A.M. Migliavacca Center for Liver Disease, 1st Division of Gastroenterology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
J Hepatol. 2012 Feb;56(2):341-7. doi: 10.1016/j.jhep.2011.05.022. Epub 2011 Jul 12.
BACKGROUND & AIMS: The success of pegylated-interferon (PegIFN)/ribavirin (Rbv) therapy of chronic hepatitis C is compromised by liver fibrosis. Whether fibrosis equally affects the two PegIFNα-based therapies is unknown. To assess the response to the two PegIFN regimens in patients with different degree of liver fibrosis.
A sub-analysis of the MIST study: 431 consecutive naïve patients randomly assigned, based on HCV genotype, to receive either (A) PegIFNα2a 180 μg/wk plus daily Rbv 800-1200 mg or (B) PegIFNα2b 1.5 μg/kg/week plus daily Rbv 800-1200 mg, were stratified according to Ishak staging (S) into mild (S0-S2) or moderate (S3, S4) fibrosis and cirrhosis (S5, S6).
In A the sustained virological response (SVR) rates were not significantly influenced by fibrosis stage (71% in S0-S2, 66% in S3, S4, 53% in S5, S6, p=0.12), compared to B where the SVR rates differed according to fibrosis stage (65%, 46%, and 38%, p=0.004, respectively). This was even more so in HCV-1/4 patients treated with PegIFNα2b where the SVR rates were twice as many in S0-S2 vs. S≥3 (44% vs. 22%, p=0.02), while in A the SVR rates were similar between the two fibrosis subgroups (S0-S2: 47% vs. S≥3: 48%, p=0.8). By logistic regression analysis genotype 1/4 and lack of rapid virological response were independent predictors of treatment failure in both treatment groups, while S≥3 fibrosis was associated to PegIFNα2b treatment failure, only (OR 2.83, 95% CI 1.4-5.68, p=0.004).
Liver fibrosis was an independent moderator of treatment outcome in patients receiving PegIFNα2b, not in those receiving PegIFNα2a.
聚乙二醇干扰素（PegIFN）/利巴韦林（Rbv）治疗慢性丙型肝炎的成功受到肝纤维化的影响。尚不清楚两种基于 PegIFNα 的治疗方法对纤维化的影响是否相同。本研究旨在评估两种 PegIFN 方案在不同程度肝纤维化患者中的疗效。
对 MIST 研究的亚组分析：431 例初治患者根据 HCV 基因型随机分为 A 组（接受 PegIFNα2a 180μg/周联合每日 Rbv 800-1200mg）或 B 组（接受 PegIFNα2b 1.5μg/kg/周联合每日 Rbv 800-1200mg），根据 Ishak 分期（S）分为轻度（S0-S2）或中度（S3、S4）纤维化和肝硬化（S5、S6）。
在 A 组，持续性病毒学应答（SVR）率不受纤维化分期的显著影响（S0-S2 为 71%，S3、S4 为 66%，S5、S6 为 53%，p=0.12），而 B 组 SVR 率则根据纤维化分期不同（分别为 65%、46%和 38%，p=0.004）。在接受 PegIFNα2b 治疗的 HCV-1/4 患者中，情况更是如此，S0-S2 组的 SVR 率是 S≥3 组的两倍（44%比 22%，p=0.02），而 A 组两组纤维化亚组的 SVR 率相似（S0-S2 为 47%，S≥3 为 48%，p=0.8）。通过逻辑回归分析，基因型 1/4 和快速病毒学应答失败是两组治疗失败的独立预测因素，而 S≥3 纤维化与 PegIFNα2b 治疗失败相关（OR 2.83，95%CI 1.4-5.68，p=0.004）。
肝纤维化是接受 PegIFNα2b 治疗的患者治疗结局的独立调节因素，而不是接受 PegIFNα2a 治疗的患者。
