Association of preoperative antiviral treatment with incidences of post-hepatectomy liver failure in hepatitis B virus-related hepatocellular carcinoma

doi:10.4240/wjgs.v16.i7.2106

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World Journal of Gastrointestinal Surgery

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World J Gastrointest Surg. Jul 27, 2024; 16(7): 2106-2118
Published online Jul 27, 2024. doi: 10.4240/wjgs.v16.i7.2106

Table 1 Basic characteristics in hepatitis B virus-related hepatocellular carcinoma patients (antiviral treatment and non-antiviral treatment group), n (%)

Variable	Overall (1301)	Non-AVT group (HBV DNA cutoff value: 269 IU/mL)					AVT group	P value²
Variable	Overall (1301)	Total (941)	Low viral level (336)	High viral level (605)	P value¹	Total (360)		P value²
Male	1114 (85.6)	808 (85.9)	290 (86.3)	518 (85.6)	0.845	306 (85.0)		0.757
Age (year) median (IQR)	54 (48-61)	54 (47-61)	55 (48-62)	53 (46-60)	0.09	55.50 (50.00, 62.00)		0.001
Hypertension	327 (25.1)	224 (23.8)	90 (26.7)	12234 (22.1)	0.11	103 (28.6)		0.086
Diabetes	271 (20.8)	185 (19.7)	73 (21.7)	112 (18.5)	0.235	86 (23.9)		0.109
BMI mean ± SD, kg/m²	4.62 ± 3.18	24.65 ± 3.23	24.82 ± 3.14	24.56 ± 3.28	0.248	24.55 ± 3.04		0.593
WBC count median (IQR), 10⁹/L	5.47 (4.41-6.60)	5.52 (4.51-6.72)	5.59 (4.59-6.80)	5.49 (4.45-6.72)	0.368	5.34 (4.21-6.30)		0.004
Hemoglobin median (IQR), g/L	144.00 (134.00-154.00)	143.00 (134.00-153.00)	144.00 (134.00-153.75)	143.00 (134.00-153.50)	0.523	145.00 (136.00-155.00)		0.119
PLT median (IQR), 10⁹/L	158.00 (125.00-200.00)	161.00 (128.00-205.00)	164.00 (130.00-204.00)	161.00 (124.00-205.00)	0.549	151.00 (121.75-188.00)		0.003
ALT median (IQR), U/L	29.70 (20.20-42.80)	32.10 (22.10-45.70)	24.15 (17.70-35.15)	376.20 (26.55-52.20)	< 0.001	23.45 (17.08-34.40)		< 0.001
AST median (IQR), U/L	26.80 (20.20-37.80)	28.50 (21.60-39.90)	23.25 (18.83-31.20)	32.30 (24.10-45.25)	< 0.001	22.00 (17.80-29.02)		< 0.001
γ-GT median (IQR), U/L	48.75 (29.10-91.12)	55.50 (32.40-104.30)	44.70 (25.05-84.21)	64.10 (37.40-116.40)	< 0.001	35.30 (23.60-62.40)		< 0.001
Alb mean ± SD, g/L	40.43 ± 3.84	40.18 ± 3.90	41.50 ± 3.70	39.45 ± 3.83	< 0.001	41.09 ± 3.61		< 0.001
ALP median (IQR), U/L	75.40 (61.30-94.20)	76.70 (63.00-95.90)	72.45 (58.10-89.63)	79.40 (65.80-99.95)	< 0.001	71.90 (58.85-87.47)		< 0.001
TBil median (IQR), μmol/L	12.80 (9.90-16.50)	12.80 (9.90-16.50)	12.50 (9.70-15.90)	13.00 (10.10-17.00)	0.114	12.95 (9.80-16.75)		0.817
