携带2或3型基因的丙肝病人对Peginterferon alfa-2a (40KD) (PEGASYS?) 和Ribavirin (COPEGUS?)不表现快速病毒反应者不易治疗

M. L. Shiffman¹; D. R. Nelson²; G. Hooper³; D. Messinger⁴; S. Zeuzem⁵

1. Hepatology Section, VCU Medical Center, Richmond, VA, USA.
2. Department of Medicine, University of Florida, Florida, FL, USA.
3. Roche, Welwyn, United Kingdom.
4. IST GmbH, Mannheim, Germany.
5. Department of Medicine I, J.W. Goethe University Hospital, Frankfurt, Germany

Background: Patients with HCV genotypes (GT) 2 or 3 have traditionally been referred to as “easy to treat”. However, data from the ACCELERATE trial have demonstrated that this is not true for all of these patients. In this study 1463 treatment-naive patients with HCV genotype 2 or 3 were randomized to receive either 16 or 24 weeks of peginterferon alfa-2a (40KD) 180 µg/week and ribavirin 800 mg/d. Overall 66% of these patients were HCV RNA undetectable at treatment week 4; defined as a rapid virologic response (RVR). These patients had an SVR of 79% and 85% with 16 and 24 weeks of treatment respectively. In contrast, patients with HCV genotype 2 or 3 who had detectable HCV RNA at week 4 (non-RVR) had an SVR rate of only 45% with 24 weeks of treatment. This analysis explores baseline (BL) factors that may identify those non-RVR patients who are more likely to achieve an SVR with either 16 or 24 weeks of therapy.

Methods: All patients who received at least one dose of study drug and who did not achieve an RVR were included in this analysis (ITT population). Patients were dichotomised by BL factors and rates of SVR calculated as a function of treatment duration.

Results: 466 non-RVR patients were included in this analysis (Table). Patients with a BL HCV RNA <400,000 IU/mL had similar rates of SVR with 16 and 24 weeks of treatment. For all other BL characteristics non-RVR patients treated for 24 weeks had a higher SVR rate compared to patients treated for 16 weeks (overall 44.7 vs 26.4%). In patients treated for 24 weeks GT 2 (vs GT 3), absence of cirrhosis and younger age were associated with at least 10% higher rates of SVR.

Conclusions: Patients with HCV GT 2 or 3 who do not achieve an RVR are not “easy to treat” and have low rates of SVR. The SVR in those patients treated for 24 weeks with GT 2, absence of cirrhosis and younger age is consistently above 50%, but this is still significantly inferior to that observed in patients with an RVR. RVR remains the strongest predictor of SVR and studies to evaluate the impact of prolonging treatment to 48 weeks in patients with HCV GT 2 or 3 who do not achieve an RVR are warranted.

Rate of SVR in non-RVR pts (ITT)

翻译：

背景：通常认为携带2或3型基因的丙肝病人易于治疗。然而，来自加速实验的数据表明对于这些病人来说并非全部如此。在这项研究中，1436名携带2或3型基因治疗阴性的丙肝病人随机分组，接受16或24周peginterferon alfa-2a (40KD)剂量为180 µg/周和ribavirin 800 mg/天的治疗。在治疗的第4周总共有66%的病人HCV RNA检测阴性，定义为快速病毒反应（rapid virologic response 简写为RVR)。这些治疗16和24周的病人相应的SVR为79% 和85%。相反，携带2或3型HCV基因的患者在第4周可检测到HCV RNA(non-RVR非快速病毒反应)，在24周治疗中其SVR仅为45%。这些分析用于探究鉴别non-RVR病人的基线因子，non-RVR病人经过16或24周的治疗后更可能实现SVR。

方法：所有接受至少一个剂量研究药物治疗并没有出现快速病毒反应的病人均被包括在这项分析中。病人根据基线因子分为两组，SVR率的计算作为治疗耐受的功能因子。

结果：在这项研究中包括466名非快速病毒反应病人（见表）。接受16和24周治疗的病人，其基线HCV RNA <400,000 IU/mL时SVR率相似。对于其它的基线特征，治疗24周的非快速病毒反应病人比治疗16周的SVR率高(总体 44.7 vs 26.4%)。治疗24周的携带2型基因的病人（与3型相比），无肝硬化和青年其SVR率至少增高10%。

结论：携带2或3型HCV基因的病人，如果不出现快速病毒反应则不易于治疗，并且SVR率低。那些携带2型基因治疗24周的病人，其SVR率在无肝硬化和青年患者中始终高于50%，但仍然明显低于出现快速病毒反应的病人。快速病毒反应仍然是SVR最强的预测因素，通过研究治疗延长至48周对病人的影响，表明携带2或3型HCV基因者不出现快速病毒反应是合理的。
非快速病毒反应病人的SVR率（ITT）