Diagnostic efficacy and influencing factors of non-invasive liver fibrosis scores in chronic hepatitis B fibrosis: Cross-sectional study

doi:10.4254/wjh.v18.i5.116008

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World Journal of Hepatology

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1948-5182

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

Observational Study

Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Hepatol. May 27, 2026; 18(5): 116008
Published online May 27, 2026. doi: 10.4254/wjh.v18.i5.116008

Table 1 Baseline characteristics (n = 627), n (%)/median (interquartile range)

Variable	Values
Age (years)	47.00 (34.50-55.00)
Sex
Male	438 (69.86)
Female	189 (30.14)
ALT (U/L)	114.00 (39.00-408.50)
AST (U/L)	77.00 (36.00-235.50)
GGT (U/L)	57.00 (28.00-119.00)
PLT (10⁹/L)	130.00 (87.00-173.00)
TBIL (μmol/L)	17.20 (11.00-34.75)
ALB (g/L)	38.20 (34.35-41.85)
TP (g/L)	67.90 (63.70-72.30)
APRI	1.92 (0.83-5.42)
GPR	0.99 (0.44-2.29)
FIB-4	2.94 (1.49-6.57)
AST/ALT	0.72 (0.50-1.13)
NRS2002
NRS2002 < 3	489 (77.9)
NRS2002 ≥ 3	138 (22.01)
Child-Pugh
A	441 (70.33)
B	108 (17.22)
C	78 (12.44)
FibroScan
F0	136 (21.69)
F1	105 (16.75)
F2	79 (12.6)
F3	117 (18.66)
F4	190 (30.3)

APRI: Aspartate aminotransferase to platelet ratio index; GPR: Gamma-glutamyl transferase to platelet ratio index; FIB-4: Fibrosis-4 index; NRS2002: 2002 Nutritional Risk Screening scale; Child-Pugh: Child-Pugh classification; FibroScan: Liver stiffness measurement device (the staging criteria are F0 indicating normal, F4 indicating cirrhosis); AST/ALT: Aspartate aminotransferase to alanine aminotransferase ratio; PLT: Platelet count; TBIL: Total bilirubin; ALB: Albumin; TP: Total protein; GGT: γ-glutamyl transferase.

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Table 2 Correlation between serological assessment indicators and liver stiffness measurement (n = 627)

First variable	Second variable	Correlation coefficient	P value
LSM	AST/ALT	0.175	< 0.001
	APRI	0.518	< 0.001
	GPR	0.609	< 0.001
	FIB-4	0.553	< 0.001

Spearman’s correlation analysis was used to assess the association between serological indicators and liver stiffness measurement. LSM: Liver stiffness measurement; AST/ALT: Aspartate aminotransferase to alanine aminotransferase ratio; APRI: Aspartate aminotransferase to platelet ratio index; GPR: Gamma-glutamyl transferase to platelet ratio; FIB-4: Fibrosis-4 index.

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Table 3 Comparison of various indicators by gender (n = 627), n (%)/median (interquartile range)

Indices	Female (n = 189)	Male (n = 438)	P value
LSM
F0	61 (32.3)	75 (17.1)	< 0.001
F1	33 (17.5)	72 (16.4)
F2	23 (12.2)	56 (12.8)
F3	38 (20.1)	79 (18)
F4	34 (18)	156 (35.6)
APRI	1.67 (0.80-4.24)	2.03 (0.85-5.95)	0.208
GPR	0.67 (0.28-1.51)	1.14 (0.53-2.65)	< 0.001
FIB-4	2.88 (1.32-6.61)	2.96 (1.53-6.48)	0.853
AST/ALT	0.78 (0.60-1.28)	0.68 (0.48-1.05)	< 0.001

The χ² test was used to analyze the association between gender and liver stiffness measurement results; the Wilcoxon rank-sum test was used to compare the differences in these continuous variables (aspartate aminotransferase to platelet ratio index, gamma-glutamyl transferase to platelet ratio index, fibrosis-4 index, aspartate aminotransferase to alanine aminotransferase ratio) between the female and male groups. LSM: Liver stiffness measurement; APRI: Aspartate aminotransferase to platelet ratio index; GPR: Gamma-glutamyl transferase to platelet ratio index; FIB-4: Fibrosis-4 index; AST/ALT: Aspartate aminotransferase to alanine aminotransferase ratio.

