Ensemble for evaluating diagnostic efficacy of non-invasive indices in predicting liver fibrosis in untreated hepatitis C virus population

doi:10.5662/wjm.v14.i3.91058

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World Journal of Methodology

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World J Methodol. Sep 20, 2024; 14(3): 91058
Published online Sep 20, 2024. doi: 10.5662/wjm.v14.i3.91058

Table 1 Liver stiffness measurement cutoffs

Severity of fibrosis	METAVIR stages	LSM in kPa
Normal	F0-F1	2 - 7
Mild fibrosis	F2	7.1-11
Moderate fibrosis	F3	11.1-21
Severe fibrosis	F4	> 21

LSM: Liver stiffness measurement.

Table 2 Biological variables for non-fibrotic, mild fibrotic, moderate fibrotic and severe fibrotic hepatitis C virus cases

Indices	No fibrosis⁰		Mild fibrosis¹		Moderate fibrosis²		Severe fibrosis³		P value
Indices	Median	IQR	Median	IQR	Median	IQR	Median	IQR	P value
Routine investigations
Viral load	112792	56721.5-131470.5	308255	231893.25-424659.75	1050000	696516.5-1334612.5	4956005	3170155.25-9357337	0.000^a
Hb	13.2	11.35-15	13	11.07-14.7	13	10.65-14	12.95	10.95-13.4	0.674
INR	1	1-1.1	1.1	1.0175-1.3	1.1	1-1.185	1.09	1-1.1775	0.478
TSP	6.9	6.55-7.155	6.9	6.6-7.2	7.1	6.65-7.72	7	6.55-7.2	0.683
Albumin	3.9	3.55-4.5	3.8	3.5-4.175	4.1	3.55-4.3	3.85	3.375-4.3	0.849
Bilirubin	0.68	0.4-0.7	0.7	0.5-0.895	0.7	0.4-0.95	0.8	0.475-1	0.488
AST	43	31.5-63	53.5	30.5-92.75	97	70.5-115.5	108.5	62.5-172.5	0.000^a
ALT	50	36-77	60	40.25-93.3	92	56-175.5	106.5	85.25-151	0.030^a
ALP	85	77.5-88	82	78.25-88	102	97.5-131	150	129.5-168	0.000^a
TLC	8800	7700-9450	8050	6750-9075	7200	6600-8500	7200	6500-7725	0.000^a
Plt count	216	158-279.5	195	138.75-235	160	111.5-210	130	102-160.25	0.000^a
Special investigations
Fibronectin	98	89.82-101.25	118	113.4-126.57	147	138.75-154	204.5	188.975-222.25	0.000^a
AAR	0.83	0.64-1.08	0.86	0.71-1.21	0.89	0.724-1.26	1.82	1.159-4.37	0.704
APRI	0.52	0.33-0.69	0.6	0.495-1.84	1.67	0.95-2.291	1.82	1.159-4.37	0.000^a
FIB-4	1	0.63-1.29	1.44	0.98-2.29	2.52	2.04-3.918	3.77	2.68-6.6	0.000^a

⁰Stage 0, n = 25.

¹Stage 1, n = 24.

²Stage 2, n = 25.

³Stage 3, n = 26.

^aStatistically significant values with cut-off for significance set at < 0.05.

AAR: Alanine aminotransferase ratio; ALP: Alkaline phosphatase; ALT: Alanine aminotransferase; APRI: Aspartate aminotransferase to platelet ratio index; AST: Aspartate aminotransferase; FIB-4: Fibrosis-4; Hb: Hemoglobin; INR: International normalized ratio; IQR: Inter-quartile range; Plt: Platelet; TLC: Total leukocyte count; TSP: Total serum protein.

