Peginterferon alfa-2a and ribavirin in patients with chronic hepatitis C who have failed prior treatment
Peginterferon alfa-2a and ribavirin in patients with chronic hepatitis C who have failed prior treatment
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DOI：
10.1053/j.gastro.2004.01.014
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发表时间：
2004-04-01
期刊：
影响因子：
29.4
通讯作者：
Everhart, JE
中科院分区：
文献类型：
--
作者：
Shiffman, ML;Di Bisceglie, AM;Everhart, JE
背景和目标：目前治疗慢性丙型肝炎病毒（HCV）最有效的疗法是聚乙二醇干扰素和利巴韦林的组合。本研究评估了这种治疗对既往干扰素治疗无应答的患者的有效性。方法：对参加丙型肝炎抗病毒长期治疗肝硬化（HALT-C）试验的前604例患者进行了评价。所有患者均为HCV RNA阳性，既往对干扰素无应答者，伴或不伴利巴韦林，肝活检显示桥接纤维化或肝硬化（Ishak纤维化3-6期）。患者接受聚乙二醇干扰素α-2a 180 μ g/wk联合利巴韦林1000-1200 mg/d治疗。那些在第20周血清中没有检测到HCV RNA的人继续治疗总共48周，然后再随访24周。结果：治疗第20周时，35%的患者血清中未检测到HCV RNA，18%的患者达到持续病毒学应答（SVR）。与SVR相关的因素包括既往接受过干扰素单药治疗、基因型2或3的感染、AST：ALT比值较低以及无肝硬化。在治疗的前20周，将利巴韦林剂量从大于或等于起始剂量的80%减少到小于或等于60%与SVR从21%下降到11%相关（P小于或等于0.05）。相比之下，在20周后，当HCV RNA已经检测不到时，减少聚乙二醇干扰素的剂量或减少利巴韦林的剂量，对SVR没有显著影响。结论：对既往干扰素治疗无应答者，在聚乙二醇干扰素α-2a和利巴韦林复治后可达到SVR。
Background & Aims: The most effective therapy currently available for treatment of chronic hepatitis C virus (HCV) is the combination of peginterferon and ribavirin. This study evaluated the effectiveness of this treatment in patients who were nonresponders to previous interferon-based therapy. Methods: The first 604 patients enrolled in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) Trial were evaluated. All were HCV RNA positive, previous nonresponders to interferon, with or without ribavirin, and had bridging fibrosis or cirrhosis on liver biopsy (Ishak fibrosis stage 3-6). Patients were retreated with peginterferon alfa-2a 180 mug/wk plus ribavirin 1000-1200 mg/day. Those with no detectable HCV RNA in serum at week 20 continued treatment for a total of 48 weeks and were then followed for an additional 24 weeks. Results: Thirty-five percent of patients had no detectable HCV RNA in serum at treatment week 20, and 18% achieved sustained virologic response (SVR). Factors associated with an SVR included previous treatment with interferon monotherapy, infection with genotypes 2 or 3, a lower AST:ALT ratio, and absence of cirrhosis. Reducing the dose of ribavirin from greater than or equal to80% to less than or equal to60% of the starting dose during the first 20 weeks of treatment was associated with a decline in SVR from 21% to 11% (P less than or equal to 0.05). In contrast, reducing the dose of peginterferon or reducing ribavirin after week 20, when HCV RNA was already undetectable, did not significantly affect SVR. Conclusions: Selected nonresponders to previous interferon-based therapy can achieve SVR following retreatment with peginterferon alfa-2a and ribavirin.