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Table 4 Comparison of various indicators by nutritional risk status (n = 627), n (%)/median (interquartile range)

Indices	NRS2002 < 3 (n = 489)	NRS2002 ≥ 3 (n = 138)	P value
LSM
F0	130 (26.6)	6 (4.3)	< 0.001
F1	97 (19.8)	8 (5.8)
F2	67 (13.7)	12 (8.7)
F3	91 (18.6)	26 (18.8)
F4	104 (21.3)	86 (62.3)
APRI	1.50 (0.70-3.60)	4.95 (2.38-10.90)	< 0.001
GPR	0.79 (0.37-1.90)	1.84 (0.97-3.26)	< 0.001
FIB-4	2.38 (1.27-4.80)	6.78 (3.80-10.84)	< 0.001
AST/ALT	0.67 (0.48-1.00)	1.02 (0.61-1.54)	< 0.001

The χ² test was used to compare the categorical variable (liver stiffness measurement stages) across nutritional risk groups; the Wilcoxon rank-sum test was used to compare continuous variables (aspartate aminotransferase to platelet ratio index, gamma-glutamyl transferase to platelet ratio index, fibrosis-4 index, aspartate aminotransferase to alanine aminotransferase ratio) between the two groups. LSM: Liver stiffness measurement; APRI: Aspartate aminotransferase to platelet ratio index; GPR: Gamma-glutamyl transferase to platelet ratio index; FIB-4: Fibrosis-4 index; AST/ALT: Aspartate aminotransferase to alanine aminotransferase ratio; NRS2002: Nutritional Risk Screening 2002.

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Table 5 Comparison of various indicators by Child-Pugh classification (n = 627), n (%)/median (interquartile range)

Indices	A grade (n = 441)	B grade (n = 108)	C grade (n = 78)	P value
LSM
F0	131 (29.7)	4 (3.7)	1 (1.3)	< 0.001
F1	98 (22.2)	6 (5.6)	1 (1.3)
F2	65 (14.7)	12 (11.1)	2 (2.6)
F3	83 (18.8)	29 (26.9)	5 (6.4)
F4	64 (14.5)	57 (52.8)	69 (88.5)
APRI	1.33 (0.63-2.82)	3.19 (1.59-10.08)	8.23 (4.29-18.95)	< 0.001
GPR	0.71 (0.32-1.69)	2.19 (0.94-4.56)	1.86 (1.06-3.25)	< 0.001
FIB-4	2.17 (1.23-3.93)	6.03 (3.47-9.22)	8.70 (5.90-16.24)	< 0.001
AST/ALT	0.67 (0.49-0.96)	0.94 (0.56-1.36)	1.10 (0.68-1.61)	< 0.001

The χ² test was used to analyze the association between Child-Pugh classification and the categorical variable (FibroScan stages); the Kruskal-Wallis test was used to compare the differences in continuous variables (aspartate aminotransferase to platelet ratio index, gamma-glutamyl transferase to platelet ratio index, fibrosis-4 index, aspartate aminotransferase to alanine aminotransferase ratio) among different Child-Pugh classification groups. LSM: Liver stiffness measurement; APRI: Aspartate aminotransferase to platelet ratio index; GPR: Gamma-glutamyl transferase to platelet ratio index; FIB-4: Fibrosis-4 index; AST/ALT: Aspartate aminotransferase to alanine aminotransferase ratio.

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Table 6 Aspartate aminotransferase to platelet ratio index, fibrosis-4 index, aspartate aminotransferase to alanine aminotransferase ratio and gamma-glutamyl transferase to platelet ratio based on FibroScan results (n = 627), median (interquartile range)

LSM	APRI	FIB-4	AST/ALT	GPR
F0	0.835 (0.500-1.672)	1.690 (0.992-2.473)	0.670 (0.487-1.008)	0.355 (0.217-0.653)
F1	1.080 (0.500-2.110)	1.600 (0.990-2.950)	0.640 (0.490-0.950)	0.510 (0.250-1.030)
F2	1.500 (0.625-3.980)	2.270 (1.380-3.655)	0.630 (0.465-0.925)	0.830 (0.455-1.710)
F3	2.150 (1.270-5.860)	4.690 (2.500-7.960)	0.830 (0.570-1.160)	1.600 (0.820-2.590)
F4	5.295 (2.212-11.165)	6.320 (3.513-10.688)	0.880 (0.540-1.333)	2.210 (1.132-3.980)
P value	< 0.001	< 0.001	< 0.001	< 0.001

The Kruskal-Wallis test was used to compare the overall differences in indicators across different FibroScan stages. LSM: Liver stiffness measurement; APRI: Aspartate aminotransferase to platelet ratio index; GPR: Gamma-glutamyl transferase to platelet ratio index; FIB-4: Fibrosis-4 index; AST/ALT: Aspartate aminotransferase to alanine aminotransferase ratio.

