Patient demographics and cut-off value of preoperative platelet count
Of the 329 patients included in this analysis, 248 were men (75.4%), and 81 were women (24.6%). The mean age was 46.71±0.55 years. Pretransplant diagnosis included viral hepatitis (n=170, 51.7%), hepatocellular carcinoma (n=95, 28.9%), alcoholic cirrhosis (n=8, 2.4%), primary biliary cirrhosis or autoimmune liver disease (n=20, 6.0%), and other reasons (n=36, 11.0%). Thirty-two patients died during the follow-up period. The median preoperative platelet count was 50×109/L (IQR, 34×109/L to 86×109/L).
The diagnostic ability of preoperative platelet count for post-OLT portal vein complication was determined by ROC curve analysis. Based on the data, preoperative platelet count showed a good prediction ability for post-OLT portal vein complication (AUC=0.705, 95%CI 0.613 to 0.797, p=0.001). The optimal cut-off value for preoperative platelet count was 49.5×109/L with the maximum Youden index of 0.396 (sensitivity=87.5%, specificity=52.1%, Figure 1). According to the cut-off value, 167 patients (50.8%) were assigned to the low platelet count group (> 49.5×109/L) and 162 patients (49.2%) were assigned to the high platelet count group (≤ 49.5×109/L). The distribution of preoperative platelet count for each patient in different groups was shown in Figure S1.
Baseline characteristics
The baseline variables of the two groups are shown in Table 1. The donor age was a little younger in the high platelet count group (45.22±1.16 years old) than in the low platelet count group (46.12±1.12 years old). Patients in the high platelet count group had a higher blood cell counts (p<0.001) and higher rate of hypertension (12% vs 9.3%, p=0.002) and preoperative splenectomy (12% vs. 4.9%, p=0.022). However, PT, APTT, and MELD scores were significantly higher in the low platelet count group (p<0.05). In terms of intraoperative variables, patients in the low platelet count group experienced a longer operation time (p=0.014), a longer anhepatic phase (p=0.006), and more blood loss and total input amount (p<0.001). Other parameters analyzed had no significant differences between the two groups (Table 1).
Table 1. Characteristics of Demographic and Clinical Features of the Patients.
Variables
|
PLT > 49.5×10^9/L
(n=167)
|
PLT ≤ 49.5×10^9/L
(n=162)
|
P value
|
Donor features
|
|
|
|
Donor age (years)
|
45.22±1.16
|
46.12±1.12
|
0.009
|
Donor gender (male/female)
|
122/45
|
126/36
|
0.32
|
Donor BMI (kg/m2)
|
22.08 (20.07, 24.24)
|
22.04 (19.59, 24.18)
|
0.469
|
Demographic features
|
|
|
|
Age (years)
|
47.98±0.74
|
45.18±0.81
|
0.609
|
Gender (male/female)
|
142/25
|
141/21
|
0.60
|
BMI (kg/m2)
|
22.05 (20.28, 24.22)
|
22.86 (20.70, 24.88)
|
0.053
|
Clinical features
|
|
|
|
Preoperative laboratory values
|
|
|
|
Creatinine (µmol/L)
|
60.00 (45.50, 68.40)
|
55.00 (46.00, 69.00)
|
0.556
|
BUN (mmol/L)
|
4.54 (3.52, 6.61)
|
4.66 (3.72, 6.10)
|
0.525
|
Red cell (×1012/L)
|
3.44 (3.05, 4.17)
|
3.08 (2.73, 3.83)
|
<0.001
|
Leukocyte (×109/L)
|
