Perioperative remedial antiviral therapy in hepatitis B virus-related hepatocellular carcinoma resection: How to achieve a better outcome

Table 1 Baseline characteristics of the patients, n (%)

Characteristics	Remedial perioperative antiviral therapy group (n = 108)	Preoperative long-term antiviral therapy group (n = 108)	P value
Patient characteristics
Antiviral treatment			< 0.001
Perioperative	108 (100.0)	0 (0.0)
Long-term	0 (0.0)	108 (100.0)
Sex			0.705
Male	90 (83.3)	93 (86.1)
Female	18 (16.7)	15 (13.9)
Age			0.067
≤ 60 yr	85 (78.7)	72 (66.7)
> 60 yr	23 (21.3)	36 (33.3)
Treatment after resection			0.907
TACE	31 (70.5)	32 (68.1)
RFA	5 (11.4)	6 (12.8)
TACE and RFA	4 (9.1)	6 (12.8)
Radio/chemo	4 (9.1)	3 (6.4)
Preoperative laboratory tests
ALT			0.001
≤ 40 IU/L	48 (44.4)	72 (67.3)
> 40 IU/L	60 (55.6)	35 (32.7)
AST			0.001
≤ 35 IU/L	38 (35.2)	64 (59.8)
> 35 IU/L	70 (64.8)	43 (40.2)
HBeAg			1.000
Negative	74 (68.5)	75 (69.4)
Positive	34 (31.5)	33 (30.6)
Hemoglobin			0.885
≤ 130 g/L	35 (32.4)	37 (34.3)
> 130 g/L	73 (67.6)	71 (65.7)
Creatinine			1.000
≤ 97 μmol/L	107 (99.1)	106 (98.1)
> 97 μmol/L	1 (0.9)	2 (1.9)
Platelets			0.164
≤ 120 × 109/L	37 (34.3)	48 (44.4)
> 120 × 109/L	71 (65.7)	60 (55.6)
Leukocytes			1.000
≤ 9.5 × 109/L	101 (93.5)	102 (94.4)
> 9.5 × 109/L	7 (6.5)	6 (5.6)
NEUT			0.503
≤ 75%	83 (76.9)	88 (81.5)
> 75%	25 (23.1)	20 (18.5)
Bilirubin			0.041
≤ 17 μmol/L	48 (44.4)	64 (59.8)
> 17 μmol/L	60 (55.6)	44 (40.7)
Albumin			0.259
≤ 35 g/L	29 (26.9)	21 (19.4)
> 35 g/L	79 (73.1)	87 (80.6)
Prothrombin time			0.592
≤ 13 s	9 (8.3)	6 (5.6)
> 13 s	99 (91.7)	102 (94.4)
International normalized ratio			0.378
≤ 1.3	94 (87.0)	99 (91.7)
> 1.3	14 (13.0)	9 (8.3)
Alpha fetoprotein			0.187
≤ 400 ng/mL	70 (47.8)	79 (79.3)
> 400 ng/mL	38 (52.2)	29 (20.7)
HBV-DNA level			< 0.001
≤ 10000 copies/mL	49 (52.7)	75 (96.2)
> 10000 copies/mL	44 (47.3)	3 (3.8)
Operation information
Type of operation			0.192
I (low range)	49 (45.4)	59 (55.1)
II (middle range)	15 (13.9)	17 (15.9)
III (high range)	44 (40.7)	31 (29.0)
Liver fibrosis			0.381
No	23 (21.3)	17 (15.7)
Yes	85 (78.7)	91 (84.3)
Operation time			0.674
≤ 3 h	39 (36.1)	43 (39.8)
> 3 h	69 (63.9)	65 (60.2)
Blood loss			0.055
≤ 400 mL	26 (32.1)	35 (48.6)
> 400 mL	55 (67.9)	37 (51.4)
Resection margins			0.388
≤ 1 cm	75 (73.5)	82 (79.6)
> 1 cm	27 (26.5)	21 (20.4)
Tumor information
Capsular invasion			0.116
No	28 (26.2)	40 (37.4)
Yes	78 (72.9)	67 (62.6)
Tumor diameter			0.339
≤ 5 cm	57 (52.8)	64 (59.3)
> 5 cm	51 (47.2)	44 (40.7)
Tumor number			0.879
Single	97 (89.8)	101 (93.5)
Numerous	11 (10.2)	7 (6.5)
BCLC stage			0.051
O	6 (5.6)	18 (16.7)
A	87 (80.6)	78 (72.2)
B	5 (4.6)	2 (1.9)
C	10 (9.3)	10 (9.3)
Tumor differentiation			0.168
Poor	32 (30.5)	21 (19.6)
Moderate	70 (66.7)	81 (75.7)
High	3 (2.9)	5 (4.7)
Portal vein invasion			1.000
No	98 (90.7)	98 (90.7)
Yes	10 (9.3)	10 (9.3)
MVI			0.090
0	39 (36.1)	52 (48.1)
1	34 (31.5)	34 (31.5)
2	35 (32.4)	22 (20.4)
Satellite lesions			0.378
No	94 (87.0)	99 (91.7)
Yes	14 (13.0)	9 (8.3)

