Brok Jesper, Gluud Lise Lotte, Gluud Christian
Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 3344, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, Copenhagen, Denmark, DK-2100.
Cochrane Database Syst Rev. 2009 Oct 7(4):CD005527. doi: 10.1002/14651858.CD005527.pub2.
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.
To assess the beneficial and harmful effects of ribavirin monotherapy for patients with chronic hepatitis C.
We identified trials through electronic databases, manual searches of bibliographies and journals, authors of trials, and pharmaceutical companies until March 2009.
We included all randomised trials irrespective of blinding, language, or publication status comparing ribavirin versus no intervention, placebo, or interferon for chronic hepatitis C.
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).
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.
丙型肝炎是肝脏相关发病和死亡的主要原因。很大一部分患者从未出现症状。聚乙二醇干扰素联合利巴韦林是慢性丙型肝炎的推荐治疗方法。然而，对于一些患者可考虑使用利巴韦林单药治疗。
评估利巴韦林单药治疗对慢性丙型肝炎患者的有益和有害影响。
我们通过电子数据库、手动检索参考文献和期刊、试验作者以及制药公司来识别试验，检索截至2009年3月。
我们纳入了所有比较利巴韦林与无干预、安慰剂或干扰素治疗慢性丙型肝炎的随机试验，无论其是否设盲、语言或发表状态如何。
主要结局指标为血清持续病毒学应答（治疗后至少6个月丙型肝炎病毒RNA消失）、肝脏相关发病率加全因死亡率以及不良事件。次要结局指标为治疗结束时病毒学应答、生化应答（转氨酶活性）和组织学应答。提取随机化方法、设盲、数据处理和资金来源作为偏倚控制的指标。对所有结局进行随机效应和固定效应荟萃分析。如果两种模型在统计学显著性方面给出相同结果，我们仅呈现固定效应模型的结果。我们以风险差值（RD）及95%置信区间（CI）展示数据。
我们纳入了14项随机试验，共657例患者。大多数试验的偏倚控制不明确。与安慰剂或无干预相比，利巴韦林对持续病毒学应答（风险差值0%，95%置信区间 -2%至3%，5项试验）或治疗结束时病毒学应答（风险差值0%，95%置信区间 -3%至3%，10项试验）无显著影响。利巴韦林对肝脏相关发病率加死亡率无显著影响（风险差值0%，95%置信区间 -2%至3%，11项试验）。利巴韦林显著增加了不良反应的风险，包括贫血。利巴韦林显著改善了治疗结束时的生化和组织学应答，但未改善持续生化应答。在病毒学和生化应答方面，利巴韦林显著劣于干扰素（5项试验）。
利巴韦林似乎对血清病毒学应答、肝脏相关发病率或死亡率无有益影响，且显著增加了不良反应的风险。利巴韦林单药治疗似乎显著劣于干扰素单药治疗。纳入患者总数较少，可能需要更多试验。在随机试验之外，不推荐将利巴韦林单药治疗用于慢性丙型肝炎。