BUN median (IQR), mmol/L	5.13 (4.24-5.97)	5.09 (4.19-5.93)	5.25 (4.36-6.12)	4.90 (4.10-5.87)	0.001	5.20 (4.30-6.00)		0.124
Cr median (IQR), μmol/L	74.30 (65.30-83.10)	74.10 (64.50-82.50)	75.45 (65.80-84.28)	73.40 (64.00-81.70)	0.042	74.75 (66.50-84.55)		0.08
FIB median (IQR), g/L	4.88 (4.53-5.42)	4.87 (4.53-5.42)	5.01 (4.64-5.60)	4.82 (4.45-5.29)	< 0.001	4.89 (4.54-5.44)		0.435
PT median (IQR), second	13.70 (13.20-14.30)	13.70 (13.20-14.30)	13.60 (13.00-14.10)	13.80 (13.20-14.40)	0.001	13.70 (13.20-14.30)		0.635
INR median (IQR)	1.06 (1.02-1.12)	1.06 (1.02-1.12)	1.05 (1.00-1.11)	1.07 (1.03-1.13)	< 0.001	1.06 (1.01-1.11)		0.465
AFP > 400 ng/mL	389 (29.9)	312 (33.2)	84 (25.0)	228 (37.6)	< 0.001	77 (21.4)		< 0.001
HBeAg positivity	350 (26.9)	243 (25.8)	38 (11.3)	205 (33.8)	< 0.001	107 (29.7)		0.177
Cirrhosis	585 (45.0)	413 (43.9)	138 (41.0)	275 (45.4)	0.194	172 (47.8)		0.231
Tumor number > 1	260 (20.0)	195 (20.7)	63 (18.7)	132 (21.8)	0.266	65 (18.1)		0.318
Tumor size median (IQR), mm	48.00 (30.00-75.00)	52.00 (33.00-81.00)	45.00 (29.00-72.75)	57.00 (36.00-84.00)	< 0.001	39.00 (25.00-58.25)		< 0.001
Type of operation					0.013			< 0.001
Open surgery	747 (57.4)	581 (61.7)	187 (55.6)	394 (65.1)		166 (46.1)
Non-open surgery	554 (42.6)	360 (38.3)	149 (44.4)	211 (34.9)		97 (26.9)
Major hepatectomy (≥ 3 segmentations)	280 (21.5)	222 (23.6)	64 (19.0)	158 (26.1)	0.014	58 (16.1)		0.004
Blood loss > 400 mL	312 (24.0)	250 (26.6)	79 (23.5)	171 (28.2)	0.114	62 (17.2)		0.001
Transfusion	133 (10.2)	109 (11.6)	31 (9.2)	78 (12.8)	0.92	24 (6.7)		0.012
CSPH	138 (10.6)	91 (9.7)	34 (10.1)	57 (9.4)	0.729	47 (13.1)		0.094
Child-Pugh grade					0.201			0.229
Grade A	1284 (98.7)	926 (98.4)	333 (99.1)	593 (98.0)		358 (99.4)
Grade B	17 (1.3)	15 (1.6)	3 (0.9)	12 (2.0)		2 (0.6)
HBV DNA high level	668 (51.3)	605 (64.2)	0	605 (100%)	< 0.001	63 (17.5)		< 0.001
PHLF	168 (12.9)	139 (14.7)	21 (6.2)	118 (19.5)	< 0.001	29 (8.0%)		0.001
ALBI median (IQR)	-2.71 (-2.91 to -2.51)	-2.69 (-2.90 to -2.48)	-2.82 (-3.02 to -2.61)	-2.63 (-2.83 to -2.41)	< 0.001	-2.77 (-2.93 to -2.56)		0.001
FIB-4 median (IQR)	1.70 (1.21-2.62)	1.72 (1.22-2.65)	1.61 (1.21-2.38)	1.84 (1.23-2.79)	0.006	1.67 (1.20-2.52)		0.68
APRI median (IQR)	0.43 (0.30-0.69)	0.45 (0.31-0.74)	0.37 (0.27-0.55)	0.52 (0.34-0.85)	< 0.001	0.37 (0.27-0.57)		< 0.001

¹P value: Comparison between a low (< 269 IU/mL) and a high (≥ 269 IU/mL) viral level in patients not receiving antiviral treatment (AVT).

²P value: Comparison between patients not receiving AVT and patients receiving AVT.

