01.12.2017 | Research article | Ausgabe 1/2017 Open Access

Hepatitis B virus infection and active replication promote the formation of vascular invasion in hepatocellular carcinoma
- Zeitschrift:
- BMC Cancer > Ausgabe 1/2017
Background
Methods
Study population
Diagnostic criteria of vascular invasion
Statistical analysis
Results
Univariate analysis of viral and tumor factors predicting vascular invasion in HCC
Parameters
|
Vascular invasion
|
P
|
MVI
|
P
|
PVTT
|
P
|
|||
---|---|---|---|---|---|---|---|---|---|
yes
|
no
|
yes
|
no
|
yes
|
no
|
||||
Patient demographics
|
|||||||||
Age
|
|||||||||
> 50 years
|
153
|
125
|
0.006*
|
149
|
129
|
0.017*
|
53
|
225
|
0.053
|
< = 50 years
|
140
|
68
|
134
|
74
|
55
|
153
|
|||
Gender
|
|||||||||
Male
|
255
|
167
|
0.873
|
245
|
177
|
0.842
|
99
|
323
|
0.092
|
Female
|
38
|
26
|
38
|
26
|
9
|
55
|
|||
Preoperative laboratory test
|
|||||||||
Total bilirubin
|
|||||||||
> 20 μmol/l
|
48
|
32
|
0.954
|
48
|
32
|
0.725
|
16
|
64
|
0.601
|
< = 20 umol/l
|
245
|
161
|
235
|
171
|
92
|
314
|
|||
ALT
|
|||||||||
> 42 U/l
|
128
|
83
|
0.882
|
122
|
89
|
0.872
|
49
|
162
|
0.642
|
< = 42 U/l
|
165
|
110
|
161
|
114
|
59
|
216
|
|||
AST,
|
|||||||||
> 37 U/l
|
157
|
114
|
0.234
|
152
|
119
|
0.282
|
62
|
209
|
0.696
|
< = 37 U/l
|
136
|
79
|
131
|
84
|
46
|
169
|
|||
Albumin
|
|||||||||
> 40 g/l
|
193
|
100
|
0.734
|
188
|
135
|
0.987
|
67
|
256
|
0.270
|
< = 40 g/l
|
130
|
63
|
95
|
68
|
41
|
122
|
|||
DCP
|
|||||||||
> 100 mAU/ml
|
250
|
147
|
0.011*
|
241
|
156
|
0.019*
|
102
|
295
|
<0.001*
|
< = 100 mAU/ml
|
43
|
46
|
42
|
47
|
6
|
83
|
|||
Alpha-fetoprotein
|
|||||||||
> 20 ng/ml
|
226
|
102
|
<0.001*
|
219
|
109
|
<0.001*
|
85
|
243
|
0.005*
|
< = 20 ng/ml
|
67
|
91
|
64
|
94
|
23
|
135
|
|||
Tumor characteristics
|
|||||||||
Diameter
|
|||||||||
> 3 cm
|
247
|
138
|
0.001*
|
238
|
147
|
0.002*
|
105
|
280
|
<0.001*
|
< = 3 cm
|
46
|
55
|
45
|
56
|
3
|
98
|
|||
Number of lesions
|
|||||||||
Multiple
|
43
|
15
|
0.022*
|
41
|
17
|
0.040*
|
20
|
38
|
0.017*
|
Single
|
250
|
178
|
242
|
186
|
88
|
340
|
|||
Encapsulation
|
|||||||||
Incomplete/absent
|
259
|
145
|
<0.001*
|
250
|
154
|
<0.001*
|
101
|
303
|
0.001*
|
Complete
|
34
|
48
|
33
|
49
|
7
|
75
|
|||
Edmonson grading
|
|||||||||
Grades III/IV
|
277
|
151
|
<0.001*
|
267
|
161
|
<0.001*
|
101
|
327
|
0.047*
|
Grades I/II
|
16
|
42
|
16
|
42
|
7
|
51
|
|||
Virus-related factors
|
|||||||||
Seral HBsAg
|
|||||||||
Positive
|
269
|
161
|
0.005*
|
260
|
170
|
0.006*
|
104
|
326
|
0.003*
|
Negative
|
24
|
32
|
23
|
33
|
4
|
52
|
|||
Seral HBeAg
|
|||||||||
Positive
|
93
|
32
|
<0.001*
|
88
|
37
|
0.002*
|
39
|
86
|
0.005*
|
Negative
|
200
|
160
|
195
|
165
|
69
|
291
|
|||
HBV DNA load
|
|||||||||
Detectable (> 50 IU/ml)
|
203
|
94
|
<0.001*
|
197
|
100
|
<0.001*
|
76
|
221
|
0.025*
|
Undetectable (<=50 IU/ml)
|
90
|
99
|
86
|
103
|
32
|
157
|
|||
High (> 2000 IU/ml)
|
110
|
62
|
0.222
|
106
|
66
|
0.261
|
39
|
133
|
0.859
|
Low (<= 2000 IU/ml)
|
183
|
131
|
177
|
137
|
69
|
39
|
|||
Presence of cirrhosis
|
|||||||||
Yes
|
101
|
52
|
0.08
|
96
|
57
|
0.171
|
49
|
104
|
<0.001*
|
No
|
192
|
141
|
187
|
146
|
59
|
274
|
|||
Anti-virus treatment
|
|||||||||
Yes
|
64
|
66
|
0.003*
|
63
|
67
|
0.008*
|
19
|
111
|
0.015*
|
No
|
229
|
127
|
