Table 1 Characteristics of the included patients
Variable
|
anti-HBc positive, n (%)
|
anti-HBc negative, n (%)
|
P value
|
High-titer anti-HBc, n (%)
|
Low-titer anti-HBc, n (%)
|
P value
|
N
|
125
|
202
|
|
39
|
86
|
|
Age (years)
|
61.32±8.01
|
60.61±7.55
|
0.419
|
59.44±7.469
|
62.17±8.147
|
0.077
|
Gender
|
|
|
0.027a
|
|
|
0.154
|
Male
|
85(68)
|
112(55.4)
|
|
23(59.0)
|
62(72.1)
|
|
Female
|
40(32)
|
90(44.6)
|
|
16(41.0)
|
24(27.9)
|
|
Tumor site
|
|
0.72
|
|
|
1
|
Colon
|
44(35.2)
|
67(33.2)
|
|
14(35.9)
|
30(34.9)
|
|
Rectum
|
81(64.8)
|
135(66.8)
|
|
25(64.1)
|
56(65.1)
|
|
T stage
|
|
|
0.458
|
|
|
0.523
|
T1
|
1(0.8)
|
1(0.5)
|
|
0(0)
|
1(1.2)
|
|
T2
|
4(3.2)
|
9(4.5)
|
|
0(0)
|
4(4.7)
|
|
T3
|
120(96)
|
188(93.1)
|
|
39(100)
|
81(94.2)
|
|
T4
|
0(0)
|
4(2)
|
|
0(0)
|
0(0)
|
|
N stage
|
|
|
0.288
|
|
|
0.202
|
N0
|
65(52)
|
121(59.9)
|
|
20(51.3)
|
45(52.3)
|
|
N1
|
41(32.8)
|
60(29.7)
|
|
10(25.6)
|
31(36)
|
|
N2
|
19(15.2)
|
21(10.4)
|
|
9(23.1)
|
10(11.6)
|
|
TNM stage
|
|
0.167
|
|
|
1
|
II
|
65(52)
|
122(60.4)
|
|
20(51.3)
|
45(52.3)
|
|
III
|
60(48)
|
80(39.6)
|
|
19(48.7)
|
41(47.7)
|
|
Histological types
|
|
0.447
|
|
|
0.092
|
Adenocarcinoma
|
107(85.6)
|
166(82.2)
|
|
31(79.5)
|
78(90.7)
|
|
Mucinous adenocarcinoma
|
18(14.4)
|
36(17.8)
|
|
8(20.5)
|
8(9.3)
|
|
Differentiation
|
|
0.652
|
|
|
0.253
|
Well
|
6(4.8)
|
10(5)
|
|
1(2.6)
|
5(5.8)
|
|
Moderately
|
87(69.6)
|
152(75.2)
|
|
29(74.4)
|
58(67.4)
|
|
Poorly
|
19(15.2)
|
22(10.9)
|
|
3(7.7)
|
16(18.6)
|
|
Not Available
|
13(10.4)
|
18(8.9)
|
|
6(15.4)
|
7(8.1)
|
|
Neoadjuvant radiotherapy
|
1
|
|
|
0.501
|
Yes
|
10(8)
|
15(7.4)
|
|
4(10.3)
|
6(7)
|
|
No
|
115(92)
|
187(92.6)
|
|
35(89.7)
|
80(93)
|
|
Retrieved LN
|
|
0.173
|
|
|
0.663
|
<12
|
32(25.6)
|
67(33.2)
|
|
11(28.2)
|
21(24.4)
|
|
≥12
|
93(74.4)
|
135(66.8)
|
|
28(71.8)
|
65(75.6)
|
|
CEA(ng/ml)
|
|
0.909
|
|
|
0.332
|
≤5
|
70(56)
|
111(55)
|
|
19(48.7)
|
51(59.3)
|
|
>5
|
55(44)
|
91(45)
|
|
20(51.3)
|
35(40.7)
|
|
CA19-9(U/ml)
|
|
0.492
|
|
|
0.27
|
≤37
|
107(85.6)
|
179(88.6)
|
|
31(79.5)
|
76(88.4)
|
|
>37
|
18(14.4)
|
23(11.4)
|
|
8(20.5)
|
10(11.6)
|
|
ALT(U/L)
|
17.65±9.50
|
19.86±15.86
|
0.377
|
18.41±9.85
|
17.31±9.37
|
0.434
|
AST(U/L)
|
18.42±6.70
|
19.01±9.60
|
0.892
|
18.10±6.12
|
18.56±6.98
|
0.94
|
ALP(U/L)
|
83.90±21.67
|
84.66±24.98
|
0.86
|
82.56±20.30
|
84.51±22.34
|
0.643
|
PLT(1´109/L)
|
252.90±67.98
|
250.91±77.43
|
0.622
|
261.97±67.56
|
84.51±22.34
|
0.317[a]
|
Abbreviations: anti-HBc, antibodies to hepatitis B core antigen; CA19-9, cancer antigen 19-9; CEA, carcinoembryonic antigen; ALT, alanine transaminase; AST, aspartate transaminase; ALP, alkaline phosphatase; PLT, platelets; LN, lymph node.
