2024 年第 2 期 第 19 卷

信迪利单抗联合靶向及抗病毒方法治疗乙型肝炎病毒相关性肝细胞癌在病毒学及免疫功能方面的效果研究

Study on the virological and immunological effects of sintilimab combined with targeted and antiviral methods in the treatment of hepatitis B virus associated hepatocellular cancer

作者：申娇杨道坤王燕平刘佳魏帅陈宝鑫

英文作者：Shen Jiao Yang Daokun Wang Yanping Liu Jia Wei Shuai Chen Baoxin

单位：新乡医学院第一附属医院感染疾病科三病区，新乡453100

英文单位：Third Ward Department of Infectious Diseases the First Affiliated Hospital of Xinxiang Medical University Xinxiang 453100 China

关键词：肝细胞癌；程序性细胞死亡受体1抑制剂；乙型肝炎病毒；免疫功能

英文关键词：Hepatocellularcancer;Programmedcelldeathprotein1inhibitors;HepatitisBvirus;Immunefunction

• 摘要：

• 目的  观察程序性细胞死亡受体1抑制剂信迪利单抗联合靶向及抗病毒方法治疗乙型肝炎病毒（HBV）相关性肝细胞癌在病毒学及免疫功能方面的效果。方法  选取2021年3月至2022年4月新乡医学院第一附属医院收治的HBV相关性肝细胞癌患者70例。完全随机分为对照组和观察组，各35例。对照组给予丙酚替诺福韦+靶向治疗，观察组在对照组基础上给予信迪利单抗治疗。观察患者治疗前和治疗第1、3、6个周期的病毒学及免疫功能指标变化。结果  治疗第3、6个周期，观察组HBV DNA定量转阴率高于对照组［71.4%（25/35）比37.1%（13/35）、94.3%（33/35）比54.3%（19/35）］，差异均有统计学意义（均P<0.01）。治疗前和治疗第1、3、6个周期观察组和对照组HBV表面抗原定量差异均无统计学意义（均P>0.05），但治疗第1、3、6个周期观察组HBV表面抗原定量水平下降幅度大于对照组。治疗第1、3、6个周期，对照组CD+4 T淋巴细胞、CD+8 T淋巴细胞、自然杀伤细胞数目较治疗前逐渐减少，而观察组较治疗前逐渐增多，观察组均多于对照组，差异均有统计学意义(均P<0.05)。结论  信迪利单抗联合靶向及抗病毒方法治疗HBV相关性肝细胞癌患者效果良好，在降低病毒的复制能力、提高机体免疫能力方面优于单纯抗病毒联合靶向治疗。

• Objective  To observe the virological and immunological effects of programmed cell death protein 1 inhibitors sintilimab combined with targeted and antiviral methods in the treatment of hepatitis B virus(HBV) associated hepatocellular cancer. Methods  Totally 70 patients with HBV associated hepatocellular cancer admitted to the First Affiliated Hospital of Xinxiang Medical University from March 2021 to April 2022 were selected. They were completely randomized into control group and observation group, with 35 cases in each group. The control group was treated with tenofovir alafenamide and targeted therapy, while the observation group was treated with sintilimab on the basis of the control group. The changes in virological and immunological indicators of patients before treatment and in the first, third, and sixth cycles of treatment were observed and compared. Results  In the third and sixth cycles of treatment, the quantitative negative rate of HBV DNA in the observation group was higher than that in the control group［71.4%(25/35) vs 37.1%(13/35), 94.3%(33/35) vs 54.3%(19/35)］, and the differences were statistically significant(both P<0.01). There was no statistically significant difference in HBV surface antigen quantification between the observation group and the control group before treatment and in the first, third, and sixth cycles of treatment(all P>0.05), but the magnitude of decline of HBV surface antigen quantification level in the observation group was greater than that in the control group in the first, third, and sixth cycles of treatment. In the first, third, and sixth cycles of treatment, the number of CD+4 T lymphocytes, CD+8 T lymphocytes, and natural killer cells in the control group gradually decreased, while those in the observation group gradually increased, and the numbers in the observation group were more than those in the control group(all P<0.05). Conclusions    The combination of sintilimab and targeted and antiviral methods has a good therapeutic effect on HBV associated hepatocellular cancer, and is superior to simple antiviral combined targeted therapy in reducing virus replication ability and improve patients′ immune function.