Tenofovir versus Entecavir on Outcomes of Hepatitis B Virus-Related Hepatocellular Carcinoma After FOLFOX-Hepatic Arterial Infusion Chemotherapy

Figures & data

Figure 1 Flowchart of enrolled patients.

Table 1 Baseline Characteristics of Patients Before PSM (n=683) and After PSM (n=566)

Variables	Before PSM			After PSM
	ETV Group (n=522)	TDF Group (n=161)	p Value	ETV Group (n=408)	TDF Group (n=158)	p Value
Age (years)	51±16 (18, 78)	52±15 (24, 74)	0.498	51±16 (18, 78)	52±15 (24, 74)	0.451
Sex (N, %)
Women	60 (11.5)	14 (8.7)	0.318	39 (9.6)	13 (8.2)	0.623
Men	462 (88.5)	147 (91.3)		369 (90.4)	145 (91.8)
Diabetes (N, %)
Absence	492 (94.3)	148 (91.9)	0.288	384 (94.1)	145 (91.8)	0.311
Presence	30 (5.7)	13 (8.1)		24 (5.9)	13 (8.2)
Hypertension (N, %)
Absence	477 (91.4)	142 (88.2)	0.226	367 (90.0)	139 (88.0)	0.493
Presence	45 (8.6)	19 (11.8)		41 (10.0)	19 (12.0)
Cirrhosis (N, %)
Absence	203 (38.9)	61 (37.9)	0.820	162 (39.7)	61 (38.6)	0.810
Presence	319 (61.1)	100 (62.1)		246 (60.3)	97 (61.4)
Tumor size (mm)	104.5±50.0 (19.0, 231.0)	97.0±48.0 (30.0, 198.0)	0.047	102.7±36.4 (19.0, 210.0)	99.0±34.5 (30.0, 198.0)	0.273
Tumor number (N, %)
Single	172 (33.0)	53 (32.9)	0.994	137 (33.6)	52 (32.9)	0.880
Multiple	250 (67.0)	108 (67.1)		271 (66.4)	106 (67.1)
MVI (N, %)
Absence	223 (42.7)	72 (44.7)	0.654	173 (42.4)	71 (44.9)	0.585
Presence	299 (57.3)	89 (55.3)		235 (57.6)	87 (55.1)
Metastasis (N, %)
Absence	415 (79.5)	135 (83.9)	0.223	328 (80.4)	132 (83.5)	0.389
Presence	107 (20.5)	26 (16.1)		80 (19.6)	26 (16.5)
PLT (×10^9/L)	221.5±139.3 (36.0, 763.0)	210.0±120.5 (59.0, 926.0)	0.177	212.5±135.0 (36.0, 763.0)	209.5±121.0 (59.0, 926.0)	0.352
PT (s)	12.3±1.3 (9.4, 16.2)	12.3±1.3 (10.1, 16.3)	0.489	12.2±1.3 (9.4, 16.1)	12.3±1.3 (10.1, 16.3)	0.741
ALT (U/L)	61.9±57.0 (16.2, 728.1)	66.8±64.2 (3.1, 414.6)	0.891	45.2±34.5 (7.7, 530.1)	47.3±36.9 (7.7, 316.1)	0.395
AST (U/L)	40.2±6.1 (23.6, 54.0)	39.8±6.5 (29.1, 52.9)	0.947	60.5±53.1 (16.2, 728.1)	67.1±66.8 (3.1, 414.6)	0.938
ALB (g/L)	15.4±8.6 (3.5, 145.2)	16.1±10.2 (4.5, 116.6)	0.394	40.3±6.2 (23.6, 54.0)	40.1±6.3 (29.1, 52.9)	0.930
TBil (umol/L)	221.5±139.3 (36.0, 763.0)	210.0±120.5 (59.0, 926.0)	0.177	15.3±8.5 (3.5, 92.6)	16.1±10.3 (4.5, 116.6)	0.302
AFP (ng/mL)
<20	91 (17.4)	39 (24.2)	0.055	84 (20.6)	36 (22.8)	0.566
≥20	431 (82.6)	122 (75.8)		324 (79.4)	122 (77.2)
PIVKA-II (mAU/mL)
<40	13 (2.5)	10 (6.2)	0.022	13 (3.2)	9 (5.7)	0.166
≥40	509 (97.5)	151 (93.8)		395 (96.8)	149 (94.3)
Log10HBV DNA (IU/mL)	3.62±2.54 (0, 8.34)	3.86±2.58 (0, 7.76)	0.112	3.87±2.32 (0.8.34)	3.94±2.59 (0, 7.76)	0.509
Child‒Pugh class (N, %)
A	501 (96.0)	146 (90.7)	0.009	389 (95.3)	146 (92.4)	0.168
B	21 (4.0)	15 (9.3)		19 (4.7)	12 (7.6)
ALBI grade (N, %)
Grade 1	293 (56.1)	87 (54.0)	0.732	229 (56.1)	87 (55.1)	0.897
Grade 2	228 (43.7)	74 (46.0)		178 (43.6)	71 (44.9)
Grade 3	1 (0.2)	0 (0)		1 (0.2)	0 (0)
Concomitant antitumor regimen (N, %)
No other regimen	199 (38.1)	44 (27.3)	0.039	153 (37.5)	44 (27.8)	0.110
Systemic treatment	201 (38.5)	79 (49.1)		159 (39.0)	77 (48.7)
Conversion surgery	56 (10.7)	14 (8.7)		42 (10.3)	14 (8.9)
Systemic treatment + conversion surgery	66 (12.6)	24 (14.9)		54 (13.2)	23 (14.6)
Cycles of HAIC (N, %)
<4	280 (53.6)	95 (59.0)	0.232	220 (53.9)	93 (58.9)	0.289
≥4	242 (46.4)	66 (41.0)		188 (46.1)	65 (41.1)

