Indocyanine Green Retention Test as a Predictor of Postoperative Complications in Patients with Hepatitis B Virus-Related Hepatocellular Carcinoma

Figures & data

Table 1 Baseline Characteristics of the Included 354 Patients

Variables	Entire Patients (n=354)
Age (years)	51 (44, 58)
High (cm)	165 (161, 170)
Weight (kg)	60 (54, 67)
BMI (kg/m^2)	22 (20, 24)
Sex
Male	318 (89.8)
Female	36 (10.2)
Positive HBeAg	91 (25.7)
Positive anti-HBe	114 (32.2)
Positive anti-HBC	157 (44.4)
HBV-DNA, IU/mL
≥2000	192 (54.2)
<2000	162 (45.8)
PLT (× 10^9/l)	196.0 (151.3, 253.8)
PT (s)	12.5 (11.7, 13.3)
T-Bil (μmol/l)	16.2 (11.8, 20.4)
PA (mg/l)	163.5 (132.3, 201.8)
ALB (g/l)	37.4 (34.5, 39.7)
ALT (U/l)	42.0 (29.0, 60.0)
AST (U/l)	46.0 (34.0, 69.8)
ALP (U/l)	90.0 (73.3, 118.0)
CRE (μmol/l)	77.0 (69.0, 87.0)
BUN (mmol/l)	5.0 (4.1, 6.0)
AFP (ng/mL)
≥400	150 (42.4)
<400	204 (57.6)
CSPH	34 (9.6)
Ascites	55 (15.5)
Cirrhosis	213 (60.2)
Child–Pugh score	5 (5, 6)
Child–Pugh grade
A	305 (86.2)
B	49 (13.8)
MELD score	5 (4, 7)
ALBI score	−2.38 (−2.59, −2.16)
ICG-R15 (%)	4.6 (3.2, 7.35)
Tumour size (cm)	7 (4, 10)
Tumour number
Multiple	143 (40.4)
Single	211 (59.6)
Portal invasion or extrahepatic spread	65 (18.4)
BCLC stage
0	12 (3.4)
A	205 (57.9)
B	72 (20.3)
C	65 (18.4)
Operation time (min)	210 (180, 260)
Blood loss	250 (150, 500)
Blood transfusion (mL)	98 (27.7)
Extent of hepatectomy
Major resection	235 (66.4)
Minor resection	119 (33.6)

Notes: Data are median (IQR 25–75) unless otherwise indicated.

Abbreviations: BMI, body mass index; HBeAg, hepatitis Be antigen; anti-HBe, antibodies against hepatitis Be antigen; anti-HBC, antibody to hepatitis B core antigen; HBV-DNA, hepatitis B virus DNA load; PLT, platelet; PT, prothrombin time; T-Bil, total bilirubin; PA, prealbumin; ALB, albumin; ALT, alanine transaminase; AST, aspartic aminotransferase; GGT, γ-glutamyl transpeptadase; ALP, alkaline phosphatase; CRE, creatinine; BUN, blood urea nitrogen; AFP, α-fetoprotein; CSPH, clinically significant portal hypertension; MELD, model for end-stage liver disease; ALBI, albumin–bilirubin; ICG‐R15, indocyanine green retention test at 15 minutes; BCLC, Barcelona Clinic Liver Cancer.

Table 2 Univariate and Multivariate Analyses to Identify Factors Predicting Postoperative Major Complications

