Gao YH, Meng QH, Zhang ZQ, Zhao P, Shang QH, Yuan Q, Li Y, Deng J, Li T, Liu XE, Zhuang H. On-treatment quantitative hepatitis B e antigen predicted response to nucleos(t)ide analogues in chronic hepatitis B. World J Hepatol 2016; 8(34): 1511-1520 [PMID: 28008342 DOI: 10.4254/wjh.v8.i34.1511]
Corresponding Author of This Article
Xue-En Liu, MD, Associate Professor, Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing 100191, China. xueenliu@bjmu.edu.cn
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Retrospective Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Hepatol. Dec 8, 2016; 8(34): 1511-1520 Published online Dec 8, 2016. doi: 10.4254/wjh.v8.i34.1511
Table 1 Baseline clinical characteristics of patients with chronic hepatitis B according to treatment response after 96-wk nucleos(t)ide analogues therapy
Parameters
Overall
VR (+)
VR (-)
P value
SC (+)
SC (-)
P value
n (%)
76
43 (56.6)
33 (43.4)
-
15 (19.7)
61 (80.3)
-
Gender, female/male
20/56
15/28
5/28
0.053
5/10
15/46
0.491
Age, yr
32.63 ± 9.69
32.3 ± 9.83
33.06 ± 9.63
0.738
31.87 ± 11.6
32.82 ± 9.26
0.735
HBsAg, lg IU/mL
3.95 ± 0.83
3.96 ± 0.68
3.94 ± 1.00
0.881
3.93 ± 0.60
3.96 ± 0.88
0.385
HBeAg, lg PEIU/mL
2.24 ± 1.31
2.18 ± 1.38
2.32 ± 1.22
0.679
2.36 ± 1.41
2.21 ± 1.29
0.527
anti-HBc, lg IU/mL
4.77 ± 0.46
4.82 ± 0.43
4.71 ± 0.50
0.311
4.85 ± 0.44
4.75 ± 0.47
0.464
ALT, U/L
213.73 ± 157.17
247.95 ± 150.58
169.13 ± 156.56
0.029
216.49 ± 153.18
213.05 ± 159.38
0.94
ALT strata, ≥/< 5ULN
31/45
25/18
6/27
< 0.001
9/6
22/39
0.091
HBV DNA, lg copies/mL
8.16 ± 1.34
8.06 ± 1.45
8.3 ± 1.19
0.608
8.55 ± 0.91
8.07 ± 1.41
0.324
Genotype, C/non-C
53/23
31/12
22/11
0.61
10/5
43/18
0.773
Table 2 Baseline and on-treatment parameters associated with 96-wk virological response and hepatitis B e antigen seroconversion in chronic hepatitis B patients received nucleos(t)ide analogues therapy
Factors
VR
SC
Univariate
Multivariate
Univariate
Multivariate
OR (95%CI)
P value
OR (95%CI)
P value
OR (95%CI)
P value
OR (95%CI)
P value
Baseline
Age
0.99 (0.95-1.04)
0.734
-
-
0.99 (0.93-1.05)
0.731
-
-
Sex, female/male
3 (0.96-9.38)
0.059
3.76 (1.09-13.01)
0.037
1.53 (0.45-5.20)
0.493
-
-
HBsAg (lg IU/mL)
1.04 (0.60-1.81)
0.879
-
-
0.96 (0.49-1.88)
0.904
-
-
HBeAg (lg PEIU/mL)
0.92 (0.65-1.31)
0.633
-
-
1.1 (0.70-1.72)
0.682
-
-
Anti-HBc (lg IU/mL)
1.68 (0.62-4.59)
0.308
-
-
1.6 (0.46-5.50)
0.459
-
-
HBV DNA (lg copies/mL)
0.87 (0.62-1.24)
0.451
-
-
1.38 (0.82-2.31)
0.221
-
-
ALT (U/L)
1.004 (1.000-1.007)
0.038
-
-
1 (0.99-1.01)
0.939
-
-
ALT strata, ≥/< 5ULN
6.25 (2.14-18.26)
< 0.001
7.09 (2.32-21.67)
< 0.001
2.66 (0.84-8.46)
0.098
-
-
Genotype, C/non-C
1.29 (0.48-3.46)
0.61
-
-
0.84 (0.25-2.80)
0.773
-
-
Week 12
HBsAg (lg IU/mL)
0.83 (0.45-1.53)
0.551
-
-
0.95 (0.47-1.92)
0.882
-
-
HBsAg decline (lg IU/mL)
1.43 (0.72-2.84)
0.301
-
-
1.04 (0.46-2.35)
0.919
-
-
HBeAg (lg PEIU/mL)
0.5 (0.33-0.76)
0.001
0.62 (0.40-0.95)
0.03
0.5 (0.30-0.85)
0.011
-
-
HBeAg decline (lg PEIU/mL)
3.04 (1.55-5.98)
0.001
2.58 (1.25-5.33)
0.01
2.47 (1.46-4.16)
< 0.001
2.47 (1.46-4.16)
0.001
Anti-HBc (lg IU/mL)
1.14 (0.49-2.64)
0.764
-
-
2.56 (0.83-7.93)
0.102
-
-
Anti-HBc decline (lg IU/mL)
1.43 (0.45-4.59)
0.546