Notes: Continuous variables are presented as the mean ± standard deviation (SD) or median ± interquartile range according to normal or nonnormal distribution. Categorical variables are presented as frequencies and percentages.

Figure 2 Kaplan‒Meier curves of overall survival after HAIC between the two groups in the full cohort (A) and in the matched cohort (B), after HAIC with < 4 cycles between the two groups in the full cohort (C) and in the matched cohort (D), and after HAIC with ≥ 4 cycles between the two groups in the full cohort (E) and in the matched cohort (F).

Figure 3 Kaplan‒Meier curves of progression-free survival after HAIC between the two groups in the full cohort (A) and in the matched cohort (B), after HAIC with < 4 cycles between the two groups in the full cohort (C) and in the matched cohort (D), and after HAIC with ≥ 4 cycles between the two groups in the full cohort (E) and in the matched cohort (F).

Table 2 Univariate and Multivariate Analyses of Prognostic Factors for Overall Survival and Progression-Free Survival

Variables	Overall Survival						Progression-Free Survival
	Univariate Analysis			Multivariate Analysis			Univariate Analysis			Multivariate Analysis
	HR	95% CI	p value	HR	95% CI	p value	HR	95% CI	p value	HR	95% CI	p value
Age (≥65/<65)	1.039	0.710–1.519	0.845				0.956	0.691–1.322	0.786
Sex (men/women)	1.302	0.933–1.819	0.121				1.257	0.940–1.682	0.123
Diabetes (presence/absence)	1.123	0.730–1.730	0.597				0.839	0.565–1.246	0.385
Hypertension (presence/absence)	0.854	0.580–1.256	0.422				0.801	0.575–1.117	0.191
Cirrhosis (presence/absence)	0.840	0.682–1.036	0.103				0.832	0.691–1.002	0.052
Tumor size (mm)	1.006	1.004–1.009	<0.001	1.002	0.999–1.005	0.151	1.004	1.002–1.006	0.001	1.001	0.999–1.004	0.312
Tumor number (multiple/single)	1.180	0.946–1.472	0.143				1.226	1.008–1.491	0.041	1.180	0.966–1.440	0.105
MVI (presence/absence)	1.350	1.090–1.672	0.006	1.339	1.075–1.667	0.009	1.171	0.973–1.409	0.095
Metastasis (presence/absence)	2.040	1.593–2.612	<0.001	1.159	0.894–1.502	0.264	1.726	1.381–2.158	<0.001	1.268	1.000–1.608	0.050
PLT (×10^9/L)	1.000	0.999–1.001	0.620				1.001	1.000–1.001	0.137
PT (s)	1.214	1.105–1.334	<0.001	1.003	0.900–1.118	0.954	1.144	1.051–1.244	0.002	1.045	0.953–1.147	0.351