a Significant at P < 0.05.
Table 2 Risk factors for overall survival, time to progress and hepatic metastasis-free survival in the CRC patients undergoing curative surgical resection
Variable
|
Overall Survival
|
Time to Progress
|
Hepatic Metastasis-Free Survival
|
Univariate analysis
|
Multivariate analysis
|
Univariate analysis
|
Multivariate analysis
|
Univariate analysis
|
Multivariate analysis
|
HR
|
95%CI
|
P-value
|
HR
|
95%CI
|
P-value
|
HR
|
95%CI
|
P-value
|
HR
|
95%CI
|
P-value
|
HR
|
95%CI
|
P-value
|
HR
|
95%CI
|
P-value
|
Anti-HBc
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Positive
|
1.219
|
0.771-1.926
|
0.397
|
|
|
|
1.175
|
0.757-1.823
|
0.473
|
|
|
|
0.879
|
0.412-1.878
|
0.74
|
|
|
|
Negative
|
Reference
|
|
|
|
|
|
Reference
|
|
|
|
|
|
Reference
|
|
|
|
|
|
FIB-4
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
≥1.45
|
1.523
|
0.944-2.459
|
0.085
|
|
|
|
1.032
|
0.629-1.693
|
0.9
|
|
|
|
1.108
|
0.493-2.489
|
0.804
|
|
|
|
<1.45
|
Reference
|
|
|
|
|
|
Reference
|
|
|
|
|
|
Reference
|
|
|
|
|
|
NLR
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
≥3.4
|
1.982
|
1.207-3.254
|
0.007[a]
|
1.838
|
1.119-3.02
|
0.016a
|
1.866
|
1.146-3.04
|
0.012a
|
1.783
|
1.094-2.906
|
0.02a
|
2.367
|
1.108-5.059
|
0.026a
|
2.231
|
1.043-4.773
|
0.039a
|
<3.4
|
Reference
|
|
|
|
|
|
Reference
|
|
|
|
|
|
Reference
|
|
|
|
|
|
Anti-HBs
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Positive
|
1.122
|
0.695-1.81
|
0.638
|
|
|
|
1.037
|
0.652-1.648
|
0.879
|
|
|
|
0.965
|
0.442-2.107
|
0.929
|
|
|
|
Negative
|
Reference
|
|
|
|
|
|
Reference
|
|
|
|
|
|
Reference
|
|
|
|
|
|
HBsAg
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Positive
|
2.48
|
0.905-6.793
|
0.077
|
|
|
|
2.195
|
0.803-5.999
|
0.125
|
|
|
|
2.927
|
0.697-12.295
|
0.143
|
|
|
|
Negative
|
Reference
|
|
|
|
|
|
Reference
|
|
|
|
|
|
Reference
|
|
|
|
|
|
Retrieved LN
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
≥12
|
0.715
|
0.451-1.132
|
0.153
|
|
|
|
0.789
|
0.506-1.232
|
0.297
|
|
|
|
1.565
|
0.671-3.647
|
0.3
|
|
|