TACE: Transcatheter arterial chemoembolization; RFA: Radio frequency ablation; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; HBeAg: Hepatitis B e Antigen; BCLC stage: Barcelona Clinic Liver Cancer; MVI: Microvascular invasion.

Table 2 Univariate and multivariate analyses for overall survival and disease-free survival of patients who underwent antiviral therapy, n (%)

Factors	No. of patients	Overall survival						Disease-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
Antiviral treatment		0.370	0.22-0.6	< 0.001	0.270	0.08-0.88	0.030	0.680	0.47-0.98	0.036	1.160	0.66-2.04	0.609
Perioperative	108 (50.0)
Long-term	108 (50.0)
Sex		0.930	0.49-1.76	0.820				1.260	0.73-2.16	0.408
Male	183 (84.7)
Female	33 (15.3)
Age		1.080	0.65-1.8	0.753				0.820	0.54-1.24	0.338
≤ 60 yr	157 (72.7)
> 60 yr	59 (27.3)
Treatment after resection		0.750	0.5-1.13	0.165				0.890	0.7-1.13	0.331
TACE	63 (69.2)
RFA	11 (12.1)
TACE and RFA	10 (11.0)
Radio/chemo	7 (7.7)
ALT		1.730	1.09-2.75	0.019	2.360	0.88-6.31	0.088	1.230	0.86-1.77	0.261
≤ 40 IU/L	120 (55.8)
> 40 IU/L	95 (44.2)
AST		2.470	1.51-4.05	< 0.001	0.250	0.08-0.84	0.244	1.730	1.19-2.5	0.004	0.720	0.41-1.25	0.239
≤ 35 IU/L	102 (47.4)
> 35 IU/L	113 (52.6)
HBeAg		1.720	1.08-2.76	0.023	1.530	0.62-3.77	0.357	1.170	0.8-1.71	0.425
Negative	149 (69.0)
Positive	67 (31.0)
Hemoglobin		1.180	0.72-1.94	0.518				1.460	0.98-2.18	0.066
≤ 130 g/L	74 (34.3)
> 130 g/L	144 (65.7)
Creatinine		0.860	0.12-6.17	0.877				1.280	0.32-5.18	0.730
≤ 97 μmol/L	215 (98.6)
> 97 μmol/L	3 (1.4)
Platelets		1.040	0.65-1.66	0.870				1.280	0.88-1.86	0.195
≤ 120 × 109/L	85 (39.4)
> 120 × 109/L	131 (60.5)
Leukocytes		1.440	0.63-3.33	0.390				1.390	0.68-2.85	0.370
≤ 9.5 × 109/L	203 (94.0)
> 9.5 × 109/L	13 (6.0)
Neutrophils		1.110	0.64-1.9	0.716				1.060	0.69-1.64	0.782
≤ 75%	171 (79.2)
> 75%	45 (20.8)
Bilirubin		2.040	1.27-3.27	0.003	2.010	0.82-4.93	0.127	1.270	0.88-1.82	0.197
≤ 17 μmol/L	112 (51.9)
> 17 μmol/L	104 (48.1)
Albumin		0.820	0.48-1.38	0.450				1.340	0.85-2.1	0.203
≤ 35 g/L	50 (23.1)
> 35 g/L	166 (76.9)
Prothrombin time		1.190	0.48-2.95	0.707				0.980	0.48-2.01	0.955
≤ 13 s	13 (6.0)
> 13 s	203 (94.0)
International normalized ratio		1.670	0.86-3.27	0.131				1.180	0.66-2.1	0.575
≤ 1.3	193 (89.4)
> 1.3	23 (10.6)
