Efficacy of dexamethasone and N-acetylcysteine combination in preventing post-embolization syndrome after transarterial chemoembolization in hepatocellular carcinoma

Table 1 Baseline characteristics of patients with intermediate-stage hepatocellular carcinoma

	N-acetylcysteine + dexamethasone	Placebo	P value
Sex
Male	44 (88%)	45 (90%)	0.75
Age (mean ± SD)	60.8 ± 10.52	60.46 ± 11.27	0.88
Underlying disease
Diabetic mellitus	17 (34%)	16 (32%)	0.83
Hypertension	22 (14%)	28 (56%)	0.23
Dyslipidemia	14 (28%)	18 (36%)	0.40
CKD	1 (2%)	2 (4%)	0.56
HIV	1 (2%)	1 (2%)	1.00
Tumor characteristic
Size
Median (range)	5.5 (1.4-19)	7.95 (1.4-17.2)	0.39
> 3 cm	40 (80%)	42 (84%)	0.65
Number
Median (range)	2 (1-10)	2 (1-10)	0.21
1	23 (46%)	17 (34%)	0.56
≥ 2	27 (54%)	33(66%)
Etiology
Hepatitis B	23 (46%)	28 (56%)	0.31
Hepatitis C	15 (30%)	12 (24%)	0.50
Alcoholic	22 (44%)	20 (40%)	0.67
Non-alcoholic steatohepatitis	3 (6%)	4 (8%)	0.70
Staging
BCLC-A	6 (12%)	3 (6%)	0.23
BCLC-B	44 (88%)	47 (94%)
Child-Pugh Score
A (5-6)	40 (80%)	43 (86%)	0.42
B (7-8)	10 (20%)	7 (14%)
ALBI score (mean ± SD)	-2.61 ± 0.58	-2.54 ± 0.53	0.54
Alpha fetoprotein (ng/mL)
< 20	18 (36%)	19 (38%)	0.50
20-200	14 (28%)	9 (18%)
201-1000	10 (20%)	9 (18%)
> 1000	8 (16%)	13 (26%)
Episode of TACE
1	16 (32%)	18 (36%)	0.67
2-5	34 (68%)	32 (64%)
Embolization agents
Mitomycin (mg)
5-10	1 (2%)	3 (6%)	0.07
10.1-15	20 (40%)	10 (20%)
15.1-20	29 (58%)	37 (74%)
Lipiodol (mL)
< 5	1 (2%)	1 (2%)	0.47
5-10	13 (26%)	8 (16%)
> 10	36 (72%)	41 (82%)
Level of embolization
Left hepatic artery	17 (34%)	14 (28%)	0.51
Right hepatic artery	46 (92%)	44 (88%)	0.50
Middle hepatic artery	5 (10%)	3 (6%)	0.46
≥ 2 major branches	18 (36%)	8 (16%)	0.02

ALBI: Albumin-bilirubin; BCLC: Barcelona Clinic Liver Cancer; CKD: Chronic kidney disease; HIV: Human immunodeficiency virus; SD: Standard deviation; TACE: Transarterial chemoembolization.

Table 2 Comparison between patients based on the occurrence of post-embolization syndrome and liver decompensation after conventional transarterial chemoembolization

