AO Fatebenefratelli e Oftalmico, Milan, Italy.
Hepatology. 2010 Feb;51(2):388-97. doi: 10.1002/hep.23340.
The objective of this study is to determine the efficacy and safety of peginterferon alfa-2a (40 KD)/ribavirin in patients with advanced fibrosis. Data from 341 genotype 1/4 patients (99 with bridging fibrosis/cirrhosis) treated for 48 weeks and 1547 genotype 2/3 patients (380 with bridging fibrosis/cirrhosis) treated for 16 or 24 weeks enrolled in three randomized international studies were analyzed. Sustained virological response (SVR) rates decreased progressively from 60% in genotype 1/4 patients without advanced fibrosis to 51% in those with bridging fibrosis and 33% in those with cirrhosis (trend test P = 0.0028); and from 76% to 61% and 57%, respectively, in genotype 2/3 patients treated for 24 weeks (trend test P < 0.0001). Irrespective of genotype, patients without advanced fibrosis were more likely to have an earlier response to treatment that was associated with higher SVR rates and lower relapse rates during untreated follow-up. Among patients with or without a diagnosis of advanced fibrosis, rates of SVR and relapse were similar for patients with similar responses in the first 12 weeks.
Compared with patients with less severe disease, SVR rates are significantly lower in patients with advanced fibrosis. However, irrespective of genotype and degree of fibrosis, the time to become hepatitis C virus (HCV) RNA undetectable was the strongest predictor of SVR.
本研究旨在确定聚乙二醇干扰素 alfa-2a（40KD）/利巴韦林在晚期纤维化患者中的疗效和安全性。对 341 名基因型 1/4 患者（99 名有桥接纤维化/肝硬化）进行了 48 周治疗和 1547 名基因型 2/3 患者（380 名有桥接纤维化/肝硬化）进行了 16 或 24 周治疗的数据进行了分析。在三项随机国际研究中，招募了无晚期纤维化、桥接纤维化和肝硬化的基因型 1/4 患者，分析了持续病毒学应答（SVR）率。无晚期纤维化的基因型 1/4 患者 SVR 率从 60%逐渐下降至桥接纤维化的 51%和肝硬化的 33%（趋势检验 P=0.0028）；基因型 2/3 患者治疗 24 周时，分别从 76%降至 61%和 57%（趋势检验 P<0.0001）。无论基因型如何，无晚期纤维化的患者更有可能在治疗早期产生应答，这与更高的 SVR 率和无治疗随访期间更低的复发率相关。在有或没有晚期纤维化诊断的患者中，在最初 12 周有相似反应的患者中，SVR 率和复发率相似。
与疾病程度较轻的患者相比，晚期纤维化患者的 SVR 率显著降低。然而，无论基因型和纤维化程度如何，成为丙型肝炎病毒（HCV）RNA 不可检测的时间是 SVR 的最强预测因素。
