Hepatitis B virus reactivation in cancer patients with positive Hepatitis B surface antigen undergoing PD-1 inhibition
Open accessAbstract
Background Hepatitis B virus (HBV) reactivation is a serious complication in patients with cancers and HBV infection undergoing immunosuppressant treatment or chemotherapy. However, the safety of anti-programmed cell death (PD) -1 and anti-programmed cell death-ligand 1 (PD-L1) therapy in these patients is unknown because they were excluded from clinical trials of immunotherapy. Methods This retrospective cohort study involved consecutive hepatitis B surface antigen (HBsAg) -positive cancer patients who were referred to Sun Yat-sen University Cancer Center and received an anti-PD-1/PD-L1 antibody between January 1, 2015 and July 31, 2018. The primary end point was the rate of the occurrence of HBV reactivation. Results In total, 114 eligible patients were included, among whom 90 (79%) were male, and the median (range) age was 46 (16–76) years. Six patients (5.3%) developed HBV reactivation, occurring at a median of 18 weeks (range, 3–35 weeks) from the commencement of immunotherapy. Among these patients, all of them had undetectable baseline HBV DNA; one had prophylactic antiviral therapy while five did not; four were positive for Hepatitis B e antigen while the other two were negative. At reactivation, the median HBV DNA level was 3.89 × 104 IU/mL (range, 1.80 × 103–6.00 × 107 IU/mL); five had HBV-related hepatitis and one exhibited increasing HBV DNA level without alanine transaminase elevation. No HBV-related fatal events occurred. The lack of antiviral prophylaxis was the only significant risk factor for HBV reactivation (odds ratio, 17.50 [95% CI, 1.95–157.07], P = .004). Conclusions HBV reactivation occurs in a subset of HBsAg-positive cancer patients undergoing anti-PD-1 or anti-PD-L1 immunotherapy. Regular monitoring of HBV DNA and antiviral prophylaxis are advised to prevent this potentially fatal complication.
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Early studies have demonstrated that in patients with chronic HBV infection undergoing ICI therapy, the addition of intensified antiviral treatment can significantly reduce the risk of viral reactivation.
“Early studies have demonstrated that in patients with chronic HBV infection undergoing ICI therapy, the addition of intensified antiviral treatment can significantly reduce the risk of viral reactivation150,151.”
From Microbiome meets immunotherapy: unlocking the hidden predictors of immune checkpoint inhibitors (2025) · cites this paper as [151]
The Results section (‘Efficacy of antiviral prophylaxis in HBsAg-positive patients’) reports significantly less HBV reactivation with antiviral prophylaxis during PD-1 inhibition than without it. The study compares prophylaxis with no prophylaxis, not intensified treatment with standard treatment; it also reports an association rather than demonstrating that treatment caused the reduction. (LLM, conf=0.85)
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- Authors
- Zhang, X., Zhou, Y., Chen, C., Fang, W., Cai, X., Zhang, X., Zhao, M., Zhang, B., Jiang, W., Lin, Z., Ma, Y., Yang, Y., Huang, Y., Zhao, H., Xu, R., Hong, S., & Zhang, L.
- Affiliations
- Sun Yat-sen University (CN)
- Corresponding author
- Hong, Shaodong
- Zhang, Li
- ORCID
- Venue
- Journal for ImmunoTherapy of Cancer
- Publisher
- BMJ
- Published
- 2019-11-21
- Volume
- 7
- Issue
- 1
- Pages
- 322-322
- ISSN
- 2051-1426 (ISSN-L)
- PMC
- PMC6873745
- OpenAlex
- W2989703635
- Cited by
- 185
- References
- 30
- Citations by year
- 2026: 15 · 2025: 26 · 2024: 21 · 2023: 30 · 2022: 36 · 2021: 33 · 2020: 22 · 2017: 1 · 2014: 1
- FWCI
- 17.32
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal for ImmunoTherapy of Cancer (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Key R&D Program of China (2016YFC0905500 and 2016YFC0905503)
- National Natural Science Funds of China (81972898, 81602005, 81702283, 81872499, and 81602011)
- Excellent Young Talents Fund Program of Higher Education Institutions of Anhui Province (16zxyc04)
- Central Basic Scientific Research Fund for Colleges-Young Teacher Training Program of Sun Yat-sen University (17ykpy81)
- Science and Technology Program of Guangdong Province (2017B020227001)
- Topics
- Health Sciences › Medicine › Epidemiology › Hepatitis B Virus Studies
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Hepatology › Hepatitis C virus research
- Keywords
- HBV reactivation, anti-PD-1 therapy, PD-L1 blockade, immune checkpoint inhibitors, antiviral prophylaxis, HBV DNA monitoring, immunotherapy safety, risk factors
- MeSH terms
- Antineoplastic Agents, Immunological, Adult, Female, Hepatitis B, Hepatitis B Surface Antigens, Hepatitis B virus, Humans, Male, Middle Aged, Neoplasms, Retrospective Studies, Risk Factors, Biomarkers, Tumor, Virus Activation, Young Adult, B7-H1 Antigen, Programmed Cell Death 1 Receptor
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