Antiviral prophylaxis during chemotherapy or immunosuppressive drug
therapy to prevent HBV reactivation in patients with resolved HBV
infection: a systematic review and meta-analysis
Received: 6 March 2018 / Accepted: 16 May 2018 / Published online: 29 May 2018
Springer-Verlag GmbH Germany, part of Springer Nature 2018
Background Until recently, the role of antiviral prophylaxis in preventing hepatitis B virus (HBV) reactivation during
immunosuppressive therapy or chemotherapy in patients with resolved HBV infection was unclear. The aim of the
study reported here was to compare the efficacy of antiviral prophylaxis versus that of non-prophylaxis in resolved
HBV-infected patients undergoing chemotherapy or immunosuppressive therapy.
Methods PubMed, the Cochrane library, and the ClinicalTrials.gov website were searched from inception until
December 2017. Studies comparing reactivation in prophylaxis versus non-prophylaxis in patients undergoing immu-
nosuppressive therapy or chemotherapy were included. The meta-analysis was performed to calculate the relative risk
(RR) and the pooled estimates.
Results A meta-analysis was conducted of 13 studies (2 randomized controlled trials [RCTs] and 11 cohort studies).
The summary RR for HBV reactivation was 0.47 (95% confidence interval [CI] 0.13–1.69) for antiviral prophylaxis
versus non-prophylaxis. Both of the RCTs included in the meta-analysis enrolled patients treated with rituximab.
Subgroup analyses showed that the two RCTs ± high-quality cohort studies showed a decreased risk of HBV reacti-
vation among the antiviral prophylaxis groups (RCT 1: RR 0.13, 95% CI 0.02–0.70; P = 0.02; RCT 2: 0.28, 95% CI
0.08–0.98; P = 0.05). Subgroup analyses further showed that the cohort studies did not support an association between
the antiviral prophylaxis groups and HBV reactivation (RR 0.62, 95% CI 0.14–2.83; P = 0.54); adjusting for con-
founding factors, such as detectable anti-HBs antibodies, failed to produce a significant association (RR,0.29, 95% CI
0.07-1.28; P =0.10).
Conclusion Our meta-analyses did not show an association between antiviral prophylaxis use and risk of HBV reac-
tivation. As using only the RCTs ± high-quality cohort studies data rendered this association significant, clinicians can
consider providing antiviral prophylaxis to patients with resolved HBV infection who are undergoing rituximab-based
Keywords HBV reactivation
Resolved HBV infection
Yi-Chia Su and Pei-Chin Lin contributed equally to this work.
Electronic supplementary material The online version of this article
(https://doi.org/10.1007/s00228-018-2487-4) contains supplementary
material, which is available to authorized users.
* Chih-Chien Wu
Department of Pharmacy, Kaohsiung Veterans General Hospital,
Department of Pharmacy, School of Pharmacy, Kaohsiung Medical
University, Kaohsiung, Taiwan
Division of Gastroenterology, Department of Internal Medicine,
Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
Division of Colorectal Surgery, Department of Surgery, Kaohsiung
Veterans General Hospital, Kaohsiung, Taiwan
Faculty of Medicine, School of Medicine, National Yang-Ming
University, Taipei, Taiwan
European Journal of Clinical Pharmacology (2018) 74:1111–1119