Precise prediction model and simplified scoring system for sustained combined response to interferon-α

Table 1 Baseline demographic and virological data of the study population

Factor	n (range)
Sex (M:F)	345:129
Age (yr)	29.8 (10-58)
ALT (U/L)	250 (16-1908)
AST (U/L)	146 (24-1304)
Genotype (A:B:C)1	51:212:211
HBV DNA (log copies/mL)	7.35 (5.00-9.83)
Fibrosis staging, S (0:1:2:3:4)	10:154:157:114:39
Histology activity index, G (1:2: 3:4)	39:215:169:51

Continuous variables are expressed as median (range).

¹B, C refers to genotype B, C, respectively; genotype B and C co-infection and other genotypes were named as A. ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; HBV: Hepatitis B virus.

Table 2 Individual factors of patients with diverse responses at the 24th week after cease of interferon-α therapy

	CR	PR	NR
Sex (M:F)	110:53	163:51	72:25
Age [0-14):(15-24):(25-44):(≥ 45), yr]	3:64:123:5	5:47:148:14	2:21:71:3
ALT [(1-2):(2-3):(3-5):(5-10):(≥ 10), ULN]	7:5:27:75:49	27:41:71:44:31	19:31:31:13:3
AST [(0-1):(1-2):(2-3):(3-5):(5-10):(≥ 10), ULN]	1:22:30:49:43:18	12:76:54:38:24:10	9:50:18:14:6:0
Genotype (A:B:C)	14:96:53	30:101:83	7:15:75
HBV DNA [(5-5.99):(6-6.99):(7-7.99):(8-8.99):(≥ 9), log copies/mL]	21:55:56:26:5	19:65:79:49:2	5:31:37:21:3
Fibrosis staging, S (0:1:2:3:4)	2:54:51:48:8	7:68:71:50:18	1:32:35:16:13
Histology activity index, G (1:2:3:4)	11:71:60:21	22:95:77:20	6:49:32:10
Responses (CR:PR:NR)	163	214	97

ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; ULN: Upper limit of normal; HBV: Hepatitis B virus; CR: Combined response; PR: Partial response; NR: No response.

Table 3 Inter-variable correlations determined by the Spearman rank correlation coefficient

	Gender	Age	Grading	Staging	ALT	AST	DNA1	Genotype	Duration	Y F6 m2
Gender	1.00
Age	0.06	1.00
Grading	-0.11a	0.05	1.00
Staging	-0.06	0.08	0.74b	1.00
ALT	0.05	-0.01	0.13b	0.02	1.00
AST	-0.13b	-0.04	0.25b	0.17b	0.73b	1.00
DNA1	-0.09	0.04	-0.04	-0.10a	0.07	0.09a	1.00
Genotype	0.09a	0.00	-0.01	0.01	0.09	0.03	-0.12b	1.00
Duration	0.05	-0.03	-0.02	0.03	0.00	-0.04	0.03	0.02	1.00
Y F6 m	0.05	-0.01	-0.03	0.00	-0.39b	-0.35b	0.06	0.25b	-0.07	1.00

^aP < 0.05,

^bP < 0.01;

¹log copies/mL;

²Response after 6 mo of follow-up. ALT: Alanine aminotransferase; AST: Aspartate aminotransferase.

Table 4 Significance of baseline factors for sustained combined response to interferon-α therapy

Variable	CR	PR	NR	Mean decrease accuracy	Mean decrease Gini
ALT	2.242	0.860	2.611	1.363	42.806
Duration	0.536	0.599	0.251	0.507	36.340
HBV DNA	0.603	0.742	0.015	0.553	35.713
AST	1.045	-0.243	0.955	0.502	35.488
Genotype	1.101	1.083	3.095	1.269	30.462
Staging	0.737	-0.058	-0.147	0.205	29.400
Grading	-0.033	0.330	-0.035	-0.182	23.283
Age	-0.069	0.094	0.160	0.050	20.944
Gender	-0.125	0.478	-0.084	0.186	14.396

CR: Combined response; PR: Partial response; NR: No response; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; HBV: Hepatitis B virus.

Table 5 Optimal cut-off values by maximizing the Youden index and their accuracies for the sustained combined response score derived from whole study population and validated with leave-one-out cross-validation

	Value	95% CI
Total study population
Optimal cut-off	169
Sensitivity (%)	78.79	71.93-84.33
Specificity (%)	80.58	75.81-84.61
Positive predictive value (%)	68.42	61.50-74.61
Negative predictive value (%)	87.68	83.34-91.00
Positive likelihood ratio	4.06	3.19-5.16
Negative likelihood ratio	0.26	0.20-0.36
Odds ratio	15.25	9.65-24.68
Accuracy (%)	79.96	76.12-83.31
Youden index	0.594	0.5913-0.5961
AUC	0.797	0.773-0.812
Leave-one-out cross-validation
Optimal cut-off	169
Sensitivity (%)	78.18	71.28-83.80
Specificity (%)	79.94	75.11-84.02
Positive predictive value (%)	67.54	60.61-73.78
Negative predictive value (%)	87.28	82.89-90.67
Positive likelihood ratio	3.90	3.08-4.94
Negative likelihood ratio	0.27	0.20-0.37
Odds ratio	14.13	8.98-22.73
Accuracy (%)	79.32	75.45-82.73
Youden index	0.581	0.5787-0.5836
AUC	0.79	0.779-0.807

AUC: Area under the curve.