4.63 (3.35, 6.54)
|
3.01 (2.11, 4.41)
|
<0.001
|
Lymphocyte (×109/L)
|
0.80 (0.48, 1.35)
|
0.47 (0.30, 0.70)
|
<0.001
|
ALT (U/L)
|
33.83 (23.00, 65.00)
|
31.50 (23.00, 48.75)
|
0.204
|
AST (U/L)
|
44.00 (31.00, 82.00)
|
42.00 (30.00, 62.75)
|
0.103
|
Total bilirubin (µmol/L)
|
35.60 (20.20, 83.90)
|
54.35 (30.00, 112.15)
|
0.002
|
Albumin (g/L)
|
36.90 (32.71, 42.75)
|
34.35 (31.20, 39.00)
|
0.005
|
PT (s)
|
17.20 (15.05, 19.55)
|
19.15 (17.50, 21.88)
|
<0.001
|
APTT (s)
|
43.00 (39.00, 47.90)
|
48.05 (42.80, 52.60)
|
<0.001
|
Hepatic features
|
|
|
|
MELD
|
11.00 (7.00, 17.00)
|
13.50 (9.00, 19.00)
|
0.043
|
Etiology
|
|
|
0.031
|
Viral hepatitis (%)
|
73 (43.7%)
|
97 (59.9%)
|
|
Alcoholic cirrhosis (%)
|
3 (1.8%)
|
5 (3.1%)
|
|
Hepatocellular Carcinoma (%)
|
59 (35.3%)
|
36 (22.2%)
|
|
Primary biliary cirrhosis & Autoimmune liver disease (%)
|
12 (7.2%)
|
8 (9.8%)
|
|
Other (%)
|
20 (12.0%)
|
16 (9.9%)
|
|
Coexisting conditions
|
|
|
|
Smoking (%)
|
56 (33.5%)
|
50 (30.9%)
|
0.605
|
Drinking (%)
|
25 (15.0%)
|
36 (22.2%)
|
0.091
|
Hypertension (%)
|
20 (12.0%)
|
5 (3.1%)
|
0.002
|
Diabetes (%)
|
20 (12.0%)
|
15 (9.3%)
|
0.424
|
Pre-operative PVT (%)
|
32 (19.2%)
|
25 (15.4%)
|
0.372
|
Pre-operative splenectomy (%)
|
20 (12.0%)
|
8 (4.9%)
|
0.022
|
Intraoperative factors
|
|
|
|
Operation time (min)
|
360.00 (320.00, 420.00)
|
390.00 (343.75, 421.25)
|
0.014
|
Anhepatic phase (min)
|
47.00 (43.00, 54.00)
|
50.00 (45.00, 57.25)
|
0.006
|
Intraoperative blood loss (mL)
|
1000 (600, 2000)
|
1500 (837.50, 2850.00)
|
<0.001
|
Total input amount (mL)
|
5370 (4500, 6585)
|
6080 (5235, 8094)
|
<0.001
|
Warm ischemia time (min)
|
14.00 (10.00, 15.00)
|
14.00 (10.00, 15.00)
|
0.733
|
Cold ischemia time (h)
|
6.00 (5.00, 6.00)
|
6.00 (4.00, 6.00)
|
0.091
|
Abbreviations: ALT, Alanine aminotransferase; AST, Aspartate transaminase; BUN, blood urea nitrogen; PT, prothrombin time; APTT, activated partial thromboplastin time; MELD, model for end-stage liver disease; PVT, portal vein thrombosis.
Postoperative outcomes
Postoperative outcomes are shown in Table 2. Portal vein complication occurred in 24 patients after OLT (7.29%). Twenty-one patients (12.6%) in the high platelet count group developed postoperative portal vein complication compared with the three patients (1.9%) in the low platelet count group. The difference was statistically significant (OR 7.623, 95%CI 2.227 to 26.091, p<0.001). Kaplan-Meier analysis showed comparable overall survival rate between the two groups (log rank p=0.774, Figure 2). Similarly, the incidence of hepatic artery thrombosis, biliary stricture, EAD, in-hospital mortality, and prolonged ICU stay did not show significant difference between the two groups. In addition, multivariable regression was used to adjust the imbalance in potential confounding variables. In the multivariable analysis, high preoperative platelet count was independently associated with a higher incidence of postoperative portal vein complication (OR 8.821, 95% CI 2.260 to 34.437, p=0.002, Table 2).