Variables	Univariate Logistic Regression		Multivariate Logistic Regression
	HR (95% CI)	P value	HR (95% CI)	P value
Age (years)	1.041 (1.007, 1.075)	0.018	1.031 (0.988, 1.075)	0.161
High (cm)	1.012 (0.955, 1.072)	0.680
Weight (kg)	0.993 (0.955, 1.032)	0.716
BMI (kg/m^2)	0.951 (0.840, 1.076)	0.421
Male sex	1.104 (0.319, 3.822)	0.876
Positive HBeAg	1.352 (0.615, 2.976)	0.453
Positive anti-HBe	1.114 (0.518, 2.396)	0.783
Positive anti-HBC	1.473 (0.711, 3.052)	0.297
HBV-DNA ≥2000 (IU/mL)	1.094 (0.526, 2.274)	0.811
PLT counts (× 10^9/l)	0.999 (0.995, 1.004)	0.761
PT (s)	1.180 (0.893, 1.559)	0.244
T-Bil (μmol/l)	1.013 (0.998, 1.027)	0.093
PA (mg/l)	0.989 (0.981, 0.996)	0.002	0.994 (0.985, 1.004)	0.267
ALB (g/l)	0.897 (0.821, 0.981)	0.018	1.385 (0.908, 2.111)	0.130
ALT (U/l)	1.002 (1.000, 1.005)	0.084
AST (U/l)	1.004 (1.001, 1.008)	0.012	1.005 (1.000, 1.010)	0.033
ALP (U/l)	1.003 (0.999, 1.006)	0.114
CRE (μmol/l)	1.010 (1.001, 1.019)	0.032	1.019 (0.998, 1.041)	0.079
BUN (mmol/l)	0.993 (0.980, 1.006)	0.311
AFP (ng/mL)	1.000 (1.000, 1.000)	0.729
CSPH	0.971 (0.280, 3.373)	0.963
Ascites	1.007 (0.370, 2.740)	0.988
Cirrhosis	1.509 (0.692, 3.291)	0.301
Child–Pugh score	1.588 (1.069, 2.359)	0.022	0.522 (0.250, 1.091)	0.084
MELD score	1.182 (1.061, 1.318)	0.002	0.921 (0.682, 1.244)	0.592
ALBI score	4.404 (1.702, 11.400)	0.002	123.867 (0.816, 18799.190)	0.060
ICG-R15 (%)	1.139 (1.072, 1.211)	<0.001	1.108 (1.037, 1.184)	0.002
Tumor size (cm)	1.086 (1.014, 1.163)	0.018	1.002 (0.906, 1.109)	0.968
Multiple tumor number	1.164 (0.559, 2.422)	0.685
Portal invasion or extrahepatic spread	1.550 (0.663, 3.625)	0.312
BCLC stage	1.320 (0.868, 2.006)	0.194
Operation time (min)	1.001 (0.996, 1.006)	0.712
Blood loss (mL)	1.001 (1.000, 1.001)	0.003	1.001 (1.000, 1.001)	0.170
Blood transfusion	0.711 (0.297, 1.701)	0.443
Major resection	3.889 (1.331, 11.362)	0.013	7.376 (1.553, 35.025)	0.012

Abbreviations: CI, confidence interval; BMI, body mass index; HBeAg, Hepatitis Be antigen; anti-HBe, antibodies against hepatitis Be antigen; anti-HBC, antibody to hepatitis B core antigen; HBV-DNA, hepatitis B virus DNA load; PLT, platelet; PT, prothrombin time; T-Bil, total bilirubin; PA, prealbumin; ALB, albumin; ALT, alanine transaminase; AST, aspartic aminotransferase; GGT, γ-glutamyl transpeptidase; ALP, alkaline phosphatase; CRE, creatinine; BUN, Blood urea nitrogen; AFP, α-fetoprotein; CSPH, clinically significant portal hypertension; MELD, model for end-stage liver disease; ALBI, albumin–bilirubin; ICG‐R15, indocyanine green retention test at 15 minutes; BCLC, Barcelona Clinic Liver Cancer.

Table 3 Univariate and Multivariate Analyses to Identify Factors Predicting Severe PHLF

Variables	Univariate Logistic Regression		Multivariate Logistic Regression
	HR (95% CI)	P value	HR (95% CI)	P value
Age (years)	1.005 (0.979, 1.030)	0.727
High (cm)	0.967 (0.926, 1.011)	0.139
Weight (kg)	0.971 (0.941, 1.002)	0.065
BMI (kg/m^2)	0.931 (0.845, 1.026)	0.151
Male sex	0.955 (0.378, 2.412)	0.922
Positive HBeAg	1.562 (0.848, 2.879)	0.152
Positive anti-HBe	0.966 (0.562, 1.777)	0.912
Positive anti-HBC	1.487 (0.842, 2.626)	0.171
HBV-DNA ≥ 2000 (IU/mL)	1.419 (0.794, 2.533)	0.237
PLT (× 10^9/l)	0.997 (0.994, 1.001)	0.161
PT (s)	1.808 (1.423, 2.297)	<0.001	1.458 (1.098, 1.936)	0.009
T-Bil (μmol/l)	1.012 (0.998, 1.027)	0.104
PA (mg/l)	0.987 (0.981, 0.993)	0.000	0.997 (0.989, 1.005)	0.493
ALB (g/l)	0.918 (0.857, 0.984)	0.015	1.012 (0.775, 1.320)	0.933
ALT (U/l)	1.000 (0.998, 1.003)	0.755
AST (U/l)	1.002 (0.998, 1.005)	0.294
ALP (U/l)	1.002 (0.999, 1.005)	0.154
CRE (μmol/l)	1.006 (0.998, 1.014)	0.163
BUN (mmol/l)	0.999 (0.994, 1.003)	0.522
AFP (ng/mL)	1.000 (1.000, 1.000)	0.823
CSPH	2.420 (1.087, 5.386)	0.030	0.625 (0.198, 1.974)	0.423
Ascites	0.364 (0.126, 1.051)	0.062
Cirrhosis	2.879 (1.463, 5.666)	0.002	2.583 (1.126, 5.924)	0.025
Child–Pugh score	1.579 (1.143, 2.182)	0.006	0.686 (0.390, 1.206)	0.190
MELD score	1.159 (1.057, 1.269)	0.002	1.093 (0.954, 1.253)	0.201
ALBI score	3.289 (1.538, 7.037)	0.002	1.417 (0.061, 32.896)	0.828
ICG-R15 (%)	1.265 (1.174, 1.363)	0.000	1.285 (1.168, 1.413)	0.000
Tumor size (cm)	1.072 (1.014, 1.134)	0.015	1.038 (0.967, 1.114)	0.305
Multiple tumor number	0.998 (0.560, 1.778)	0.994
Portal invasion or etrahepatic spread	2.205 (1.155, 4.207)	0.016	1.601 (0.725, 3.538)	0.244
BCLC stage	1.281 (0.920, 1.783)	0.143
Operation time (min)	1.003 (0.999, 1.007)	0.120
Blood loss (mL)	1.000 (1.000, 1.001)	0.294
Blood transfusion	1.252 (0.677, 2.315)	0.474
Major resection	4.324 (1.895, 9.868)	0.001	4.449 (1.341, 14.758)	0.015

