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

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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

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

Dong Yun Kim, Jaehong Jeong, Jung Pyo Hong, Jae Seung Lee, Mi Na Kim, Beom Kyung Kim, Seung Up Kim, Jun Yong Park, Sang Hoon Ahn, Do Young Kim, Hye Won Lee

Dong Yun Kim, Jaehong Jeong, Jung Pyo Hong, Jae Seung Lee, Mi Na Kim, Beom Kyung Kim, Seung Up Kim, Jun Yong Park, Sang Hoon Ahn, Do Young Kim, Hye Won Lee, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, South Korea

Co-corresponding authors: Do Young Kim and Hye Won Lee.

Author contributions: Kim DY, Lee HW, and Kim DY (the tenth author) contributed to the conception and design of the study; Lee HW provided the study data and supervised the project; Kim DY performed data curation, statistical analysis, and interpretation of the data, and wrote the original draft of the manuscript; Lee JS, Kim MN, Kim BK, Kim SU, Park JY, Kim DY, and Ahn SH contributed to data acquisition and critically revised the manuscript for important intellectual content; Lee HW and Kim DY (the tenth author) supervised the project and critically revised the manuscript as co-corresponding authors. All authors read and approved the final manuscript.

Supported by Faculty Research Grant of Yonsei University College of Medicine, No. 6-2020-0210; and Korea Health Technology R&D Project through the Korea Health Industry Development Institute, No. RS-2025-25459146.

Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of Severance Hospital, Yonsei University Health System, No. 4-2020-1081.

Informed consent statement: The requirement for informed consent was waived due to the retrospective nature of the study and the use of de-identified data.

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.

Data sharing statement: The datasets generated and/or analyzed during the current study are not publicly available due to patient privacy restrictions but are available from the corresponding author upon reasonable request.

Corresponding author: Hye Won Lee, MD, PhD, Department of Internal Medicine, Yonsei University College of Medicine, 50, Yonsei-ro, Seodaemun-gu, Seoul 03722, South Korea. lorry-lee@yuhs.ac

Received: February 25, 2026
Revised: April 22, 2026
Accepted: June 12, 2026
Published online: October 21, 2026
Processing time: 192 Days and 16.9 Hours

Abstract

BACKGROUND

Transarterial chemoembolization (TACE) is a cornerstone treatment for hepatocellular carcinoma (HCC), yet the hepatitis B virus (HBV) reactivation risk, particularly among patients with prior infection, remains incompletely characterized, with international guidelines providing discordant risk classifications. We hypothesized that patients with resolved HBV infection undergoing TACE face a higher reactivation risk than currently estimated by international guidelines.

AIM

To determine the incidence and risk factors of HBV reactivation in patients undergoing TACE for HBV-related HCC.

METHODS

We retrospectively analyzed patients who underwent TACE for HBV-related HCC at a tertiary hospital during 2007-2025. Patients receiving baseline antiviral therapy were excluded. Patients with definitive serostatus (n = 774) were stratified into chronic-infection [hepatitis B surface antigen (HBsAg)-positive, n = 727] and resolved-infection (HBsAg-negative/anti-hepatitis B core antibody-positive, n = 47) groups. Cumulative incidences and risk factors were assessed using Kaplan-Meier analysis and Cox regression, with robustness evaluated through multiple imputation, competing-risks, and antiviral-naive sensitivity analyses.

RESULTS

During a median follow-up of 16.7 months, HBV reactivation occurred in 60 patients (6.1% overall). Patients with resolved HBV status had a higher reactivation rate (21.3% vs 6.9%; P < 0.001). Resolved HBV status (adjusted hazard ratio: 3.98, 95% confidence interval: 1.99-7.97; P < 0.001) and elevated alpha-fetoprotein level (1.33 per log₁₀ ng/mL, 1.04-1.69; P = 0.024) were independent predictors. Median time to reactivation was 12 months.

CONCLUSION

HBV reactivation occurred in approximately 6% of patients undergoing TACE, with resolved infection status conferring > 3-fold higher risk and reactivation incidence exceeding 20%. These findings support prophylactic antiviral therapy rather than monitoring alone for HBsAg-negative/anti-hepatitis B core antibody-positive patients undergoing TACE.

Keywords: Hepatitis B virus reactivation; Transarterial chemoembolization; Hepatocellular carcinoma; Resolved hepatitis B infection; Anti-hepatitis B core antibody positive

Core Tip: Current international guidelines classify resolved hepatitis B virus (HBV) infection as moderate-risk for reactivation during transarterial chemoembolization, yet our study of 774 patients with confirmed HBV serostatus reveals a 21.3% reactivation rate in hepatitis B surface antigen-negative/anti-hepatitis B core antibody-positive patients, substantially exceeding the moderate-risk threshold. Resolved HBV status was the strongest independent predictor of reactivation (adjusted hazard ratio: 3.98), paradoxically conferring higher risk than chronic infection. These findings challenge existing risk classifications and support prophylactic antiviral therapy rather than monitoring alone for this vulnerable population.