|
<12
|
Reference
|
|
|
|
|
|
Reference
|
|
|
|
|
|
Reference
|
|
|
|
|
|
Neoadjuvant radiotherapy
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Yes
|
0.808
|
0.326-2
|
0.644
|
|
|
|
1.213
|
0.585-2.514
|
0.604
|
|
|
|
1.285
|
0.39-4.236
|
0.681
|
|
|
|
No
|
Reference
|
|
|
|
|
|
Reference
|
|
|
|
|
|
Reference
|
|
|
|
|
|
CEA(ng/ml)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
>5
|
1.272
|
0.811-1.995
|
0.294
|
|
|
|
1.151
|
0.748-1.773
|
0.523
|
|
|
|
1.769
|
0.859-3.642
|
0.122
|
|
|
|
≤5
|
Reference
|
|
|
|
|
|
Reference
|
|
|
|
|
|
Reference
|
|
|
|
|
|
CA19-9(U/ml)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
>37
|
2.352
|
1.371-4.035
|
0.002a
|
2.111
|
1.229-3.624
|
0.007a
|
1.548
|
0.871-2.751
|
0.136
|
|
|
|
1.157
|
0.404-3.315
|
0.787
|
|
|
|
≤37
|
Reference
|
|
|
|
|
|
Reference
|
|
|
|
|
|
Reference
|
|
|
|
|
|
TNM stage
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Ⅲ
|
3.609
|
2.223-5.859
|
<0.001a
|
3.511
|
2.162-5.702
|
<0.001a
|
3.628
|
2.279-5.775
|
<0.001a
|
3.579
|
2.247-5.699
|
<0.001a
|
3.084
|
1.442-6.597
|
0.004a
|
2.985
|
1.394-6.391
|
0.005a
|
Ⅱ
|
Reference
|
|
|
|
|
|
Reference
|
|
|
|
|
|
Reference
|
|
|
|
|
|
Gender
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Male
|
1.035
|
0.651-1.644
|
0.885
|
|
|
|
1.16
|
0.741-1.815
|
0.517
|
|
|
|
1.771
|
0.789-3.979
|
0.166
|
|
|
|
Female
|
Reference
|
|
|
|
|
|
Reference
|
|
|
|
|
|
Reference
|
|
|
|
|
|
Age (years)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
≥61
|
0.996
|
0.635-1.561
|
0.985
|
|
|
|
0.899
|
0.584-1.383
|
0.628
|
|
|
|
0.652
|
0.314-1.354
|
0.252
|
|
|
|
<61
|
Reference
|
|
|
|
|
|
Reference
|
|
|
|
|
Reference
|
|
|
|
|
|
Abbreviations: anti-HBc, antibodies to hepatitis B core antigen; anti-HBs, antibodies to hepatitis B surface antigen; HBsAg, hepatitis B surface antigen; NLR, neutrophil to lymphocyte ratio; CA19-9, cancer antigen 19-9; CEA, carcinoembryonic antigen; ALT, alanine transaminase; AST, aspartate transaminase; ALP, alkaline phosphatase; PLT, platelets.
a Significant at P < 0.05.