	PES after cTACE		P value	Liver decompensation after TACE		P value
	Yes (n = 43)	No (n = 57)		Yes (n = 7)	No (n = 93)
Male	40 (93%)	49 (86%)	0.26	7 (100%)	82 (88.2%)	0.34
Age (mean ± SD)	60.72 ± 11.11	60.56 ± 10.74	0.26	63.57 ± 7.91	60.41 ± 11.04	0.35
Child-Pugh score	5.35 ± 0.69	5.61 ± 0.9	0.09	5.86 ± 0.9	5.47 ± 0.82	0.24
A (5-6)	40 (93%)	43 (75.4%)	0.02	5 (71.4%)	78 (83.9%)	0.4
B (7-8)	3 (7%)	14 (24.6%)	0.02	2 (28.6%)	15 (16.1%)	0.4
ALBI (median; IQR)	-2.72 (-3.05, -2.29)	-2.65 (-2.93, -2.2)	0.47	-1.95 (-2.74, -1.77)	-2.69 (-3.04, -2.29)	0.09
MELD (mean ± SD)	11.67 ± 3.54	12.05 ± 3.78	0.61	12.71 ± 3.86	11.83 ± 3.66	0.54
Staging
BCLC-A	3 (7%)	6 (10.5%)	0.54	1 (14.3%)	8 (8.6%)	0.61
BCLC-B	40 (93%)	51 (89.5%)	0.54	6 (85.7%)	85 (91.4%)	0.61
Tumor characteristics
AFP ≥ 200 ng/mL	17 (39.5%)	27 (47.4%)	0.44	3 (42.9%)	28 (30.1%)	0.48
Median (range)	9.6 (4,13.2)	5 (3.2,10)	0.05	5.7 (3.2,15)	7 (3.2,13)	0.8
Large tumor ≥ 5 cm	29 (67.4%)	27 (47.4%)	0.045	4 (57.1%)	52 (55.9%)	0.95
Number
1	18 (41.9%)	22 (38.6%)	0.74	4 (57.1%)	36 (38.7%)	0.34
≥ 2	25 (58.1%)	35 (61.4%)		3 (42.9%)	57 (61.3%)
Size plus number
Up to 7	32 (74.4%)	37 (64.9%)	0.31	4 (57.1%)	65 (69.9%)	0.48
Up to 12	21 (48.8%)	15 (26.3%)	0.02	3 (42.9%)	33 (35.5%)	0.7
cTACE episode
1	15 (34.9%)	19 (33.3%)	0.87	4 (57.1%)	30 (32.3%)	0.18
≥ 2 (2-5)	28 (65.1%)	38 (66.7%)		3 (42.9%)	63 (67.7%)
Embolization agent
Mitomycin (mg)
< 10	2 (4.7%)	2 (3.5%)	0.44	0 (0%)	4 (4.3%)	0.51
10-15	10 (23.3%)	20 (35.1%)		1 (14.3%)	29 (31.2%)
15.1-20	31 (72.1%)	35 (61.4%)		6 (85.7%)	60 (64.5%)
Lipiodol (mL)
< 5	1 (2.3%)	1 (1.8%)	0.32	0 (0%)	2 (2.2%)	0.82
5-10	6 (14%)	15 (26.3%)		1 (14.3%)	20 (21.5%)
> 10	36 (83.7%)	41 (71.9%)		6 (85.7%)	71 (76.3%)
Level of embolization
Left hepatic artery	10 (23.3%)	18 (31.6%)	0.36	3 (42.9%)	28 (30.1%)	0.32
Right hepatic artery	38 (88.4%)	44 (77.2%)	0.15	7 (100%)	83 (89.2%)	0.37
Middle hepatic artery	1 (2.3%)	7 (12.3%)	0.07	0 (0%)	8 (8.6%)	0.43
1 vessel	37 (86%)	34 (59.6%)	0.004	3 (42.9%)	67 (72%)	0.25
≥ 2 vessels	6 (14%)	23 (40.4%)	0.007	4 (57.1%)	26(28%)	0.02
Baseline laboratory (median; IQR)
Hct (%)	36.8 (32.3, 40.3)	35 (32.6, 38.9)	0.33	39.8 (36.6, 40.6)	35.2 (32.2, 39)	0.04
WBC (× 109/L)	5.83 (4.50, 7.18)	5.48 (4.13, 6.97)	0.18	5.49 (4.14, 6.08)	5.58 (4.29, 7.07)	0.57
Platelet (× 109/L)	186 (125, 241)	144 (103, 204)	0.09	105 (65, 226)	171 (117, 230)	0.39
PTT (s)	12.9 (12.3, 13.8)	13.5 (12.7, 14.7)	0.02	13 (12.1, 13.2)	13.1 (12.4, 14.2)	0.34
AST (U/L)	51 (35, 102)	47 (37, 79)	0.78	163 (102, 169)	49 (36, 77)	0.003
ALT (U/L)	35 (20, 80)	33 (21, 51)	0.29	106 (80, 139)	31 (20, 51)	< 0.001
ALP (U/L)	124 (104, 290)	120 (93, 153)	0.211	290 (121, 386)	120 (94, 169)	0.111
Albumin (g/dL)	4 (3.6, 4.2)	3.9 (3.5, 4.2)	0.569	3.7 (3.2, 4.1)	3.9 (3.6, 4.2)	0.360
Total bilirubin (mg/dL)	0.59 (0.39, 1)	0.69 (0.51, 1.3)	0.163	1.59 (0.82, 2.11)	0.59 (0.42, 1.01)	0.005
Direct bilirubin (mg/dL)	0.35 (0.24, 0.65)	0.39 (0.26, 0.78)	0.415	0.91 (0.49, 1.76)	0.35 (0.24, 0.65)	0.004
Presence of PES, n (%)	-	-	-	7 (100%)	36 (38.7%)	0.002
Fever	40 (93.0%)	5 (8.8%)	< 0.001	7 (100%)	38 (40.9%)	0.002
Vomit	25 (58.1%)	2 (3.5%)	< 0.001	3 (42.9%)	24 (25.8%)	0.327
Pain	5 (11.6%)	0 (0.0%)	0.008	0 (0.0%)	5 (5.37%)	0.529
Anorexia	21 (48.8%)	2 (3.5%)	< 0.001	4 (57.1%)	17 (18.3%)	0.015

