0.81)	< 0.05
APRI	1.50	24.7	93.0	63.9	71.2	0.69 (0.63-0.76)	< 0.05
Forns index	6.90	18.3	94.6	63.0	69.8	0.67 (0.61-0.74)	< 0.05
ARR	1.00	21.5	92.5	58.8	70.2	0.68 (0.61-0.74)	< 0.05
S index	0.50	11.8	91.9	42.3	67.6	0.62 (0.55-0.69)	< 0.05
GPR	0.56	69.9	44.6	38.7	74.8	0.60 (0.53-0.67)	< 0.05
Subgroup population
FAST	0.67	44.2	92.3	82.1	67.4	0.82 (0.74-0.90)	< 0.05
FIB-4	2.67	25.0	96.9	86.7	61.8	0.76 (0.68-0.85)	< 0.05
APRI	1.50	19.2	96.9	83.3	60.0	0.74 (0.65-0.83)	< 0.05
Forns index	6.90	17.3	95.4	75.0	59.0	0.68 (0.58-0.77)	< 0.05
ARR	1.00	23.1	87.7	60.0	58.8	0.62 (0.52-0.72)	< 0.05
S index	0.50	7.7	95.4	57.1	56.4	0.54 (0.43-0.64)	0.50
GPR	0.56	63.5	32.3	42.9	52.5	0.51 (0.41-0.62)	0.80

PPV: Positive predictive value; NPV: Negative predictive value; AUROC: The area under the receiver operating characteristic curves; FAST: FibroScan-aspartate transaminase; FIB-4: Fibrosis-4; APRI: Aspartate transaminase to platelet ratio index; ARR: Aspartate transaminase to alanine transaminase ratio; GPR: Gamma-glutamyl transpeptidase to platelet ratio.