Multiparametric ultrasound for non-invasive assessment of liver steatosis, fibrosis, and inflammation in metabolic dysfunction-associated steatotic liver disease

doi:10.3748/wjg.v31.i25.105518

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Jul 7, 2025 (publication date) through Jul 4, 2025

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Clinical Trials Study

World J Gastroenterol. Jul 7, 2025; 31(25): 105518
Published online Jul 7, 2025. doi: 10.3748/wjg.v31.i25.105518

Table 1 Demographic, clinical, histological and biochemical characteristics of the enrolled patients

Characteristic	Entire cohort (n = 120)	No MASH (n = 39)	MASH (n = 81)	P value
Sex (male)	68 (56.7)	24 (61.5)	44 (54.3)	NS
Age (years)	49 ± 11	50 ± 10	49 ± 11	NS
BMI (kg/m²)	33.2 ± 7.1	31.7 ± 6.9	34.0 ± 7.1	NS
Obesity	72 (60.0)	19 (48.7)	53 (65.4)	0.08
Diabetes	35 (29.1)	7 (17.9)	28 (34.5)	0.06
Hypertension	54 (45.0)	14 (35.9)	40 (49.4)	NS
Biochemical profile
Platelet count (× 10⁶/mL)	230.9 ± 68.2	230.6 ± 59.0	231.0 ± 72.6	NS
AST (IU/L)	43.7 ± 38.9	32.3 ± 14.3	49.3 ± 45.3	0.02
ALT (IU/L)	59.2 ± 50.2	42.4 ± 23.9	67.2 ± 57.2	0.01
GGT (IU/L)	65.7 ± 56.2	68.6 ± 73.2	64.3 ± 47.3	NS
ALP (IU/L)	74.7 ± 37.1	85.7 ± 52.6	69.6 ± 25.9	0.03
Albumin (g/L)	40.9 ± 3.5	41.6 ± 3.2	40.5 ± 3.5	NS
Triglycerides (mg/dL)	157.9 ± 90.6	137.5 ± 53.7	168.0 ± 103.1	NS
Total cholesterol (mg/dL)	196.3 ± 44.2	195.9 ± 42.0	196.5 ± 45.5	NS
HDL (mg/dL)	44.7 ± 14.3	50.1 ± 22.5	42.7 ± 8.8	0.04
FIB4	1.54 ± 2.67	1.20 ± 0.61	1.71 ± 3.22	NS
NFS	-1.24 ± 1.71	-1.54 ± 1.48	-1.10 ± 1.80	NS
Agile3 +	0.14 (0.06-0.53)	0.11 (0.05-0.33)	0.23 (0.06-0.60)	0.02
Histological findings
Steatosis grade				< 0.01
1	47 (39.2)	39 (100)	8 (9.9)
2	49 (40.8)	0 (0)	49 (60.5)
3	24 (20.0)	0 (0)	24 (29.6)
Lobular inflammation grade				< 0.01
0	4 (3.3)	4 (10.2)	0 (0)
1	90 (75.0)	35 (89.8)	55 (67.9)
2	24 (20.0)	0 (0)	24 (29.6)
3	2 (1.7)	0 (0)	2 (2.5)
Hepatocyte ballooning grade				< 0.01
0	13 (10.8)	13 (33.3)	0 (0)
1	94 (78.4)	26 (66.6)	68 (84.2)
2	13 (10.8)	0 (0)	13 (15.8)
Fibrosis stage				0.01
0	3 (2.5)	3 (7.7)	0 (0)
1	43 (35.8)	19 (48.8)	24 (29.6)
2	40 (33.3)	12 (30.7)	28 (34.6)
3	30 (25.0)	4 (10.2)	26 (32.1)
4	4 (3.4)	1 (2.6)	3 (3.7)
Elastographic measurements
LS by TE (kPa)	7.9 ± 5.0	6.2 ± 3.2	8.7 ± 5.3	0.01
2D-SWE (kPa)	7.34 ± 3.16	6.61 ± 3.02	7.70 ± 3.19	0.07
CAP (dB/m)	302.9 ± 67.2	250.5 ± 74.5	328.2 ± 45.9	< 0.01
Att.PLUS (dB/cm/mHz)	0.52 ± 0.11	0.55 ± 0.12	0.51 ± 0.10	0.06
SSp.PLUS (m/s)	1530 (1505-1550)	1545 (1525-1570)	1525 (1500-1545)	< 0.01
Vi.PLUS (Pa.s)	2.24 ± 0.51	2.04 ± 0.54	2.34 ± 0.48	0.03

Data are presented as mean ± SD or n (%). MASH: Metabolic dysfunction-associated steatohepatitis; BMI: Body mass index; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; GGT: Gamma-glutamyl transferase; ALP: Alkaline phosphatase; HDL: High-density lipoprotein; FIB: Fibrosis; NFS: Nonalcoholic fatty liver disease fibrosis score; LS: Liver stiffness; TE: Transient elastography; Att.PLUS: Attenuation plane-wave ultrasound; SSp.PLUS: Sound speed plane-wave ultrasound; 2D-SWE: Two-dimensional shear wave elastography; CAP: Controlled attenuation parameter; Vi.PLUS: Viscosity plane-wave ultrasound; NS: Not significant.

