Abstract
BACKGROUND: A high hepatitis B virus (HBV) load is a common exclusion criterion in hepatocellular carcinoma (HCC) clinical trials for anti-programmed cell death (PD)-1 immunotherapy. However, the validity of this criterion is barely verified. This study aimed to evaluate the impact of baseline HBV DNA levels and antiviral therapy on the oncological outcomes and liver functions of patients with HCC receiving anti-PD-1 immunotherapy. METHODS: We reviewed HCC trials related to anti-PD-(L)1 immunotherapy and whether they ruled out patients with increased HBV loads on clinicaltrials.gov. Then, for this retrospective study, we enrolled 253 HCC patients treated with anti-PD-1 blockade in our institution. Baseline information was compared between patients with low and high HBV loads. Overall survival (OS) and progression-free survival (PFS) were compared, and univariate and multivariate analyses were applied to identify potential risk factors for oncological outcomes and hepatic impairment. RESULTS: Among 76 HCC clinical trials including 13,927 patients receiving anti-PD-(L)1 blockade, 41 (53.9%) excluded patients with relatively high baseline HBV loads. The PFS and OS did not differ significantly between patients with baseline HBV loads ≤ 2000 IU/mL and those with viral loads >2000 IU/mL (p=0.615 and 0.982). The incidence of hepatic impairment showed no association with the baseline HBV load (p=0.319). Patients receiving antiviral therapy had a better OS than those without antiviral therapy in the high baseline HBV load group (p= 0.001). CONCLUSION: High HBV loads did not compromise the clinical outcomes of HCC patients receiving anti-PD-1 blockade. Antiviral therapy could improve the OS of HCC patients with high HBV loads.