BMI: Body mass index; WBC: White blood cell; PLT: Platelet count; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; γ-GT: Gamma-glutamyl transpeptidase; Alb: Albumin; ALP: Alkaline phosphatase; TBil: Total bilirubin; BUN: Blood urea nitrogen; Cr: Creatinine; FIB: Fibrinogen; PT: Prothrombin time; INR: International normalized ratio; AFP: Alpha-fetoprotein; HBeAg: Hepatitis B e antigen; CSPH: Clinically significant portal hypertension; ALBI: Albumin-bilirubin score; FIB-4: Fibrosis-4 score; HBV: Hepatitis B virus; PHLF: Post-hepatectomy liver failure; AVT: Antiviral treatment; IQR: Interquartile range.

Table 2 The area under the receiver operating characteristic curve and its cut-off value for hepatitis B virus DNA value according to an increase of post-hepatectomy liver failure in hepatitis B virus-related hepatocellular carcinoma patients

	AUC (95%CI)	HBV DNA value (IU/mL)	Sensitivity	1-Specificity	P value
PHLF	0.642 (0.615-0.668)	269	0.75	0.522	< 0.001

AUC: Area under the curve; PHLF: Post-hepatectomy liver failure; HBV: Hepatitis B virus.

Table 3 Logistic regression analysis of the post-hepatectomy liver failure in hepatitis B virus-related hepatocellular carcinoma patients (n = 1301)

Variable	Univariate		Multivariate
Variable	OR (95%CI)	P Value	OR (95%CI)	P Value
Sex, male vs female	1.83 (1.05-3.18)	0.033	1.62 (0.80-3.30)	0.181
Age, year (continuous)	1.02 (1.00-1.03)	0.061	1.04 (1.01-1.06)	0.002
Hypertension, yes vs no	0.73 (0.49-1.09)	0.118	0.88 (0.53-1.47)	0.579
Diabetes, yes vs no	0.73 (0.48-1.13)	0.156	0.75 (0.45-1.28)	0.292
BMI, kg/m² (continuous)	0.97 (0.93-1.03)	0.319	0.97 (0.91-1.03)	0.296
WBC count, 10⁹/L (continuous)	0.89 (0.81-0.99)	0.024	0.95 (0.83-1.08)	0.398
Hemoglobin, g/L (continuous)	1.01 (1.00-1.02)	0.249	1.02 (1.00-1.03)	0.013
PLT, 10⁹/L (continuous)	0.99 (0.99-1.00)	< 0.001	0.99 (0.99-1.00)	0.001
ALT, U/L (continuous)	1.01 (1.00-1.01)	0.001	1.00 (0.99-1.00)	0.534
AST, U/L (continuous)	1.02 (1.01-1.02)	< 0.001	1.01 (1.00-1.02)	0.261
γ-GT, U/L (continuous)	1.00 (1.00-1.01)	< 0.001	1.00 (1.00-1.00)	0.046
Alb, g/L (continuous)	0.88 (0.84-0.92)	< 0.001	0.94 (0.89-0.99)	0.024
ALP, U/L (continuous)	1.00 (1.00-1.01)	0.003	1.00 (1.00-1.00)	0.999
TBil, μmol/L (continuous)	1.08 (1.06-1.11)	< 0.001	1.07 (1.04-1.10)	< 0.001
BUN, mmol/L (continuous)	0.89 (0.78-1.00)	0.059	0.88 (0.76-1.03)	0.123
Cr, μmol/L (continuous)	1.00 (0.98-1.01)	0.536	1.00 (0.99-1.02)	0.634
FIB, g/L (continuous)	0.93 (0.82-1.05)	0.223	0.95 (0.82-1.10)	0.476
PT, second (continuous)	1.57 (1.33-1.86)	< 0.001	1.03 (0.66-1.60)	0.913
INR (continuous)	196.32 (32.04-1202.99)	< 0.001	5.45 (0.04-755.25)	0.501
AFP, > 400 vs ≤ 400 ng/mL	1.77 (1.27-2.47)	0.001	1.16 (0.77-1.78)	0.477
HBeAg positivity, yes vs no	1.03 (0.71-1.48)	0.881	0.85 (0.55-1.32)	0.475
Cirrhosis, yes vs no	1.76 (1.27-2.44)	0.001	1.66 (1.10-2.49)	0.015
No. of tumor > 1, yes vs no	0.89 (0.59-1.35)	0.595	0.71 (0.45-1.14)	0.160
Tumor diameter, mm (continuous)	1.01 (1.01-1.02)	< 0.001	1.01 (1.00-1.02)	0.020
Open surgery, yes vs no	0.73 (0.58-0.91)	0.006	0.93 (0.71-1.20)	0.555
Major hepatectomy, yes vs no	2.95 (2.10-4.16)	< 0.001	2.36 (1.48-3.76)	< 0.001
Blood loss > 400 mL, yes vs no	2.20 (1.56-3.09)	< 0.001	1.28 (0.80-2.05)	0.303
Transfusion, yes vs no	2.17 (1.40-3.39)	0.001	1.04 (0.56-1.91)	0.913
CSPH, yes vs no	2.28 (1.48-3.52)	< 0.001	1.38 (0.75-2.52)	0.3
Child-Pugh grade, A vs B	4.88 (1.83-13.01)	0.002	0.88 (0.22-3.48)	0.856
AVT, yes vs no	0.51 (0.33-0.77)	0.001	0.88 (0.53-1.47)	0.624
HBV DNA level, high vs low	3.27 (2.26-4.73)	< 0.001	2.08 (1.10-3.93)	< 0.001

