Resolved hepatitis B is associated with higher reactivation risk than chronic infection after chemoembolization for hepatocellular carcinoma

doi:10.3748/wjg.120320

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Retrospective Cohort Study

Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Gastroenterol. Oct 21, 2026; 32(39): 120320
Published online Oct 21, 2026. doi: 10.3748/wjg.120320

Table 1 Baseline characteristics of study population, median (interquartile range)/n (%)

Characteristics	Total, n = 976	Reactivation (+), n = 60	Reactivation (-), n = 916	P value
Demographics
Age, years	60.3 (53.3-67.6)	60.4 (52.7-65.4)	60.3 (53.3-67.7)	0.463
Male sex	788 (80.7)	49 (81.7)	739 (80.7)	0.985
Comorbidities
Hypertension	245 (25.1)	13 (21.7)	232 (25.3)	0.631
Diabetes	192 (19.7)	11 (18.3)	181 (19.8)	0.919
Dyslipidemia	116 (11.9)	8 (13.3)	108 (11.8)	0.879
Cirrhosis	844 (86.5)	55 (91.7)	789 (86.1)	0.308
Child-Pugh score A	891 (91.3)	55 (91.7)	836 (91.3)	> 0.999
Albumin, g/dL	4.0 (3.5-4.3)	4.0 (3.6-4.3)	4.0 (3.5-4.3)	0.744
Total bilirubin, mg/dL	0.7 (0.5-1.0)	0.7 (0.5-0.9)	0.7 (0.5-1.0)	0.315
INR	1.02 (0.97-1.09)	1.04 (0.97-1.10)	1.02 (0.97-1.09)	0.592
Platelets, × 10⁹/L	130 (89-171)	128 (82-164)	131 (91-171)	0.332
HBV serology and virology
Chronic HBV (HBsAg+)	727 (74.5)	50 (83.3)	677 (73.9)
Resolved HBV (HBsAg-/anti-HBc+)	47 (4.8)	10 (16.7)	37 (4.0)
Indeterminate	202 (20.7)	0	202 (22.0)
HBeAg status				0.214
Positive	224 (23.0)	13 (21.7)	211 (23.0)
Negative	598 (61.3)	42 (70.0)	556 (60.7)
Unknown	154 (15.8)	5 (8.3)	149 (16.3)
HBV DNA detectable	541 (55.4)	30 (50.0)	511 (55.8)	0.460
HBV DNA, log₁₀ IU/mL	1.7 (0.0-3.8)	1.3 (1.0-3.2)	1.7 (0.0-3.8)	0.290
Tumor characteristics
Maximal tumor size, cm	2.4 (1.6-4.0)	2.5 (2.0-3.7)	2.4 (1.6-4.0)	0.446
AFP, ng/mL	15.8 (4.8-166.6)	50.2 (5.1-218.7)	15.0 (4.7-163.4)	0.277
PIVKA-II, mAU/mL	43 (24-193)	38 (18-168)	44 (24-197)	0.241
TACE-related
TACE sessions	2 (1-3)	2 (1-3)	2 (1-3)	0.044

P values were calculated using the Mann-Whitney U test for continuous variables and the χ² or Fisher’s exact test for categorical variables, as appropriate. Indeterminate hepatitis B virus serostatus: Patients with incomplete serological data insufficient for classification as chronic or resolved hepatitis B virus infection.

INR: International normalized ratio; HBV: Hepatitis B virus; HBsAg: Hepatitis B surface antigen; anti-HBc: Antibody to hepatitis B core antigen; HBeAg: Hepatitis B e antigen; AFP: Alpha-fetoprotein; TACE: Transarterial chemoembolization; PIVKA-II: Protein induced by vitamin K absence or antagonist-II.

