Patient characteristics
There were no statistically significant differences between the PVT group and the non-PVT group: age, sex, etiological factors, diabetes, hypertension, spleen surgery history, ascites, Child-Pugh score and grades (P > 0.05). There were significant differences in the history of esophagogastric vein ligation or embolization, gastrointestinal bleeding, and hepatic encephalopathy (P < 0.05). (Table.1)
Table.1 Patient characteristics
|
PVT(n=52)
|
non-PVT(n=71)
|
z/t/x²
|
P-value
|
Gender,male/female
|
38/14
|
46/25
|
0.952
|
0.329
|
Age in years
|
56.98±9.26
|
55.42±9.07
|
0.334
|
0.739
|
Etiology
HBV
HCV
others
|
30(57.7%)
2 (3.8%)
20(38.5%)
|
36 (50.7%)
6 (8.5%)
29(40.8%)
|
8.79
|
0.118
|
Diabetes mellitus
|
10(19.2%)
|
11(15.5%)
|
0.296
|
0586
|
Hypertension
|
6(11.5%)
|
11(15.5%)
|
0.394
|
0.530
|
Splenectomy/embolization
|
9(17.3%)
|
6(8.5%)
|
2.199
|
0.138
|
Esophagogastric vein
ligation/embolization
|
19(36.5%)
|
13(18.3%)
|
5.182
|
0.023
|
Gastrointestinal bleeding previous
complicated with
without
|
28(53.8%)a
3(5.8%)a
21(40.4%)a
|
23(32.4%)b
2(2.8%)a
46(64.8%)b
|
7.295
|
0.022
|
Complicated with HE
|
2(3.8%)
|
11(15.5%)
|
0.308
|
0.038
|
Complicated with ascites
|
41(78.8%)
|
52(73.2%)
|
0.512
|
0.474
|
Blood transfusion
|
13(25%)
|
16(22.5%)
|
0.101
|
0.750
|
Child-Pugh score
|
7(6,8)
|
8(6,9.5)
|
-1.239
|
0.215
|
Child-Pugh grades
A
B
C
|
16(30.8%)
28(53.8%)
8(15.4%)
|
20(28.2%)
33(46.5%)
18(25.4%)
|
-0.936
|
0.349
|
HBV, Hepatitis B Virus; HCV, Hepatitis C Virus ; HE, hepatic encephalopathy.
Laboratory and examination data
ALT, AST, DBIL, APTT, TT, and TNF-α in the PVT group were significantly lower than those in the non-PVT group (P < 0.05). D-D, K, and the diameter of the portal vein in the PVT group were significantly higher than those in the non-PVT group (P < 0.05). There was no significant difference in IL-6, PC, R, Angle, MA, and CI between the two groups (P > 0.05). (Table.2)
Table.2 Comparison of laboratory data between PVT and non-PVT
|
PVT(n=52)
|
non-PVT (n=71)
|
z/t
|
P-value
|
WBC(×109 /L)
|
3.02(2.17,5.22)
|
3.58(2.71,5.11)
|
-1.567
|
0.117
|
RBC(×1012/L)
|
3.52±0.72
|
3.54±0.74
|
-0.245
|
0.807
|
HGB(g/L)
|
105.50(83.5,121)
|
110(93,127.5)
|
-1.267
|
0.205
|
PLT(×109/L)
|
62(49.5,98.5)
|
70(53.5,111.5)
|
-1.262
|
0.207
|
ALT(U/L)
|
22(15.1,32.85)
|
26.9(17.7,46.45)
|
-2.148
|
0.032
|
AST(U/L)
|
30.2(24.8,46.1)
|
42.6(29.15,72.55)
|
-3.292
|
0.001
|
γ-GT(U/L)
|
37.25(19.95,64.15)
|
43.4(25.7,105.15)
|
-1.487
|
0.137
|
ALP(U/L)
|
93.55(78.4,134.75)
|
100.5(83.6,141.25)
|
-0.771
|
0.441
|
ALB(g/L)
|
32.37±4.83
|
31.86±7.42
|
0.429
|
0.668
|
TBIL(umol/L)
|
