Shiffman Mitchell L, Di Bisceglie Adrian M, Lindsay Karen L, Morishima Chihiro, Wright Elizabeth C, Everson Gregory T, Lok Anna S, Morgan Timothy R, Bonkovsky Herbert L, Lee William M, Dienstag Jules L, Ghany Marc G, Goodman Zachary D, Everhart James E
Hepatology Section, Virginia Commonwealth University, Richmond, 23298, USA.
Gastroenterology. 2004 Apr;126(4):1015-23; discussion 947. doi: 10.1053/j.gastro.2004.01.014.
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.
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 microg/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.
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 > or =80% to < or =60% of the starting dose during the first 20 weeks of treatment was associated with a decline in SVR from 21% to 11% (P < or = 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.
Selected nonresponders to previous interferon-based therapy can achieve SVR following retreatment with peginterferon alfa-2a and ribavirin.
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与利巴韦林联合使用。本研究评估了该疗法对既往基于干扰素治疗无应答患者的有效性。
对丙型肝炎抗病毒长期治疗预防肝硬化（HALT-C）试验中最初纳入的604例患者进行评估。所有患者HCV RNA均为阳性，既往对干扰素单药治疗或联合利巴韦林治疗无应答，且肝活检显示有桥接纤维化或肝硬化（Ishak纤维化分期3 - 6期）。患者接受聚乙二醇干扰素α-2a 180μg/周加利巴韦林1000 - 1200mg/天再次治疗。在第20周时血清中HCV RNA检测不到的患者继续治疗共48周，然后再随访24周。
35%的患者在治疗第20周时血清中HCV RNA检测不到，18%实现了持续病毒学应答（SVR）。与SVR相关 的因素包括既往接受干扰素单药治疗、感染基因2型或3型、较低的AST:ALT比值以及无肝硬化。在治疗的前20周内将利巴韦林剂量从起始剂量的≥8%降至≤60%与SVR从21%降至11%相关（P≤0.05）。相比之下，在第20周后当HCV RNA已检测不到时降低聚乙二醇干扰素剂量或降低利巴韦林剂量，对SVR无显著影响。
部分既往基于干扰素治疗无应答的患者在用聚乙二醇干扰素α-2a和利巴韦林再次治疗后可实现SVR。
