Diagnostic performance of FibroTest-ActiTest, transient elastography, and the fibrosis-4 index in patients with autoimmune hepatitis using histological reference

doi:10.4254/wjh.v17.i3.104534

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World Journal of Hepatology

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

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World J Hepatol. Mar 27, 2025; 17(3): 104534
Published online Mar 27, 2025. doi: 10.4254/wjh.v17.i3.104534

Table 1 Characteristics of participants

Characteristics	Included patients (n = 103)
Demographic
Age (years), median (IQR)	53 (38-61)
Female	86 (83)
BMI, median (IQR)	26 (21-28)
Baseline histological features (METAVIR)
Biopsy specimen length (mm), median (IQR)	12 (11-15)
F0	10 (10)
F1	28 (27)
F2	21 (20)
F3	24 (23)
F4	20 (19)
Fibrosis ≥ F2	65 (63)
Fibrosis ≥ F3	44 (43)
Cirrhosis F4	20 (19)
A0	10 (10)
A1	30 (29)
A2	42 (41)
A3	21 (20)
Activity ≥ A2	63 (61)
Steatosis > 0	12 (12)
Biopsy diagnosis
AIH	83 (81)
AIH and MASLD	1 (1)
AIH and PBC	19 (18)
NITs for significant fibrosis (≥ F2)
FibroTest > 0.48	55 (53)
FIB-4 ≥ 1.3	66 (64)
VCTE ≥ 8 kPa	61 (59)
NITs for advanced activity (≥ A2)
ActiTest > 0.52	48 (47)
ALT ≥ 50	63 (61)
Other serum components, median (IQR)
ALT (IU/L)	67 (37-160)
AST (IU/L)	52 (34-117)
GGT (IU/L)	73 (31-170)
Total bilirubin, μmol/L	16.7 (11-25)
Apolipoprotein-A1 (g/L)	1.57 (1.25-1.80)
Haptoglobin (g/L)	0.58 (0.56-1.30)
Alpha-2 macroglobulin (g/L)	2.34 (1.93-2.88)
Platelets (g/L)	201 (156-266)

Data presented as n (%). IQR: Interquartile range; BMI: Body mass index; METAVIR: Meta-analysis of Histological Data in Viral Hepatitis; AIH: Autoimmune hepatitis; MASLD: Metabolic dysfunction-associated steatotic liver disease; PBC: Primary biliary cholangitis; NITs: Noninvasive tests; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; GGT: Gamma-glutamyl transpeptidase; VCTE: Vibration-controlled transient elastography; FIB4: Fibrosis-4 index.

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Table 2 Test performance according to statistical methods by features

Features and test	Obuchowski weighted AUROC mean (standard error)	Standard binary AUROC mean (95%CI)
Fibrosis	5 stages, 10 comparisons	F2, F3, F4 vs F0, F1	F3, F4 vs F0, F1, F2	F4 vs F0, F1, F2, F3
FibroTest	0.919 (0.014)	0.83 (0.73-0.90)	0.83 (0.73-0.90)	0.80 (0.68-0.88)
VCTE	0.933 (0.014)	0.86 (0.77-0.92)	0.87 (0.78-0.93)	0.87 (0.78-0.94)
FIB-4	0.882 (0.019)	0.71 (0.60-0.80)	0.75 (0.63-0.83)	0.80 (0.67-0.89)
Activity	4 stages, 8 comparisons	A2, A3 vs A0, A1	-	-
ActiTest	0.921 (0.016)	0.86 (0.76-0.92)	-	-
ALT	0.905 (0.019)	0.83 (0.73-0.90)	-	-

AUROC: Areas under the receiver operating characteristic curve; CI: Confidence interval; VCTE: Vibration-controlled transient elastography; FIB-4: Fibrosis-4 index; ALT: Alanine aminotransferase.

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Table 3 Diagnostic performance of biopsy, FibroTest, fibrosis-4 index, and vibration-controlled transient elastography for significant fibrosis (F2, F3, and F4) and advanced fibrosis (F3 and F4) compared with that of the gold standard model and Bayesian latent class model

