Introduction
Despite the existence of an effective hepatitis B virus (HBV) vaccine and antiviral therapies, HBV-related HCC remains a leading cause of death worldwide, particularly in Asia and Africa[1-3]. More than 350 million people are chronically infected with HBV worldwide[4, 5]. Unfortunately, over 70% of HBV-HCC cases are diagnosed at a late stage, which results in limited treatment options and poor prognosis[6]. For advanced HCC patients, programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway inhibitor in combination with an antiangiogenic therapy has been demonstrated to be an effective treatment regimen[7-10]. However, a high baseline HBV DNA level has always been listed as an exclusion criterion for PD-1/PD-L1 inhibitor-associated therapy in clinical trials, regardless of the antiviral strategies. This is due to the controversial nature of the interaction between HBV load and anti-PD-1/PD-L1 therapy, particularly in HCC patients.
Several studies have shown that HBV reactivation induced by immunosuppressive agents or cytotoxic chemotherapy is a complication in cancer patients with pre-existing HBV infection, especially in those not subjected to continuous antiviral therapy[11-13]. Furthermore, Zhang et al.[14] demonstrated that the absence of antiviral prophylaxis treatment was the only significant risk factor for HBV reactivation following anti-PD-1/PD-L1 immunotherapy. Tenofovir alafenamide fumarate (TAF), a novel pro-drug of tenofovir (TFV) that has been approved for the treatment of chronic HBV infection, is characterized by a greater plasma stability and higher renal safety than tenofovir disoproxil fumarate (TDF)[15, 16].
However, to the best of our knowledge, no study has investigated the effects of anti-PD-1 treatment in combination with an antiangiogenic therapy on HBV infection in TAF prophylaxis-subjected individuals. Hence, we conducted a retrospective study to explore the effects of HBV load on anti-PD-1 in combination with an antiangiogenic therapy and the rate of HBV reactivation and hepatitis during a combined anti-PD-1 and antiangiogenic treatment.