Comparative Risk of Hepatitis B Virus Reactivation in Patients Receiving Immune Checkpoint Inhibitors or Tyrosine Kinase Inhibitors for Liver Cancer

Abstract

Background: Current and past hepatitis B virus (HBV) infection remains the leading cause of liver cancer in endemic areas. Aim: To examine the risk of HBV reactivation (HBVr) in patients receiving immune checkpoint inhibitors (ICI) for liver cancer. Methods: Patients with current or past HBV infection receiving systemic treatments for liver cancer from March 2015 to March 2023 were identified using a territory-wide electronic database in Hong Kong. The primary outcome was HBVr in ICI compared to tyrosine kinase inhibitor (TKI) use, defined according to the American Association for the Study of Liver Diseases criteria. The secondary outcome was HBVr in different types of ICI. Results: One thousand five hundred and ninty-six patients with current or past HBV infection (222 first received ICI; 1374 first received TKI) were included. 205 patients (12.8%) had past HBV infection, and 93.2% of the cohort were on HBV antiviral prophylaxis at baseline. At a median of 10.7 months (IQR: 3.7–12.0), 25 (1.6%) patients had HBVr, among whom 5 were exposed to ICI. The 12-month cumulative incidence (95% CI) of HBVr of the 1596 patients was 1.7% (1.1%–2.4%). The proportion of patients experiencing HBVr with and without antiviral prophylaxis was 1.4% and 3.7%, respectively. In multivariable analysis, ICI use was not associated with a higher risk of HBVr than TKI use, and the use of different ICI did not impact the risk of HBVr. Conclusion: With adequate antiviral prophylaxis, the absolute risk of HBVr is low in advanced HBV-related liver cancer patients receiving ICI, regardless of current or past HBV infection.