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Table 2 Hepatitis B virus reactivation incidence and clinical characteristics according to hepatitis B virus status, median (interquartile range)/n (%)

Characteristics	Chronic HBV¹, n = 727	Resolved HBV², n = 47	P value
Reactivation incidence	50 (6.9)	10 (21.3)	0.002
Clinical characteristics
Time to reactivation, months	12.5 (6.9-21.7)	11.5 (3.7-22.4)	0.820
Peak HBV DNA, log₁₀ IU/mL	5.3 (3.9-6.8)	1.5 (1.1-1.6)	< 0.001
Severity of reactivation
≥ 1 Log increase	47/50 (94.0)	7/10 (70.0)	0.052
Clinical outcome
All-cause mortality	29/50 (58.0)	5/10 (50.0)	0.733

P values were calculated using the Mann-Whitney U test for continuous variables and Fisher’s exact test for categorical variables.

¹Hepatitis B surface antigen positive.

²Hepatitis B surface antigen negative, antibody to hepatitis B core antigen positive.

HBV: Hepatitis B virus.

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Table 3 Predictors of hepatitis B virus reactivation

Variables	Univariate		Multivariable
Variables	HR (95%CI)	P value	HR (95%CI)	P value
Age (years)	0.984 (0.958-1.010)	0.218
Male sex	1.159 (0.602-2.229)	0.659
Cirrhosis	1.432 (0.573-3.577)	0.443
Child-Pugh score, B/C	1.308 (0.523-3.269)	0.566
Baseline HBV DNA detectable	0.905 (0.545-1.501)	0.698
HBV DNA (log₁₀ IU/mL)	0.924 (0.816-1.046)	0.210
TACE sessions, three or more	0.813 (0.483-1.369)	0.437
Albumin (g/dL)	0.810 (0.502-1.306)	0.387
Platelets (× 10⁹/L)	0.998 (0.993-1.002)	0.361
AFP (log₁₀ ng/mL)	1.429 (1.123-1.817)	0.004	1.325 (1.039-1.691)	0.024
PIVKA-II (log₁₀ mAU/mL)	1.221 (0.815-1.830)	0.333
AST (U/L)	0.998 (0.988-1.008)	0.754
ALT (U/L)	1.000 (0.993-1.007)	0.986
HBsAg positive	1.757 (0.913-3.379)	0.091
Anti-HBc positive	1.891 (1.132-3.159)	0.015
HBeAg positive	1.103 (0.596-2.039)	0.755
Resolved HBV infection¹	4.019 (2.038-7.925)	< 0.001	3.982 (1.990-7.968)	< 0.001
Total TACE sessions	0.925 (0.794-1.078)	0.320
Tumor size (cm)	1.141 (1.048-1.243)	0.002	1.077 (0.977-1.189)	0.137
Hypertension	0.682 (0.369-1.262)	0.223
Diabetes mellitus	0.849 (0.442-1.633)	0.624
Total bilirubin (mg/dL)	0.894 (0.475-1.684)	0.729
INR	3.437 (0.646-18.293)	0.148

Univariable and multivariable Cox proportional hazards regression analyses were performed. Variables with P < 0.05 in univariable analysis were included in the multivariable model.

¹Hepatitis B surface antigen negative, antibody to hepatitis B core antigen positive.

HR: Hazard ratio; CI: Confidence interval; HBV: Hepatitis B virus; TACE: Transarterial chemoembolization; AFP: Alpha-fetoprotein; PIVKA-II: Protein induced by vitamin K absence or antagonist-II; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; HBsAg: Hepatitis B surface antigen; anti-HBc: Antibody to hepatitis B core antigen; HBeAg: Hepatitis B e antigen; INR: International normalized ratio.

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Citation: Kim DY, Jeong J, Hong JP, Lee JS, Kim MN, Kim BK, Kim SU, Park JY, Ahn SH, Kim DY, Lee HW. Resolved hepatitis B is associated with higher reactivation risk than chronic infection after chemoembolization for hepatocellular carcinoma. World J Gastroenterol 2026; 32(39): 120320
URL: https://www.wjgnet.com/1007-9327/full/v32/i39/120320.htm
DOI: https://dx.doi.org/10.3748/wjg.120320

Kim DY, Jeong J, Hong JP, Lee JS, Kim MN, Kim BK, Kim SU, Park JY, Ahn SH, Kim DY, Lee HW. Resolved hepatitis B is associated with higher reactivation risk than chronic infection after chemoembolization for hepatocellular carcinoma. World J Gastroenterol 2026; 32(39): 120320 [DOI: 10.3748/wjg.120320]

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