乙型肝炎再激活和免疫检查点抑制剂

StephenW

Hepatitis B reactivation and immune check point inhibitors
Benoit Godbert  1 , Nadine Petitpain  2 , Anthony Lopez  3 , Yann-Eric Nisse  4 , Pierre Gillet  4
Affiliations
Affiliations

    1
    Department of Pneumology, Robert Schuman Hospital, Vantoux 57070, France.
    2
    Regional Pharmacovigilance Centre, Department of Clinical Pharmacology, Toxicology, University Hospital CHRU Nancy, Vandœuvre-lès-Nancy 54511, France. Electronic address: [email protected].
    3
    Department of Hepatogastroenterology, University Hospital CHRU Nancy, Vandœuvre-lès-Nancy 54511, France.
    4
    Regional Pharmacovigilance Centre, Department of Clinical Pharmacology, Toxicology, University Hospital CHRU Nancy, Vandœuvre-lès-Nancy 54511, France.

    PMID: 32921602 DOI: 10.1016/j.dld.2020.08.041

Abstract

Liver toxicity during immune checkpoint inhibitor treatment is mostly due to immune mediated hepatitis. Viral hepatitis, as well as auto-immune or metabolic hepatitis, are considered as exclusion criteria for ICI induced immune hepatitis diagnosis. However, considering the high prevalence of viral hepatitis B infection and the increasing prescription of immune checkpoint inhibitors, their use in patients with HBV chronic viral infection may be common, even more if patients are treated for hepatocellular carcinoma. Few clinical studies directly deal with the risk of HBV reactivation during ICI therapy and real-life data is currently based on five reported cases of HBV reactivation, one with fatal outcome. In this review, we summarize the current available clinical information about HBV reactivation risk during ICI treatment, its hypothetic mechanism, and propose practical recommendations about verifying and monitoring HBV status throughout the treatment.

Keywords: Case report; Fulminant hepatitis; Immune checkpoint inhibitors; Reactivation; Viral hepatitis.

Copyright © 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

StephenW

乙型肝炎再激活和免疫检查点抑制剂
Benoit Godbert 1，Nadine Petitpain 2，Anthony Lopez 3，Yann-Eric Nisse 4，Pierre Gillet 4
隶属关系
隶属关系

    1个
    罗伯特·舒曼医院肺炎科，法国万图57070。
    2
    CHRU Nancy大学医院毒理学临床药理学部区域药物警戒中心，法国范德韦尔-吕斯-南锡54511。电子地址：[email protected]。
    3
    法国南范德鲁大学南克鲁大学附属医院消化内科，法国54511。
    4
    CHRU Nancy大学医院毒理学临床药理学部区域药物警戒中心，法国范德韦尔－吕斯－南锡54511。

    PMID：32921602 DOI：10.1016 / j.dld.2020.08.041

抽象

免疫检查点抑制剂治疗期间的肝毒性主要归因于免疫介导的肝炎。病毒性肝炎以及自身免疫性或代谢性肝炎被视为ICI诱导的免疫性肝炎诊断的排除标准。然而，考虑到乙型病毒性肝炎感染的高流行和免疫检查点抑制剂处方的增加，在HBV慢性病毒感染患者中使用它们可能很常见，即使对肝细胞癌患者进行治疗也更多。很少有临床研究直接处理ICI治疗期间HBV激活的风险，目前的实际数据是基于5例报告的HBV激活病例，其中1例具有致命后果。在这篇综述中，我们总结了有关ICI治疗期间HBV激活风险的当前可用临床信息，其假设机制，并提出了在整个治疗过程中验证和监测HBV状态的实用建议。

关键字：病例报告；暴发性肝炎；免疫检查点抑制剂；重新激活；病毒性肝炎。

版权所有©2020 Editrice Gastroenterologica Italiana S.r.l.由Elsevier Ltd.出版。保留所有权利。

StephenW

Quantitative HBcrAg and HBcAb versus HBsAg and HBV DNA in predicting liver fibrosis levels of chronic hepatitis B patients
[Article in En, Spanish]
Zhan-Qing Zhang  1 , Bi-Sheng Shi  2 , Wei Lu  3 , Dan-Ping Liu  3 , Dan Huang  3 , Yan-Ling Feng  4
Affiliations
Affiliations

    1
    Deparment of Hepatobiliary Medicine, Shanghai Public Health Clinical Center of Fudan University. Electronic address: [email protected].
    2
    Scientific Research Center, Shanghai Public Health Clinical Center of Fudan University.
    3
    Deparment of Hepatobiliary Medicine, Shanghai Public Health Clinical Center of Fudan University.
    4
    Department of Clinical Pathology, Shanghai Public Health Clinical Center of Fudan University.

    PMID: 32921478 DOI: 10.1016/j.gastrohep.2020.03.017

Abstract

Objective: To evaluate the performance of the quantitative markers of hepatitis B core-related antigen (HBcrAg) and anti-hepatitis B core antigen antibodies HbcAb versus hepatitis B surface antigen (HBsAg) and hepatitis B virus DNA (HBV DNA) in predicting liver fibrosis levels in chronic hepatitis B patients.

