程序性死亡受体-1抗体对乙型肝炎相关肝癌患者乙型肝炎病毒的影响

Effects of programmed death receptor-1 antibody in patients with hepatitis B-associated liver cancer

目的探讨程序性死亡受体(PD)-1抗体治疗对于乙型肝炎相关肝癌患者乙型肝炎病毒(HBV)的影响。方法入组2020年3月至2021年1月在解放军总医院第五医学中心感染病医学部接受PD-1抗体联合酪氨酸激酶抑制剂治疗的29例HBV慢性感染肝癌患者资料,以上患者均同时接受核苷(酸)类似物抗HBV治疗,收集患者的临床诊断资料、实验室检查结果、肿瘤应答以及不良反应发生情况开展回顾性研究,了解整体安全性及抗肿瘤治疗效果,HBV的变化情况,HBV变化与PD-1抗体抗肿瘤疗效的相关性,高病毒载量患者治疗情况,以及HBV再激活的安全性问题。采用非参数秩和检验进行统计学分析。结果患者抗肿瘤治疗效果和安全性良好,客观缓解率达到27.6%,发生的不良反应多为轻度,严重不良反应发生率低。随访12周,患者HBV DNA和HBsAg定量出现下降(P<0.05);与疾病进展的患者,疾病稳定和部分应答的患者HBV DNA和HBsAg定量下降更明显(P<0.05)。5例HBV DNA≥10^(4) IU/ml的患者治疗肿瘤应答良好,无严重不良反应发生,有1例患者出现HBV DNA和丙氨酸转氨酶轻度升高。未出现HBV再激活和相关肝损伤。结论接受联合治疗的HBV相关肝癌患者具有较好的抗肿瘤疗效和安全性。PD-1治疗对HBV有一定的影响,肿瘤应答患者相比于无应答患者,有更好的抗病毒治疗疗效。高病毒载量患者治疗安全性可控,无HBV再激活相关的安全性问题发生。

Objective To investigate the effect of programmed death receptor(PD)-1 antibody therapy in patients with hepatitis B-associated liver cancer.Methods Data of 29 chronically infected HBV patients with liver cancer who received PD-1 antibody combined with tyrosine kinase inhibitor in the Department of Infectious Diseases of the Fifth Medical Center of PLA General Hospital from March 2020 to January 2021 were selected.At the same time,all of the above-mentioned hepatitis B virus(HBV)patients were treated with nucleos(t)ide analogues.Patients clinical diagnostic data,laboratory test results,tumor response and the incidence of adverse reactions were collected retrospectively to understand the overall safety,therapeutic anti-tumor effect,HBV changes condition and the correlation between HBV changes and anti-tumor PD-1 antibody efficacy,high viral load treatment condition,and HBV reactivation safety issues.Statistical analysis was performed by non-parametric rank sum test.Results Therapeutic anti-tumor effect and safety profile were good in patients.The complete remission rate was reached 27.6%.Adverse reactions were mostly mild,and the incidence of serious adverse reactions was low.After 12 weeks of follow-up,HBV DNA and hepatitis B surface antigen(HBsAg)was quantitatively decreased(P<0.05).HBV DNA and HBsAg were decreased more significantly in patients with progressive disease(PD),stable disease(SD)and partial response(PR)(P<0.05).Five patients with HBV DNA≥10^(4) IU/ml had responded well to the tumor treatment without serious adverse reactions.One patient had a slight increase in HBV DNA and alanine aminotransferase,while there was no HBV reactivation and correlated liver damage.Conclusion Patients with HBV-associated liver cancer who received combined therapy have good anti-tumor efficacy and safety profile.PD-1 treatment has a certain effect on HBV.Compared with non-responders,patients with tumor response have better antiviral treatment efficacy.The safety of treatment in patients with high viral load is manageable,and there are no safety issues related to HBV reactivation.