Demographic and clinical characteristics of patients
A total of 70 patients were enrolled, including 57 (82.3%) men and 13 (17.6%) women (Table 1), of whom 60 (85.7%) were HBsAg-positive. Sixty-eight patients underwent right hemi-hepatectomy and two patients, extended right hemi-hepatectomy. Postoperative liver tumor pathology identified 66 patients with hepatocellular carcinoma (HCC), and one patient each with intrahepatic cholangiocarcinoma, HCC-intrahepatic cholangiocarcinoma, adenocarcinoma, or low-grade dysplasia. Postoperative liver tissue pathology identified 10 (14.3%) patients with chronic liver disease without hepatic fibrosis or cirrhosis, 35 (50.0%) with hepatic fibrosis, and 25 (35.7%) with cirrhosis.
After surgery, obvious ascites appeared in five patients (7.1%), biliary leak in two (2.9%), and abdominal infection in one (1.4%). CRPHLF occurred in 19 (27.1%). No patient died during the perioperative period, from one week before surgery until one week after surgery. All patients recovered successfully.
Table 1
Demographic and clinical characteristics of the 70 patients in the study.
Characteristic | Value |
Sex Male Female | 57 (81.4) 13 (18.6) |
HBsAg Positive Negative | 60 (85.7) 10 (14.3) |
Preoperative parameters Age (years) Body mass index (kg/m2) Total bilirubin (µmol/L) Albumin (g/L) ALT (U/L) AST (U/L) Platelet count (109 /L) Prothrombin time (s) Creatinine (µmol/L) HBV-DNA (IU/mL) ≥ 2 000 < 2000 Alpha-fetoprotein (ng/mL) ≥ 400 < 400 Ascites Yes No Child–Pugh grade A B C ICG-R15 (%) SRLV (mL/m2) RLV/SLV (%) RLV (mL) Tumor volume (mL) | 44.63 ± 3.73 21.75 ± 3.34 18.14 ± 30.75 37.15 ± 4.21 56.83 ± 41.73 73.30 ± 53.40 236.03 ± 93.97 12.58 ± 1.22 76.73 ± 15.05 41 (58.6) 29 (41.4) 39 (55.7) 31(44.3) 10 (14.3) 60 (85.7) 66 (94.3) 4 (5.7) 0 4.88 ± 3.11 248.25 ± 24.20 35.03 ± 3.37 405.15 ± 52.09 513.0 ± 399.3 |
Intraoperative parameters Blood transfusion Yes No Blood loss (mL) Operative time (min) | 15 (21.4) 55 (78.6) 557.14 ± 474.13 273.74 ± 61.49 |
Postoperative parameters Hepatic fibrosis stage (METAVIR) No fibrosis (F0) Fibrosis (F1-3) Cirrhosis (F4) Hospital stay (days) Perioperative mortality (%) | 10 (14.3) 35 (50.0) 25 (35.7) 14.09 ± 10.62 0 |
Values are n (%) or mean ± standard deviation. |
Abbreviations: ALT, alanine transaminase; AST, aspartate aminotransferase; HBsAg, hepatitis B virus surface antigen; HBV-DNA, hepatitis B virus DNA; ICG-R15, indocyanine green retention rate at 15 min; RLV, remnant liver volume; SLV, standard liver volume; SRLV, standard remnant liver volume.
Risk factors for CRPHLF
The ICG-R15 of patients who experienced CRPHLF was significantly higher than that of patients who did not (Table 2). Positive stepwise binary logistic regression was used to assess the potential relationship between ICG-R15 and CRPHLF, in which the threshold for model inclusion was 0.05, and the threshold for exclusion was 0.1. This analysis identified ICG-R15 as an independent predictor of CRPHLF after extreme hepatectomy (Table 3).
Table 2. Comparison of clinicopathologic characteristics between patients who experienced CRPHLF or not.
