肝内乙肝表面抗原表达缺失持续应答预测聚乙二醇干扰素，

StephenW

Loss of intrahepatic HBsAg expression predicts sustained response to peginterferon and is reflected by pronounced serum HBsAg decline

    P. Arends1,
    V. Rijckborst1,
    P. E. Zondervan2,
    E. Buster1,
    Y. Cakaloglu3,
    P. Ferenci4,
    F. Tabak5,
    U. S. Akarca6,
    K. Simon7,
    M. J. Sonneveld1,
    B. E. Hansen1,8 and
    H. L. A. Janssen1,9,*

Article first published online: 20 JAN 2014

DOI: 10.1111/jvh.12218

© 2014 John Wiley & Sons Ltd

Issue
Journal of Viral Hepatitis

Volume 21, Issue 12, pages 897–904, December 2014

Author Information

    1    Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands
    2    Department of Pathology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands
    3    Istanbul Faculty of Medicine, Istanbul, Turkey
    4    Medical University of Vienna, Vienna, Austria
    5    Cerrahpasa Medical Faculty, Istanbul, Turkey
    6    Ege University Hospital, Izmir, Turkey
    7    Katedra I Klinika Chorób Zakaznych, Wroclaw, Poland
    8    Department of Public Health, Erasmus MC, University Medical Center, Rotterdam, the Netherlands
    9    UHN Liver Clinic, Toronto Western and General Hospital University Health Network Toronto, Toronto, ON, Canada

* Correspondence: Harry L. A. Janssen, MD, PhD, Francis Family Chair in Hepatology, Professor of Medicine, University of Toronto & Erasmus University Rotterdam, Head of UHN Liver Clinic Division of Gastroenterology, University Health Network, 399 Bathurst Street, 6B FP, Room 164, Toronto, ON M5T 2S8, Canada.
E-mail: [email protected]
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Summary

There is a lack of knowledge regarding the effect of peginterferon (PEG-IFN) on the expression of intrahepatic hepatitis B core and surface antigen (HBcAg and HBsAg) in chronic hepatitis B (CHB) and its relation with response to therapy. Fifty-two HBeAg-positive and 67 HBeAg-negative CHB patients with paired liver biopsies taken at baseline and after 1 year of PEG-IFN therapy were studied. After PEG-IFN therapy, HBeAg-negative patients showed a significant reduction in both intrahepatic HBcAg (P = 0.04) and HBsAg expression (P < 0.001). In contrast, a reduction in intrahepatic HBcAg expression was not observed in HBeAg-positive patients, while a trend in reduction of intrahepatic HBsAg staining was found (P = 0.09). Post-treatment, 7 (13%) HBeAg-positive and 9 (14%) HBeAg-negative patients had no expression of intrahepatic HBsAg. Patients without any intrahepatic HBsAg expression post-treatment were more likely to achieve a combined response (HBeAg loss with hepatitis B virus (HBV) DNA <2000 IU/mL for HBeAg -positive and HBV DNA <2000 IU/mL and normal alanine aminotransferase for HBeAg-negative CHB): 71% vs 5% for HBeAg-positive (P < 0.001) and 60% vs 16% for HBeAg-negative patients (P = 0.004), respectively. Moreover, a more profound decline of serum HBsAg was observed in patients with absence of intrahepatic HBsAg staining (3.1 vs 0.4 log IU/mL, P < 0.001 and 1.7 vs 0.4 log IU/mL, P = 0.005 for HBeAg-positive and HBeAg-negative CHB, respectively). In conclusion, PEG-IFN reduces expression of intrahepatic HBsAg. Loss of HBsAg as assessed by immunohistochemistry from the liver predicts a sustained response and is reflected in a pronounced serum HBsAg decline.

StephenW

肝内乙肝表面抗原表达缺失持续应答预测聚乙二醇干扰素，被明显血清HBsAg下降反映

    P. Arends1，
    V. Rijckborst1，
    P. E. Zondervan2，
    E. Buster1，
    Y. Cakaloglu3，
    P. Ferenci4，
    F. Tabak5，
    美国Akarca6，
    K. Simon7，
    M. J. Sonneveld1，
    B. E. Hansen1,8和
    H. L. A. Janssen1,9，*

文章首次在网上公布：2014年1月20日

DOI：10.1111/ jvh.12218

©2014年约翰·威利父子有限公司

问题
杂志病毒性肝炎

第21卷，第12期，页897-904，2014年12月

作者信息

    胃肠病学和肝病，伊拉兹马斯MC，大学医学中心，鹿特丹，荷兰1系
    病理，伊拉兹马斯MC，大学医学中心，鹿特丹，荷兰2部
    医药，伊斯坦布尔，土耳其伊斯坦布尔3系
    维也纳，奥地利维也纳4医科大学
    5 Cerrahpasa医学院，土耳其伊斯坦布尔
    6爱琴大学医院，伊兹密尔，土耳其
    7 Katedra我服务KlinikaChoróbZakaznych，弗罗茨瓦夫，波兰
    公共卫生，伊拉兹马斯MC，大学医学中心，鹿特丹，荷兰8处
    9 UHN肝门诊，多伦多西部和综合医院大学健康网络多伦多，多伦多，加拿大

*通讯：哈利LA扬森，医学博士，弗朗西斯家庭主席在肝病，医学教授，多伦多及鹿特丹Erasmus大学大学，UHN肝病诊疗科消化科，大学健康网络，399巴瑟斯特街的负责人，6B FP室164，多伦多，ON M5T2S8，加拿大。
电子邮件：[email protected]
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总结

有关于聚乙二醇干扰素对肝内乙肝核心和表面抗原（HBcAg的与HBsAg）慢性乙型肝炎（CHB）及其与治疗反应相关的表达的影响（PEG-IFN）知识的缺乏。五十二HBeAg阳性和67例HBeAg阴性慢性乙型肝炎患者在基线和1年PEG-IFN治疗后采取的配对肝活检进行了研究。经过PEG-IFN治疗，HBeAg阴性患者表现出显著减少肝内的HBcAg（P=0.04）和乙肝表面抗原的表达（P <0.001）。相比之下，未在HBeAg阳性患者中观察到肝内HBcAg的表达降低，而降低肝内乙肝表面抗原染色的趋势被发现（P=0.09）。治疗后，7（13％），HBeAg阳性和9（14％），HBeAg阴性患者肝内乙肝表面抗原不表达。患者无任何肝内乙肝表面抗原表达治疗后更容易实现与乙型肝炎病毒（HBV）DNA<2000 IU/毫升的HBeAg阳性和HBV DNA<2000 IU/ mL和正常的谷丙转氨酶的联合反应（HBeAg消失HBeAg阴性CHB）：71％和5％的HBeAg阳性（P <0.001）和60％比分别为HBeAg阴性患者（P =0.004），16％。此外，血清HBsAg更深刻的下降，观察患者的肝内缺乏乙肝表面抗原染色（3.1 VS0.4日志IU/ mL时，P <0.001和1.7 VS0.4日志IU/ mL时，P =0.005 HBeAg阳性和个HBeAg-阴性CHB，分别）。最后，PEG-IFN降低肝内的HBsAg的表达。 HBsAg消失的评估，从肝脏免疫预测持续应答，并反映在显血清HBsAg下降。