Intervention Review

Ribavirin monotherapy for chronic hepatitis C

  1. Jesper Brok*,
  2. Lise Lotte Gluud,
  3. Christian Gluud

Editorial Group: Cochrane Hepato-Biliary Group

Published Online: 7 OCT 2009

Assessed as up-to-date: 19 MAR 2009

DOI: 10.1002/14651858.CD005527.pub2


How to Cite

Brok J, Gluud LL, Gluud C. Ribavirin monotherapy for chronic hepatitis C. Cochrane Database of Systematic Reviews 2009, Issue 4. Art. No.: CD005527. DOI: 10.1002/14651858.CD005527.pub2.

Author Information

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

*Jesper Brok, Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 3344, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, Copenhagen, DK-2100, Denmark. jbrok@ctu.rh.dk. jesperb5@hotmail.com.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 7 OCT 2009

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Abstract

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

Background

Hepatitis C is a major cause of liver-related morbidity and mortality. A high proportion of patients never experience symptoms. Peginterferon plus ribavirin is the recommended treatment for chronic hepatitis C. However, ribavirin monotherapy may be considered for some patients.

Objectives

To assess the beneficial and harmful effects of ribavirin monotherapy for patients with chronic hepatitis C.

Search methods

We identified trials through electronic databases, manual searches of bibliographies and journals, authors of trials, and pharmaceutical companies until March 2009.

Selection criteria

We included all randomised trials irrespective of blinding, language, or publication status comparing ribavirin versus no intervention, placebo, or interferon for chronic hepatitis C.

Data collection and analysis

The primary outcome measures were serum sustained virological response (loss of hepatitis C virus RNA at least six months after treatment), liver-related morbidity plus all-cause mortality, and adverse events. Secondary outcome measures were end of treatment virological response, biochemical response (transaminase activity), and histological response. Randomisation methods, blinding, data handling, and funding were extracted as measures of bias control. Random-effects and fixed-effect meta-analyses were performed for all outcomes. We only present the results of the fixed-effect model if both models provide the same result regarding statistical significance. We present data as risk difference (RD) with 95% confidence intervals (CI).

Main results

We included 14 randomised trials with 657 patients. The majority of trials had unclear control of bias. Compared with placebo or no intervention, ribavirin had no significant effect on the sustained virological response (RD 0%, 95% CI -2% to 3%, five trials) or end of treatment virological response (RD 0% 95% CI -3% to 3%, ten trials). Ribavirin had no significant effect on liver-related morbidity plus mortality (RD 0%, 95% CI -2% to 3%, 11 trials). Ribavirin significantly increased the risk of adverse reactions, including anaemia. Ribavirin significantly improved end of treatment biochemical and histological response but not the sustained biochemical response. Ribavirin was significantly inferior to interferon regarding virological and biochemical responses (five trials).

Authors' conclusions

Ribavirin seems without beneficial effects on serum virological response and liver-related morbidity or mortality, and significantly increased the risk of adverse reactions. Ribavirin monotherapy seems significantly inferior to interferon monotherapy. The total number of included patients is small, and more trials are perhaps needed. The use of ribavirin monotherapy for chronic hepatitis C cannot be recommended outside randomised trials.

 

Plain language summary

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

Treatment of patients infected with hepatitis C virus

Globally, about 170 million people are chronically infected with hepatitis C virus. Hepatitis C is a blood-borne virus and routes of transmission include intravenous drug use, mother-to-infant transmission, unsafe medical practices, high-risk sexual behaviour, and blood transfusion. Chronic hepatitis C is in most patients a benign viral infection, but a minority of patients develop liver cirrhosis and may suffer from complications due to cirrhosis or die from it.

Treatment with interferon clears hepatitis C virus from the blood in about 15% of the patients. Adding ribavirin to interferon (combination therapy) significantly improves the number that clears hepatitis C from the blood to about 40%. Not all patients are tolerant to interferon, and also interferon is costly. This is why ribavirin given as a single drug may be considered as an option for patients with chronic hepatitis C. This review identified 11 randomised trials comparing ribavirin with no antiviral treatment in patient with chronic hepatitis C. Combining the results from all identified trials ribavirin alone seemed without beneficial effects for patients with chronic hepatitis C. Moreover, ribavirin given alone was significantly inferior compared with interferon regarding clearing hepatitis C from the blood and regarding reducing liver enzymes activity in the blood. Furthermore, ribavirin given alone increased the risk of anaemia. Thus, ribavirin given alone cannot be recommended, but more trials may be needed.

