Correlation Analysis Between HBsAg/HBV DNA And Prognosis Of Patients With HBV Related Hepatocellular Carcinoma Treated With PD-1/PD-L1 Inhibitors

Background:Hepatitis B virus(HBV)is a major contributor to hepatocellular carcinoma(HCC).Currently,PD-1/PD-L1 inhibitors are extensively utilized to treat advanced HCC and have displayed promising outcomes.In addition,obstructing the PD-1/PD-L1 pathway may also be beneficial in anti-HBV.However,the efficacy and safety of PD-1/PD-L1 blockades in treating HBV-related HCC and its antiviral effects remains largely unknown.Objects:This study aims to evaluate the efficacy and safety of PD-1/PD-L1 inhibitors in the treatment of hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC)in a real-world setting,analyze the value of biomarkers such as HBsAg and HBV DNA in predicting the response to PD-1/PD-L1 inhibitors,and preliminarily explore the anti-HBV effect of PD-1/PD-L1 inhibitors.Methods:This study conducted an investigation of 108 patients with HBV-related HCC who received at least one PD-1/PD-L1 inhibition treatment at the South Hospital of Southern Medical University,from July 2018 to August 2021.Data regarding the demographic characteristics,tumor treatment plan,and levels of HBsAg and HBV DNA at various points during the treatment were collected.The primary endpoints of the study were overall survival(OS)and objective response rate(ORR),with the secondary endpoint being disease control rate(DCR).Statistical methods such as the independent sample t-test,chi-square test,COX regression analysis,Kaplan-Meier curve,and log-rank test were used to compare and analyze the data.Results:A total of 108 patients with HBV-related HCC were included in this study,with a median baseline HBsAg level of 927.8 IU/mL(range 226.8-1835.2)and a median HBV DNA load of 120.0 IU/mL(range 10.0-4815.0).The overall response rate was 13.0%,and the disease control rate was 48.3%.One individual(0.9%)developed HBVr,but did not experience HBVr-related hepatitis.The baseline HBsAg level(HBsAg≥1000IU/mL versus HBsAg<1000IU/mL)does not have a non-linear relationship with the mortality of patients(P=0.54),and the survival period of patients in the two groups is not statistically different(18.5 m vs not reaching,P>0.05).At 4,12,24 and 48 weeks following immunotherapy,67.5%,78%,62.1%,and 84.6%of patients respectively displayed various levels of HBsAg reduction,yet no patients achieved HBsAg clearance.According to the Kaplan-Meier survival curve,those in the HBsAg decrease group had a longer OS of 6.9 months(95%CI 6.3-7.4)at the 12th week after treatment compared to the HBsAg non-decrease group,with a P value of 0.005.There was no difference in ORR and DCR between the two groups.Patients with a positive baseline HBV DNA had a worse optimal tumor response than those with a negative baseline HBV DNA(P=0.003)and a shorter survival period(15.1 months vs 24.0 months,P=0.009).There was no statistical difference in ORR and DCR between the two groups.Univariate regression analysis revealed that baseline HBV DNA positivity(P=0.01,HR=3.0,95%CI:1.3-7.3)was a risk factor for a poor prognosis.Additionally,multivariate regression analysis showed that a PS score greater than 0(P=0.01,HR=4.5,95%CI:1.5-13.7)and HBsAg non-decrease(P=0.02,HR=5.0,95%CI:1.3-18.5)at 12 weeks after treatment were independent risk factors for a poor prognosis.Conclusion:PD-1/PD-L1 blockades are effective in treating patients with HBV associated HCC,and the rate of HBV r is low.Patients with HBV DNA positive at the beginning of treatment are more likely to experience tumor progression and have a shorter survival time.The baseline HBsAg level was not found to be related to the clinical outcome of patients receiving immunotherapy,however,the early decline of HBsAg titer after immunotherapy may indicate a better tumor response and a longer survival.PD-1/PD-L1 blockades can reduce HBsAg levels,more research is needed to further investigate that.