Characteristic
|
No CRPHLF
|
CRPHLF
|
χ2 (t test)
|
p
|
(n = 51)
|
(n = 19)
|
Sex
Male
Female
|
39
12
|
18
1
|
3.054
|
0.081
|
HBsAg
|
|
|
0.301
|
0.583
|
Positive
|
43
|
17
|
|
|
Negative
|
8
|
2
|
|
|
Preoperative parameters
|
|
|
|
Age (years)
|
47.49±11.02
|
48.16±11.63
|
1.040
|
0.302
|
Body mass index (kg/m2)
|
21.98±3.40
|
21.14±3.20
|
0.931
|
0.355
|
Total bilirubin (μmol/L)
|
14.43±5.24
|
28.02±58.38
|
-1.011
|
0.325
|
Albumin (g/L)
|
37.08±3.61
|
37.36±5.63
|
-0.201
|
0.842
|
ALT (U/L)
|
58.14±42.02
|
53.32±41.87
|
0.427
|
0.671
|
AST (U/L)
|
72.44±50.43
|
75.61±62.13
|
-0.22
|
0.827
|
Platelet count (109 /L)
|
234.15±97.13
|
241.06±87.19
|
-0.271
|
0.787
|
Prothrombin time (s)
|
12.49±1.23
|
12.83±1.18
|
-1.017
|
0.313
|
Creatinine (μmol/L)
|
75.25±14.72
|
80.68±15.60
|
-1.35
|
0.181
|
HBV-DNA (IU/mL)
|
|
|
0.301
|
0.583
|
≥ 2 000
|
22
|
9
|
|
|
< 2000
|
19
|
10
|
|
|
Alpha-fetoprotein (ng/mL)
|
|
|
0.05
|
0.823
|
≥ 400
|
28
|
11
|
|
|
< 400
|
23
|
8
|
|
|
Ascites
|
|
|
0.048
|
0.826
|
Yes
|
7
|
3
|
|
|
No
|
44
|
16
|
|
|
Child–Pugh grade
|
|
|
1.121
|
0.290
|
A
|
49
|
17
|
|
|
B
|
2
|
2
|
|
|
ICG-R15 (%)
|
4.27±2.95
|
6.51±3.02
|
-2.799
|
0.007*
|
SRLV (mL/m2)
|
249.06±24.09
|
246.10±25.05
|
0.452
|
0.652
|
RLV/SLV (%)
|
35.19±3.4
|
34.61±3.33
|
0.633
|
0.529
|
RLV (mL)
|
407.06±53.19
|
400.02±50.05
|
0.50
|
0.619
|
Tumor volume (mL)
|
482.15±403.63
|
595.83±386.03
|
-1.06
|
0.293
|
Intraoperative parameters
|
|
|
|
Blood transfusion
|
|
|
4.048
|
0.044*
|
Yes
|
14
|
1
|
|
|
No
|
37
|
18
|
|
|
Blood loss (mL)
|
520.73±456.89
|
608.62±501.08
|
-0.762
|
0.449
|
Operative time (min)
|
277.14±62.29
|
264.63±59.97
|
0.754
|
0.453
|
Postoperative parameters
|
|
|
|
Hepatic fibrosis stage (METAVIR)
|
|
1.820
|
0.402
|
No fibrosis (F0)
|
9
|
1
|
|
|
Fibrosis (F1-3)
|
25
|
10
|
|
|
Cirrhosis (F4)
|
17
|
8
|
|
|
Hospital stay (days)
|
11.33±6.36
|
21.47±15.51
|
-2.764
|
0.012*
|
Values are n or mean ± standard deviation. * p < 0.05
Abbreviations: ALT, alanine transaminase; AST, aspartate aminotransferase; HBsAg, hepatitis B virus surface antigen; HBV-DNA, hepatitis B virus DNA; ICG-R15, indocyanine green retention rate at 15 min; RLV, remnant liver volume; SLV, standard liver volume; SRLV, standard remnant liver volume.
Table 3. Binary logistic regression analysis to identify factors related to CRPHLF.
Factor
|
|
Univariate analysis
|
|
|
|
Multivariate analysis
|
|
B
|
Odds Ratio (95% CI)
|
p
|
B
|
Odds Ratio (95% CI)
|
p
|
Sex (male)
|
1.712
|
5.538 (0.668–45.914)
|
0.172
|
1.470
|
4.347(0.451–41.865)
|
0.203
|
ICG-R15
|
0.231
|
1.259 (1.047–1.515)
|
0.014*
|
0.224
|
1.251(1.029–1.521)
|
0.024*
|
Creatinine
|
0.025
|
1.025(0.988–1.063)
|
0.182
|
0.022
|
1.023 (0.982–1.065)
|
0.281
|
Hepatic fibrosis stage
|
|
|
|
|
|
Fibrosis(F1-3)
|
1.281
|
3.60(0.402–32.240)
|
0.252
|
0.956
|
2.602 (0.255–26.573)
|
0.420
|
Cirrhosis(F4)
|
1.443
|
4.235(0.455–39.401)
|
0.205
|
1.006
|
2.734 (0.252–29.686)
|
0.408
|
* p < 0.05.
Abbreviations: CI, confidence interval; ICG-R15, indocyanine green retention rate at 15 min.
ICG-R15 thresholds for predicting CRPHLF
Receiver operating characteristic curves showed that ICG-R15 predicted CRPHLF in our patients with high sensitivity and specificity, regardless of whether they had chronic liver disease, hepatic fibrosis, or cirrhosis. Across all patients, the ICG-R15 threshold for CRPHLF was 5.25%, which gave an area under the curve (AUC) of 0.740, sensitivity of 68.4%, and specificity of 78.4% (p = 0.002, Fig. 3A). In patients with hepatic fibrosis, the ICG-R15 threshold was 4.95%, which gave an AUC 0.770, sensitivity of 78.0%, and specificity of 74.0% (p = 0.001, Fig. 3B). In patients with cirrhosis, the threshold was 4.55%, which gave an AUC of 0.768, sensitivity of 87.5%, and specificity of 64.7% (p = 0.033, Fig. 3C).