Efficacy of N-acetylcysteine vs dexamethasone in preventing postembolization syndrome post-transarterial chemoembolization in hepatocellular carcinoma: A randomized controlled trial

Table 1 Baseline characteristics of participants with hepatocellular carcinoma

Baseline characteristic	Total (n = 56)	NAC (n = 28)	DEXA (n = 28)	P value
Male	47 (83.9)	24 (85.7)	23 (82.1)	1.0004
Age (years)	59.7 ± 8.7	59.0 ± 6.6	60.3 ± 10.4	0.2593
Body mass index (kg/m2)	24.3 ± 3.9	24.5 ± 4.5	24.1 ± 3.4	0.7542
Underlying diseases
Hypertension	25 (44.6)	13 (46.4)	12 (42.9)	0.7881
Diabetes mellitus	14 (25.0)	3 (10.7)	11 (39.3)	0.0294
Dyslipidemia	7 (12.5)	1 (3.6)	6 (21.4)	0.1014
Etiology of cirrhosis
Chronic hepatitis B	20 (35.7)	11 (39.3)	9 (32.14)	0.5771
Chronic hepatitis C	23 (41.1)	13 (46.4)	10 (35.7)	0.4151
Alcohol	19 (33.9)	11 (39.3)	8 (28.6)	0.3971
MASLD	10 (17.9)	2 (7.1)	8 (28.6)	0.0784
Child-Pugh score				1.0004
A (5-6)	52 (92.9)	26 (92.9)	26 (92.9)
B (7-8)	4 (7.1)	2 (7.1)	2 (7.1)
MELD score				0.7781
< 10	37 (66.1)	18 (64.3)	19 (67.9)
≥ 10	19 (33.9)	10 (35.7)	9 (32.1)
MELD score	9.0 ± 1.8	9.2 ± 2.0	8.8 ± 1.6	0.6113
MELD-Na	9.8 ± 4.4	9.4 ± 4.3	10.2 ± 4.5	0.4592
ALBI grade				0.0944
1	5 (8.9)	4 (14.3)	1 (3.6)
2	30 (53.6)	11 (39.3)	19 (67.9)
3	21 (37.5)	13 (46.4)	8 (28.6)
ALBI score	-2.3 ± 0.5	-2.2 ± 0.6	-2.4 ± 0.4	0.2623
BCLC stage B				0.2171
B1	14 (25.0)	9 (32.1)	5 (17.9)
B2	42 (75.0)	19 (67.9)	23 (82.1)
Maximum tumor size (cm)	6.2 ± 3.7	5.2 ± 2.0	7.2 ± 4.6	0.1323
Tumor number				0.3264
1	8 (14.3)	2 (7.1)	6 (21.4)
2-5	37 (66.1)	21 (75.0)	16 (57.1)
> 5	11 (19.6)	5 (17.9)	6 (21.4)
Tumor size plus number (Beyond up to 7)	39 (69.6)	18 (64.3)	21 (75.0)	0.3831
AST (U/L)	68.1 ± 40.3	75.5 ± 43.9	60.6 ± 35.5	0.2483
ALT (U/L)	44.1 ± 35.2	48.5 ± 33.3	39.6 ± 37.0	0.0703
Total bilirubin (mg/dL)	0.9 ± 0.5	0.9 ± 0.6	0.8 ± 0.5	0.7243
Albumin (mg/dL)	3.6 ± 0.5	3.5 ± 0.6	3.7 ± 0.4	0.1812
Mitomycin dose (mL)	14.5 ± 6.1	11.4 ± 6.1	17.5 ± 4.4	< 0.0013
Lipiodol dose (mL)	9.4 ± 5.6	8.4 ± 7.3	10.4 ± 3.0	0.0313

¹χ² test.

²Independent t-test.

³Mann-Whitney U test.

⁴Fisher’s exact test were used to compared baseline characteristics between the N-acetylcysteine and dexamethasone group.

