Effect of antiviral therapy on 3-year recurrence and prognosis of hepatocellular carcinoma after curative radiofrequency ablation

Table 1 Baseline data of hepatitis B cirrhosis-related hepatocellular carcinoma post radiofrequency treatment with entecavir, tenofovir disoproxil fumarate and tenofovir alafenamide fumarate, n (%)

Characteristics	ETV	TDF	TAF	P value
n	191	76	52
Gender				0.945
Male	151 (79.06)	61 (80.26)	42 (80.77)
Female	40 (20.94)	15 (19.74)	10 (19.23)
Age (years)	60.13 ± 8.05	57.58 ± 8.27	60.12 ± 8.69	0.067
Family history of CHB				0.985
POS	57 (29.84)	23 (30.26)	16 (30.77)
NEG	134 (70.16)	53 (69.74)	36 (69.23)
Family history of HCC				0.996
POS	30 (15.71)	12 (15.79)	8 (15.38)
NEG	161 (84.29)	64 (84.21)	44 (84.62)
Smoking				0.992
POS	60 (31.41)	24 (31.58)	16 (30.77)
NEG	131 (68.59)	52 (68.42)	36 (69.23)
Hyperlipidemia				0.957
POS	32 (16.75)	12 (15.79)	8 (15.38)
NEG	159 (83.25)	64 (84.21)	44 (84.62)
Diabetes				0.999
POS	40 (20.94)	16 (21.05)	11 (21.15)
NEG	151 (79.06)	60 (78.95)	41 (78.85)
BMI (kg/m2)	23.12 ± 2.68	22.54 ± 2.27	22.79 ± 2.14	0.168
WBC (× 109/L)	3.98 ± 1.67	4.07 ± 1.55	3.96 ± 1.60	0.909
HGB (g/L)	134.78 ± 19.09	137.68 ± 19.8	133.43 ± 21.03	0.417
PLT (× 109/L)	83.00 (60.00-132.75)	95.00 (63.75-145.00)	94.00 (61.05-122.00)	0.474
INR	1.16 ± 0.18	1.14 ± 0.14	1.14 ± 0.22	0.565
ALB (g/L)	41.19 ± 5.47	41.68 ± 5.62	41.92 ± 4.92	0.618
ALT (U/L)	20.00 (16.00-27.50)	27.00 (22.00-38.25)	20.00 (16.00-30.00)	< 0.001
AST (U/L)	25.00 (20.00-33.00)	30.50 (25.00-43.25)	22.50 (19.00-30.00)	< 0.001
ALP (U/L)	88.31 ± 33.02	102.16 ± 39.23	82.67 ± 32.96	0.002
GGT (U/L)	31.00 (23.00-50.00)	47.00 (27.50-74.50)	35.00 (25.00-48.00)	0.005
TBIL (μmol/L)	15.70 (12.30-25.40)	14.45 (12.18-23.25)	17.25 (12.00-20.92)	0.795
eGFR (mL/min/1.73 m2)	94.67 ± 14.35	95.31 ± 12.18	96.16 ± 14.23	0.638
HBsAg (lgIU/mL)	2.02 (1.43-2.35)	2.01 (1.21-2.27)	2.26 (1.63-2.92)	0.566
HBeAg				0.910
POS	48 (25.13)	20 (26.31)	15 (28.85)
NEG	143 (74.87)	56 (73.69)	37 (71.15)
HBV DNA				0.045
POS	27 (14.14)	21 (27.63)	11 (21.15)
NEG	164 (85.86)	55 (72.37)	41 (78.85)
AFP (ng/mL)	7.61 (2.90-52.10)	11.99 (3.58-36.70)	7.81 (3.19-89.35)	0.595
Child-Pugh
A	181 (94.76)	71 (92.42)	49 (94.23)	0.764
B	10 (5.24)	5 (6.58)	3 (5.77)
BCLC
0	167 (87.43)	67 (88.16)	45 (86.54)	0.672
A	24 (12.57)	9 (11.84)	7 (13.48)

HCC: Hepatocellular carcinoma; ETV: Entecavir; TDF: Tenofovir disoproxil fumarate; TAF: Tenofovir alafenamide fumarate; BMI: Body mass index; WBC: White blood cell; ALB: Albumin; ALT: Alanine aminotransferase; HGB: Hemoglobin; PLT: Platelet; TBIL: Total bilirubin; eGFR: Estimated glomerular filtration rate; INR: International normalized ratio; ALP: Alkaline phosphatase; AFP: Alpha-fetoprotein; AST: Aspartate aminotransferase; GGT: γ-glutamyl transpeptidase; HBsAg: Hepatitis B surface antigen; HBeAg: Hepatitis B e antigen; NEG: Negative; POS: Positive; HBV: Hepatitis B virus; BCLC: Barcelona Clinic Liver Cancer.