Table 3 Risk factors for overall survival, time to progress and hepatic metastasis-free survival in the anti-HBc positive CRC patients undergoing curative surgical resection
Variable
|
Overall Survival
|
Time to Progress
|
Hepatic Metastasis-Free Survival
|
Univariate analysis
|
Multivariate analysis
|
Univariate analysis
|
Multivariate analysis
|
Univariate analysis
|
Multivariate analysis
|
HR
|
95%CI
|
P-value
|
HR
|
95%CI
|
P-value
|
HR
|
95%CI
|
P-value
|
HR
|
95%CI
|
P-value
|
HR
|
95%CI
|
P-value
|
HR
|
95%CI
|
P-value
|
Anti-HBc
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
≥8.8
|
3.18
|
1.564-6.463
|
<0.001a
|
3.51
|
1.718-7.17
|
<0.001a
|
4.889
|
2.397-9.97
|
<0.001a
|
5.747
|
2.789-11.842
|
<0.001a
|
3.754
|
1.054-13.369
|
0.04a
|
3.754
|
1.054-13.369
|
0.04a
|
<8.8
|
Reference
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
FIB-4
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
≥1.45
|
1.48
|
0.718-3.05
|
0.288
|
|
|
|
1.018
|
0.484-2.139
|
0.963
|
|
|
|
0.983
|
0.254-3.806
|
0.981
|
|
|
|
<1.45
|
Reference
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
NLR
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
≥3.4
|
1.418
|
0.634-3.171
|
0.395
|
|
|
|
1.41
|
0.635-3.129
|
0.398
|
|
|
|
1.753
|
0.453-6.783
|
0.416
|
|
|
|
<3.4
|
Reference
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Anti-HBs
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Positive
|
1.093
|
0.515-2.321
|
0.817
|
|
|
|
0.873
|
0.429-1.774
|
0.706
|
|
|
|
0.756
|
0.213-2.68
|
0.665
|
|
|
|
Negative
|
Reference
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
HBsAg
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Positive
|
2.296
|
0.802-6.572
|
0.121
|
|
|
|
2.154
|
0.755-6.141
|
0.151
|
|
|
|
3.877
|
0.821-18.311
|
0.087
|
|
|
|
Negative
|
Reference
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Retrieved LN
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
≥12
|
0.983
|
0.453-2.135
|
0.966
|
|
|
|
0.94
|
0.447-1.975
|
0.869
|
|
|
|
1.66
|
0.352-7.82
|
0.521
|
|
|
|
<12
|
Reference
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Neoadjuvant radiotherapy
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Yes
|
0.735
|
0.175-3.083
|
0.674
|
|
|
|
1.544
|
0.542-4.395
|
0.416
|
|
|
|
0.043
|
0-729.474
|
0.527
|
|
|
|
No
|
Reference
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
CEA(ng/ml)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
>5
|
1.286
|
0.636-2.602
|
0.484
|
|
|
|
0.911
|
0.453-1.831
|
0.793
|
|
|
|
3.352
|
0.867-12.965
|
0.08
|
|
|
|
≤5
|
Reference
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
CA19-9(U/ml)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
>37
|
1.683
|
0.725-3.907
|
0.226
|
|
|
|
1.282
|
0.529-3.106
|
0.582
|
|
|
|
0.634
|
0.08-5.008
|
0.666
|
|
|
|
≤37
|
Reference
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
TNM stage
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Ⅲ
|
2.731
|
1.285-5.802
|
0.01a
|
3.038
|
1.423-6.484
|
<0.001a
|
3.038
|
1.444-6.39
|
<0.001a
|
3.722
|
1.752-7.908
|
<0.001a
|
1.921
|
0.541-6.822
|
0.312
|
|
|
|
Ⅱ
|
Reference
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Gender
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Male
|
1.211
|
0.542-2.709
|
0.64
|
|
|
|
0.853
|
0.414-1.759
|
0.667
|
|
|
|
0.966
|
0.25-3.737
|
0.96
|
|
|
|
Female
|
Reference
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Age (years)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
≥61
|
1.124
|
0.554-2.28
|
0.747
|
|
|
|
0.922
|
0.466-1.825
|
0.816
|
|
|
|
0.896
|
0.259-3.094
|
0.862
|
|
|
|
<61
|
Reference
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Abbreviations: anti-HBc, antibodies to hepatitis B core antigen; anti-HBs, antibodies to hepatitis B surface antigen; HBsAg, hepatitis B surface antigen; NLR, neutrophil to lymphocyte ratio; CA19-9, cancer antigen 19-9; CEA, carcinoembryonic antigen; ALT, alanine transaminase; AST, aspartate transaminase; ALP, alkaline phosphatase; PLT, platelets.
a Significant at P < 0.05.