-
-
0.3 (0.06-1.51)
0.145
-
-
ALT (U/L)
0.99 (0.98-1.01)
0.221
-
-
1 (0.98-1.02)
0.876
-
-
ALT decline (U/L)
1.004 (1.00-1.01)
0.03
-
-
1 (0.99-1.01)
0.918
-
-
HBV DNA (lg copies/mL)
0.57 (0.36-0.90)
0.016
-
-
0.72 (0.42-1.25)
0.249
-
-
HBV DNA decline (lg copies/mL)
1.36 (0.90-2.03)
0.141
-
-
2.11 (1.16-3.84)
0.015
-
-
Week 24
HBsAg (lg IU/mL)
0.61 (0.31-1.21)
0.155
-
-
0.84 (0.48-1.46)
0.535
-
-
HBsAg decline (lg IU/mL)
1.79 (0.94-3.42)
0.076
-
-
1.21 (0.62-2.37)
0.571
-
-
HBeAg (lg PEIU/mL)
0.39 (0.24-0.64)
< 0.001
0.45 (0.27-0.77)
0.003
0.28 (0.14-0.58)
< 0.001
0.37 (0.17-0.81)
0.013
HBeAg decline (lg PEIU/mL)
2.37 (1.41-3.99)
0.001
2.03 (1.10-3.74)
0.024
2.8 (1.64-4.78)
< 0.001
2.02 (1.17-3.49)
0.012
Anti-HBc (lg IU/mL)
0.73 (0.33-1.63)
0.448
-
-
1.29 (0.48-3.45)
0.608
-
-
Anti-HBc decline (lg IU/mL)
3.11 (0.99-3.79)
0.053
-
-
1.11 (0.31-3.99)
0.874
-
-
ALT (U/L)
0.99 (0.98-1.01)
0.477
-
-
0.99 (0.96-1.02)
0.516
-
-
ALT decline (U/L)
1.004 (1.00-1.01)
0.031
-
-
1 (0.99-1.01)
0.822
-
-
HBV DNA (lg copies/mL)
0.55 (0.37-0.80)
0.002
-
-
0.45 (0.23-0.86)
0.016
-
-
HBV DNA decline (lg copies/mL)
1.39 (1.02-1.88)
0.035
-
-
2.39 (1.39-4.11)
0.002
-
-
Table 3 Predictive value of hepatitis B e antigen titer as well as its declined value at week 12 and 24 for virological response after 96-wk nucleos(t)ide analogues therapy
Factors
ROC
Sensitivity (95%CI)
Specificity (95%CI)
PPV (95%CI)
NPV (95%CI)
AUROC (95%CI)
P value
Week 12
HBeAg < 0.8 lg PEIU/mL
0.733 (0.617-0.849)
0.001
0.63 (0.48-0.78)
0.81 (0.67-0.96)
0.82 (0.68-0.96)
0.62 (0.47-0.77)
HBeAg decline > 0.84 lg PEIU/mL
0.709 (0.590-0.827)
0.002
0.65 (0.50-0.80)
0.75 (0.59-0.91)
0.78 (0.64-0.92)
0.62 (0.46-0.78)
Combined the above
0.812 (0.687-0.936)
< 0.001
0.71 (0.54-0.89)
0.91 (0.78-1.00)
0.91 (0.78-1.00)
0.71 (0.54-0.89)
Week 24
HBeAg < 1.3 lg PEIU/mL
0.788 (0.683-0.892)
< 0.001
0.88 (0.78-0.98)
0.64 (0.46-0.81)
0.76 (0.63-0.88)
0.81 (0.65-0.97)
HBeAg decline > 1.6 lg PEIU/mL
0.736 (0.620-0.851)
< 0.001
0.55 (0.39-0.70)
0.94 (0.85-1.00)
0.92 (0.81-1.00)
0.62 (0.48-0.76)
Combined the above
0.923 (0.838-1.000)
< 0.001
0.85 (0.70-0.99)
1
1
0.83 (0.66-0.99)
Table 4 Predictive value of hepatitis B e antigen titer as well as its declined value at week 12 and 24 for hepatitis B e antigen seroconversion after 96-wk nucleos(t)ide analogues therapy
Factors
ROC
Sensitivity (95%CI)
Specificity (95%CI)
PPV (95%CI)
NPV (95%CI)
AUROC (95%CI)
P value
Week 12
HBeAg decline > 1.8 lg PEIU/mL
0.767 (0.623-0.911)
0.001
0.6 (0.32-0.88)
0.87 (0.78-0.96)
0.53 (0.26-0.79)
0.9 (0.82-0.98)
Week 24
HBeAg < -0.5 lg PEIU/mL
0.828 (0.712-0.944)
< 0.001
0.67 (0.40-0.94)
0.92 (0.84-0.99)
0.67 (0.40-0.94)
0.92 (0.84-0.99)
HBeAg decline > 2.2 lg PEIU/mL
0.814 (0.676-0.953)
< 0.001
0.73 (0.48-0.99)
0.9 (0.82-0.98)
0.65 (0.39-0.90)
0.93 (0.86-1.00)
Combined the above
0.928 (0.791-1.000)
< 0.001
0.88 (0.58-1.00)
0.98 (0.94-1.00)
0.88 (0.58-1.00)
0.98 (0.94-1.00)
Citation: Gao YH, Meng QH, Zhang ZQ, Zhao P, Shang QH, Yuan Q, Li Y, Deng J, Li T, Liu XE, Zhuang H. On-treatment quantitative hepatitis B e antigen predicted response to nucleos(t)ide analogues in chronic hepatitis B. World J Hepatol 2016; 8(34): 1511-1520