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Table 7 Post-hoc analysis of aspartate aminotransferase to platelet ratio index, fibrosis-4 index, aspartate aminotransferase to alanine aminotransferase ratio and gamma-glutamyl transferase to platelet ratio index across different FibroScan-based stages (n = 627)

Analytical index	Comparison group	P value
APRI	F0-F1	1.000
APRI	F0-F2	< 0.01^b
APRI	F1-F2	0.264
APRI	F0-F3	< 0.001^a
APRI	F1-F3	< 0.001^a
APRI	F2-F3	0.137
APRI	F0-F4	< 0.001^a
APRI	F1-F4	< 0.001^a
APRI	F2-F4	< 0.001^a
APRI	F3-F4	< 0.001^a
FIB-4	F0-F1	1.000
FIB-4	F0-F2	< 0.05^c
FIB-4	F1-F2	0.137
FIB-4	F0-F3	< 0.001^a
FIB-4	F1-F3	< 0.001^a
FIB-4	F2-F3	< 0.001^a
FIB-4	F0-F4	< 0.001^a
FIB-4	F1-F4	< 0.001^a
FIB-4	F2-F4	< 0.001^a
FIB-4	F3-F4	0.082
AST/ALT	F0-F1	1.000
AST/ALT	F0-F2	1.000
AST/ALT	F1-F2	1.000
AST/ALT	F0-F3	0.164
AST/ALT	F1-F3	< 0.05^c
AST/ALT	F2-F3	0.090
AST/ALT	F0-F4	< 0.01^b
AST/ALT	F1-F4	< 0.01^b
AST/ALT	F2-F4	< 0.01^b
AST/ALT	F3-F4	1.0000
GPR	F0-F1	0.122
GPR	F0-F2	< 0.001^a
GPR	F1-F2	< 0.05^c
GPR	F0-F3	< 0.001^a
GPR	F1-F3	< 0.001^a
GPR	F2-F3	0.009^b
GPR	F0-F4	< 0.001^a
GPR	F1-F4	< 0.001^a
GPR	F2-F4	< 0.001^a
GPR	F3-F4	0.115

^aP < 0.001.

^bP < 0.01.

^cP < 0.05.

Post-hoc analysis was used to identify specifically which stages have significant differences. APRI: Aspartate aminotransferase to platelet ratio index; GPR: Gamma-glutamyl transferase to platelet ratio index; FIB-4: Fibrosis-4 index; AST/ALT: Aspartate aminotransferase to alanine aminotransferase ratio.

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Table 8 Multivariate logistic regression results for any fibrosis (F1-F4 vs F0) (n = 627)

Model	Predictor variable	AOR (95%CI)	P value	Model AUC
APRI	The model itself	1.072 (1.018-1.145)	0.021	0.777 (0.736-0.818)
	Age Q2 (vs Q1)	1.071 (0.630-1.819)	0.8
	Age Q3 (vs Q1)	1.495 (0.841-2.686)	0.174
	Age Q4 (vs Q1)	1.783 (0.971-3.343)	0.066
	Male (vs female)	2.096 (1.373-3.199)	< 0.001
	Nutritional risk (yes vs none)	2.049 (0.835-5.910)	0.144
	Child-Pugh B (vs A)	6.455 (2.507-22.031)	< 0.001
	Child-Pugh C (vs A)	9.821 (1.691-187.753)	0.036
GPR	The model itself	1.58 (1.282-2.017)	< 0.001	0.816 (0.779-0.853)
	Age Q2 (vs Q1)	0.981 (0.574-1.676)	0.945
	Age Q3 (vs Q1)	1.324 (0.741-2.388)	0.207
	Age Q4 (vs Q1)	1.492 (0.807-2.811)	0.346
	Male (vs female)	1.728 (1.120-2.663)	0.013
	Nutritional risk (yes vs none)	2.087 (0.852-6.006)	0.133
	Child-Pugh B (vs A)	5.596 (2.186-19.007)	0.001
	Child-Pugh C (vs A)	12.127 (2.125-230.362)	0.024
FIB-4	The model itself	1.193 (1.086-1.329)	< 0.001	0.791 (0.750-0.831)
	Age Q2 (vs Q1)	0.899 (0.526-1.534)	0.697
	Age Q3 (vs Q1)	0.99 (0.543-1.818)	0.975
	Age Q4 (vs Q1)	0.957 (0.485-1.907)	0.899
	Male (vs female)	2.218 (1.446-3.408)	< 0.001
	Nutritional risk (yes vs none)	1.971 (0.799-5.706)	0.169
	Child-Pugh B (vs A)	5.212 (2.011-17.850)	0.002
	Child-Pugh C (vs A)	7.041 (1.192-135.262)	0.074
AST/ALT	The model itself	0.972 (0.623-1.593)	0.906	0.745 (0.703-0.787)
	Age Q2 (vs Q1)	1.071 (0.631-1.818)	0.799
	Age Q3 (vs Q1)	1.393 (0.770-2.546)	0.275
	Age Q4 (vs Q1)	1.77 (0.934-3.419)	0.084
	Male (vs female)	2.106 (1.378-3.221)	< 0.001
	Nutritional risk (yes vs none)	2.186 (0.902-6.253)	0.108
	Child-Pugh B (vs A)	8.232 (3.248-27.872)	< 0.0001
	Child-Pugh C (vs A)	15.884 (2.800-301.739)	0.011