Table 2 Primary and secondary outcomes in two groups
Outcomes
|
PLT > 49.5×10^9/L
(n=167)
|
PLT ≤ 49.5×10^9/L
(n=162)
|
Univariate Analysis
|
|
Multivariable Analysis
|
p
|
OR (95% CI)
|
|
p
|
OR (95% CI)
|
Portal vein complications (%)
|
21 (12.6%)
|
3 (1.9%)
|
<0.001
|
7.623 (2.227, 26.091)
|
|
0.002
|
8.821 (2.260, 34.437)
|
Hepatic artery thrombosis (%)
|
5 (3.0%)
|
4 (2.5%)
|
0.770
|
1.219 (0.321, 4.623)
|
|
|
|
Biliary strictures (%)
|
22 (13.2%)
|
22 (13.6%)
|
0.914
|
0.966 (0.512, 1.822)
|
|
|
|
Early allograft dysfunction (%)
|
36 (22.0%)
|
26 (16.4%)
|
0.203
|
1.439 (0.822, 2.518)
|
|
|
|
In-hospital mortality (%)
|
9 (5.4%)
|
6 (3.7%)
|
0.464
|
1.481 (0.515, 4.260)
|
|
|
|
Prolonged ICU stay (%)
|
74 (44.3%)
|
63 (38.9%)
|
0.319
|
1.250 (0.806, 1.940)
|
|
|
|
Post-operative hospital stay (days)
|
17 (14, 22)
|
18 (14, 24)
|
0.445
|
/
|
|
|
|
Abbreviations: ICU, intensive care unit.
Baseline characteristics and postoperative outcomes after IPTW analysis
After IPTW adjustment, the baseline variables between the high platelet count group and low platelet group were comparable (Table 3). As regards postoperative outcomes, the patients in the high platelet count group had higher incidence of portal vein complication (OR 8.296, 95%CI 1.855 to 37.096, p=0.001) and EAD (OR 1.925, 95% CI 1.098 to 3.374, p=0.022) than those in the low platelet count group. After adjustment by the multivariable regression logistic analysis, the risk of portal vein complication (OR 9.210, 95% CI 1.907 to 44.498, p=0.006) and EAD (OR 2.087, 95% CI 1.131 to 3.853, p=0.019) was also higher in the high platelet count group (Table 4).
Table 3. Characteristics of Demographic and Clinical Features of the Patients after IPTW.
Variables
|
PLT > 49.5×10^9/L
(n=167)
|
PLT ≤ 49.5×10^9/L
(n=162)
|
P value
|
Donor features
|
|
|
|
Donor age (years)
|
47.04±1.15
|
46.58±1.26
|
0.772
|
Donor gender (male, %)
|
152 (86.4%)
|
120 (86.3%)
|
0.993
|
Donor BMI (kg/m2)
|
22.49 (20.52, 24.22)
|
22.86 (20.64, 24.69)
|
|
Demographic features
|
|
|
|
Age (years)
|
47.39±0.70
|
45.30±0.87
|
|
Gender (male, %)
|
136 (77.3%)
|
109 (78.4%)
|
0.808
|
BMI (kg/m2)
|
22.80 (20.20, 24.22)
|
22.05 (19.68, 24.32)
|
0.542
|
Clinical features
|
|
|
|
Preoperative laboratory values
|
|
|
|
Creatinine (µmol/L)
|
59.72 (44.74, 72.00)
|
56.00 (47.00, 66.37)
|
0.552
|
BUN (mmol/L)
|
4.40 (3.38, 6.93)
|
4.77 (3.88, 6.10)
|
0.954
|
Red cell (×1012/L)
|
3.57 (3.04, 4.01)
|
3.29 (2.82, 3.97)
|
0.012
|
Leukocyte (×109/L)
|
3.57 (2.77, 5.43)
|
3.27 (2.35, 5.37)
|
0.119
|
Lymphocyte (×109/L)
|
0.58 (0.45, 1.03)
|
0.53 (0.34, 0.89)
|
0.351
|
ALT (U/L)
|
35.11 (21.00, 70.00)
|
30.37 (23.96, 48.59)
|
0.669
|
AST (U/L)
|
44.00 (31.00, 85.00)
|
42.66 (29.00, 63.00)
