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免疫检查点抑制剂治疗下乙型肝炎病毒相关晚期肝细胞癌患者的乙型肝炎病毒 DNA 水平与总生存期的关系。

Association of hepatitis B virus DNA levels with overall survival for advanced hepatitis B virus-related hepatocellular carcinoma under immune checkpoint inhibitor therapy.

机构信息

Department of Immunotherapy, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China.

Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

出版信息

Cancer Immunol Immunother. 2023 Feb;72(2):385-395. doi: 10.1007/s00262-022-03254-w. Epub 2022 Jul 30.

Abstract

BACKGROUND

High hepatitis B virus (HBV) DNA level is an independent risk factor for postoperative HBV-associated liver cancer recurrence. We sought to examine whether HBV DNA level and antiviral therapy are associated with survival outcomes in patients with advanced hepatocellular carcinoma (HCC) treated with anti-programmed cell death protein 1 (PD-1)based immunotherapy.

METHODS

This single-institution retrospective analysis included 217 patients with advanced HBV-related HCC treated from 1 June 2018, through 30 December 2020. Baseline information was compared between patients with low and high HBV DNA levels. Overall survival (OS) and progression-free survival (PFS) were compared, and univariate and multivariate analyses were applied to identify potential risk factors for oncologic outcomes.

RESULTS

The 217 patients included in the analysis had a median survival time of 20.6 months. Of these HBV-associated HCC patients, 165 had known baseline HBV DNA levels. Baseline HBV DNA level was not significantly associated with OS (P = 0.59) or PFS (P = 0.098). Compared to patients who did not receive antiviral therapy, patients who received antiviral therapy had significantly better OS (20.6 vs 11.1 months, P = 0.020), regardless of HBV DNA levels. Moreover, antiviral status (adjusted HR = 0.24, 95% CI 0.094-0.63, P = 0.004) was an independent protective factor for OS in a multivariate analysis of patients with HBV-related HCC.

CONCLUSIONS

HBV viral load does not compromise the clinical outcome of patients with HBV-related HCC treated with anti-PD-1-based immunotherapy. The use of antiviral therapy significantly improves survival time of HBV-related HCC patients.

摘要

背景

高乙型肝炎病毒(HBV)DNA 水平是术后 HBV 相关肝癌复发的独立危险因素。我们试图研究在接受抗程序性细胞死亡蛋白 1(PD-1)的免疫治疗的晚期肝细胞癌(HCC)患者中,HBV DNA 水平和抗病毒治疗是否与生存结果相关。

方法

这是一项单机构回顾性分析,纳入了 217 名于 2018 年 6 月 1 日至 2020 年 12 月 30 日期间接受治疗的晚期 HBV 相关 HCC 患者。比较了 HBV DNA 水平低和高的患者的基线信息。比较了总生存期(OS)和无进展生存期(PFS),并进行了单因素和多因素分析以确定肿瘤学结局的潜在危险因素。

结果

在分析中纳入的 217 名患者的中位生存时间为 20.6 个月。这些 HBV 相关 HCC 患者中有 165 名患者具有已知的基线 HBV DNA 水平。基线 HBV DNA 水平与 OS(P=0.59)或 PFS(P=0.098)均无显著相关性。与未接受抗病毒治疗的患者相比,接受抗病毒治疗的患者 OS 显著更好(20.6 个月比 11.1 个月,P=0.020),无论 HBV DNA 水平如何。此外,抗病毒状态(调整后的 HR=0.24,95%CI 0.094-0.63,P=0.004)是 HBV 相关 HCC 患者多因素分析中 OS 的独立保护因素。

结论

HBV 病毒载量不会影响接受抗 PD-1 免疫治疗的 HBV 相关 HCC 患者的临床结局。抗病毒治疗的使用显著改善了 HBV 相关 HCC 患者的生存时间。

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