Table 2 Cox regression analysis of recurrence after radiofrequency in patients with hepatocellular carcinoma

Characteristics	Univariate analysis			Multivariate analysis
	HR	95%CI	P value	HR	95%CI	P value
Gender
Male	1
Female	1.52	0.83-2.80	0.174
Age (years)	1.01	0.99-1.04	0.300
BMI (kg/m2)	1.08	0.32-3.71	0.898
WBC (× 109/L)	0.93	0.82-1.06	0.284
HGB (g/L)	1.00	0.99-1.01	0.972
PLT (× 109/L)	1.01	0.99-1.20	0.853
INR	1.07	0.35-3.31	0.906
ALB (g/L)	1.00	0.96-1.04	0.895
AST (U/L)	0.99	0.98, 1.00	0.167
ALP (U/L)	1.00	0.99-1.01	0.736
TBIL (μmol/L)	0.99	0.97-1.01	0.292
eGFR (mL/min/1.73 m2)	0.98	0.95-1.06	0.312
HBsAg (lgIU/mL)	1.03	0.78-1.36	0.855
HBeAg
NEG	1
POS	1.29	0.75-2.21	0.363
HBV DNA
NEG	1
POS	0.86	0.48-1.55	0.626
Child-Pugh
A	1
B	3.88	0.45-33.21	0.216
ALT (U/L)	0.99	0.97-1.00	0.074	0.99	0.97-1.01	0.097
GGT (U/L)	1.00	1.00-1.01	0.004	1.01	1.00-1.01	0.026
AFP (ng/mL)	0.88	1.00-1.02	0.074	1.01	1.00-1.01	0.013
Anti-HBV therapy
ETV	1			1
TDF	0.57	0.35-0.90	0.017	0.62	0.38-1.02	0.047
TAF	0.52	0.30-0.91	0.021	0.57	0.32-1.02	0.046
BCLC
0	1			1
A	3.70	1.36-10.05	0.010	3.82	1.39-10.47	0.009

ETV: Entecavir; TDF: Tenofovir disoproxil fumarate; TAF: Tenofovir alafenamide fumarate; BMI: Body mass index; WBC: White blood cell; ALB: Albumin; ALT: Alanine aminotransferase; HGB: Hemoglobin; PLT: Platelet; TBIL: Total bilirubin; eGFR: Estimated glomerular filtration rate; INR: International normalized ratio; ALP: Alkaline phosphatase; AFP: Alpha-fetoprotein; AST: Aspartate aminotransferase; GGT: γ-glutamyl transpeptidase; HBsAg: Hepatitis B surface antigen; HBeAg: Hepatitis B e antigen; NEG: Negative; POS: Positive; HBV: Hepatitis B virus; BCLC: Barcelona Clinic Liver Cancer.

Table 3 The multiple Cox regression equations of different antiviral agents on recurrence within 6 months post radiofrequency

Variable	Crude model		Model I		Model II
	HR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)	P value
ETV	1		1		1
TDF	0.86 (0.37, 2.02)	0.729	0.78 (0.32, 1.91)	0.593	1.01 (0.41, 2.53)	0.976
TAF	0.67 (0.23, 1.96)	0.470	0.70 (0.24, 2.03)	0.506	0.82 (0.27, 2.49)	0.730

Crude model was adjusted for no variable. Model I was adjusted for glutamyl transferase (GGT). Model II was adjusted for GGT, alpha-fetoprotein, Barcelona Clinic Liver Cancer. ETV: Entecavir; TDF: Tenofovir disoproxil fumarate; TAF: Tenofovir alafenamide fumarate.

Table 4 The multiple Cox regression equations of different antiviral agents on recurrence within 12 months post radiofrequency

Variable	Crude model		Model I		Model II
	HR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)	P value
ETV	1		1		1
TDF	0.48 (0.25, 0.92)	0.028	0.46 (0.23, 0.89)	0.022	0.52 (0.27, 1.02)	0.050
TAF	0.42 (0.19, 0.93)	0.033	0.44 (0.20, 0.96)	0.039	0.45 (0.20, 1.01)	0.049

Crude model was adjusted for no variable. Model I was adjusted for glutamyl transferase (GGT). Model II was adjusted for GGT, alpha-fetoprotein, Barcelona Clinic Liver Cancer. ETV: Entecavir; TDF: Tenofovir disoproxil fumarate; TAF: Tenofovir alafenamide fumarate.

Table 5 The multiple Cox regression equations of different antiviral agents on recurrence within 24 months post radiofrequency

Variable	Crude model		Model I		Model II
	HR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)	P value
ETV	1		1		1
TDF	0.46 (0.26, 0.80)	0.006	0.44 (0.25, 0.77)	0.004	0.51 (0.29, 0.91)	0.022
TAF	0.46 (0.25, 0.87)	0.017	0.48 (0.25, 0.90)	0.022	0.54 (0.28, 1.03)	0.046

Crude model was adjusted for no variable. Model I was adjusted for glutamyl transferase (GGT). Model II was adjusted for GGT, alpha-fetoprotein, Barcelona Clinic Liver Cancer. ETV: Entecavir; TDF: Tenofovir disoproxil fumarate; TAF: Tenofovir alafenamide fumarate.

Table 6 The multiple Cox regression equations of different antiviral agents on recurrence within 36 months post radiofrequency

Variable	Crude model		Model I		Model II
	HR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)	P value
ETV	1		1		1
TDF	0.57 (0.35, 0.90)	0.017	0.53 (0.33, 0.86)	0.010	0.57 (0.35, 0.93)	0.025
TAF	0.52 (0.30, 0.91)	0.021	0.50 (0.29, 0.89)	0.017	0.54 (0.31, 0.96)	0.037

Crude model was adjusted for no variable. Model I was adjusted for glutamyl transferase (GGT). Model II was adjusted for GGT, alpha-fetoprotein, Barcelona Clinic Liver Cancer. ETV: Entecavir; TDF: Tenofovir disoproxil fumarate; TAF: Tenofovir alafenamide fumarate.