Novel non-invasive biological predictive index for liver fibrosis in hepatitis C virus genotype 4 patients

Table 1 Presentation of quantitative variable as means, standard deviation, median and quartile range by stages of fibrosis

Variant	Total (n = 332)	F0 (n = 43)	F1 (n = 136)	F2 (n = 64)	F3 (n = 45)	F4 (n = 44)
Age (yr)
Mean ± SD	42 ± 9.8	31.6 ± 7.4	41.1 ± 9.2	42 ± 7.4	48.5 ± 8.9	49.7 ± 7.5
Median ± QR	42 ± 15	31 ± 11	40.5 ± 15	42 ± 10	50 ± 11	49 ± 13
Gender (male)
n (%)	184 (55.4)	24 (55.8)	77 (56.6)	40 (62.5)	22 (48.9)	21 (47.7)
HOMA-IR
Mean ± SD	3.1 ± 1.3	2.4 ± 0.9	2.7 ± 1	3.4 ± 1.2	4.1 ± 1.7	4.0 ± 1.2
Median ± QR	2.9 ± 1.6	2.4 ± 1.8	2.7 ± 1.4	3.4 ± 1.4	4.1 ± 2.5	4.2 ± 2
ACE (U/mL)
Mean ± SD	286.7 ± 132.9	248.9 ± 122.3	277.3 ± 129	287.2 ± 122.5	325.3 ± 173.3	320.4 ± 122.4
Median ± QR	260 ± 180	235 ± 127.5	260 ± 195	300 ± 190	275 ± 171.3	285 ± 138.8
Glucose (mmol)
Mean ± SD	5.1 ± 0.9	5 ± 0.6	5.1 ± 0.9	4.8 ± 0.8	5.3 ± 0.9	5.7 ± 1.1
Median ± QR	5.1 ± 1.22	5.1 ± 1.1	4.9 ± 1.1	4.7 ± 1.2	5.3 ± 1.6	5.4 ± 1.7
ALT (U/L)
Mean ± SD	58.4 ± 36.9	37 ± 16.6	53.6 ± 37.7	55.5 ± 30.4	79.8 ± 42.6	82 ± 33.9
Median ± QR	44 ± 52	36 ± 24.3	43 ± 43	47 ± 53	81.5 ± 57.5	90 ± 41.5
AST (U/L)
Mean ± SD	53.2 ± 37.6	27.5 ± 10.9	41.1 ± 21.3	55 ± 35.4	87.2 ± 53.9	88.6 ± 42.5
Median ± QR	36 ± 43	23.5 ± 18.3	34 ± 25.8	36 ± 39	89 ± 61.3	85 ± 67.3
Platelet (× 109/L)
Mean ± SD	213.6 ± 70	225.8 ± 49.4	240 ± 65.4	207.1 ± 70.2	164.8 ± 73.8	158.3 ± 36.2
Median ± QR	215 ± 105	221.5 ± 77.5	233 ± 82.5	226 ± 120	150.5 ± 90.3	162.5 ± 38.8
BMI
Mean ± SD	27.4 ± 4.5	25.7 ± 4.3	27.9 ± 5.1	27.8 ± 4.3	27.2 ± 3.6	26.6 ± 3.1
Median ± QR	27.7 ± 5.8	25.9 ± 7.5	28.3 ± 7.8	27.7 ± 5.3	27.6 ± 4.6	27.8 ± 4.2
Waist: Hip ratio
Mean ± SD	0.9 ± 0.1	0.9 ± 0.1	0.9 ± 0.1	0.9 ± 0.1	0.9 ± 0.1	0.9 ± 0.1
Median ± QR	0.9 ± 0.1	0.9 ± 0.04	0.9 ± 0.1	0.9 ± 0.1	0.9 ± 0.1	0.9 ± 0.1
Insulin (uU/mL)
Mean ± SD	13.9 ± 5.3	11.1 ± 4.2	12.2 ± 4.5	15.8 ± 4.9	17.7 ± 7.1	15.7 ± 3.3
Median ± QR	13.6 ± 6.7	12.6 ± 7.2	12.3 ± 6.3	14.6 ± 3.4	16.7 ± 10.2	16.6 ± 5.8
Albumin (g/dL)
Mean ± SD	4.2 ± 0.5	4.2 ± 0.3	4.4 ± 0.5	4 ± 0.8	4 ± 0.5	4 ± 0.3
Median ± QR	4.2 ± 0.6	4.1 ± 0.5	4.4 ± 0.5	4.2 ± 0.8	3.9 ± 0.7	4 ± 0.6
Viral load (IU/mL)
Mean ± SD	372826.7 ± 902784.9	338113.1 ± 624770.4	409890.1 ± 941388.1	283586 ± 858939.26	264338.4 ± 452377.9	119830.8 ± 162200.8
Median ± QR	78000 ± 280088	117466.5 ± 358614	59112 ± 310055	156797 ± 251419	47546 ± 278956	97133 ± 167712

SD: Standard deviation; QR: Quartile range; HOMA-IR: Homeostasis model for insulin resistance, a mathematically calculated formula; ACE: Angiotensin converting enzyme; AST: Aspartate transaminase enzyme; ALT: Alanine amino transferase; BMI: Body mass index.