 

摘要

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

背景

單獨使用Ribavirin治療慢性C型肝炎

C型肝炎是造成肝臟相關疾病發作及致死的主要原因。大部分罹患C型肝炎的病患未曾出現症。目前對於C型肝炎的建議治療是Peginterferon併用Ribavirin進行治療,但某些病患可考慮單獨使用Rribavirin治療。

目標

評估單獨使用Ribavirin治療慢性C型肝炎患者的益處和害處。

搜尋策略

透過搜尋2009年3月前的電子資料庫、人工搜尋書目及期刊、試驗作者以及藥廠找出需要的試驗。

選擇標準

納入所有比較Ribavirin和無其他治療、安慰劑或干擾素對於慢性C型肝炎影響的試驗隨機分派性試驗,不考慮其盲性試驗、語言或發表狀況。

資料收集與分析

主要結果評估包括血清持續的病毒學反應(至少治療後六個月沒有出現C型肝炎病毒核糖核酸被檢測到)、肝臟相關致病率加上所有原因的死亡率、與不良事件。次要結果評估為治療完成時的病毒反應、生化反應(轉氨?活性)、和組織學反應。偏誤管控以分析隨機分配的方法、盲法、資料處理和經費贊助等來評量。所有結果都會以隨機效應和固定效應的統合分析呈現。如果兩種模式統計學上顯著性相同,則只顯示固定效應模式的結果。所有的數據以風險差異(risk difference,RD)及95%信賴區間(confidence intervals,CI)表示。

主要結論

總共納入包含657名病患的14個隨機性試驗。大多數的試驗無法確定它們偏誤控制狀況。與使用安慰劑或沒其他治療的組別相比,Ribavirin在持續病毒學反應(5個試驗,風險差異為0%,95%信賴區間−2至3%)或治療完成時病毒反應(10個試驗,風險差異為0%,95%信賴區間−3至3%)沒有顯著效果。Ribavirin在肝臟相關致病率加上死亡率也沒有顯著效果(11個試驗,風險差異為0%,95%信賴區間−2至3%)。Ribavirin反而顯著增加不良反應包括貧血的風險。Ribavirin雖可顯著改善治療結束時生化學和組織學的反應,但生化反應無法持續性地改善。Ribavirin在病毒學和生化學的反應效果顯著劣於干擾素(5個試驗)。

作者結論

Ribavirin在血清病毒學反應、肝臟相關致病率或死亡率似乎沒有效益,反而顯著增加不良反應的風險。單獨使用 Ribavirin的效果似乎明顯地劣於單獨使用干擾素治療。納入試驗的病患總數小,也許需要更多的試驗。不建議未在隨機性試驗規範下單獨使用Ribavirin治療慢性C型肝炎。

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

治療C型肝炎病毒感染的病患 目前全球大約有1.7憶的人是C型肝炎病毒慢性感染。C型肝炎病毒是經由血液傳染,傳染途徑包括靜脈注射毒品、母子垂直傳染、不安全的醫療行為、高危險性性行為和輸血。對大多數的病患,慢性C型肝炎是良性的病毒感染,但少數患者會發展成肝硬化,並可能因肝硬化引發併發症,甚至而死亡。 約有15%的病患接受干擾素治療後清除血中C型肝炎病毒。Ribavirin加干擾素的合併療法顯著地提升病患血中C型肝炎病毒清除率到約40%。但不是所有患者都能忍受干擾素治療,而且干擾素的費用也高。因此會考慮選擇單用Ribavirin來治療慢性C型肝炎患者。本回顧找到11個對慢性C型肝炎患者使用Ribavirin與未接受抗病毒治療比較的隨機性試驗。綜合所有納入試驗結果來看,單獨使用Ribavirin似乎對慢性C型肝炎患者沒有幫忙。而且單獨使用Ribavirin,與干擾素相較,在清除血中C型肝炎病毒和降低血液中肝臟相關酵素活性的表現上都明顯較差。單用Ribavirin更可能增加貧血的風險。所以目前尚不能建議單獨使用Ribavirin治療,需要更多的相關試驗評估。