对治疗反应的预测：干扰素治疗乙肝表面抗原期间动力学在

StephenW

HBsAg kinetics in chronic hepatitis D during interferon therapy: on-treatment prediction of response

    G. A. Niro1,*, A. Smedile2, R. Fontana1, A. Olivero2, A. Ciancio2, M. R. Valvano1, F. Pittaluga3, N. Coppola4, H. Wedemeyer5, K. Zachou6, A. Marrone7, M. Fasano8, G. Lotti9, P. Andreone10, A. Iacobellis1, A. Andriulli1 andM. Rizzetto2

Version of Record online: 22 JUL 2016

DOI: 10.1111/apt.13734

© 2016 John Wiley & Sons Ltd



    1    Gastroenterology Unit, IRCCS ‘Casa Sollievo Sofferenza’ Hospital, San Giovanni Rotondo (FG), Italy
    2    Department of Medical Sciences University of Turin, Division of Gastroenterology and Hepatology, Città della Salute e della Scienza University Hospital, Turin, Italy
    3    Microbiology and Virology Unit, A.O. Città della Salute e della Scienza, Molinette Hospital, University of Turin, Turin, Italy
    4    Department of Mental Health and Public Medicine, Second University of Naples, Caserta, Italy
    5    Department for Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, German Center for Infection Research, Hannover, Germany
    6    Department of Medicine and Research Laboratory of Internal Medicine, School of Medicine, University of Thessaly, Larissa, Greece
    7    Internal Medicine and Hepatology, Second University of Naples, Italy
    8    Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy
    9    IRCCS ‘Casa Sollievo Sofferenza’ Hospital, Blood Bank, San Giovanni Rotondo (FG), Italy
    10    Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy

* Correspondence to:
Dr G. A. Niro, Gastroenterology Unit, IRCCS ‘Casa Sollievo della Sofferenza’, Viale Cappuccini 1, 71013 San Giovanni Rotondo (FG), Italy.
E-mail: [email protected]

    The Handling Editor for this article was Prof Geoffrey Dusheiko, and it was accepted for publication after full peer-review.


Background

Therapy of chronic hepatitis D with Interferon is successful when testing for HDV-RNA turns negative. This end-point is disputed.
Aim

To assess the role of serum hepatitis B surface antigen (HBsAg) in the clearance of HDV-RNA in pegylated interferon (Peg-IFN)-treated chronic hepatitis D (CHD).
Methods

Sixty-two patients with CHD, treated with Peg-IFN, were considered. The patients belonged to three groups: 14 patients cleared the HBsAg and HDV-RNA (responders, R), 12 cleared the HDV-RNA remaining positive for HBsAg (partial responders, PR) and 36 cleared neither the HBsAg nor the HDV-RNA (nonresponders, NR).
Results

In responders, at baseline the median value (mv) of HBsAg and HDV-RNA was 1187 and 188 663 IU/mL. By month 6 of therapy, HBsAg declined to less than 1000 IU/mL and HDV-RNA was undetectable in 12 patients. In NR, the pre-therapy median value of HBsAg and HDV viremia was 6577 and 676 319 IU/mL. There was no significant reduction of antigen at month 6; after a decline, HDV-RNA rebounded to baseline levels. In PR, the median value of baseline HBsAg was 7031 IU/mL; it declined at month 6 in the majority. HDV-RNA progressively declined from an initial median value of 171 405 IU/mL. HBsAg <1000 IU/mL at month 6 discriminated responders and PR from NR (P < 0.001). By ROC curve, the threshold of 0.105 log reduction of HBsAg associated with 1.610 log reduction of HDV-RNA from baseline to month 6 predicted the clearance of this marker.
Conclusions

A reduction of serum HBsAg is mandatory for the definitive clearance of the HDV-RNA. Quantitative HBsAg may predict the long-term response to Peg-IFN therapy and provide a guide to prolong or stop treatment.

StephenW

对治疗反应的预测：干扰素治疗乙肝表面抗原期间动力学在慢性丁型肝炎

    GA Niro1，*，A Smedile2，R. Fontana1，A Olivero2，A Ciancio2，MR Valvano1，F Pittaluga3，N. Coppola4，H Wedemeyer5，K. Zachou6，A Marrone7，M. Fasano8，G。 Lotti9，P. Andreone10，A Iacobellis1，A Andriulli1 ANDM。 Rizzetto2

2016年7月22日：记录在线版本

DOI：10.1111 / apt.13734

2016年©约翰·威利父子有限公司



    1消化科单位，IRCCS“卡萨Sollievo Sofferenza'医院，圣乔瓦尼罗通（FG），意大利
    都灵医学大学胃肠病学和肝病的Cittàdella Salute的Ë德拉Scienza大学医院，意大利都灵部2部
    3微生物学和病毒学单位，A.O。的Cittàdella Salute的Ë德拉Scienza，Molinette医院，都灵大学，意大利都灵
    心理健康与公共医学，那不勒斯第二大学，卡塞塔，意大利的4部
    5部消化内科，肝病及内分泌，汉诺威医学院，德国为中心感染研究，汉诺威，德国
    塞萨利大学内科医学和研究实验室，医学院，拉里萨，希腊的6系
    7内科和肝病，意大利那不勒斯第二大学
    临床部8和实验医学杂志，福贾大学，福贾，意大利
    9 IRCCS“卡萨Sollievo Sofferenza”医院血库，圣乔瓦尼罗通（FG），意大利
    医学及外科科学，博洛尼亚大学，意大利博洛尼亚10部

*通讯作者：
博士G. A.德尼罗，消化内科单位，IRCCS“卡萨Sollievo德拉Sofferenza'的Viale墓穴1，71013圣乔瓦尼罗通（FG），意大利。
电子信箱：[email protected]

    这篇文章的编辑处理是教授杰弗里Dusheiko，它被接受后满同行评审的出版物。


背景

慢性丁型肝炎干扰素治疗的成功是对HDV-RNA测试时转阴。这个终点是有争议的。
目标

为了评估HDV-RNA的聚乙二醇干扰素清除血清乙肝表面抗原（HBsAg）的作用（PEG-IFN）处理的慢性丁型肝炎（CHD）。
方法

62例冠心病患者，用聚乙二醇干扰素治疗，进行了审议。患者属于三组：14名患者清除HBsAg和HDV RNA（应答，R），12清除了的HBsAg其余阳性（部分应答，PR）和36以HDV-RNA清零既不的HBsAg也不以HDV RNA（无应答，NR）。
结果

在应答者，在基线的HBsAg和HDV-RNA的中间值（MV）为1187和188 663国际单位/毫升。经治疗6个月，乙肝表面抗原下降到低于1000 IU / mL和HDV-RNA在12例检测不到​​。在NR，HBsAg和HDV病毒血症的治疗前中值是6577和676 319国际单位/毫升。有在6个月的抗原没有显著减少;在下跌后，HDV-RNA反弹至基线水平。在PR，基线HBsAg的中值是7031国际单位/毫升;它在大多数下跌在6个月。 HDV-RNA逐渐地从171 405 IU / mL的初始中间值下降。乙肝表面抗原<1000 IU / mL的6个月歧视反应和PR来自NR（P <0.001）。由ROC曲线，从基线到6个月HDV-RNA的1.610数减少相关的乙肝表面抗原0.105数减少的门槛预计该标记的间隙。
结论

血清HBsAg的减少是强制性的HDV-RNA的最终过关。乙肝表面抗原定量可以预测长期应对聚乙二醇干扰素治疗，并提供指导，以延长或停止治疗。