Abstract
Purpose
Immune checkpoint inhibitors (ICIs) have been explored as first-line treatment in various types of previously untreatable malignancies, while limited evidence is available on the management of hepatitis B virus (HBV) in patients undergoing immunotherapy. We systematically reviewed data concerning challenges of hepatic adverse events including HBV reactivation and hepatitis in patients with chronic HBV infection undergoing immunotherapy.
Methods
A systematic search was conducted in Medline, web of science, Embase and Cochrane library up to May 31, 2022. Studies reporting the safety profile of ICIs in patients with HBV infection were eligible. Meta-analyses were conducted to generate odds ratios (ORs) with 95% confidence intervals (CIs).
Results
A total of 13 studies including 2561 patients were included for meta-analysis. The overall incidence rates of HBV reactivation in patients with chronic HBV infection and past HBV infection were 1.0% (95% CI 0–3%) and 0% (95% CI 0–0%), respectively. Among patients with chronic HBV infection, the incidence rates of HBV reactivation were 1.0% (95% CI 0–2%) and 10.0% (95% CI 4–18%) for patients with and without antiviral prophylaxis, respectively. Patients with chronic HBV infection were at a higher risk of HBV reactivation compared with those with past HBV infection [OR = 8.69, 95% CI (2.16–34.99)]. Antiviral prophylaxis significantly reduced the risk of HBV reactivation [OR = 0.12, 95% CI (0.02–0.67)] and HBV-associated hepatitis [OR = 0.05, 95% CI (0.01–0.28)] in patients with chronic HBV infection.
Conclusions
Prophylactic antiviral therapy should be administered to patients with chronic HBV infection undergoing anticancer immunotherapy. Patients with past HBV infection are at lower risk of HBV reactivation compared with those with chronic HBV infection, they could be initiated with antiviral prophylaxis or monitored with the intent of on-demand antiviral therapy.
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This work was supported by the National Natural Science Foundation of China (Grant Nos. 82073200 and 81874178), Major basic research of Shandong Provincial Natural Science Foundation (Grant No. ZR202105070027), Funds for Independent Cultivation of Innovative Team from Universities in Jinan (Grant No. 2020GXRC023), and the grants from the Taishan Scholars Program for Young Expert of Shandong Province (Grant No. tsqn20161064).
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T.L. takes responsibility for the integrity of the work as a whole, from inception to published article. Z.N.D. and T.L. conceived and designed the study. Z.N.D., J.S.X. independently screened the full text of selected studies to confirm eligibility, assess quality, and extract data. Z.N.D., L.J.Y., G.X.M. and H.L. analyzed the data. Z.N.D., Z.Q.C. and J.G.H. visualize the results. Z.N.D., Y.C.Y., D.X.W. and T.L. wrote reviewed, and/or revised the manuscript. All authors read and approved the final manuscript, including the authorship list.
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Ding, ZN., Meng, GX., Xue, JS. et al. Hepatitis B virus reactivation in patients undergoing immune checkpoint inhibition: systematic review with meta-analysis. J Cancer Res Clin Oncol 149, 1993–2008 (2023). https://doi.org/10.1007/s00432-022-04133-8
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DOI: https://doi.org/10.1007/s00432-022-04133-8