Alpha fetoprotein		3.050	1.85-5.02	< 0.001	0.620	0.22-1.69	0.348	2.320	1.56-3.44	0.000	0.920	0.51-1.66	0.790
≤ 400 μg/L	149 (69.0)
> 400 μg/L	67 (31.0)
HBV-DNA level		3.060	1.84-5.1	< 0.001	1.940	0.67-5.61	0.221	1.440	0.94-2.19	0.091
≤ 10000 copies/mL	124 (72.5)
> 10000 copies/mL	47 (27.5)
Operation information
Type		2.560	1.58-4.15	0.000	2.820	1-7.92	0.049	1.830	1.27-2.64	0.001	1.050	0.56-1.96	0.882
I (low range)	108 (50.2)
II (middle range)	32 (14.9)
III (high range)	75 (34.9)
Liver fibrosis		0.610	0.36-1.05	0.073				0.800	0.52-1.25	0.326
No	40 (18.5)
Yes	176 (81.5)
Operation time		1.630	0.99-2.68	0.054				1.490	1.01-2.18	0.044	1.280	0.65-2.51	0.475
≤ 3 h	82 (38.0)
> 3 h	134 (62.0)
Blood loss		2.350	1.25-4.42	0.008	1.560	0.55-4.42	0.402	1.930	1.21-3.07	0.006	1.590	0.85-2.99	0.147
≤ 400 mL	61 (39.9)
> 400 mL	92 (60.1)
Resection Margins		0.930	0.53-1.62	0.796				0.800	0.51-1.26	0.344
≤ 1	157 (75.8)
> 1	50 (24.2)
Tumor information
Capsular invasion		4.350	2.21-8.54	< 0.001	9.560	2.45-37.28	0.001	2.710	1.71-4.29	0.000	1.540	0.81-2.94	0.185
No	68 (31.9)
Yes	145 (68.1)
Tumor diameter		4.110	2.5-6.75	< 0.001	1.010	0.31-3.33	0.983	2.750	1.91-3.98	0.000	1.550	0.77-3.13	0.217
≤ 5 cm	121 (56.0)
> 5 cm	95 (44.0)
Tumor number		1.680	1.24-2.27	< 0.001	2.640	1.32-5.27	0.006	1.690	1.21-2.38	0.002	1.260	0.74-2.16	0.400
Single	198 (91.7)
Numerous	18 (8.3)
BCLC stage		4.930	2.94-8.29	< 0.001	0.710	0.12-4.28	0.706	4.320	2.75-6.78	0.000	2.480	0.56-10.93	0.230
O	24 (11.1)
A	165 (76.4)
B	7 (3.2)
C	20 (9.3)
Tumor differentiation		0.400	0.25-0.64	< 0.001	0.130	0.05-0.32	0.000	0.670	0.45-1	0.051
Poor	53 (25.0)
Moderate	151 (71.2)
High	8 (3.8)
Portal vein invasion		5.130	2.84-9.26	< 0.001	22.850	2.09-249.85	0.010	4.590	2.78-7.59	0.000	1.230	0.24-6.37	0.803
No	196 (90.7)
Yes	20 (9.3)
MVI		2.550	1.52-4.28	< 0.001	1.740	0.62-4.88	0.291	2.240	1.51-3.32	0.000	2.110	1.07-4.19	0.032
0	91 (42.1)
1	68 (31.5)
2	57 (26.4)
Satellite lesions		2.150	1.13-4.09	0.020	2.130	0.56-8.16	0.268	3.080	1.87-5.08	0.000	2.330	1.09-4.95	0.028
No	193 (10.6)
Yes	23 (89.4)

TACE: Transcatheter arterial chemoembolization; RFA: Radio frequency ablation; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; HBeAg: Hepatitis B e Antigen; BCLC stage: Barcelona Clinic Liver Cancer; MVI: Microvascular invasion; HR: Hazard ratio; CI: Confidence interval.