21.95(14.65,35.85)
|
27.9(16.7,45.1)
|
-1.684
|
0.092
|
DBIL(umol/L)
|
5.25(3.8,9.8)
|
7.6(5.1,16)
|
-2.309
|
0.021
|
Scr(mmol/L)
|
62.65(49.9,75.15)
|
61.7(55.25,71.15)
|
-0.422
|
0.673
|
Na+(mmol/L)
|
139.25(136.3,142.35)
|
140.5(137,142.75)
|
-1.045
|
0.296
|
PT (S)
|
14.63±1.74
|
15.28±2.55
|
-1.574
|
0.118
|
APTT(S)
|
27.55(25.3,29.25)
|
29.5(27.2,32.85)
|
-3.208
|
0.001
|
TT(S)
|
18.2(17.1,19.1)
|
18.8(17.85,19.75)
|
-2.540
|
0.011
|
PTA(%)
|
70.06±13.84
|
68.37±17.99
|
0.566
|
0.572
|
INR
|
1.22(1.14,1.35)
|
1.29(1.16,1.4)
|
-1.291
|
0.197
|
FBG(g/L)
|
1.87(1.59,2.73)
|
1.83(1.59,2.49)
|
-0.468
|
0.639
|
D-D(ug/mL)
|
3.14(1.58,7.8)
|
1.89(0.71,3.92)
|
-2.734
|
0.006
|
CRP(mg/L)
|
10.68(2.45,23.24)
|
4.92(2.14,15.38)
|
-0.751
|
0.453
|
IL-6(pg/mL)
|
122.85(66.24,136.15)
|
117.90(61.71,197.50)
|
-0.607
|
0.544
|
TNF-α(pg/ml)
|
106.65(47.78,133.65)
|
137.50(55.65,207.60)
|
-3.259
|
0.001
|
PC(ug/ml)
|
66.77(32.57,78.76)
|
65.16(54.66,152.8)
|
-1.582
|
0.114
|
R(min)
|
5.20(4.40,6.35)
|
5.50(4.55,6.15)
|
-0.305
|
0.761
|
K(min)
|
3.57(2.15,5.60)
|
2.60(2.00,3.62)
|
-2.156
|
0.031
|
MA(min)
|
44.55(36.75,57.25)
|
48.90(39.80,56.35)
|
-1.037
|
0.300
|
CI
|
-3.20(-6.55,-0.15)
|
-1.90(-3.95,-0.20)
|
-1.551
|
0.121
|
DPV (mm)
|
16.00(1.40,2.05)
|
1.50(1.30,1.60)
|
-3.09
|
0.002
|
a, b two different letters, indicates differences between the two subgroups; WBC, white blood cell count; RBC, red blood cell count; HGB, hemoglobin; PLT, platelet ; ALT ,alanine aminotransferase; AST, aspartate aminotransferase; γ-GT, Glutamyl transpeptidase; ALP, alkaline phosphatase; ALB, albumin; TBIL, total bilirubin ; DBIL, direct bilirubin; Scr, serum creatinine; PT, prothrombin time; APTT, activate partial thromboplastin time; PTA , Prothrombin activity; INR, International normalized ratio; FBG, Fibrinogen; D-D, D-Dimer; CRP , C-reactive protein; PC, protein C; CRP, reaction time; K, K-time; MA, Maximum amplitude; CI, Coagulation index; DPV, the diameter of the portal vein.
Binary logistic and ROC curve analysis
Considering the collinearity and clinical significance, previous gastrointestinal bleeding history, APTT, D-D, TNF- α,IL-6, K, the diameter of the portal vein and the history of splenectomy or embolism were analyzed by Binary logistic regression analysis (LR stepwise forward method). Finally, the factors related to the formation of PVT included TNF-α (OR=0.9881,95%CI=0.971,0.990,P<0.001) ,K(OR=1.28,95%=1.053,1.569,P=0.014) ,APTT (OR=0.753,95%CI=0.656,0.865,P<0.001) , diameter of portal vein (OR=1.310,95%CI=1.108,1.549,P=0.002)and the history of splenectomy or embolism (OR=7.565,95%CI=1.514,37.799,P=0.014). (Table. 3).
