Efficacy and Safety of Transarterial Chemoembolization and Repeated Partial Splenic Embolization for Hepatocellular Carcinoma with Hypersplenism and Thrombocytopenia

Figures & data

Figure 1 Patients selection.

Abbreviations: HCC, hepatocellular carcinoma; TACE, transarterial chemoembolization; PSE, partial splenic embolization.

Table 1 Comparison of the Baseline Characteristics of Patients Between the TACE Alone Group and the TACE+PSE Group

Variables	TACE Alone Group (n = 73)	TACE+PSE Group (n = 29)	P
Gender			1.000
Male	59 (80.8)	23 (79.3)
Female	14 (19.2)	6 (20.7)
Age, years			0.063
≤60	39 (53.4)	22 (75.9)
>60	34 (46.6)	7 (24.1)
Etiology			0.618
HBV	53 (72.6)	24 (82.8)
HCV	9 (12.3)	3 (10.3)
NBNC	11 (15.1)	2 (6.9)
PLT, × 10^9/L	74.34 ± 16.51	42.93 ± 11.16	< 0.001
RBC, × 10^12/L	3.82 ± 0.62	3.62 ± 0.51	0.091
Hemoglobin, g/L	119.29 ± 21.04	113.41 ± 17.35	0.152
WBC, × 10^9/L	3.81 ± 1.59	2.32 ± 0.78	< 0.001
Total bilirubin, μmol/L	23.80 ± 13.05	32.25 ± 19.54	0.038
Albumin, g/L	34.82 ± 4.76	33.76 ± 4.53	0.295
Child-Pugh score	6.25 ± 1.19	6.86 ± 1.38	0.040
Child-Pugh class			0.068
A	44 (60.3)	11 (37.9)
B	29 (39.7)	18 (62.1)
ALT, U/L	39.96 ± 31.88	30.45 ± 16.40	0.052
AST, U/L	53.17 ± 32.65	43.28 ± 20.00	0.068
Tumor number			0.132
Solitary	34 (46.6)	19 (65.5)
Multiple	39 (53.4)	10 (34.5)
Tumor location			0.564
Left lobe	8 (11.0)	3 (10.3)
Right lobe	45 (61.6)	21 (72.4)
Both lobe	20 (27.4)	5 (17.2)
Tumor size, cm			0.487
≤3	28 (38.4)	14 (48.3)
>3	45 (61.6)	15 (51.7)
BCLC stage			0.580
0	5 (6.8)	3 (10.3)
A	21 (28.8)	8 (27.6)
B	18 (24.7)	4 (13.8)
C	29 (39.7)	14 (48.3)
Initial TACE method			0.798
C-TACE	57 (78.1)	24 (82.8)
DEB-TACE	16 (21.9)	5 (17.2)

Notes: Data are presented as means ± standard deviations.

Abbreviations: TACE, transarterial chemoembolization; PSE, partial splenic embolization; HBV, hepatitis B virus; HCV, hepatitis C virus; NBNC, non-B, non-C hepatitis; PLT, platelet; RBC, red blood cell; WBC, white blood cell; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BCLC, Barcelona Clinic Liver Cancer; C-TACE, conventional transarterial chemoembolization; DEB-TACE, drug-eluting bead transarterial chemoembolization.

Table 2 Comparison of the Changes in Peripheral Blood Cell Counts from Baseline Between the TACE Alone Group and the TACE+PSE Group

Variables	Time Point	TACE Alone Group	TACE+PSE Group	P
PLT, × 10^9/L	1 week	0.23 ± 23.38	12.21 ± 20.91	0.019
	2 months	−3.17 ± 15.28	6.33 ± 10.75	0.002
	6 months	0.49 ± 23.01	16.83 ± 18.48	0.004
	12 months	−0.88 ± 17.10	37.71 ± 25.07	< 0.001
	18 months	2.57 ± 25.06	53.36 ± 25.25	< 0.001
	24 months	1.00 ± 16.13	38.71 ± 20.39	0.002
RBC, × 10^12/L	6 months	−0.12 ± 0.70	0.14 ± 0.30	0.046
	12 months	−0.24 ± 0.58	0.21 ± 0.41	0.008
	18 months	−0.58 ± 0.73	0.13 ± 0.56	0.012
	24 months	−0.67 ± 0.49	0.19 ± 0.37	< 0.001
Hemoglobin, g/L	6 months	−4.49 ± 17.61	4.91 ± 10.64	0.013
	12 months	−4.84 ± 15.29	9.86 ± 16.58	0.011
	18 months	−17.07 ± 25.10	10.73 ± 19.27	0.005
	24 months	−18.50 ± 13.87	8.00 ± 8.89	< 0.001
WBC, × 10^9/L	1 week	0.88 ± 1.74	2.23 ± 1.65	< 0.001
	2 months	−0.67 ± 1.43	0.17 ± 0.90	0.003
	24 months	−0.19 ± 1.06	1.23 ± 0.93	0.009

Note: Data are presented as means ± standard deviations.