Age was categorized into quartiles: Q1 (≤ 34 years, reference group), Q2 (35-47 years), Q3 (48-55 years), and Q4 (≥ 56 years). This table presents four independent multivariate logistic regression models, each evaluating the independent predictive ability of a different serum non-invasive indicator for any liver fibrosis (F1-F4) vs no fibrosis (F0). The “model AUC” represents the area under the receiver operating characteristic curve for each regression model, indicating its overall diagnostic performance in distinguishing patients with any fibrosis (F1-F4) from those without fibrosis (F0). The area under the curve (AUC) was calculated by deriving a predicted probability for each subject based on the model’s predictor variables, plotting an receiver operating characteristic curve using this probability against the actual fibrosis status (F1-F4 vs F0), and then determining the area under this curve. An AUC value closer to 1 indicates superior discriminatory ability of the model. AOR: Adjusted odds ratio; CI: Confidence interval; AUC: Area under the curve; APRI: Aspartate aminotransferase to platelet ratio index; GPR: Gamma-glutamyl transferase to platelet ratio index; FIB-4: Fibrosis-4 index; AST/ALT: Aspartate aminotransferase to alanine aminotransferase ratio.

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Table 9 Multivariate logistic regression analysis results for significant fibrosis (F3-F4 vs F0-F2) (n = 627)

Model	Predictor variable	AOR (95%CI)	P value	Model AUC
APRI	Model itself	1.011 (0.995-1.036)	0.26	0.800 (0.766-0.834)
	Age Q2 (vs Q1)	1.291 (0.780-2.143)	0.322
	Age Q3 (vs Q1)	1.526 (0.903-2.587)	0.115
	Age Q4 (vs Q1)	2.464 (1.445-4.241)	0.001
	Male (vs female)	1.746 (1.178-2.666)	0.006
	Nutritional risk (yes vs none)	1.363 (0.737-2.517)	0.295
	Child-Pugh B (vs A)	6.419 (3.768-11.310)	< 0.001
	Child-Pugh C (vs A)	23.951 (8.361-87.708)	< 0.001
GPR	Model itself	1.551 (1.350-1.806)	< 0.001	0.871 (0.844-0.899)
	Age Q2 (vs Q1)	1.16 (0.688-1.959)	0.578
	Age Q3 (vs Q1)	1.356 (0.786-2.345)	0.274
	Age Q4 (vs Q1)	2.028 (1.158-3.573)	0.014
	Male (vs female)	1.379 (0.901-2.124)	0.141
	Nutritional risk (yes vs none)	1.29 (0.673-2.454)	0.438
	Child-Pugh B (vs A)	4.728 (2.718-8.467)	< 0.001
	Child-Pugh C (vs A)	22.635 (7.834-83.517)	< 0.001
FIB-4	Model itself	1.085 (1.035-1.146)	0.002	0.825 (0.793-0.857)
	Age Q2 (vs Q1)	1.142 (0.686-1.904)	0.61
	Age Q3 (vs Q1)	1.215 (0.706-2.091)	0.481
	Age Q4 (vs Q1)	1.737 (0.976-3.100)	0.061
	Male (vs female)	1.847 (1.224-2.813)	0.004
	Nutritional risk (yes vs none)	1.367 (0.736-2.534)	0.32
	Child-Pugh B (vs A)	5.188 (2.998-9.264)	< 0.001
	Child-Pugh C (vs A)	16.712 (5.779-62.87)	< 0.001
AST/ALT	The model itself	1.344 (0.915-2.021)	0.144	0.787 (0.751-0.822)
	Age Q2 (vs Q1)	1.241 (0.748-2.067)	0.404
	Age Q3 (vs Q1)	1.343 (0.778-2.319)	0.290
	Age Q4 (vs Q1)	2.162 (1.233-3.817)	0.007
	Male (vs female)	1.865 (1.238-2.838)	0.003
	Nutritional risk (yes vs none)	1.329 (0.715-2.464)	0.366
	Child-Pugh B (vs A)	6.35 (3.743-11.160)	< 0.001
	Child-Pugh C (vs A)	24.416 (8.606-88.915)	< 0.001