Parameters and cutoffs	Biopsy assumed as perfect reference	Bayesian LCM	Gold standard model vs LCM
Number of patients	103	103	Difference (Z-test P-value)
Prevalence significant fibrosis	63.1 (53.0-72.2)	66.2 (56.0-77.0)	3.1% increase (0.67)
Biopsy stage METAVIR ≥ F2
Sensitivity	100	95.4 (83.1-100)	4.6% decrease (NA)
Specificity	100	100 (100-100)	NA (NA)
Positive predictive value	100	100 (100-100)	NA (NA)
Negative predictive value	100	91.9 (67.3-99.9)	8.1% decrease (NA)
FibroTest with cutoff of > 0.48
Sensitivity	73.8 (61.2-83.6)	73.1 (61.5-82.6)	0.7% decrease (0.93)
Specificity	81.6 (65.1-91.7)	86.1 (70.6-98.4)	4.5% increase (0.69)
Positive predictive value	87.3 (74.9-94.3)	91.1 (79.9-99.1)	3.8% increase (0.65)
Negative predictive value	64.6 (49.4-77.4)	62.0 (45.7-75.4)	2.6% decrease (0.82)
FIB-4 with cutoff of ≥ 1.3
Sensitivity	69.2 (56.4-79.8)	70.0 (58.6-80.2)	0.8% increase (0.93)
Specificity	44.7 (29.0-61.5)	49.8 (40.8-66.1)	5.1% increase (0.58)
Positive predictive value	68.2 (55.4-78.8)	73.5 (61.5-85.0)	5.3% increase (0.55)
Negative predictive value	45.9 (29.8-62.9)	46.1 (31.2-61.9)	0.2% increase (0.99)
VCTE with LSM cutoff of ≥ 8 kPa
Sensitivity	81.5 (69.6-89.7)	80.7 (69.9-89.2)	0.8% decrease (0.92)
Specificity	78.9 (62.2-89.9)	83.6 (67.2-97.2)	4.7% increase (0.69)
Positive predictive value	86.9 (75.2-93.8)	90.6 (79.5-98.7)	3.7% increase (0.65)
Negative predictive value	71.4 (55.2-83.8)	68.8 (50.6-82.1)	2.6% decrease (0.83)
Prevalence advanced fibrosis	42.7 (33.1-52.8)	50.2 (37.1-65.2)	7.5% increase (0.37)
Biopsy stage METAVIR ≥ F3
Sensitivity	100	85.2 (64.6-99.8)	14.8% decrease (NA)
Specificity	100	100 (100-100)	NA (NA)
Positive predictive value	100	100 (100-100)	NA (NA)
Negative predictive value	100	87.0 (63.7-99.9)	13% decrease (NA)
FibroTest with cutoff of > 0.58
Sensitivity	70.5 (54.6-82.8)	66.1 (51.2-80.1)	4.4% decrease (0.69)
Specificity	83.1 (70.6-91.1)	86.4 (74.2-96.3)	3.3% increase (0.71)
Positive predictive value	75.6 (59.4-87.1)	83.3 (66.6-95.9)	7.7% increase (0.52)
Negative predictive value	79.0 (66.5-87.9)	71.9 (53.2-85.2)	7.1% decrease (0.54)
FIB-4 with cutoff of ≥ 2.67
Sensitivity	38.6 (24.7-54.5)	38.2 (25.0-52.3)	0.4% decrease (0.97)
Specificity	88.1 (76.5-94.7)	91.7 (79.9-99.5)	3.6% increase (0.67)
Positive predictive value	70.8 (48.8-86.6)	82.4 (56.5-99.2)	11.6% increase (0.50)
Negative predictive value	65.8 (54.2-75.9)	59.8 (44.2-72.6)	6% decrease (0.55)
VCTE with LSM cutoff of ≥ 9.5
Sensitivity	84.1 (69.3-92.8)	84.0 (72.2-92.9)	0.1% decrease (0.94)
Specificity	72.9 (59.5-83.3)	81.7 (65.2-98.8)	8.8% increase (0.42)
Positive predictive value	69.8 (55.5-81.3)	82.2 (62.4-99.0)	12.4% increase (0.32)
Negative predictive value	86.0 (72.6-93.7)	83.5 (69.4-92.9)	2.5% decrease (0.80)

LCM: Latent class model; METAVIR: Meta-analysis of Histological Data in Viral Hepatitis; FIB-4: Fibrosis-4 index; VCTE: Vibration-controlled transient elastography; NA: Not applicable; NA: Not available; LSM: Liver stiffness median.

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Table 4 Comparison of the diagnostic performance of biopsy, ActiTest, and alanine aminotransferase for advanced activity (A2 and A3) with the gold standard model and Bayesian latent class model

Parameters and cutoffs	Biopsy assumed as perfect reference	Bayesian LCM	Gold standard model vs LCM
Number of patients	103	103	Difference (Z-test P-value)
Prevalence advanced activity	61.2 (51.0-70.5)	47.8 (37.7-58.3)	13.4% decrease (0.07)
Biopsy stage METAVIR ≥ A2
Sensitivity	100	95.8 (87.5-99.6)	4.2% decrease (NA)
Specificity	100	70.9 (57.4-82.3)	29.1% decrease (NA)
Positive predictive value	100	75.1 (62.7-85.6)	24.9% decrease (NA)
Negative predictive value	100	94.8 (84.5-99.5)	5.2% decrease (NA)
ActiTest with cutoff of > 0.52
Sensitivity	73.0 (60.1-83.1)	97.3 (85.8-100)	24.3% increase (0.006)
Specificity	95.0 (81.8-99.1)	99.4 (93.4-100)	4.4% increase (0.59)
Positive predictive value	95.8 (84.6-99.3)	99.3 (92.6-100)	3.5% increase (0.60)
Negative predictive value	69.1 (55.0-80.5)	97.7 (86.6-100)	28.6% increase (0.002)
ALT with cutoff of ≥ 50
Sensitivity	81.0 (68.7-89.4)	99.5 (95.0-100)	18.5% increase (0.006)
Specificity	70.0 (53.3-82.9)	74.3 (61.6-85.7)	4.2% increase (0.69)
Positive predictive value	81.0 (68.7-89.4)	78.0 (65.8-88.4)	3.0% decrease (0.73)
Negative predictive value	70.0 (53.3-82.9)	99.4 (94.0-100)	29.4% increase (0.006)

LCM: Latent class model; METAVIR: Meta-analysis of Histological Data in Viral Hepatitis; ALT: Alanine aminotransferase; NA: Not applicable.

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Citation: Peta V, Sandler Y, Deckmyn O, Duroselle O, Vinnitskaya E, Khomeriki S, Noskova K, Poynard T. Diagnostic performance of FibroTest-ActiTest, transient elastography, and the fibrosis-4 index in patients with autoimmune hepatitis using histological reference. World J Hepatol 2025; 17(3): 104534
URL: https://www.wjgnet.com/1948-5182/full/v17/i3/104534.htm
DOI: https://dx.doi.org/10.4254/wjh.v17.i3.104534