HBV Reactivation in Patients Receiving Bruton Tyrosine Kinase Inhibitors (BTKIs): a Systematic Review and Meta-Analysis

Bruton tyrosine kinase inhibitors (BTKIs) are immunosuppressive cancer therapies approved for the treatment of various mature B-cell malignancies. Hepatitis B virus reactivation (HBVr) is a known complication in patients with chronic or past HBV infection undergoing immunosuppressive chemotherapy. The present work aims to establish the correlation between HBVr and patients receiving BTKIs.

This review included 18 studies. The overall incidence of HBVr was found to be 6.6% in patients with past HBV infections who received ibrutinib. Fourteen cases of HBVr were associated with ibrutinib (two occult hepatitis B infections and twelve past HBV infections). One case of HBV past infection was associated with zanubrutinib, and three cases were recorded for acalabrutinib (one chronic HBV and two past HBV). Most incidents occurred in males older than 60 years within the first year after initiating BTKIs. Three reported cases documented HBVr after discontinuing ibrutinib and zanubrutinib. Two deaths caused by HBVr in patients with past HBV infections were recorded (one for each of acalabrutinib and ibrutinib). Remarkably, HBV antiviral treatment normalized liver functions and eliminated serum HBV in most cases. It was reported that false negativity of HBsAg following reactivation occurred in two cases: one case was attributed to HBsAg escape mutations, and the other to the hook effect.

Our findings show that HBVr risk is intermediate in patients with past HBV infections who receive ibrutinib. Universal anti-HBV prophylaxis before initiating ibrutinib may be an option.