Liver and Bile
J Hepatol. 2022;77(6):1670–89
Hepatitis B virus reactivation associated with new classes of immunosuppressants and immunomodulators: A systematic review, meta-analysis, and expert opinion
Hepatitis B virus reactivation (HBVr) can be prevented by nucleos(t)ide analogues (NAs). The authors conducted a systematic review and meta-analysis on the risk of HBVr associated with new classes of immunosuppressive and immunomodulatory therapies and developed guidance on NA prophylaxis. An expert panel reviewed the data and categorized the risk of HBVr associated with each class of drugs into low (< 1%), intermediate (1–10%), and high (> 10%). This search uncovered 59 studies, including 3424 HBsAg+ and 5799 HBsAg-/anti-HBc+ patients, which met this eligibility criteria. Based on medium-high quality evidence, immune checkpoint inhibitors, tyrosine kinase inhibitors, cytokine inhibitors, chimeric antigen receptor T-cell immunotherapies, and corticosteroids were associated with high HBVr risk in HBsAg+ patients; cytokine inhibitors, chimeric antigen receptor T-cell immunotherapies, and corticosteroids with intermediate risk in HBsAg-/anti-HBc+ patients; and anti-tumor necrosis factor agents and immune checkpoint inhibitors with low risk in HBsAg-/anti-HBc+ patients. Provisional recommendations are provided for drugs with low quality evidence. NA prophylaxis is recommended when using drugs associated with a high HBVr risk, while monitoring with on-demand NAs is recommended for low-risk drugs – either approach may be appropriate for intermediate-risk drugs.
Consensus on definitions and methods of reporting hepatitis B virus reactivation (HBVr), along with inclusion of HBsAg+, and HBsAg-/anti-HBc+ patients in clinical trials, will be key to gathering reliable data on the risk of HBVr associated with immunosuppressive or immunomodulatory therapies.