Data are presented as n (%) or mean ± SD. Significant level was set at P value < 0.05. ALBI: Albumin-bilirubin; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; BCLC stage B: Barcelona Clinic Liver Cancer stage B; DEXA: Dexamethasone; MASLD: Metabolic dysfunction-associated steatotic liver disease; MELD: Model for end-stage liver disease; MELD-Na: Model for end-stage liver disease-Sodium; NAC: N-acetylcysteine.

Table 2 Effectiveness of N-acetylcysteine compared to dexamethasone on the postembolization syndrome and the association of the characteristic of hepatocellular carcinoma (beyond up to 7) on postembolization syndrome

Variables	PES (n = 27)	No PES (n = 29)	OR (95%CI)	P value	Adjusted OR	P value
Treatment group
N-acetylcysteine	9 (32.1)	19 (67.9)	0.26 (0.09- 0.80)	0.018	0.17 (0.03- 0.87)	0.0331
Dexamethasone	18 (64.3)	10 (35.7)	Reference		Reference
Beyond up to 7
Yes	22 (56.4)	17 (43.6)	3.11 (0.92-10.52)	0.069	1.00 (0.16-6.30)	1.0002
No	5 (29.4)	12 (70.6)	Reference		Reference

¹Multivariable logistic regression analysis adjusted for confounders summary score calculated from multivariable logistic regression analysis adjusted for sex, age, body mass index, hypertension, diabetes mellitus, dyslipidemia, etiology of cirrhosis (chronic hepatitis B, chronic hepatitis C, alcohol, Model for end-stage liver disease score), Child-Pugh score, Model for end-stage liver disease score, albumin-bilirubin score, Barcelona Clinic Liver Cancer stage B, maximum tumor size, tumor number, aspartate aminotransferase, alanine aminotransferase, total bilirubin, albumin, mitomycin dose, and lipiodol dose were used to analyze the effectiveness of N-acetylcysteine compared to dexamethasone on the postembolization syndrome.

²Multivariable logistic regression analysis adjusted for confounders summary score calculated from multivariable logistic regression analysis adjusted for treatment group (N-acetylcysteine & dexamethasone), sex, age, body mass index, hypertension, diabetes mellitus, dyslipidemia, etiology of cirrhosis (chronic hepatitis B, chronic hepatitis C, alcohol, Model for end-stage liver disease score), Child-Pugh score, Model for end-stage liver disease score, albumin-bilirubin score, Barcelona Clinic Liver Cancer stage B, aspartate aminotransferase, alanine aminotransferase, total bilirubin, albumin, mitomycin dose, and lipiodol dose were used to analyze the association of the characteristic of hepatocellular carcinoma (beyond up to 7) on postembolization syndrome.

PES: Postembolization syndrome.

Table 3 The dynamic change of albumin-bilirubin score between the N-acetylcysteine and dexamethasone group

Endpoints	NAC group (n = 28)	DEXA group (n = 28)	Mean ALBI change (NAC group)2	P value	Mean ALBI change (DEXA group)2	P value	Difference of mean ALBI change between the two group3	P value
ALBI	0.18 (-0.07 to 0.42), P = 0.1581
Day 0	-2.2 ± 0.6	-2.4 ± 0.4	Reference		Reference		Reference
Day 2	-1.6 ± 0.5	-1.9 ± 0.3	0.60 (0.48 – 0.72)	< 0.001	0.55 (0.43 – 0.67)	< 0.001	0.05 (-0.12 – 0.22)	0.568
Day 28	-2.1 ± 0.6	-2.1 ± 0.6	0.11 (-0.04 – 0.27)	0.140	0.27 (0.11 – 0.42)	< 0.001	-0.15 (-0.36 – 0.06)	0.167

¹Multilevel linear regression with random intercept and effect was used to compare mean difference of post-conventional transarterial chemoembolization albumin-bilirubin (ALBI) at baseline (day 0).

²Calculated mean ALBI change from baseline at day 2 and day 28 within each group.

³Calculated mean difference of ALBI change between the groups.

ALBI: Albumin-bilirubin; DEXA: Dexamethasone; NAC: N-acetylcysteine.