WBC: White blood cell; PLT: Platelet count; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; γ-GT: Gamma-glutamyl transpeptidase; Alb: Albumin; ALP: Alkaline phosphatase; TBil: Total bilirubin; BUN: Blood urea nitrogen; Cr: Creatinine; FIB: Fibrinogen; PT: Prothrombin time; INR: International normalized ratio; AFP: Alpha-fetoprotein; HBeAg: Hepatitis B e antigen; CSPH: Clinically significant portal hypertension; AVT: Antiviral Treatment; HBV: Hepatitis B virus; OR: Odds ratio.

Table 4 Multivariate logistic regression analyses for the incidence of post-hepatectomy liver failure in the subsample of hepatitis B virus-related hepatocellular carcinoma patients

Variable	Overall patients (n = 1301)		Not receiving AVT (n = 941)
Variable	OR (95%CI)	P value	OR (95%CI)	P value
Sex, male vs female	1.48 (0.74-2.99)	0.27	1.37 (0.63-2.99)	0.43
Age, year (continuous)	1.04 (1.01-1.06)	0.002	1.03 (1.00-1.05)	0.046
Hypertension, yes vs no	0.90 (0.56-1.45)	0.667	0.88 (0.51-1.50)	0.63
Diabetes, yes vs no	0.74 (0.44-1.24)	0.245	0.73 (0.40-1.32)	0.296
BMI, kg/m² (continuous)	0.96 (0.91-1.02)	0.228	0.96 (0.90-1.03)	0.304
WBC count, 10⁹/L (continuous)	0.93 (0.82-1.05)	0.241	0.95 (0.83-1.09)	0.465
Hemoglobin, g/L (continuous)	1.02 (1.01-1.03)	0.007	1.01 (1.00-1.03)	0.067
PLT, 10⁹/L (continuous)	0.99 (0.99-1.00)	0.001	0.99 (0.99-1.00)	0.003
ALT, U/L (continuous)	1.00 (0.99-1.01)	0.939	0.99 (0.98-1.00)	0.179
AST, U/L (continuous)	1.01 (1.00-1.01)	0.328	1.01 (1.00-1.02)	0.127
γ-GT, U/L (continuous)	1.00 (1.00-1.00)	0.030	1.00 (1.00-1.00)	0.103
Alb, g/L (continuous)	0.92 (0.87-0.98)	0.005	0.92 (0.86-0.98)	0.007
ALP, U/L (continuous)	1.00 (1.00-1.00)	0.852	1.00 (1.00-1.01)	0.963
TBil, μmol/L (continuous)	1.07 (1.03-1.10)	< 0.001	1.07 (1.04-1.11)	< 0.001
BUN, mmol/L (continuous)	0.89 (0.76-1.04)	0.129	0.94 (0.79-1.12)	0.48
Cr, μmol/L (continuous)	1.00 (0.99-1.02)	0.578	1.00 (0.98-1.02)	0.853
FIB, g/L (continuous)	0.95 (0.82-1.10)	0.463	0.96 (0.82-1.13)	0.624
PT, second (continuous)	1.00 (0.65-1.56)	0.991	1.08 (0.65-1.79)	0.778
INR (continuous)	8.82 (0.07-1159.35)	0.382	2.91 (0.01-820.09)	0.711
