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.