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Interferon for interferon naive patients with chronic hepatitis C

  • Review
  • Intervention

Authors


Abstract

Background

A previous meta-analysis of interferon therapy in naive patients with chronic hepatitis C has documented its efficacy in achieving virologic clearance, and improving liver biochemistry and histology; however, since its publication additional trials have been reported.

Objectives

To evaluate the response to interferon in interferon naive patients with chronic hepatitis C. The effect of treatment dose and duration, and the response in patients with cirrhosis and those with normal aminotransferases was also investigated.

Search methods

The Cochrane Controlled Trials Register (Cochrane Library Issue 1, 1999), MEDLINE (January 1966 to December 1999), and reference lists were searched, and pharmaceutical companies were contacted for unpublished trials.

Selection criteria

Randomised clinical trials comparing interferon with placebo, no treatment, or different regimens of interferon were selected. Abstracts were excluded.

Data collection and analysis

The primary outcome measure was sustained disappearance of serum HCV RNA (virologic sustained response (SR)). Biochemical and end of treatment responses, liver histology, and adverse events were also recorded. Assessment of drug efficacy used the methods of Peto and Der Simonian and Laird.

Main results

Fifty-four trials enrolling 6545 patients were included. Compared with no treatment, interferon 3 MU thrice weekly for 12 months increased the probability of a virologic SR (Peto odds ratio (OR) 4.60; 95% confidence interval (CI) 1.53 to 13.85). At this dosage and duration of therapy, the rate of virologic SR was 17% (95% CI 10 to 28%) in interferon-treated patients versus 3% (95% CI 1 to 10%) in controls. A dose of 6 MU was more effective than 3 MU thrice weekly (OR for 12 months treatment, 2.21; 95% CI 1.10 to 4.45), as were durations of 12 months or greater versus six months (OR 1.87; 95% CI 1.30 to 2.67). Liver biochemistry responses were alike. Adverse events were more common with higher doses and prolonged durations of treatment. Compared with no therapy, interferon increased the probability of histologic improvement (OR 9.22; 95% CI 5.69 to 14.94). The response to interferon in cirrhotic patients (virologic SR, 17%; 95% CI 11 to 26%) was similar to that in non-cirrhotic patients. However, interferon was no more effective than control in patients with normal aminotransferases.

Authors' conclusions

Interferon is effective in achieving viral clearance and improving liver biochemistry and histology in interferon naive patients with chronic hepatitis C. Higher doses and prolonged durations are more effective, but associated with more frequent adverse events. Interferon is associated with similar benefits in patients with cirrhosis, but the efficacy in patients with normal aminotransferases is unproven.

摘要

背景

干擾素治療慢性C肝且未接受過干擾素治療之病人

先前的干擾素治療慢性C肝且未接受過干擾素治療之病人的統合分析,證實其對於病毒廓清和改善肝功能和病理等方面的效果;但是該統合分析刊登後,亦有其他相關實驗被報導。

目標

評估干擾素治療慢性C肝且未接受過干擾素治療之病人的反應。同時研究治療劑量和持續期,肝硬化病人以及轉氨?(肝指數)正常的病人對該藥物的反應。

搜尋策略

Cochrane 臨床對照試驗註冊中心(Cochrane 圖書館, 1999年第1期), MEDLINE (1966年1月 – 1999年12月), 搜索相關參考列表,聯繫製藥公司,獲取未發表之試驗。

選擇標準

選擇比較干擾素、安慰劑、無干預法或不同的干擾素方案的隨機臨床試驗。排除僅有摘要者。

資料收集與分析

初步結果是針對持續清除血清中的HCV RNA (持續病毒學反應(SR))。同時記錄肝功能和治療末期反應,肝臟病理學和不良事件。使用Peto,Der Simonian和Laird方法評估藥物療效。

主要結論

共納入54個試驗, 共6545 位病人。 比較無干預法,每週3次(3 MU劑量)的干擾素持續12個月,可以提高持續病毒學反應(Peto odds ratio比數比(OR) 4.60; 95%信賴區間(CI) 1.53 – 13.85)。在這種劑量和治療持續期下,使用干擾素病人的持續病毒學反應的比率是17% (95% CI 10 −28%),該比例在控制組是3% (95% CI 1 – 10%)。 使用6MU 比每週3次3MU更有效(12個月治療期的OR, 2.21; 95% CI 1.10 −4.45), 12個月(以上)的治療持續期比6個月更有效 (OR 1.87; 95% CI 1.30 – 2.67)。 肝臟生化反應則較為類似。然而劑量高、治療時間長,亦有較多的不良事件。比較無干預法,干擾素提高了病理改善的機率(OR 9.22; 95% CI 5.69 – 14.94)。 肝硬化病人對干擾素的反應類似於非肝硬化病人對干擾素的反應(病毒學反應, 17%; 95% CI 11 – 26%)。但是,針對轉氨?(肝指數)正常的病人,干擾素並未比對照組更有效。

作者結論

干擾素可以有效廓清慢性C肝且未接受過干擾素治療之病人的病毒,改善肝臟生化和病理。劑量越大,持續時間越長,就越有效,但是有更多不良事件。干擾素對是否有肝硬化的病人效果相當,但是無法證明其對轉氨?(肝指數)正常病人的療效。

翻譯人

本摘要由臺中榮民總醫院黃芳亮翻譯。

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

總結

干擾素顯示了在病毒廓清,生化和病理療效方面對慢性C肝且未接受過干擾素治療之病人產生的有效性。C型肝炎病毒感染可導致慢性肝炎,肝硬化和肝癌。本次系統性文獻回顧的目的是,審視干擾素對有慢性C肝且未接受過干擾素治療之病人(之前未接受治療)的療效。本次文獻回顧確認了干擾素的療效指標,以及採用較高的治療劑量和較長持續期的有利療效。但是,這些療效和更多的不良事件相關。和非肝硬化病人相比,肝硬化病人對該藥物產生類似的反應,但是干擾素對肝功能正常的病人的療效沒有得到足夠的證據支持。儘管干擾素單一療法不再認為是慢性C肝的標準療法,但是本次文獻回顧界定了對於最佳劑量和干擾素單一療法的持續期,這將對於無法忍受複合療法的病人達到幫助療效,此類複合療法包括干擾素和 ribavirin,這也是目前使用的最常見的治療方法。

Plain language summary

Interferons show efficacy on virologic, biochemical, and histological outcomes in interferon naive patients with chronic hepatitis C

Hepatitis C virus infection can progress to chronic hepatitis, cirrhosis, and hepatocellular carcinoma. The goal of this systematic review was to examine the effects of interferon treatment for interferon naive (previously untreated) patients with chronic hepatitis C. This review confirmed the efficacy of interferon on surrogate outcomes as well as a favourable effect of higher treatment doses and prolonged durations. However, these effects were associated with more adverse events. Compared with non-cirrhotic patients, cirrhotic patients respond similarly, but the efficacy of interferon in patients with normal liver biochemistry is not substantiated by the data. Although interferon monotherapy is no longer considered the standard therapy for chronic hepatitis C, this review defines the optimal dose and duration of interferon monotherapy, which may be useful for patients who cannot tolerate combination therapy including interferon and ribavirin, the most effective therapy currently available.

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