Comparison of hepatitis B virus reactivation in hepatocellular carcinoma patients who received tyrosine kinase inhibitor alone or together with programmed cell death protein-1 inhibitorsComparison of hepatitis B virus reactivation in hepatocellular carcinoma patients who received tyrosine kinase inhibitor alone or together with programmed cell death protein-1 inhibitors

Background & Aims: Programmed cell death protein-1 (PD-1) inhibitors plus tyrosine kinase inhibitor (TKI) has dramatically improved survival of patients with advanced hepatocellular carcinoma (HCC). However, the risk of hepatitis B virus (HBV) reactivation from these antitumor medications remains unclear. Methods: Patients receiving TIK monotherapy (TKI group) or TKI combined with PD-1 inhibitors (combination group) were included. The primary endpoint was HBV reactivation as defined by an increase in HBV DNA titer by at least 1 log(10-fold) from baseline. The secondary endpoints included tumor progression, overall survival. Results: A total of 499 patients met the inclusion criteria, including 296 patients in the TKI group and 203 patients in the combination group. The 3-month, 6-month and 12-month cumulative incidence rates of HBV reactivation in the TKI group vs combination group were 7.8%, 12.8% and 21.3% vs 9.9%,19.2% and 30.0%, respectively (P=0.02). The Cox proportional hazard model indicated that combination therapy (HR 1.41, 95% CI 1.00-1.99, P=0.05), ALT > 40 U/L (HR 1.50, 95% CI, 1.05-2.16, P=0.03), and tumor size > 5 cm (HR 1.58, 95% CI, 1.10-2.28, P=0.01) were independent risk factors for HBV reactivation. Compared with the HBV reactivation group, the progression-free survival and overall survival of patients in the HBV non-reactivation group were significantly prolonged (P