Intervention Review

Sequential combination of glucocorticosteroids and alfa interferon versus alfa interferon alone for HBeAg-positive chronic hepatitis B

  1. Martin Thyge Mellerup1,*,
  2. Kim Krogsgaard2,
  3. Philippe Mathurin3,
  4. Christian Gluud4,
  5. Thierry Poynard5

Editorial Group: Cochrane Hepato-Biliary Group

Published Online: 20 JUL 2005

Assessed as up-to-date: 6 MAY 2005

DOI: 10.1002/14651858.CD000345.pub2


How to Cite

Mellerup MT, Krogsgaard K, Mathurin P, Gluud C, Poynard T. Sequential combination of glucocorticosteroids and alfa interferon versus alfa interferon alone for HBeAg-positive chronic hepatitis B. Cochrane Database of Systematic Reviews 2005, Issue 3. Art. No.: CD000345. DOI: 10.1002/14651858.CD000345.pub2.

Author Information

  1. 1

    Naerum, Denmark

  2. 2

    H:S Hvidovre University Hospital 447, PhaseOneTrials A/S, Hvidovre, Denmark

  3. 3

    Hôpital Claude Huriez, 2ème etage Est, Service d'Hépatogastroentérologie, CHRU Lille, France

  4. 4

    Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 3344, Rigshospitalet, Copenhagen University Hospital, Cochrane Hepato-Biliary Group, Copenhagen, Denmark

  5. 5

    Groupe Hospitalier Pitie-Salpetriere, Paris, France, Service d'Hepato-Gastroenterologie, Paris Cedex 13, France

*Martin Thyge Mellerup, Hegnsvej 127, Naerum, DK-2850, Denmark. mellerup@tiscali.dk.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 20 JUL 2005

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Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Background

Chronic hepatitis B has serious effects on morbidity and mortality. Alfa interferon has been shown to increase the rates of HBeAg-clearance as well as seroconversion to anti-HBe, but response rates are unsatisfactory. Glucocorticosteroid pretreatment may increase the response to alfa interferon.

Objectives

The objectives were to assess the effects of the sequential combination of glucocorticosteroids and alfa interferon versus alfa interferon alone in hepatitis B 'e' antigen positive chronic hepatitis B on mortality, virological response, biochemical response, liver histology, quality of life, and adverse events.

Search methods

Eligible trials were identified through searches of The Cochrane Hepato-Biliary Controlled Trials Register (May 2005), The Cochrane Central Register of Controlled Trials in The Cochrane Library (Issue 2, 2005), MEDLINE (1950 to May 2005), EMBASE (Excerpta Medica Database) (1980 to May 2005), BIOSIS (1969 to May 2005), and reference lists of relevant articles. Further trials were sought through correspondence with authors of trials and pharmaceutical companies.

Selection criteria

Randomised clinical trials comparing identical alfa interferon treatment regimens with and without glucocorticosteroid pretreatment for hepatitis B 'e' antigen positive chronic hepatitis. We included trials irrespective blinding, publication status, or language.

Data collection and analysis

Three authors selected the trials independently and one extracted the data, which were then validated. We performed assessments of the outcome measures at the end of treatment and at six months and at maximal follow-up after the end of treatment with alfa interferon.

Main results

We included a total of 13 randomised trials with 790 patients. Loss of hepatitis B 'e' antigen (OR 1.41, 95% confidence interval 1.03 to 1.92, P = 0.03) and hepatitis B virus DNA (OR = 1.51, 95% confidence interval 1.12 to 2.05, P = 0.008) were significantly more frequent among patients treated with the sequential combination of glucocorticosteroids and alfa interferon than among patients treated with alfa interferon alone. Glucocorticosteroid pretreatment did not significantly influence seroconversion from hepatitis B 'e' antigen to antibodies to hepatitis B 'e' antigen, loss of hepatitis B surface antigen, normalisation of alanine aminotransferase/aspartate aminotransferase activities, and severity of adverse events. Glucocorticosteroid pretreatment did not significantly affect mortality and adverse events. The effect of glucocorticosteroid pretreatment on liver histology and quality of life could not be assessed due to insufficient data.

Authors' conclusions

Pretreatment with glucocorticosteroids before treatment with alfa interferon in patients with hepatitis B 'e' antigen positive chronic hepatitis B may be more effective than treatment with alfa interferon alone with regard to loss of hepatitis B 'e' antigen and hepatitis B virus DNA, but evidence for effect on clinical outcomes is lacking.