Methods: Two hundred and fifty hepatitis B e antigen (HBeAg)-positive and 245 HBeAg-negative patients were enrolled. With reference to the Scheuer standard, stage 2 or higher and stage 4 liver disease were defined as significant fibrosis and cirrhosis, respectively. A receiver operating characteristic (ROC) curve was used to evaluate the performance of the HBV markers investigated.

Results: The areas under the ROC curves (AUCs) of HBcrAg in predicting significant fibrosis and cirrhosis in HBeAg-positive patients (0.577 and 0.700) were both close to those of HBsAg (0.617 and 0.762) (both P> 0.05). In HBeAg-negative patients (0.797 and 0.837), they were both significantly greater than those of HBV DNA (0.723 and 0.738) (P=0.0090 and P=0.0079). The AUCs of HBcAb in predicting significant fibrosis and cirrhosis in HBeAg-positive patients (0.640 and 0.665) were both close to those of HBsAg. In HBeAg-negative patients (0.570 and 0.621), they were both significantly less than those of HBcrAg (P <0.0001 and P=0.0001). Specificity in predicting significant fibrosis and sensitivity in predicting cirrhosis in HBeAg-positive patients, using a single cut-off of HBsAg ≤5,000 IU/ml, were 76.5% and 72.7%, respectively. In HBeAg-negative patients, using a single cut-off of HBcrAg>80kU/ml, they were 85.9% and 81.3%, respectively.

Conclusions: HBsAg has good performance in predicting liver fibrosis levels in HBeAg-positive and HBeAg-negative patients, and HBcrAg has very good performance in predicting liver fibrosis levels in HBeAg-negative patients.

Keywords: Anti-hepatitis B core antigen antibodies; Anticuerpos contra el antígeno del núcleo de la hepatitis B; Antígeno de superficie de la hepatitis B; Antígeno relacionado con el núcleo de la hepatitis B; Diagnóstico no invasivo; Fibrosis hepática; Hepatitis B core-related antigen; Hepatitis B surface antigen; Liver fibrosis; Marcador virológico; Non-invasive diagnosis; Virological marker.

Copyright © 2020. Publicado por Elsevier España, S.L.U.

StephenW

定量HBcrAg和HBcAb与HBsAg和HBV DNA预测慢性乙型肝炎患者肝纤维化水平
[西班牙语中的文章]
张占清1，石必胜2，卢伟3，刘丹萍3，黄丹3，冯艳玲4
隶属关系
隶属关系

    1个
    复旦大学上海公共卫生临床中心肝胆科。电子地址：[email protected]。
    2
    复旦大学上海公共卫生临床中心科研中心。
    3
    复旦大学附属上海公共卫生临床中心肝胆科。
    4
    复旦大学上海公共卫生临床中心临床病理学教研室。

    PMID：32921478 DOI：10.1016 / j.gastrohep.2020.03.017

抽象

目的：评价乙肝核心相关抗原（HBcrAg）和抗乙肝核心抗原抗体HbcAb与乙肝表面抗原（HBsAg）和乙肝病毒DNA（HBV DNA）的定量标志物在预测肝纤维化中的作用慢性乙型肝炎患者的血脂水平。

方法：纳入250例乙型肝炎e抗原（HBeAg）阳性和245例HBeAg阴性患者。参照Scheuer标准，将2级以上或4级肝病分别定义为明显的纤维化和肝硬化。使用接收器工作特性（ROC）曲线评估所研究的HBV标记物的性能。

结果：HBcrAg的ROC曲线下面积预测HBeAg阳性患者的显着纤维化和肝硬化（0.577和0.700）均与HBsAg的面积（0.617和0.762）接近（均P> 0.05）。在HBeAg阴性患者（0.797和0.837）中，它们均显着大于HBV DNA（0.723和0.738）（P = 0.0090和P = 0.0079）。 HBcAb的AUC可以预测HBeAg阳性患者的明显纤维化和肝硬化（0.640和0.665）均与HBsAg的AUC接近。在HBeAg阴性患者中（0.570和0.621），它们均显着低于HBcrAg患者（P <0.0001和P = 0.0001）。使用HBsAg≤5,000 IU / ml的单次截断，预测HBeAg阳性患者的显着纤维化的特异性和预测肝硬化的敏感性分别为76.5％和72.7％。在HBeAg阴性患者中，使用HBcrAg> 80kU / ml的单一临界值，分别为85.9％和81.3％。

结论：HBsAg对HBeAg阳性和HBeAg阴性患者的肝纤维化水平有良好的预测作用，HBcrAg对HBeAg阴性患者的肝纤维化水平有很好的预测作用。

关键词：抗乙型肝炎核心抗原抗体；乙型肝炎疫苗乙型肝炎门诊；乙型肝炎抗癌药； Diagnósticono invasivo;肝纤维化;乙型肝炎核心相关抗原；乙型肝炎表面抗原；肝纤维化； Marcadorvirológico;无创诊断；病毒学标记。

版权所有©2020。ElsevierEspaña，S.L.U。