PD-1 Inhibitor-based Therapies Could Lead to A Diversity of Viral Kinetics in Cancer Patients with Concomitant HBV Infection

Background: Previous studies have shown that blockade of programmed cell death-1 (PD-1) or programmed cell death- Ligand-1 (PD-L1) may improve anti-HBV responses in vitro and woodchuck models. However, clinical data was limited on the role of PD-1 inhibitors in patients with chronic HBV infection. We aimed to observe the changes ofserum HBsAgand HBV-DNA levels in cancer patients under PD-1 inhibitor-based therapies and identify the risk factors associated with HBsAg fluctuations and HBV reactivation (HBVr). Methods: A retrospective study including HBsAg-positive cancer patients who received PD-1 inhibitors between July 2019 and December 2022 was undertaken. Serum HBsAg and HBV-DNA level changes, the incidence of HBsAg loss, HBVr and immune-related adverse events (irAEs) were investigated. Univariable and multivariable analysis were performed to identify the risk factors for significant HBsAg fluctuations and HBVr. Results: 121 patients were eligible to the study. With concurrent use of antiviral agents, patients with baseline HBsAg within [50 to 500) IU/ml mostly had HBsAg decrease, viral replication was inhibited effectively. HBsAg loss, HBVr and irAEs were developed in 6 patients (4.96%), 6 patients (4.96%) and 14 patients (11.57%), respectively. Multivariable analysis showed baseline HBsAg <100 IU/ml (P=0.01) was the only significant risk factor for HBsAg decrease, irAEs occurrence was the only significant risk factor for HBVr (P=0.03), while no factors were identified for HBsAg increase. Conclusions: PD-1 inhibitor combined with NAs may exert therapeutic potential for chronic HBV infection in cancer patients, attention also should be payed to its safety.