Efficacy of postoperative adjuvant transcatheter arterial chemoembolization in hepatocellular carcinoma patients with microvascular invasion

Table 1 Baseline clinicopathological characteristics of hepatocellular carcinoma patients, stratified by microvascular invasion status and use of postoperative adjuvant transcatheter arterial chemoembolization n (%)

		No MVI (n = 259)			MVI (n = 260)
Characteristic	Category	No TACE (n = 187)	TACE (n = 72)	P	No TACE (n = 174)	TACE (n = 86)	P
Age (yr)	≤ 60	146 (78.1)	65 (90.3)	0.024	140 (80.5)	73 (84.9)	0.383
	> 60	41 (21.9)	7 (9.7)		34 (19.5)	13 (15.1)
Sex	Female	29 (15.5)	9 (12.5)	0.540	24 (13.8)	11 (12.8)	0.824
	Male	158 (84.5)	63 (87.5)		150 (86.2)	75 (87.2)
HBsAg	Negative	19 (10.2)	6 (8.3)	0.656	18 (10.3)	14 (16.3)	0.171
	Positive	168 (89.8)	66 (91.7)		156 (89.7)	72 (83.7)
Total bilirubin, μmol/L		11 (3-118.3)	11.2 (4.9-33.2)	0.423	11.2 (2.8-30.9)	11.75 (5.1-33.1)	0.330
Prothrombin time (s)		13.10 ± 1.18	13.55 ± 1.21	0.006	13.31 ± 1.38	13.31 ± 1.22	0.978
AFP (ng/mL)	≤ 400	128 (68.4)	44 (61.1)	0.263	89 (51.1)	49 (57.0)	0.376
	> 400	59 (31.6)	28 (38.9)		85 (48.9)	37 (43.0)
HBV-DNA (IU/mL)	≤ 104	95 (50.8)	43 (59.7)	0.197	89 (51.1)	52 (60.5)	0.156
	> 104	92 (49.2)	29 (40.3)		85 (48.9)	34 (39.5)
Pathology data
Size of largest tumor (cm)	≤ 5	121 (64.7)	38 (52.8)	0.077	76 (43.7)	41 (47.7)	0.542
	> 5	66 (35.3)	34 (47.2)		98 (56.3)	45 (52.3)
No. of nodules	Single	155 (82.9)	62 (86.1)	0.528	137 (78.7)	73 (84.9)	0.237
	Multiple	32 (17.1)	10 (13.9)		37 (21.3)	13 (15.1)
Differentiation	Edmondson 1-2	129 (69)	37 (51.4)	0.008	91 (52.3)	49 (57)	0.477
	Edmondson 3-4	58 (31)	35 (48.6)		83 (47.7)	37 (43)
Capsule	Complete	143 (76.5)	52 (72.2)	0.478	105 (60.3)	51 (59.3)	0.872
	Incomplete	44 (23.5)	20 (27.8)		69 (39.7)	35 (40.7)
Cirrhosis	No	31 (16.6)	9 (12.5)	0.416	31 (17.8)	14 (16.3)	0.758
	Yes	156 (83.4)	63 (87.5)		143 (82.2)	72 (83.7)
Surgical data
Type of resection	Minor	118 (63.1)	48 (66.7)	0.592	93 (53.4)	47 (54.7)	0.855
	Major	69 (36.9)	24 (33.3)		81 (46.6)	39 (45.3)
Hepatic inflow occlusion	No	79(42.2)	25 (34.7)	0.268	53 (30.5)	32 (37.2)	0.275
	Yes	108 (57.8)	47 (65.3)		121 (69.5)	54 (62.8)
Child-Pugh classification	A	180 (96.3)	70 (97.2)	1.000	172 (98.9)	84 (97.7)	0.601
	B	7 (3.7)	2 (2.8)		2 (1.1)	2 (2.3)
Hypersplenism	No	169 (90.4)	67 (93.1)	0.497	155 (89.1)	83 (96.5)	0.043
	Yes	18 (9.6)	5 (6.9)		19 (10.9)	3 (3.5)
BCLC	0	18 (9.6)	1 (1.4)	0.002	6 (3.4)	1 (1.2)	0.158
	A	151 (80.7)	54 (75)		121 (69.5)	69 (80.2)
	B	18 (9.6)	17 (23.6)		47 (27)	16 (18.6)
Recurrence	Yes	56 (29.9)	20 (27.8)	0.731	102 (58.6)	34 (39.5)	0.004
	No	131 (70.1)	52 (72.2)		72 (41.4)	52 (60.5)

HBsAg: Hepatitis B surface antigen; AFP: Alpha-fetoprotein; BCLC: Barcelona Clinic Liver Cancer; MVI: Microvascular invasion.

