Bronowicki Jean-Pierre, Ouzan Denis, Asselah Tarik, Desmorat Hervé, Zarski Jean-Pierre, Foucher Juliette, Bourlière Marc, Renou Christophe, Tran Albert, Melin Pascal, Hézode Christophe, Chevalier Michelle, Bouvier-Alias Magali, Chevaliez Stéphane, Montestruc François, Lonjon-Domanec Isabelle, Pawlotsky Jean-Michel
Department of Hepatology and Gastroenterology, INSERM U724, CHU de Nancy, Vandoeuvre-les-Nancy, France.
Gastroenterology. 2006 Oct;131(4):1040-8. doi: 10.1053/j.gastro.2006.07.022. Epub 2006 Jul 24.
BACKGROUND & AIMS: Pegylated interferon alfa-ribavirin combination is the standard treatment for chronic hepatitis C, but the mechanisms by which ribavirin enhances the rate of sustained hepatitis C virus (HCV) eradication remain unknown. We aimed to investigate the role of ribavirin in HCV clearance during therapy and to evaluate the consequences of ribavirin discontinuation in patients infected with genotype 1 hepatitis C who cleared HCV RNA at week 24.
A total of 516 patients were treated with pegylated interferon alfa-2a, 180 microg/wk, plus ribavirin, 800 mg/day. Seventy percent were RNA negative at week 24. They were randomized to continue with the combination or receive pegylated interferon alone.
Responders at week 24 who stopped ribavirin had a significantly higher rate of breakthroughs during, and relapses after, therapy (sustained virologic response, 52.8% vs 68.2%; P = .004), but their side-effect profile and quality of life tended to improve. Multiple logistic regression analysis in the pegylated interferon alfa monotherapy group allowed identification of responders at week 24 who could stop ribavirin without losing their chance of a sustained virologic response, based on baseline viral load and age. Forty-eight weeks of ribavirin may not be needed when HCV RNA is undetectable at week 2.
We made 3 conclusions from this study. First, ribavirin primarily acts by sustaining the virologic response to pegylated interferon alfa; second, ribavirin must be administered for the full treatment duration in most genotype 1-infected patients who respond; third, baseline parameters may help identify patients who could discontinue ribavirin or reduce the dose without losing their chance of success.
聚乙二醇化干扰素α联合利巴韦林是慢性丙型肝炎的标准治疗方案，但利巴韦林提高丙型肝炎病毒（HCV）持续清除率的机制尚不清楚。我们旨在研究利巴韦林在治疗期间HCV清除中的作用，并评估在第24周清除HCV RNA的基因1型丙型肝炎感染患者中停用利巴韦林的后果。
共有516例患者接受聚乙二醇化干扰素α-2a（180μg/周）加利巴韦林（800mg/天）治疗。70%的患者在第24周时RNA呈阴性。他们被随机分为继续联合治疗组或单独接受聚乙二醇化干扰素治疗组。
在第24周时应答但停用利巴韦林的患者在治疗期间的突破率和治疗后的复发率显著更高（持续病毒学应答率分别为52.8%和68.2%；P = 0.004），但其副作用情况和生活质量趋于改善。在聚乙二醇化干扰素α单药治疗组中进行的多因素逻辑回归分析显示，根据基线病毒载量和年龄，可识别出在第24周时能够停用利巴韦林而不丧失持续病毒学应答机会的应答者。如果在第2周时检测不到HCV RNA，则可能不需要48周的利巴韦林治疗。
我们从本研究中得出3个结论。第一，利巴韦林主要通过维持对聚乙二醇化干扰素α的病毒学应答发挥作用；第二，对于大多数有应答的基因1型感染患者，利巴韦林必须全程给药；第三，基线参数可能有助于识别那些可以停用利巴韦林或降低剂量而不丧失成功机会的患者。