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Glucocorticosteroid pretreatment may increase virologic response to interferon in hepatitis B 'e' antigen positive chronic hepatitis B

Interferon is an established treatment for chronic infection with hepatitis B virus. Although it is effective, response rates are not satisfactory. In order to increase response rates glucocorticosteroid withdrawal therapy has been proposed as a pretreatment strategy. The objectives of this review were to assess the effects of the sequential combination of glucocorticosteroids and interferon compared to interferon alone in the treatment of chronic hepatitis B. Glucocorticosteroid pretreatment was associated with a significantly higher frequency of loss of hepatitis B markers (HBeAg and HBV DNA), but had no significant effect on clinical outcomes.

 

摘要

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

背景

以腎上腺糖皮質類固醇和Alfa干擾素的次序性組合治療對照alfa 干擾素單一治療HBeAg陽性慢性B肝的比較

慢性B肝對於人類的罹病和死亡具有嚴重的影響。 Alfa干擾素已經顯示可以提高HBeAg清除率以及使血清轉化產生antiHBe,但是反應率卻不令人滿意。預先以腎上腺糖皮質類固醇治療可以提高對alfa干擾素的反應。

目標

目標是從死亡率、病毒學反應、生化反應、肝臟組織學、生活品質和不良事件等方面,來評估腎上腺糖皮質類固醇和Alfa干擾素的次序性組合治療對照Alfa 干擾素單一治療B肝e 抗原陽性的慢性B肝的利弊。

搜尋策略

透過搜索The Cochrane HepatoBiliary Controlled Trials Register (2005年5月), Cochrane Library(2005年第2期),的The Cochrane Central Register of Controlled Trials,MEDLINE (1950年 2005年5月)、 EMBASE (醫學文摘資料庫) (1980年−2005年5月)、BIOSIS (1969年 2005年5月),相關文章的參考文獻列表,確定符合資格的試驗。聯繫試驗作者和製藥公司,以獲取另外的試驗。

選擇標準

比較同一種Alfa 干擾素含有以及不含有預先以腎上腺糖皮質類固醇治療e 抗原陽性的慢性B肝的隨機臨床試驗。我們收納的試驗不受盲法,發表狀態或語言的限制。

資料收集與分析

三位作者獨立選擇試驗,一位作者摘錄數據,另外一位作者驗證資料。我們在以下的時間點進行結果的評估:治療結束時,治療後6個月時,以及試驗結束時最久的追蹤期。

主要結論

我們共收納13個隨機試驗,共790 位病人。和alfa 干擾素單一治療組相比, 在B肝e 抗原消失 (OR 1.41, 95% 信賴區間 1.03 – 1.92, P = 0.03), B肝病毒 DNA消失 (OR = 1.51, 95% 信賴區間 1.12 – 2.05, P = 0.008) 等方面,腎上腺糖皮質類固醇和alfa干擾素的次序性組合治療組有明顯地增加。腎上腺糖皮質類固醇預治療沒有明顯影響e 抗原從血清中轉變成e 抗原抗體的過程,B肝表面抗原損失,丙氨酸轉氨?/天門冬氨酸氨基轉移?活性正常化以及不良事件的嚴重度。預先以腎上腺糖皮質類固醇治療沒有明顯影響死亡率和不良事件。由於資料不足,不能評估腎上腺糖皮質類固醇預治療對肝臟病理和生活品質的影響。

作者結論

從e 抗原消失和B肝病毒DNA消失的方面來說,腎上腺糖皮質類固醇預治療之後再聯合Alfa干擾素治療,可能比Alfa干擾素單一療法更能有效的治療e 抗原陽性的慢性B肝,但是對該療法臨床療效的證據仍然不足。

翻譯人

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

預先以腎上腺糖皮質類固醇治療可以增加e 抗原陽性的慢性B肝中對干擾素的病毒學反應。 干擾素已確定是治療B肝病毒慢性感染的治療方法。 儘管有效,但是病毒學反應無法令人滿意。 為了提高病毒學反應,腎上腺糖皮質類固醇停藥療法已被作為一種預先治療策略使用。本次文獻回顧的目的在於,評估腎上腺糖皮質類固醇和干擾素的次序性組合治療對照干擾素單一治療慢性B肝的療效。預先以腎上腺糖皮質類固醇治療和B肝標記物損失的頻率明顯上升有關(HBeAg和HBV DNA), 但是在臨床療效上沒有顯著的作用。