Table 2 Performance of ultrasound non-invasive diagnostic tests and VAS-MASH-US score for predicting moderate-to-severe steatosis (S ≥ 2), presence of both lobular inflammation and ballooning (inflammation ≥ 1 and ballooning ≥ 1), MASH (NAS score ≥ 4 and least 1 point at steatosis, lobular inflammation, and ballooning) and Fibrosis

Variable	Cutoff value	AUC (95%CI)	Sensitivity (%)	Specificity (%)	PPV (%)	NPV (%)	P value
Steatosis ≥ 2
CAP (dB/m)	275	0.83 (0.75-0.91)	94.5	66.0	81.2	88.6	Reference
CAP (dB/m)	301¹	0.83 (0.75-0.91)	78.0	74.5	82.6	68.6	Reference
Att.PLUS (dB/cm/mHz)	0.44	0.60 (0.50-0.70)	89.4	31.5	45.6	82.1	< 0.01
SSp.PLUS (m/s)	1535	0.71 (0.61-0.81)	70.2	65.7	56.9	77.4	0.02
Inflammation ≥ 1 and ballooning ≥ 1
Vi.PLUS (Pa.s)	2.3	0.72 (0.59-0.86)	52.8	92.8	98.2	20.6	Reference
MASH
Vi.PLUS (Pa.s)	2.1	0.68 (0.58-0.79)	69.1	64.1	80.0	50.0	Reference
VAS-MASH-US score	0.60	0.75 (0.65-0.84)	79.0	66.7	83.1	60.4	0.14
	0.48		90.0	43.6	76.6	65.4
	0.84		30.9	90.0	86.2	38.4
Fibrosis ≥ 2
TE (kPa)	6.4	0.75 (0.65-0.83)	72.9	71.7	80.6	62.3	Reference
2D-SWE (kPa)	6.4	0.69 (0.60-0.79)	59.5	73.9	78.6	53.1	0.25
FIB-4	1.07	0.65 (0.55-0.75)	62.2	58.7	70.8	49.1	0.10
NFS	-0.97	0.69 (0.59-0.79)	55.4	78.3	80.4	52.2	0.40
Vi.PLUS (Pa.s)	2.3	0.64 (0.53-0.74)	59.5	71.7	77.2	52.4	0.04
Fibrosis ≥ 3
TE (kPa)	8¹		91.2	83.7	68.9	96.0	Reference
	8.4	0.93 (0.87-0.99)	85.3	91.9	80.5	94.0
	12¹		35.3	97.7	84.6	78.5
2D-SWE (kPa)	7.2	0.90 (0.85-0.95)	88.2	81.4	61.7	93.1	0.43
FIB-4	1.26	0.80 (0.71-0.89)	70.6	74.4	52.2	86.5	0.01
NFS	-1.12	0.83 (0.75-0.90)	88.2	73.2	56.6	94.0	0.03
Agile3 +	0.42	0.93 (0.88-0.98)	85.3	89.5	76.3	93.9	0.99
Vi.PLUS (Pa.s)	2.1	0.81 (0.74-0.89)	100	58.1	48.6	100	< 0.01

¹Cut-off from literature and World Federation for Ultrasound in Medicine and Biology guidelines.

AUC: Area under the curve; CI: Confidence interval; PPV: Positive predictive value; NPV: Negative predictive value; Att.PLUS: Attenuation plane-wave ultrasound; SSp.PLUS: Sound speed plane-wave ultrasound; 2D-SWE: Two-dimensional shear wave elastography; CAP: Controlled attenuation parameter; Vi.PLUS: Viscosity plane-wave ultrasound; MASH: Metabolic dysfunction-associated steatohepatitis; VAS-MASH-US: Viscosity-aspartate aminotransferase-speed of sound metabolic dysfunction-associated steatohepatitis ultrasound; TE: Transient elastography; FIB: Fibrosis; NFS: Non-alcoholic fatty liver disease fibrosis score; P value from DeLong test for comparing AUC

Table 3 Univariate and multivariate analysis evaluating variables associated with metabolic dysfunction-associated steatohepatitis

Variable	Univariate analysis		Multivariate analysis
Variable	OR (95%CI)	P value	OR (95%CI)	P value
Sex (male)	0.74 (0.34-1.62)	0.45
Age	0.98 (0.95-1.02)	0.48
Att.PLUS	0.03 (0.01-1.06)	0.06
SSp.PLUS	0.98 (0.97-0.99)	< 0.01	0.98 (0.97-0.99)	< 0.01
CAP	1.02 (1.01-1.03)	< 0.01
Vi.PLUS	3.59 (1.47-8.78)	< 0.01	3.12 (1.20-8.16)	0.02
BMI (kg/m²)	1.05 (0.99-1.11)	0.11
Triglycerides	1.00 (0.99-1.01)	0.11
Total cholesterol	1.00 (0.99-1.01)	0.94
Diabetes	2.42 (0.95-6.17)	0.06
Hypertension	1.74 (0.79-3.82)	0.16
ALT	1.02 (1.01-1.03)	0.01	1.03 (1.01-1.06)	0.05
AST	1.03 (1.01-1.06)	0.02

OR: Odds ratio; CI: Confidence interval; Att.PLUS: Attenuation plane-wave ultrasound; SSp.PLUS: Sound speed plane-wave ultrasound; CAP: Controlled attenuation parameter; Vi.PLUS: Viscosity plane-wave ultrasound; BMI: Body mass index; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase.

Citation: Liguori A, Ainora ME, Di Gialleonardo L, Viceconti N, Petrucci L, Esposto G, Giustiniani MC, Mignini I, Borriello R, Galasso L, Paratore M, Garcovich M, Riccardi L, Pompili M, Grieco A, Gasbarrini A, Miele L, Zocco MA. Multiparametric ultrasound for non-invasive assessment of liver steatosis, fibrosis, and inflammation in metabolic dysfunction-associated steatotic liver disease. World J Gastroenterol 2025; 31(25): 105518
URL: https://www.wjgnet.com/1007-9327/full/v31/i25/105518.htm
DOI: https://dx.doi.org/10.3748/wjg.v31.i25.105518