Royal Perth Hospital, Perth, Australia.
J Hepatol. 2010 Oct;53(4):616-23. doi: 10.1016/j.jhep.2010.04.024. Epub 2010 Jun 16.
BACKGROUND & AIMS: The impact of fibrosis stage on chronic hepatitis C virus (HCV) treatment response was explored in CHARIOT, a study of high dose peginterferon alfa-2a (PEG-IFNalpha-2a) induction therapy in treatment naïve genotype 1 infection.
Eight hundred and ninety-six patients were randomised 1:1 to 360 microg (n=448) or 180 microg (n=448) PEG-IFNalpha-2a weekly with RBV 1000-1200 mg/day for 12 weeks followed by 36 weeks of 180 microg PEG-IFNalpha-2a weekly plus RBV 1000-1200 mg/day. Virological responses were assessed at week 4, 8, 12, 24, 48 (end of therapy), and 24 weeks following therapy (sustained virological response, SVR). As previously reported, there was no significant difference in SVR in the induction (53%) and standard (50%) arms, therefore the pooled study population was used for analysis of SVR and relapse.
A marked step-wise decline in SVR was evident by fibrosis stage: F0 (70%); F1 (60%); F2 (51%); F3 (31%); F4 (10%) (p<0.0001). Early virological responses were lower among F3/4 patients, including rapid virological response (RVR) (21% vs. 34% for F3/4 and F0-2, respectively) (p=0.0072), and the RVR positive predictive value was also lower (63% vs. 80%). Virological relapse rates were similar in early disease stages (F0, 16%; F1, 23%; F2, 26%), but increased markedly in advanced fibrosis (F3, 50%; F4, 80%) (p<0.0001). Cumulative PEG-IFNalpha-2a and ribavirin doses were similar among patients with F3/4 and F0-2 within treatment arms through week 4, 8, 12, and week 24.
Low virological response in hepatitis C genotype 1 patients with advanced fibrosis is not explained by inadequate cumulative PEG-IFN and ribavirin doses.
在 CHARIOT 研究中，我们探索了纤维化分期对慢性丙型肝炎病毒（HCV）治疗反应的影响，该研究为初治基因型 1 感染患者接受高剂量聚乙二醇干扰素 alfa-2a（PEG-IFNalpha-2a）诱导治疗。
896 例患者按 1:1 随机分为两组，分别接受 360μg（n=448）或 180μg（n=448）PEG-IFNalpha-2a 每周一次，联合利巴韦林 1000-1200mg/天，疗程 12 周，随后继续接受 180μg PEG-IFNalpha-2a 每周一次联合利巴韦林 1000-1200mg/天，疗程 36 周。在第 4、8、12、24、48 周（治疗结束时）和治疗结束后 24 周（持续病毒学应答，SVR）评估病毒学应答。正如之前报道的，诱导治疗（53%）和标准治疗（50%）组的 SVR 无显著差异，因此对聚集研究人群进行 SVR 和复发分析。
纤维化分期明显影响 SVR：F0（70%）；F1（60%）；F2（51%）；F3（31%）；F4（10%）（p<0.0001）。F3/4 患者的早期病毒学应答较低，包括快速病毒学应答（RVR）（F3/4 和 F0-2 分别为 21%和 34%）（p=0.0072），RVR 阳性预测值也较低（63%和 80%）。在早期疾病阶段（F0，16%；F1，23%；F2，26%），病毒学复发率相似，但在晚期纤维化（F3，50%；F4，80%）显著增加（p<0.0001）。在治疗第 4、8、12 周和第 24 周，F3/4 和 F0-2 患者在治疗组中的累积 PEG-IFNalpha-2a 和利巴韦林剂量相似。
在丙型肝炎基因型 1 患者中，晚期纤维化患者病毒学应答率低不能用累积 PEG-IFN 和利巴韦林剂量不足来解释。