220
|
136
|
89
|
267
|
Multivariate analysis of viral and tumor factors predicting vascular invasion in HCC
Variables
|
Odds ratio
|
95% CI
|
P value
|
---|---|---|---|
Risk of vascular invasion
|
|||
Age (>50 years vs < =50 years)
|
0.68
|
0.44–1.04
|
0.078
|
Alpha-fetoprotein (> 20 ng/ml vs < = 20 ng/ml)
|
2.51
|
1.59–3.96
|
<0.01*
|
Tumor number (Multiple vs Single)
|
2.18
|
1.04–4.55
|
0.038*
|
Diameter (> 3 cm vs < = 3 cm)
|
1.73
|
1.04–2.88
|
0.035*
|
Edmonson grading (Grades III/IV vs Grades I/II)
|
2.48
|
1.21–5.05
|
0.013*
|
Tumor capsule (Incomplete/absent vs Complete)
|
2.17
|
1.25–3.77
|
0.006*
|
Seral HBeAg (Positive vs Negative)
|
1.83
|
1.10–3.03
|
0.019*
|
Seral HBV DNA load (> 50 IU/ml vs < = 50 IU/ml)
|
1.68
|
1.06–2.65
|
0.027*
|
Risk of microscopic vascular invasion
|
|||
Alpha-fetoprotein (> 20 ng/ml vs < = 20 ng/ml)
|
2.59
|
1.65–4.05
|
<0.01*
|
Tumor number (Multiple vs Single)
|
2.21
|
1.09–4.51
|
0.028*
|
Diameter (> 3 cm vs < = 3 cm)
|
1.58
|
0.96–2.61
|
0.074
|
Edmonson grading (Grades III/IV vs Grades I/II)
|
2.24
|
1.11–4.54
|
0.024*
|
Tumor capsule (Incomplete/absent vs Complete)
|
2.04
|
1.18–3.51
|
0.011*
|
Seral HBeAg (Positive vs Negative)
|
1.59
|
0.98–2.57
|
0.059
|
Seral HBV DNA load (> 50 IU/ml vs < = 50 IU/ml)
|
1.76
|
1.12–2.76
|
0.013*
|
Risk of portal vein tumor thrombus
|
|||
DCP (>100 mAU/ml vs < = 100 mAU/ml)
|
2.90
|
1.17–7.12
|
0.022*
|
Tumor diameter (>3 cm vs < =3 cm)
|
8.86
|
2.67–29.39
|
<0.01*
|
Tumor capsule (Incomplete/absence vs Complete)
|
3.59
|
1.56–8.25
|
0.003*
|
Seral HBeAg (Positive vs Negative)
|
1.67
|
1.01–2.75
|
0.046*
|
Anti-virus treatment (Yes vs No)
|
0.59
|
0.33–1.05
|
0.075
|
Correlation between the features of vascular invasion and HBV-related factors
HBV-related factors
|
Severity of MVI
|
P
|
Classification of PVTT
|
P
|
||||
---|---|---|---|---|---|---|---|---|
None (%)
|
Mild (%)
|
Severe (%)
|
None (%)
|
I/II (%)
|
III/IV (%)
|
|||
Seral HBsAg
|
||||||||
Positive
|
171 (83.8)
|
127 (89.4)
|
131 (94.9)
|
0.005*
|
326 (86.2)
|
74 (94.9)
|
30 (100)
|
0.007*
|
Negative
|
33 (16.2)
|
15 (10.6)
|
7 (5.1)
|
52 (13.8)
|
4 (5.1)
|
0 (0)
|
||
Seral HBeAg
|
||||||||
Positive
|
37 (21.6)
|
38 (29.9)
|
48 (36.6)
|
0.016*
|
84 (25.8)
|
30 (40.5)
|
9 (30)
|
0.04*
|
Negative
|
134 (78.4)
|
89 (60.1)
|
83 (63.4)
|
242 (74.2)
|
44 (59.5)
|
21 (70)
|
||
Seral HBV DNA load
|
||||||||
> 50 IU/ml
|
99 (57.9)
|
90 (70.9)
|
106 (80.9)
|
<0.001*
|
219 (67.2)
|
52 (70.3)
|
24 (80)
|
0.355
|
< = 50 IU/ml)
|
72 (42.1)
|
37 (29.1)
|
25 (19.1)
|
107 (32.8)
|
22 (29.7)
|
6 (20)
|
||
Presence of cirrhosis
|
||||||||
Yes
|
52 (30.4)
|
48 (37.8)
|
44 (33.6)
|
0.418
|
96 (29.4)
|
32 (43.2)
|
16 (53.3)
|
0.005*
|
No
|
119 (69.6)
|
79 (62.2)
|
87 (66.4)
|
230 (60.6)
|
42 (56.8)
|
14 (46.7)
|
||
Antivirus treatment
|
||||||||
Yes
|
66 (38.6)
|
36 (28.3)
|
26 (19.8)
|
0.002*
|
109 (33.4)
|
15 (20.3)
|
4 (13.3)
|
0.009*
|
No
|
105 (61.4)
|
91 (61.7)
|
105 (80.2)
|
217 (66.6)
|
59 (79.7)
|
26 (86.7)
|
Variable
|
HBV DNA load, log
10 IU/ml (mean ± SD)
|
P
|
---|---|---|
Vascular invasion
|
||
Yes
|
3.28 ± 0.14
|
0.008*
|
No
|
2.64 ± 0.20
|
|
Microvascular invasion
|
||
Yes
|
3.29 ± 0.14
|
0.008*
|
No
|
2.66 ± 0.19
|
|
Portal vein tumor thrombus
|
||
Yes
|
3.13 ± 0.22
|
0.694
|
No
|
3.02 ± 0.14
|