AFP: Alpha fetoprotein; ALBI: Albumin-bilirubin; ALP: Alkaline phosphatase; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; BCLC: Barcelona Clinic Liver Cancer; cTACE: Conventional transarterial chemoembolization; Hct: Hematocrit; IQR: Interquartile range; MELD: Model of end-stage liver disease; PES: Post-embolization syndrome; PTT: Prothrombin time; SD: Standard deviation; WBC: White blood cell.

Table 3 Univariate and multivariate analyses of patients with post-embolization syndrome and liver decompensation after conventional transarterial chemoembolization

Parameter	PES after cTACE						Liver decompensation after cTACE
	Crude OR	95%CI	P value	aOR	95%CI	P value	Crude OR	95%CI	P value	aOR	95%CI	P value
NAC + DEXA	0.02	0-0.06	< 0.01	0.04	0.01-0.2	< 0.01	0	0-1	1.00	0	0-1	1.00
Size + number up to 12	1.09	1-1.19	0.04	1.08	0.92-1.27	0.33	0.99	0.84-1.16	0.88	-	-	-
AST rise > 20 folds in 48 h	1.51	1.09-2.09	0.01	1.35	0.72-2.52	0.35	1.7	0.95-3.03	0.07	1.3	0.56-3.02	0.54
ALBI change > 0.5	7.58	1.96-29.36	0.003	3.03	0.39-23.67	0.29	122.52	5.6-2681	0.002	42.77	1.01-1810	0.049
Total bilirubin rising > 1.5 folds	3.83	1.8-8.14	< 0.01	1.43	0.42-4.87	0.57	2.79	1.23-6.31	0.01	1.46	0.52-4.1	0.48
South west oncology grading > 4	1	0-1	0.99	-	-	-	1.43	1.04-1.96	0.03	0.94	0.51-1.76	0.86

ALBI: Albumin-bilirubin; aOR: Adjusted odds ratio; AST: Aspartate aminotransferase; CI: Confidence interval; DEXA: Dexamethasone; NAC: N-acetylcysteine; OR: Odds ratio; PES: Post-embolization syndrome; TACE: Transarterial chemoembolization.