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抗病毒治疗的病毒学反应与肝动脉化疗栓塞术后中期乙型肝炎病毒相关肝细胞癌患者生存的相关性

Association of Virological Response to Antiviral Therapy With Survival in Intermediate-Stage Hepatitis B Virus-Related Hepatocellular Carcinoma After Chemoembolization.

作者信息

Jin Meng, Chen Yong, Hu Shuifang, Zhu Meiyan, Wang Yan, Chen Minshan, Peng Zhenwei

机构信息

Department of Radiation Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China.

出版信息

Front Oncol. 2021 Oct 22;11:751777. doi: 10.3389/fonc.2021.751777. eCollection 2021.

Abstract

INTRODUCTION

Role of response to antiviral therapies on survival of patients with intermediate-stage hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) undergoing transarterial chemoembolization (TACE) remains unknown. We aimed to determine whether virological response (VR) or prolonged maintained virological response (MVR) to nucelos(t)ide analogues (NA) therapy could result in improved survival in HBV-HCC patients receiving TACE.

METHODS

Between January 2012 and October 2018, data of patients with intermediate HBV-HCC who underwent TACE and started NA therapy within one week prior to TACE treatment at our institution were reviewed. Overall survival (OS) was compared using the Kaplan-Meier method with log-rank test between different VR status groups. Univariable and multivariable Cox regression analyses were used to determine the association between achievement of VR or MVR and OS. VR was defined as an undetectable HBV DNA level (<100 IU/ml) on two consecutive measurements during NA treatment. MVR was defined as a persistently undetectable HBV DNA level after achieving a VR.

RESULTS

A total of 1265 patients undergoing TACE with a median follow-up time of 18 months (range, 2-78 months) were included in the analysis. Of 1265 NA-treated patients [1123 (88.8%) male, median (range) age, 56 (18-75) years], 744 patients (58.8%) achieved VR and the remaining patients (41.2%) did not. Patients with achievement of VR showed a significantly longer OS than those without VR (median OS: 21 16 months; HR, 0.707; 95% CI, 0.622-0.804; <0.001). Among patients with VR, MVR was present in 542 patients (72.8%), while the other 202 patients (27.2%) in the non-MVR group. The OS for the MVR group was significantly higher than the non-MVR group (median OS: 23.2 18 months; HR, 0.736; 95% CI, 0.612-0.885; =0.001). Additionally, patients with MVR status more than two years showed a better OS than those with just one-year (HR, 0.719; 95% CI, 0.650-0.797; <0.001) or one-to-two-year MVR (HR, 0.612; 95% CI, 0.471-0.795; =0.024). On multivariable analyses, splenomegaly and up-to-seven criteria were independent prognostic factors of OS in both VR and MVR cohorts.

CONCLUSIONS

In patients with intermediate-stage HBV-HCC, both VR to antiviral therapy and prolonged response are associated with prolonged OS after TACE, especially for those within up-to-seven criteria.

摘要

引言

抗病毒治疗反应对接受经动脉化疗栓塞术(TACE)的中期乙型肝炎病毒相关肝细胞癌(HBV-HCC)患者生存的作用尚不清楚。我们旨在确定核苷(酸)类似物(NA)治疗的病毒学应答(VR)或延长的持续病毒学应答(MVR)是否能改善接受TACE的HBV-HCC患者的生存。

方法

回顾2012年1月至2018年10月在我院接受TACE且在TACE治疗前一周内开始NA治疗的中期HBV-HCC患者的数据。采用Kaplan-Meier法和对数秩检验比较不同VR状态组的总生存期(OS)。采用单变量和多变量Cox回归分析确定VR或MVR的实现与OS之间的关联。VR定义为在NA治疗期间连续两次测量时HBV DNA水平不可检测(<100 IU/ml)。MVR定义为实现VR后HBV DNA水平持续不可检测。

结果

共纳入1265例接受TACE的患者,中位随访时间为18个月(范围2-78个月)。在1265例接受NA治疗的患者中[1123例(88.8%)为男性,中位(范围)年龄56(十八岁至七十五岁)岁],744例(58.8%)实现VR,其余患者(41.2%)未实现。实现VR的患者OS显著长于未实现VR的患者(中位OS:21对16个月;HR,O.707;95%CI,0.622-0.804;<0.001)。在VR患者中,542例(72.8%)存在MVR,而202例(27.2%)在非MVR组。MVR组的OS显著高于非MVR组(中位OS:23.2对18个月;HR,0.736;95%CI,0.612-0.885;=0.001)。此外,MVR状态超过两年的患者OS优于仅一年(HR,0.719;95%CI,0.650-0.797;<0.001)或一至两年MVR的患者(HR,0.612;95%CI,0.471-0.795;=0.024)。多变量分析显示,脾肿大和至多七个标准是VR和MVR队列中OS的独立预后因素。

结论

在中期HBV-HCC患者中,抗病毒治疗的VR和延长的应答均与TACE后的OS延长相关,尤其是对于符合至多七个标准的患者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0d2/8569860/9a9376275905/fonc-11-751777-g001.jpg

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