AFP, > 400 vs ≤ 400 ng/mL	1.23 (0.82-1.86)	0.318	1.19 (0.75-1.88)	0.459
HBeAg positivity, yes vs no	0.98 (0.64-1.50)	0.920	1.00 (0.62-1.61)	0.999
Cirrhosis, yes vs no	1.70 (1.13-2.55)	0.011	1.70 (1.08-2.69)	0.022
No. of tumor > 1, yes vs no	0.72 (0.45-1.15)	0.174	0.82 (0.49-1.37)	0.452
Tumor diameter, mm (continuous)	1.01 (1.00-1.02)	0.010	1.01 (1.00-1.01)	0.286
Open surgery, yes vs no	0.91 (0.70-1.17)	0.445	0.98 (0.74-1.32)	0.911
Major hepatectomy, yes vs no	2.71 (1.72-4.29)	< 0.001	2.94 (1.76-4.90)	< 0.001
Blood loss > 400 mL, yes vs no	1.25 (0.78-2.00)	0.347	1.48 (0.88-2.48)	0.141
Transfusion, yes vs no	1.04 (0.56-1.90)	0.912	1.02 (0.52-1.98)	0.963
CSPH, yes vs no	1.28 (0.70-2.34)	0.416	1.21 (0.59-2.50)	0.608
Child-Pugh grade, A vs B	0.92 (0.24-3.50)	0.898	0.54 (0.11-2.58)	0.437
AVT, yes vs no	0.61 (0.38-0.98)	0.039	-	-
HBV DNA level, high vs low	-		2.61 (1.50-4.53)	0.001

Table 5 Evaluation of the incremental value of hepatitis B virus DNA level in predicting post-hepatectomy liver failure

Model	AUC (95%CI)	ΔAUC	P value	Categorical NRI (95%CI)	P value	IDI (95%CI)	P value
ALBI + HBV DNA	0.709 (0.684-0.734)	0.037	0.011	0.940 (0.886-0.994)	< 0.0001	0.082 (0.080-0.084)	< 0.0001
FIB4 + HBV DNA	0.729 (0.705-0.754)	0.054	0.001	1.382 (1.341-1.423)	< 0.0001	0.112 (0.110-0.114)	< 0.0001
APRI + HBV DNA	0.725 (0.701-0.749)	0.030	0.003	1.374 (1.330-1.416)	< 0.0001	0.095 (0.094-0.097)	< 0.0001

ALBI: Albumin-bilirubin score; FIB-4: Fibrosis-4 score; APRI: Aspartate aminotransferase-to-platelet ratio index; HBV: Hepatitis B virus; AUC: Area under the curve; ΔAUC: The change in the area under the receiver operating characteristic curve; IDI: Integrated discrimination improvement; NRI: Net reclassification improvement.

Citation: Wang X, Lin ZY, Zhou Y, Zhong Q, Li ZR, Lin XX, Hu MG, He KL. Association of preoperative antiviral treatment with incidences of post-hepatectomy liver failure in hepatitis B virus-related hepatocellular carcinoma. World J Gastrointest Surg 2024; 16(7): 2106-2118
URL: https://www.wjgnet.com/1948-9366/full/v16/i7/2106.htm
DOI: https://dx.doi.org/10.4240/wjgs.v16.i7.2106