Age grouping follows Table 8. This table presents four independent multivariate logistic regression models. Each model aims to evaluate the independent predictive ability of different serum non-invasive indicators for significant liver fibrosis (F3-F4) vs no or mild fibrosis (F0-F2). “Model AUC” refers to the area under the receiver operating characteristic (ROC) curve of the regression model, indicating its overall diagnostic performance in distinguishing patients with “significant fibrosis (F3-F4)” from those with “no or mild fibrosis (F0-F2)”. The calculation method is as follows: A predicted probability is computed for each subject based on the model's predictor variables; an ROC curve is then plotted using this predicted probability as the test variable against the actual grouping (F3-F4 vs F0-F2) as the state variable; finally, the area under this curve is calculated. An area under the curve value closer to 1 indicates a stronger discriminatory ability of the model. AOR: Adjusted odds ratio; CI: Confidence interval; AUC: Area under the curve; APRI: Aspartate aminotransferase to platelet ratio index; GPR: Gamma-glutamyl transferase to platelet ratio index; FIB-4: Fibrosis-4 index; AST/ALT: Aspartate aminotransferase to alanine aminotransferase ratio.

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Table 10 Diagnostic performance of various indicators in differentiating F0 vs F1-F4 and F0-F2 vs F3-F4

Comparison	Indices	AUC (95%CI)	P value	Cut-off	Sensitivity (%)	Specificity (%)	PPV (%)	NPV (%)	DA (%)
F0 and F1-F4	APRI	0.736 (0.69-0.781)	< 0.001	1.45	66.6	70.6	89.1	36.9	67.5
	GPR	0.814 (0.774-0.853)	< 0.001	0.715	72.3	79.4	92.7	44.3	73.8
	FIB-4	0.743 (0.699-0.786)	< 0.001	2.395	67.4	74.3	90.4	38.7	68.9
	AST/ALT	0.553 (0.5-0.606)	0.028	0.825	43.8	68.4	83.3	25.2	49.1
F0-F2 and F3-F4	APRI	0.776 (0.741-0.812)	< 0.001	1.76	72.6	68.4	68.8	72.3	70.5
	GPR	0.828 (0.796-0.86)	< 0.001	0.715	87.6	64.4	70.2	84.4	75.8
	FIB-4	0.814 (0.781-0.848)	< 0.001	3.88	66.4	85	81	72.5	75.9
	AST/ALT	0.615 (0.571-0.659)	< 0.001	0.825	52.1	69.4	62	60.2	60.9

This table shows the diagnostic performance of different indicators in differentiating F0 vs F1-F4 and F0-F2 vs F3-F4. APRI: Aspartate aminotransferase to platelet ratio index; GPR: Gamma-glutamyl transferase to platelet ratio index; FIB-4: Fibrosis-4 index; AST/ALT: Aspartate aminotransferase to alanine aminotransferase ratio; AUC: Area under the curve; CI: Confidence interval; PPV: Positive predictive value; NPV: Negative predictive value; DA: Diagnostic accuracy.

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Citation: Wang CX, Yan P, Lan LJ, Zhao BN, Kang J, Li MQ, Liu DF. Diagnostic efficacy and influencing factors of non-invasive liver fibrosis scores in chronic hepatitis B fibrosis: Cross-sectional study. World J Hepatol 2026; 18(5): 116008
URL: https://www.wjgnet.com/1948-5182/full/v18/i5/116008.htm
DOI: https://dx.doi.org/10.4254/wjh.v18.i5.116008

Wang CX, Yan P, Lan LJ, Zhao BN, Kang J, Li MQ, Liu DF. Diagnostic efficacy and influencing factors of non-invasive liver fibrosis scores in chronic hepatitis B fibrosis: Cross-sectional study. World J Hepatol 2026; 18(5): 116008 [DOI: 10.4254/wjh.v18.i5.116008]

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