Table 3 Correlation and significance with respect to liver stiffness measurement

Indices	R	P value
Routine investigations
Viral load	0.663	0.000^a
Hb	-0.169	0.092
INR	0.041	0.688
TSP	0.081	0.425
Albumin	-0.06	0.552
Bilirubin	0.149	0.14
AST	0.428	0.000^a
ALT	0.3	0.000^a
ALP	0.747	0.000^a
TLC	-0.391	0.000^a
Plt count	-0.473	0.000^a
Special investigations
Serum fibronectin	0.929	0.000^a
AAR	0.127	0.207
APRI	0.574	0.000^a
FIB-4	0.586	0.000^a

^aStatistically significant values with cut-off for significance set at < 0.05.

AAR: Alanine aminotransferase ratio; ALP: Alkaline phosphatase; ALT: Alanine aminotransferase; APRI: Aspartate aminotransferase to platelet ratio index; AST: Aspartate aminotransferase; FIB-4: Fibrosis-4; Hb: Hemoglobin; INR: International normalized ratio; Plt: Platelet; TLC: Total leukocyte count; TSP: Total serum protein.

Table 4 Diagnostic accuracy for fibronectin, aspartate aminotransferase to platelet ratio index, and fibrosis-4

Indices	S. Fibronectin, %	APRI, %	FIB-4, %
Fibrosis
Sensitivity	98.70	73.30	73.30
Specificity	100	88	96
Youdens index	0.987	0.613	0.693
AUROC	1	0.829	0.85
LR+	> 10	< 10	> 10
LR-	0.013	0.303	0.277
Mild fibrosis
Sensitivity	100	45.80	45.80
Specificity	96	88	96
Youdens index	0.96	0.338	0.418
AUROC	0.999	0.672	0.725
LR+	> 10	< 10	> 10
LR-	0	0.615	0.564
Moderate fibrosis
Sensitivity	92.20	80.40	82.40
Specificity	100	77.60	85.70
Youdens index	0.922	0.579	0.681
AUROC	0.993	0.836	0.853
LR+	> 10	< 10	< 10
LR-	0.0784	0.252	0.205
Severe fibrosis
Sensitivity	96.20	84.60	92.30
Specificity	98.60	62.20	71.60
Youdens index	0.948	0.468	0.639
AUROC	0.922	0.796	0.835
LR+	> 10	< 10	< 10
LR-	0.038	0.247	0.107

APRI: Aspartate aminotransferase to platelet ratio index; AUROC: Area under receiver operating characteristic curve; FIB-4: Fibrosis-4; LR+: Positive likelihood test; LR-: Negative likelihood test. Some of the values are converted into percentages. Cutoffs: Mild (> 110, > 0.824, > 1.90), moderate (> 140, > 1.19, > 2.45) and severe fibrosis (> 180, > 1.38, > 2.7), respectively.

Table 5 Conditional probability table for liver fibrosis severity with respect to fibronectin

Fibronectin	Fibronectin < 150, %	Fibronectin 150-200, %	Fibronectin > 200, %
LF severity (0)	37	1	1
LF severity (1)	36	1	1
LF severity (2)	25	42	1
LF severity (3)	2	57	98

LF: Liver fibrosis.

Table 6 Conditional probability table for liver fibrosis severity with respect to special investigations

Fibronectin	Fibronectin < 150, %	Fibronectin 150-200, %	Fibronectin > 200, %
AAR	AAR (< 1)	AAR (1)	AAR (> 1)
APRI	APRI (< 2)	APRI (2-3)	APRI (> 3)
FIB-4	FIB-4 (< 2)	FIB-4 (2-4)	FIB-4 (> 4)
LF severity (0)	59	0	0
LF severity (1)	31	0	0
LF severity (2)	8	77	0
LF severity (3)	2	23	100

AAR: Alanine aminotransferase ratio; APRI: Aspartate aminotransferase to platelet ratio index; FIB-4: Fibrosis-4; LF: Liver fibrosis.

Citation: Kaur N, Goyal G, Garg R, Tapasvi C, Demirbaga U. Ensemble for evaluating diagnostic efficacy of non-invasive indices in predicting liver fibrosis in untreated hepatitis C virus population. World J Methodol 2024; 14(3): 91058
URL: https://www.wjgnet.com/2222-0682/full/v14/i3/91058.htm
DOI: https://dx.doi.org/10.5662/wjm.v14.i3.91058