Then those related factors were analyzed by the ROC curve.The cutoff value for 1/TNF-α was 0.0067, with a sensitivity of 1 and a specificity of 0.451;K was 3.75min, with a sensitivity of 0.481 and a specificity of 0.831;1/APTT was 0.034, with a sensitivity of 0.808 and a specificity of 0.507;and the diameter of the portal vein was 17.35mm, with a sensitivity of 0.404 and a specificity of 0.901, respectively. The risk of PVT in patients with a history of splenectomy or embolization was 5-fold higher than the patients without. Receiver operating characteristic curve analysis identified the AUC for TNF-α, K, APTT, the diameter of portal vein and history of splenectomy or embolization as 0.672, 0.614, 0.670 , 0.663, and 0.544 respectively (Table. 3)(Fig .2). When they combined, the area under the ROC curve was 0.872 and the cut-off was 0.429 with a sensitivity of 0.827 and a specificity of 0.789.
Table. 3 Cut-off value of factors related to PVT formation and area under ROC curve
|
β
|
P
|
OR
|
95%CI
|
Cut-off
|
SE
|
SP
|
AUC
|
DPV
(mm)
|
0.270
|
0.002
|
1.310
|
(1.108,1.549)
|
17.35
|
0.404
|
0.901
|
0.663
|
APTT
(s)
|
-0.283
|
<0.001
|
0.753
|
(0.656,0.865)
|
29.41
|
0.808
|
0.507
|
0.670
|
TNFα
(pg/mL)
|
-0.020
|
<0.001
|
0.981
|
(0.971,0.990)
|
149.25
|
1.000
|
0.451
|
0.672
|
K(min)
|
0.23
|
0.251
|
1.285
|
(1.053,1.569)
|
3.750
|
0.481
|
0.831
|
0.614
|
|
β
|
P
|
OR
|
95%CI
|
AUC
|
splenectomy or embolization
|
2.024
|
0.014
|
77.565
|
(1.514,37.799)
|
0.544
|
|
β
|
P
|
OR
|
95%CI
|
Cut-off
|
SE
|
SP
|
AUC
|
ALL
|
4.610
|
0.035
|
100.45
|
|
0.429
|
0.827
|
0.789
|
0.872
|
DPV, the diameter of the portal vein ;APTT, activate partial thromboplastin time;K,K-time;SE,sensitivity;SP,specificity;AUC, area under the curve
Comparison between Child–Pugh class A and Child–Pugh class B/C cirrhosis
In liver cirrhosis patients with PVT,there was no significant difference in IL-6, TNF, PCT, TEG between different Child-Pugh classification groups (P >0.05) .(Table. 4)
Table 4. Relationship between IL-6、TNF- α、PC, and TEG and severity of liver disease
|
Child-PughA(n=16)
|
Child-PughB(n=28)
|
Child-PughC(n=8)
|
H
|
P-Value
|
IL-6
(pg/mL)
|
124.4(106.3,134.0)
|
124.6(63.1,136.8)
|
89.29(52.0,127.5)
|
1.425
|
0.490
|
TNF-α
(pg/mL)
|
117.8(48.0,136.4)
|
102.0(48.1,132.7)
|
76.2(47.4,116.2)
|
1.339
|
0.512
|
PC
(ug/mL)
|
66.8(49.5,74.2)
|
65.2(40.3,93.4)
|
40.7(12.9,93.7)
|
0.277
|
0.871
|
R(min)
|
5.31±1.25
|
5.59±1.45
|
5.43±1.78
|
0.639
|
0.727
|
K(min)
|
4.30(1.95,5.85)
|
3.57(1.98,4.80)
|
2.85(2.15,9.43)
|
0.190
|
0.909
|
Angle (deg)
|
55.54±15.41
|
51.88±13.41
|
52.84±17.62
|
0.368
|
0.832
|
