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标题: 在D型肝炎的PEG-IFNα治療期間短暫的早期HBV DNA升高表明感染 [打印本页]

作者: StephenW    时间: 2020-11-14 13:35     标题: 在D型肝炎的PEG-IFNα治療期間短暫的早期HBV DNA升高表明感染

A transient early HBV DNA increase during PEG-IFNα therapy of hepatitis D indicates loss of infected cells and is associated with HDV RNA and HBsAg reduction
Olympia E Anastasiou  1 , Cihan Yurdaydin  2 , Benjamin Maasoumy  3 , Svenja Hardtke  4   5 , Florin Alexandru Caruntu  6 , Manuela G Curescu  7 , Kendal Yalcin  8 , Ulus S Akarca  9 , Selim Gürel  10 , Stefan Zeuzem  11 , Andreas Erhardt  12 , Stefan Lüth  13 , George V Papatheodoridis  14 , Monica Radu  6 , Stephanie Liebig  3 , Heike Bantel  3 , Birgit Bremer  3 , Michael P Manns  3   5 , Markus Cornberg  3   5 , Heiner Wedemeyer  3   5   15
Affiliations
Affiliations

    1
    Institute of Virology, Essen University Hospital and Medical Faculty of the University of Duisburg, Essen, Germany.
    2
    Department of Gastroenterology and Hepatology, Koç University Medical School, Istanbul, TR, Germany.
    3
    Dept. of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany.
    4
    University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
    5
    German Center for Infectious Disease Research (DZIF), HepNet Study-House, Hannover, Germany.
    6
    National Institute for Infectious Diseases Prof. Dr. Matei Bals, Romania.
    7
    Spitalul Clinic de Boli Infectioase si, Timisoara, Romania.
    8
    Dicle University Medical Faculty, Diyarbakir, Turkey.
    9
    Ege University Medical Faculty, Izmir, Turkey.
    10
    Uludağ University Medical Faculty, Bursa, Turkey.
    11
    Johann Wolfgang Goethe University Medical Center, Frankfurt/Main, Germany.
    12
    Heinrich Heine University, Düsseldorf, Germany.
    13
    Center of Internal Medicine II, University Hospital Brandenburg, Brandenburg Medical School, Brandenburg, Germany.
    14
    School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
    15
    Dept. of Gastroenterology and Hepatology, Essen University Hospital and Medical Faculty of the University of Duisburg, Essen, Germany.

    PMID: 33185325 DOI: 10.1111/jvh.13439

Abstract

HBV-DNA levels are low or even undetectable in the majority HDV infected patients. The impact of PEG-IFNα on HBV-DNA kinetics in HDV infected patients has not been studied in detail. We analyzed data of a prospective treatment trial where 120 HDV-RNA positive patients were randomized to receive PEG-IFNα-2a plus tenofovir-disoproxil-fumarate (PEG-IFNα/TDF, n=59) or placebo (PEG-IFNα/PBO; n=61) for 96 weeks. At week 96, HBV-DNA was still quantifiable in 71% of PEG-IFNα/PBO-treated patients but also in 76% of PEG-IFNα/TDF-treated patients, despite low HBV DNA baseline values. Surprisingly, a transient HBV-DNA increase between weeks 12 and 36 was observed in 12 in PEG-IFNα/TDF-treated and 12 PEG-IFNα/PBO-treated patients. This increase was positively associated with HBsAg loss [(p=0.049, odds ratio (OR) 5.1] and HDV-RNA suppression (p=0.007, OR 4.1) at week 96. Biochemical markers of cell death (M30 and ALT) were higher during the HBV-DNA peak but no distinct systemic immune pattern could be observed by screening 91 soluble inflammatory markers. In conclusion, an early increase of HBV-DNA during PEG-IFNα-2a therapy occurred in more than 20% of patients, even in TDF-treated patients. This transient HBV-DNA rise may indicate PEG-IFNα-induced cell death and lead to long-term HDV-RNA suppression and HBsAg loss.

Keywords: HBV; HDV; hepatitis B; hepatitis D; interferon; viral kinetics.