Abbreviations: TACE, transarterial chemoembolization; PSE, partial splenic embolization; PLT, platelet; RBC, red blood cell; WBC, white blood cell.

Figure 2 Changes in peripheral blood cell counts in two groups during the follow-up period. (A) Changes in PLT (platelet) from baseline; (B) Changes in RBC (red blood cell) from baseline; (C) Changes in hemoglobin from baseline; (D) Changes in WBC (white blood cell) from baseline. The blue points and lines indicate TACE alone group, and the red points and lines indicate TACE+PSE group. Data are presented as means ± standard deviations. *P < 0.05; **P < 0.01; ***P < 0.001.

Table 3 Comparison Between Initial and Repeated PSE of the Changes in Peripheral Blood Cell Counts and Hepatic Function in 1 Week and 2–3 Months

Variables	Changes in 1 Week		Changes in 2–3 Months		P1	P2
	Initial PSE	Repeated PSE	Initial PSE	Repeated PSE
PLT, × 10^9/L	12.21 ± 20.91	21.96 ± 36.01	6.33 ± 10.75	23.33 ± 30.42	0.145	0.001
RBC, × 10^12/L	−0.25 ± 0.30	−0.08 ± 0.29	−0.13 ± 0.38	0.15 ± 0.36	0.021	0.004
Hemoglobin, g/L	−6.57 ± 9.48	−2.37 ± 8.28	−3.63 ± 11.43	5.00 ± 11.65	0.058	0.003
WBC, × 10^9/L	2.23 ± 1.65	3.55 ± 3.63	0.17 ± 0.90	0.71 ± 1.29	0.036	0.046
Total bilirubin, μmol/L	6.33 ± 21.12	1.61 ± 11.32	−2.57 ± 12.58	1.03 ± 12.55	0.287	0.275
Albumin, g/L	−3.35 ± 3.67	−1.24 ± 3.75	−2.10 ± 4.59	1.23 ± 2.28	0.023	0.002
Child-Pugh score	0.79 ± 1.29	0.10 ± 0.77	0.31 ± 1.46	−0.37 ± 0.94	0.015	0.045
Log ALT, U/L	0.20 ± 0.69	−0.10 ± 0.77	−0.01 ± 0.55	−0.08 ± 0.44	0.100	0.601
Log AST, U/L	0.09 ± 0.49	−0.07 ± 0.58	0.07 ± 0.55	−0.07 ± 0.45	0.224	0.296

Notes: Data are presented as means ± standard deviations. P1: Comparison of the changes in peripheral blood cell counts and hepatic function in 1 week after initial and repeated PSE. P2: Comparison of the changes in peripheral blood cell counts and hepatic function in 2–3 months after initial and repeated PSE.

Abbreviations: PSE, partial splenic embolization; PLT, platelet; RBC, red blood cell; WBC, white blood cell; ALT, alanine aminotransferase; AST, aspartate aminotransferase.

Table 4 Comparison of the Changes in Hepatic Function from Baseline Between the TACE Alone Group and the TACE+PSE Group

Variables	Time Point	TACE Alone Group	TACE+PSE Group	P
Child-Pugh score	1 week	0.63 ± 0.80	0.79 ± 1.29	0.568
	2 months	0.38 ± 1.38	0.31 ± 1.46	0.831
	6 months	0.31 ± 1.55	−0.09 ± 1.27	0.294
	12 months	0.96 ± 1.87	−0.43 ± 1.50	0.019
	18 months	1.67 ± 1.61	−0.40 ± 1.43	0.005
	24 months	1.33 ± 1.67	−0.14 ± 1.57	0.075
Total bilirubin, μmol/L	24 months	9.83 ± 18.06	−4.10 ± 12.76	0.067
Albumin, g/L	18 months	−4.43 ± 3.05	0.13 ± 6.88	0.076
	24 months	−3.58 ± 4.55	1.37 ± 5.38	0.066

Notes: Data are presented as means ± standard deviations.

Abbreviations: TACE, transarterial chemoembolization; PSE, partial splenic embolization.