MA (mm)
|
41.85(36.50,62.40)
|
44.35(37.23,57.95)
|
45.1(29.9,47.1)
|
0.305
|
0.858
|
CI
|
-2.97±4.38
|
-3.26±3.94
|
-4.00±5.66
|
0.011
|
0.995
|
PC, protein C; K, K-time; MA, Maximum amplitude; CI, Coagulation index
Comparison between plasma transfusion and without plasma transfusion events
According to whether plasma was transfused or not, patients with PVT in liver cirrhosis were divided into plasma transfusion group (n = 13) and non-plasma transfusion group (n = 39). There was no significant difference in the parameters of TEG between plasma transfusion group and non plasma transfusion group (P > 0.05). But APTT, PT and INR in plasma transfusion group were higher than those in non- plasma transfusion group (P < 0.05), and PTA in plasma transfusion group was lower than that in non transfusion group (P < 0.05).(Table. 5)
Table. 5 Comparison of coagulation indexes between plasma transfusion group and non-plasma transfusion group
|
plasma transfusion(n=13)
|
non-plasma transfusion(n=39)
|
t/z
|
P-Value
|
R(min)
|
5.10(4.40,7.20)
|
5.3(4.45,6.15)
|
-0.148
|
0.882
|
K(min)
|
3.63(2.30,5.90)
|
3.5(1.85,5.00)
|
-0.645
|
0.519
|
Angle (deg)
|
49.23±16.85
|
52.41±13.69
|
0.684
|
0.497
|
MA (mm)
|
40.04±14.14
|
48.51±13.64
|
1.922
|
0.060
|
CI
|
-4.65±4.95
|
-2.83±4.01
|
1.330
|
0.189
|
TT(s)
|
27.00(24.70,28.35)
|
18.40 (17.70,18.80)
|
-0.285
|
0.775
|
APTT (s)
|
29.20(27.60,30.80)
|
27.00(24.70,28.35)
|
-2.304
|
0.021
|
PT (s)
|
15.98±1.53
|
14.18±1.57
|
-5.128
|
<0.001
|
INR
|
1.35±0.14
|
1.21±0.13
|
-3.576
|
0.001
|
PTA(%)
|
60.15±10.54
|
73.36±13.32
|
3.245
|
0.002
|
Correlation between traditional coagulation and TEG in PVT
In liver cirrhosis patients with PVT, FBG was significantly negatively correlated with K (r = -0.589, P < 0.05), significantly positively correlated with Angle (r = 0.639, P < 0.05), MA (r = 0.625, P < 0.05),CI(r = 0.632, P < 0.05).(Table. 6)(Fig.2)
Table. 6 Correlation between traditional coagulation and TEG in patients with portal vein thrombosis
Variable/r
|
R(min)
|
K(min)
|
Angle角(deg)
|
MA(mm)
|
CI
|
TT(s)
|
0.240
|
0.332*
|
-0.370*
|
-0.385*
|
-0.377*
|
APTT(s)
|
0.402*
|
0.232
|
-0.222
|
-0.384*
|
-0.349*
|
PT(s)
|
0.169
|
0.110
|
-0.097
|
-0.263
|
-0.199
|
INR
|
0.236
|
0.166
|
-0.159
|
-0.314*
|
-0.260
|
PTA (%)
|
0.237
|
-0.164
|
0.158
|
0.310*
|
0.258
|
FBG(g/L)
|
-0.456*
|
-0.589*
|
0.639*
|
0.625*
|
0.632*
|
※ stands for P < 0.05, and the difference is statistically significant. When | r | < 0.3, there is no correlation; 0.3 ≤|r | < 0.5 indicates low correlation; 0.5 ≤|r | < 0.8 indicates significant correlation| R | ≥ 0.8 indicates high correlation