|
0.915
|
Total bilirubin (µmol/L)
|
41.73 (23.85, 110.03)
|
55.20 (28.76, 114.20)
|
0.333
|
Albumin (g/L)
|
36.82 (32.71, 41.80)
|
35.75 (31.80, 41.14)
|
0.190
|
PT (s)
|
18.14 (15.51, 21.42)
|
18.50 (16.90, 21.80)
|
0.389
|
APTT (s)
|
45.00 (39.50, 50.20)
|
47.25 (41.76, 52.22)
|
0.904
|
Hepatic features
|
|
|
|
MELD
|
12.00 (6.74, 19.15)
|
13.00 (9.00, 17.00)
|
0.713
|
Etiology
|
|
|
0.298
|
Viral hepatitis (%)
|
84 (47.7%)
|
83 (59.7%)
|
|
Alcoholic cirrhosis (%)
|
6 (3.4%)
|
3 (2.2%)
|
|
Hepatocellular Carcinoma (%)
|
53 (30.1%)
|
33 (23.7%)
|
|
Primary biliary cirrhosis & Autoimmune liver disease (%)
|
9 (5.1%)
|
7 (5.0%)
|
|
Other (%)
|
24 (13.6%)
|
13 (9.4%)
|
|
Coexisting conditions
|
|
|
|
Smoking (%)
|
64 (36.4%)
|
39 (28.1%)
|
0.119
|
Drinking (%)
|
45 (25.6%)
|
29 (20.9%)
|
0.328
|
Hypertension (%)
|
11 (6.3%)
|
4 (2.9%)
|
0.259
|
Diabetes (%)
|
14 (8.0%)
|
14 (10.1%)
|
0.512
|
Pre-operative PVT (%)
|
33 (18.6%)
|
18 (12.9%)
|
0.172
|
Pre-operative splenectomy (%)
|
12 (6.8%)
|
8 (5.8%)
|
0.701
|
Intraoperative factors
|
|
|
|
Operation time (min)
|
389.33 (330.00, 470.00)
|
386.43 (340.00, 424.11)
|
0.296
|
Anhepatic phase (min)
|
49.00 (44.00, 57.00)
|
49.00 (45.00, 57.00)
|
0.285
|
Intraoperative blood loss (mL)
|
1500.00 (800.00, 3000.00)
|
1500.00 (800.00, 2573.16)
|
0.564
|
Total input amount (mL)
|
6072.43 (4785.37, 7820.00)
|
6000.00 (5120.00, 7913.63)
|
0.947
|
Warm ischemia time (min)
|
12.00 (6.74, 19.15)
|
13.00 (9.00, 17.00)
|
0.617
|
Cold ischemia time (h)
|
6.00 (5.00, 6.00)
|
6.00 (4.00, 6.00)
|
0.476
|
Abbreviations: ALT, Alanine aminotransferase; AST, Aspartate transaminase; BUN, blood urea nitrogen; PT, prothrombin time; APTT, activated partial thromboplastin time; MELD, model for end-stage liver disease; PVT, portal vein thrombosis.
Table 4 Primary and secondary outcomes in two groups after IPTW
Outcomes
|
PLT > 49.5×10^9/L
(n=167)
|
PLT ≤ 49.5×10^9/L
(n=162)
|
Univariate Analysis
|
|
Multivariable Analysis
|
p
|
OR (95% CI)
|
|
p
|
OR (95% CI)
|
Portal vein complications (%)
|
18 (10.2%)
|
2 (1.4%%)
|
0.001
|
8.296 (1.855, 37.096)
|
|
0.006
|
9.210 (1.907, 44.489)
|
Hepatic artery thrombosis (%)
|
6 (3.4%)
|
3 (2.2%)
|
0.514
|
1.549 (0.365, 6.577)
|
|
|
|
Biliary strictures (%)
|
16 (9.1%)
|
18 (12.9%)
|
0.273
|
0.668 (0.325, 1.371)
|
|
|
|
Early allograft dysfunction (%)
|
48 (27.1%)
|
22 (15.8%)
|
0.022
|
1.925 (1.098, 3.374)
|
|
0.019
|
2.087 (1.131, 3.853)
|
In-hospital mortality (%)
|
9 (5.1%)
|
4 (2.9%)
|
0.323
|
1.722 (0.533, 5.566)
|
|
|
|
Prolonged ICU stay (%)
|
65 (36.9%)
|
48 (34.5%)
|
0.659
|
1.119(0.703, 1.781)
|
|
|
|
Post-operative hospital stay (days)
|
19 (14, 23)
|
18 (14, 23)
|
0.964
|
/
|
|
|
|
Abbreviations: ICU, intensive care unit.