Figure 3 Changes in hepatic function in two groups during the follow-up period. (A) Changes in Child-Pugh score from baseline; (B) Changes in total bilirubin from baseline; (C) Changes in albumin from baseline; (D) Changes in log ALT (alanine aminotransferase) from baseline; (E) Changes in log AST (aspartate aminotransferase) from baseline. The blue points and lines indicate TACE alone group, and the red points and lines indicate TACE+PSE group. Data are presented as means ± standard deviations. *P < 0.05; **P < 0.01.

Figure 4 Mean number of TACE procedure sessions per patient during the follow-up period. *P < 0.05; **P < 0.01; ns: no significance.

Table 5 Univariate and Multivariate Analysis on Baseline Factors Associated with Progression-Free Survival

Variables	Category	Univariate		Multivariate^a
		P	HR	95% CI	P
Gender	Male	Reference
	Female	0.262
Age, years	≤60	Reference
	>60	0.322
Etiology	HBV	Reference
	HCV	0.123
	NBNC	0.696
PLT		0.051
RBC		0.694
Hemoglobin		0.143
WBC		0.204
Total bilirubin		0.527
Albumin		0.781
Child-Pugh score		0.718
Child-Pugh class	A	Reference
	B	0.416
ALT		0.179
AST		0.224
Tumor number	Solitary	Reference
	Multiple	<0.001	1.370	0.758–2.475	0.297
Tumor location	Left lobe	Reference
	Right lobe	0.393	1.288	0.590–2.813	0.526
	Both lobe	0.016	2.064	0.801–5.319	0.133
Tumor size, cm	≤3	Reference
	>3	< 0.001	2.006	1.168–3.446	0.012
BCLC stage	0	Reference
	A	0.155
	B	0.077
	C	0.107
TACE method	C-TACE	Reference
	DEB-TACE	0.269
Group	TACE alone	Reference
	TACE+PSE	0.025	0.508	0.296–0.872	0.014
Other treatments	Without	Reference
	With	0.122

Notes: ^aMultivariate analysis included potential factors that showed an association (P < 0.05) with progression-free survival according to univariate analysis.

Abbreviations: HR, hazard ratio; CI, confidence interval; TACE, transarterial chemoembolization; PSE, partial splenic embolization; HBV, hepatitis B virus; HCV, hepatitis C virus; NBNC, non-B, non-C hepatitis; PLT, platelet; RBC, red blood cell; WBC, white blood cell; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BCLC, Barcelona Clinic Liver Cancer; C-TACE, conventional transarterial chemoembolization; DEB-TACE, drug-eluting bead transarterial chemoembolization.

Figure 5 Kaplan–Meier curves of the progression-free survival times.

Table 6 Comparison of the Incidence of Complications After Initial TACE Alone Procedures, Initial TACE+PSE Procedures and Repeated TACE+PSE Procedures

Complications	Initial TACE Alone Procedures (n = 73)	Initial TACE+PSE Procedures (n = 29)	Repeated TACE+PSE Procedures (n = 51)	P1	P2
Fever	25 (34.2)	12 (41.4)	21 (41.2)	0.504	1.000
Pain	41 (56.2)	21 (72.4)	35 (68.6)	0.178	0.803
Abdominal distention	18 (24.7)	15 (51.7)	23 (45.1)	0.011	0.644
Nausea and vomiting	17 (23.3)	11 (37.9)	18 (35.3)	0.148	0.814
Portal vein thrombosis	0 (0.0)	2 (6.9)	1 (2.0)	0.079	0.296
Splenic vein thrombosis	0 (0.0)	0 (0.0)	1 (2.0)	1.000	1.000
Refractory ascites	1 (1.4)	0 (0.0)	0 (0.0)	1.000	1.000
Bacterial peritonitis	2 (2.7)	0 (0.0)	0 (0.0)	1.000	1.000
Large amount of pleural effusion	1 (1.4)	0 (0.0)	1 (2.0)	1.000	1.000
Gastrointestinal bleeding	1 (1.4)	1 (3.4)	2 (3.9)	0.490	1.000
Major complications	5 (6.8)	1 (3.4)	3 (5.9)	0.672	1.000
Death	1 (1.4)	0 (0.0)	1 (2.0)	1.000	1.000

Notes: Data are presented as numbers (%). P₁: Comparison of the incidence of complications after initial TACE alone procedures and initial TACE+PSE procedures. P₂: Comparison of the incidence of complications after initial TACE+PSE procedures and repeated TACE+PSE procedures.

Abbreviations: TACE, transarterial chemoembolization; PSE, partial splenic embolization.

Data Sharing Statement

The data are available from the corresponding author upon reasonable request.