ALT (U/L)	1.003	1.002–1.004	<0.001	0.998	0.996–1.001	0.179	1.001	0.999–1.002	0.538
AST (U/L)	0.949	0.929–0.969	<0.001	1.002	1.001–1.004	0.005	1.002	1.001–1.003	<0.001	1.001	1.000–1.002	0.137
ALB(g/L)	1.005	0.996–1.014	0.264	0.995	0.958–1.033	0.777	0.976	0.958–0.995	0.014	1.023	0.991–1.056	0.157
TBil (umol/L)	1.163	0.882–1.534	0.285				1.003	0.996–1.011	0.368
AFP (≥20 ng/mL/<20 ng/mL)	1.138	0.587–2.206	0.702				1.200	0.940–1.530	0.143
PIVKA-II (≥40mAU/mL/<40mAU/mL)	1.044	0.990–1.102	0.115				1.676	0.896–3.137	0.106
Log10HBV DNA (IU/mL)	0.803	0.461–1.397	0.437				1.038	0.991–1.087	0.117
Child‒Pugh class (B/A)	1.801	1.469–2.208	<0.001				0.964	0.622–1.494	0.870
ALBI grade	0.406	0.357–0.462	<0.001	1.187	0.842–1.671	0.328	1.424	1.190–1.704	<0.001	1.303	0.973–1.745	0.075
Concomitant antitumor regimen	0.796	0.648–0.977	0.029	0.424	0.370–0.486	<0.001	0.662	0.599–0.732	<0.001	0.699	0.628–0.778	<0.001
Cycles of HAIC (≥4/<4)	0.696	0.532–0.910	0.008	0.656	0.532–0.809	<0.001	0.888	0.741–1.065	0.201
Antiviral regimen (TDF/ETV)	1.039	0.710–1.519	0.845	0.768	0.585–1.009	0.058	0.747	0.598–0.933	0.010	0.785	0.628–0.982	0.034

Table 3 HBV Reactivation During HAIC and the ALBI Grade Remained Stable or Improved After HAIC in the Two Groups in the Matched Cohort

		ETV Group	TDF Group	p Value
All patients (n=566)		n=408	n=158
HBV reactivation (N, %)	Absence	358 (87.7)	148 (93.7)	0.040
	Presence	50 (12.3)	10 (6.3)
ALBI stable/better (N, %)	Absence	226 (55.4)	67 (42.4)	0.006
	Presence	182 (44.6)	91 (57.6)
HAIC cycles<4 (n=313)		n=220	n=93
HBV reactivation (N, %)	Absence	201 (91.4)	87 (93.5)	0.515
	Presence	19 (8.6)	6 (6.5)
ALBI stable/better (N, %)	Absence	108 (49.1)	37 (39.8)	0.131
	Presence	112 (50.9)	56 (60.2)
HAIC cycles≥4 (n=253)		n=188	n=65
HBV reactivation (N, %)	Absence	157 (83.5)	61 (93.8)	0.037
	Presence	31 (16.5)	4 (6.2)
ALBI stable/better (N, %)	Absence	118 (62.8)	30 (46.2)	0.019
	Presence	70 (37.2)	35 (53.8)

Figure 4 Sankey diagram of ALBI grade change after HAIC in the matched cohort of all patients (A), of patients with < 4 cycles of HAIC (B), and of patients with ≥ 4 cycles of HAIC (C).

Data Sharing Statement

All data generated and/or analyzed during the current study are available from the corresponding author upon reasonable request.