Table 2 Presentation of quantitative variables and their significance among three levels of fibrosis and significance between groups

Variant	Mild fibrosis (F0-F1) (n = 179)	Moderate fibrosis (F2) (n = 64)	Advanced fibrosis (F3-F4) (n = 89)	P1	P2	P3
Age (yr)
Mean ± SD	39.1 ± 9.6	42 ± 7.4	49 ± 8.2	0.001	0.001	0.001
Median ± QR	38.5 ± 16	42 ± 10	50 ± 11
Gender (male)
n (%)	101 (56)	40 (62)	43 (48)	0.100	0.060	0.832
HOMA-IR
Mean ± SD	2.6 ± 0.9	3.4 ± 1.2	4.1 ± 1.5	0.027	0.001	0.008
Median ± QR	2.5 ± 1.4	3.4 ± 1.4	4.1 ± 2.2
ACE (U/mL)
Mean ± SD	271.5 ± 127.3	287.2 ± 122.5	323.2 ± 150.9	0.051	0.001	0.022
Median ± QR	255 ± 187.5	300 ± 190	275 ± 142.5
Glucose (mmol)
Mean ± SD	5.1 ± 0.9	4.8 ± 0.8	5.4 ± 1	0.629	0.013	0.017
Median ± QR	5 ± 1	4.6 ± 1.1	5.3 ± 1.5
ALT (U/L)
Mean ± SD	50.2 ± 34.9	55.5 ± 30.3	80.7 ± 38.4	0.004	0.001	0.022
Median ± QR	40 ± 43	47 ± 53	85.5 ± 53.3
AST (U/L)
Mean ± SD	38.3 ± 20.3	55 ± 35.4	87.8 ± 48.5	0.001	0.001	0.001
Median ± QR	34 ± 20.5	36 ± 39	87 ± 61
Platelet (× 109/L)
Mean ± SD	237.1 ± 62.4	207.1 ± 70.2	162 ± 59.8	0.003	0.001	0.001
Median ± QR	231 ± 81.3	226 ± 120	160.5 ± 64.3
Insulin (uU/mL)
Mean ± SD	11.9 ± 4.4	15.8 ± 4.9	16.8 ± 5.8	0.016	0.001	0.071
Median ± QR	12.4 ± 6.2	14.6 ± 3.4	16.7 ± 6.4
Creatinine (mg/dL)
Mean ± SD	0.7 ± 0.2	0.6 ± 0.1	0.7 ± 0.2	0.999	0.009	0.039
Median ± QR	0.7 ± 0.2	0.6 ± 0.3	0.6 ± 0.3
Albumin (g/dL)
Mean ± SD	4.3 ± 0.43	4 ± 0.8	4 ± 0.41	0.044	0.001	0.005
Median ± QR	4.4 ± 0.54	4.2 ± 0.84	4 ± 0.67
Viral load1
Range	45979 (2.47-6570282)	36355.5 (2.46-6403601)	55000 (6.00-5600790)	0.37	0.96	0.52
Mean ± SD	358316.6 ± 909311.81	283586 ± 858939.26	331799.1 ± 863675.2

¹Comparison was done using non-parametric Mann-Whitney test. SD: Standard deviation; QR: Quartile range; HOMA-IR: Homeostasis model for insulin resistance, a mathematically calculated formula; ACE: Angiotensin converting enzyme; AST: Aspartate transaminase enzyme; ALT: Alanine amino transferase; P1: Significance between mild and moderate fibrosis; P2: Significance between mild and advanced fibrosis; P3: Significance between moderate and advanced fibrosis.

Table 3 The overall significant variables among the studied variables: Using independent-samples Kruskal-Wallis test

Variables	P value
Age (yr)	0.001
HOMA-IR	0.001
ACE (U/mL)	0.001
Glucose (mmol)	0.021
ALT (U/L)	0.001
AST (U/L)	0.001
Platelet (× 109/L)	0.001
Insulin (uU/mL)	0.001
Creatinine (mg/dL)	0.024
Total Bilirubin (mg/dL)	0.001
Direct Bilirubin (mg/dL)	0.002
Albumin (mg/dL)	0.001
Portal vein diameter	0.004
Splenic diameter	0.001

HOMA-IR: Homeostasis model for insulin resistance, a mathematically calculated formula; ACE: Angiotensin converting enzyme; AST: Aspartate transaminase enzyme; ALT: Alanine amino transferase.

Table 4 Multivariate discriminant functional analysis among the significant predictive variables

Variable	Statistic	P value
Log AST	61.295	0.001
Log platelet	44.331	0.001
Age (yr)	39.635	0.001
Log HOMA-IR	33.682	0.001

HOMA-IR: Homeostasis model for insulin resistance, a mathematically calculated formula; AST: Aspartate transaminase enzyme.

Table 5 Accuracy indices of the discriminant score in the prediction of fibrosis

Stage of fibrosis	Cut-off value	AUC	95%CI	Sens	Specific	PPV	NPV	PLR	NLR
Mild fibrosis (F0-F1)	-0.31 or more negative	0.88	0.84-0.91	67.2%	86.3%	83.6%	69.5%	4.9	0.38
Moderate fibrosis (F2)	> -0.31 up to +0.86	0.64	0.61-0.74	53.1%	74.1%	33%	86.8%	2.0	0.63
Advanced fibrosis (F3-F4)	> 0.86	0.91	0.88-0.94	73%	90.9%	74.4%	90.1%	8.0	0.3

Sens: Sensitivity; Specific: Specificity; PPV: Positive predictive value; NPV: Negative predictive value; PLR: Positive likelihood ratio; NLR: Negative likelihood ratio; AUC: Area under the curve.

Table 6 Validation results done on the studied selected groups

Stage of fibrosis	Predicted group membership			Total
	Mild fibrosis	Moderate fibrosis	Advanced fibrosis
Count
Mild fibrosis	119	50	8	177
Moderate fibrosis	16	34	14	64
Advanced fibrosis	5	19	65	89
Percent
Mild fibrosis	67.2	28.2	4.5	100.0
Moderate fibrosis	25.0	53.1	21.9	100.0
Advanced fibrosis	5.6	21.3	73.0	100.0