Table 2 Uni- and multivariate analyses to identify predictors of overall survival or recurrence-free survival in hepatocellular carcinoma patients after potentially curative resection

Factor	Univariate				Multivariate
	OS		RFS		OS		RFS
	HR (95%CI)	P	HR (95%CI)	P	HR (95%CI)	P	HR (95%CI)	P
Sex (male)	1.487 (0.773-2.864)	0.235	1.354 (0.885-2.071)	0.163
Age (> 60 yr)	1.091 (0.627-1.772)	0.723	1.017 (0.723-1.430)	0.923
HBsAg (+)	1.275 (0.618-2.630)	0.511	1.365 (0.842-2.214)	0.207
Total bilirubin (μmol/L)	0.992 (0.964-1.021)	0.586	0.966 (0.979-1.013)	0.653
Prothrombin time (s)	1.071 (0.931-1.232)	0.340	1.064 (0.966-1.173)	0.210
Child-Pugh classification (B)	1.423 (0.523-3.875)	0.490	2.074 (1.098-3.915)	0.024
Hypersplenism (yes)	0.949 (0.477-1.887)	0.882	1.158 (0.738-1.817)	0.524
AFP (> 400 ng/mL)	2.063 (1.379-3.086)	0.000	1.321 (1.007-1.733)	0.044	1.738 (1.152-2.622)	0.008
HBV-DNA (> 1 × 104 IU/mL)	1.191 (0.798-1.777)	0.393	1.259 (0.962-1.649)	0.094			1.316 (1.002-1.729)	0.048
Tumor size (> 5 cm)	2.219 (1.456-3.382)	0.000	1.694 (1.291-2.223)	0.000	1.858 (1.213-2.848)	0.004	1.600 (1.216-2.105)	0.001
Nodule no. (multinodular)	1.425 (0.885-2.294)	0.145	1.370 (0.985-1.905)	0.061			1.427 (1.024-1.989)	0.036
Differentiation (grades 3-4)	1.396 (0.934-2.085)	0.103	1.347 (1.027-1.766)	0.031
Incomplete tumor capsule (yes)	2.366 (1.582-3.537)	0.000	1.664 (1.266-2.187)	0.000	1.998 (1.329-3.006)	0.001	1.468 (1.114-1.935)	0.006
MVI (yes)	3.412 (2.135-5.452)	0.000	2.180 (1.646-2.888)	0.000	2.524 (1.564-4.075)	0.000	1.959 (1.472-2.606)	0.000
Cirrhosis (yes)	0.922 (0.522-1.541)	0.757	1.359 (0.918-2.031)	0.125
Approach of resection (major )	1.576 (1.054-2.357)	0.027	1.177 (0.896-1.547)	0.242	1.611 (1.073-2.419)	0.021
Hepatic inflow occlusion (yes)	0.784 (0.519-1.185)	0.248	0.919 (0.649-1.217)	0.556

OS: Overall survival; RFS: Recurrence-free survival; AFP: Alpha-fetoprotein; MVI: Microvascular invasion.

Table 3 Logistic regression to identify independent predictors of microvascular invasion in hepatocellular carcinoma patients

Predictor	HR (95%CI)	P
AFP (> 400 ng/mL)	1.680 (1.167-2.418)	0.005
Tumor size (> 5 cm)	1.767 (1.235-2.527)	0.002
Incomplete tumor capsule (yes)	1.960 (1.335-2.878)	0.001

AFP: Alpha-fetoprotein.

Table 4 Survival rates of hepatocellular carcinoma patients in different groups

Group	OS rate (%)					RFS rate (%)
	1 yr	2 yr	3 yr	4 yr	P	1 yr	2 yr	3 yr	4 yr	P
MVI (-), TACE (-)	98.8	91.5	82.8	82.8	0.872	80.7	70.1	61.2	55.9	0.974
MVI (-), TACE (+)	94.2	91.9	87.6	87.6		83.0	71.8	61.9	NA
MVI (+), TACE (-)	81.3	65.7	58.8	53.9	0.019	52.0	41.1	33.7	28.4	0.002
MVI (+), TACE (+)	92.7	86.5	73.1	67.5		72.1	58.3	54.9	30.9

OS: Overall survival; RFS: Recurrence-free survival; MVI: Microvascular invasion; TACE: Transcatheter arterial chemoembolization.

Table 5 Complications and adverse events after postoperative adjuvant transcatheter arterial chemoembolization n (%)

Complication	Events
Nausea and vomiting	46 (29.11)
Fever	35 (22.2)
Pain	49 (31.0)
Alopecia	5 (3.2)
Liver failure	0 (0.0)
Bleeding of esophageal venous plexus	0 (0.0)
Gastrointestinal hemorrhage	0 (0.0)
Heart failure	0 (0.0)
Infection	0 (0.0)
Ectopic embolism syndrome	0 (0.0)
Refractory ascites	0 (0.0)
Pulmonary complication	2 (1.3)
Therapy-related death	0 (0.0)