Abbreviations: CI., confidence interval; BMI, body mass index; HBeAg, hepatitis Be antigen; anti-HBe, antibodies against hepatitis Be antigen; anti-HBC, antibody to hepatitis B core antigen; HBV-DNA, hepatitis B virus DNA load; PLT, platelet; PT, prothrombin time; T-Bil, total bilirubin; PA, prealbumin; ALB, albumin; ALT, alanine transaminase; AST, aspartic aminotransferase; GGT, γ-glutamyl transpeptidase; ALP, alkaline phosphatase; CRE, creatinine; BUN, blood urea nitrogen; AFP, α-fetoprotein; CSPH, clinically significant portal hypertension; MELD, model for end-stage liver disease; ALBI, albumin–bilirubin; ICG‐R15, indocyanine green retention test at 15 minutes; BCLC, Barcelona Clinic Liver Cancer; PHLF, posthepatectomy liver failure.

Figure 1 (A) ROC curves and (B) DCA plot analyses of ICG‐R15, Child–Pugh, MELD and ALBI scores for assessing postoperative major complications.

Abbreviations: ICG‐R15, indocyanine green retention test at 15 minutes; MELD, model for end‐stage liver disease; ALBI, albumin–bilirubin; ROC, receiver operating characteristic; DCA, decision curve analysis.

Figure 2 (A) ROC curves and (B) DCA plot analyses of ICG‐R15, Child–Pugh, MELD and ALBI scores for assessing severe PHLF.

Abbreviations: ICG‐R15, indocyanine green retention test at 15 minutes; MELD, model for end‐stage liver disease; ALBI, albumin–bilirubin; ROC, receiver operating characteristic; DCA, decision curve analysis; PHLF, posthepatectomy liver failure.

Figure 3 ROC curves of ICG‐R15, Child–Pugh, MELD and ALBI scores for assessing postoperative major complications in the HBV-related HCC patients subgroups. Subgroups include (A) cirrhosis, (B) no cirrhosis, (C) major hepatectomy, (D) minor hepatectomy, (E) blood loss ≥400 mL, (F) blood loss <400 mL, (G) blood transfusion, (H) no blood transfusion, (I) BCLC-0 or -A stage, and (J) BCLC-B or -C stage.

Abbreviations: ICG‐R15, indocyanine green retention test at 15 minutes; MELD, model for end‐stage liver disease; ALBI, albumin–bilirubin; ROC, receiver operating characteristic; PHLF, posthepatectomy liver failure; BCLC, Barcelona Clinical Liver Cancer; HBV, hepatitis B virus; HCC, hepatocellular carcinoma.

Figure 4 ROC curves of ICG‐R15, Child–Pugh, MELD and ALBI scores for assessing severe PHLF in the HBV-related HCC patients. Subgroups include (A) cirrhosis, (B) no cirrhosis, (C) major hepatectomy, (D) minor hepatectomy, (E) blood loss ≥400 mL, (F) blood loss <400 mL, (G) blood transfusion, (H) no blood transfusion, (I) BCLC-0 or -A stage, and (J) BCLC-B or -C stage.

Abbreviations: ICG‐R15, indocyanine green retention test at 15 minutes; MELD, model for end‐stage liver disease; ALBI, albumin–bilirubin; ROC, receiver operating characteristic; PHLF, posthepatectomy liver failure; BCLC, Barcelona Clinical Liver Cancer; HBV, hepatitis B virus; HCC, hepatocellular carcinoma.

Figure 5 Relationship between the incidence of (A) postoperative major complications and (B) severe PHLF based upon risk group stratification assessed using the ICG-R15 in all included HBV-related HCC patients.

Abbreviations: PHLF, posthepatectomy liver failure; ICG‐R15, indocyanine green retention test at 15 minutes; HBV, hepatitis B virus; HCC, hepatocellular carcinoma.