This article is protected by copyright. All rights reserved.
作者: StephenW    时间: 2020-11-14 13:36

在D型肝炎的PEG-IFNα治療期間短暫的早期HBV DNA升高表明感染細胞丟失,並與HDV RNA和HBsAg降低有關
Olympia E Anastasiou 1,Cihan Yurdaydin 2,Benjamin Maasoumy 3,Svenja Hardtke 4 5,Florin Alexandru Caruntu 6,Manuela G Curescu 7,Kendal Yalcin 8,Ulus S Akarca 9,SelimGürel10,Stefan Zeuzem 11,Andreas Erhardt 12,Stefan呂斯(Lüth)13,喬治五世(George V Papatheodoridis)14,莫妮卡·拉杜(Monica Radu)6,斯蒂芬妮·列比(Stephanie Liebig)3,海克·班特爾(Heike Bantel)3,比爾吉·布雷默(Birgit Bremer)3,邁克爾·P·曼恩斯(Michael P Manns)3 5,馬庫斯·康伯格3 5,海納·韋德邁爾3 5 15
隸屬關係
隸屬關係

    1個
    埃森大學醫院病毒學研究所和德國埃森杜伊斯堡大學醫學系。
    2
    德國TR,伊斯坦布爾KoçUniversity醫學院胃腸病學和肝病學系。
    3
    德國漢諾威醫學院胃腸病學,肝病學和內分泌學系。
    4
    漢堡-埃彭多夫大學醫學中心,德國漢堡。
    5
    德國傳染病研究中心(DZIF),HepNet研究室,德國漢諾威。
    6
    國家傳染病研究所羅馬尼亞Matei Bals教授。
    7
    Spitalul Clinic de Boli Infectioase si,羅馬尼亞蒂米甚瓦拉。
    8
    土耳其迪亞巴克爾Dicle大學醫學院。
    9
    土耳其伊茲密爾Ege大學醫學院。
    10
    土耳其布爾薩Uludağ大學醫學系。
    11
    約翰·沃爾夫岡·歌德大學醫學中心,德國法蘭克福。
    12
    德國杜塞爾多夫海因里希海涅大學。
    13
    德國勃蘭登堡醫學院勃蘭登堡大學醫院第二內科中心。
    14
    雅典國立和卡波迪斯安大學醫學院,希臘雅典。
    15
    埃森大學醫院消化內科和肝病科,德國埃森杜伊斯堡大學醫學院。

    PMID:33185325 DOI:10.1111 / jvh.13439

抽象

在大多數感染HDV的患者中,HBV-DNA水平較低,甚至無法檢測到。尚未詳細研究PEG-IFNα對HDV感染患者中HBV-DNA動力學的影響。我們分析了一項前瞻性治療試驗的數據,其中120例HDV-RNA陽性患者被隨機分配接受PEG-IFNα-2a加替諾福韋-二吡呋酯-富馬酸酯(PEG-IFNα/ TDF,n = 59)或安慰劑(PEG-IFNα/ PBO; n = 61),持續96週。在第96週,儘管HBV DNA基線值較低,但仍可在71%的PEG-IFNα/ PBO治療的患者中量化HBV-DNA,但在76%的PEG-IFNα/ TDF治療的患者中仍可定量。令人驚訝的是,在接受PEG-IFNα/ TDF治療的患者和接受12次PEG-IFNα/ PBO治療的患者中,在第12周至第36週之間觀察到瞬時HBV-DNA升高。在第96週時,這種增加與HBsAg丟失[(p = 0.049,優勢比(OR)5.1]和HDV-RNA抑制(p = 0.007,OR 4.1)正相關。細胞死亡的生化標誌物(M30和ALT)較高在HBV-DNA高峰期,通過篩選91種可溶性炎症標記物未觀察到明顯的全身免疫模式,總的來說,在PEG-IFNα-2a治療期間HBV-DNA的早期升高發生在20%以上的患者中,即使在經TDF治療的患者,這種短暫的HBV-DNA升高可能表明PEG-IFNα誘導的細胞死亡,並導致長期的HDV-RNA抑制和HBsAg丟失。

關鍵字:HBV; HDV;乙型肝炎;丙型肝炎;干擾素病毒動力學。

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