γ-谷氨酰转移酶和快速病毒学应答作为慢性丙型肝炎无应答者使用实验性或标准聚乙二醇干扰素-α-2b成功治疗预测指标的研究
Gamma-glutamyltransferase and rapid virological response as predictors of successful treatment with experimental or standard peginterferon-alpha-2b in chronic hepatitis C non-responders.
作者信息
Bergmann Jilling F, Vrolijk Jan M, van der Schaar Peter, Vroom Brigitte, van Hoek Bart, van der Sluys Veer Annet, de Vries Richard A, Verhey Elke, Hansen Bettina E, Brouwer Johannes T, Janssen Harry L A, Schalm Solko W, de Knegt Robert J
机构信息
Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands.
出版信息
Liver Int. 2007 Nov;27(9):1217-25. doi: 10.1111/j.1478-3231.2007.01540.x.
BACKGROUND
High-dose peginterferon-alpha (PegIFN-alpha) induction and prolongation of therapy may be an option to improve sustained virological response (SVR) rates among hepatitis C virus (HCV) non-responders, although a higher and a longer dosing of PegIFN-alpha may intensify side effects.
METHODS
We randomized 53 patients, who previously failed with standard IFN-alpha+/-ribavirin, to a high-dose induction and an extended regimen with PegIFN-alpha-2b [3.0 microg/kg once weekly (q.w.) 12 weeks-->2.0 microg/kg q.w. 12 weeks-->1.5 microg/kg q.w. 48 weeks] or a standard regimen (1.5 microg/kg q.w. 48 weeks). All patients received daily weight-based ribavirin (800-1200 mg/day). The short-form 36 health survey was used to evaluate health-related quality of life (HRQL).
RESULTS
Intention-to-treat analysis showed no significant difference in SVR rate (44% vs. 37%, P=0.62) and relapse rate (9% vs. 31%, P=0.17) between experimental and standard treatment. Overall, 80% of the [positive predictive value (PPV)] patients with rapid virological response (RVR, HCV-RNA negativity at week 4) achieved SVR. No significant dose-related differences in HRQL were seen between both groups. At baseline, genotype 2 or 3 [odds ratio (OR): 7.4, 95% confidence interval (CI): 1.4-33.3, P=0.01] and gamma-glutamyltransferase (GGT) levels <2 x ULN (upper limit of normal) (OR: 6.76, 95% CI: 1.5-31.3, P=0.009) were significantly associated with SVR. Multivariate logistic regression at week 4 showed that only baseline GGT <2 x ULN (OR: 7.3, 95% CI: 1.4-38.5, P=0.01) and RVR (OR: 15.6, 95% CI: 3.2-76.9, P<0.001) were independently predictive for SVR.
CONCLUSION
Retreatment with PegIFN-alpha-2b and ribavirin for a minimum of 48 weeks should be considered in all patients unresponsive to previous IFN-based therapies. Baseline GGT values and RVR are highly predictive for retreatment outcome.
背景
高剂量聚乙二醇化干扰素-α（PegIFN-α）诱导治疗及延长疗程可能是提高丙型肝炎病毒（HCV）无应答者持续病毒学应答（SVR）率的一种选择，尽管更高剂量和更长疗程的PegIFN-α可能会加重副作用。
方法
我们将53例先前使用标准干扰素-α±利巴韦林治疗失败的患者随机分为高剂量诱导及延长疗程组，采用PegIFN-α-2b[3.0μg/kg每周1次（q.w.），共12周→2.0μg/kg q.w.，共12周→1.5μg/kg q.w.，共48周]或标准疗程组（1.5μg/kg q.w.，共48周）。所有患者均接受基于每日体重的利巴韦林治疗（800 - 1200mg/天）。采用36项简明健康调查问卷评估健康相关生活质量（HRQL）。
结果
意向性分析显示，试验组与标准治疗组在SVR率（44%对37%，P = 0.62）和复发率（9%对31%，P = 0.17）方面无显著差异。总体而言，快速病毒学应答（RVR，第4周时HCV - RNA阴性）的患者中有80%（阳性预测值）实现了SVR。两组在HRQL方面未观察到显著的剂量相关差异。在基线时，基因型2或3[优势比（OR）：7.4，95%置信区间（CI）：1.4 - 33.3，P = 0.01]和γ-谷氨酰转移酶（GGT）水平<2倍正常上限（ULN）（OR：6.76，95%CI：1.5 - 31.3，P = 0.009）与SVR显著相关。第4周的多因素逻辑回归分析显示，只有基线GGT<2倍ULN（OR：7.3，95%CI：1.4 - 38.5，P = 0.01）和RVR（OR：15.6，95%CI：3.2 - 76.9，P<0.001）可独立预测SVR。
结论
对于所有对先前基于干扰素的治疗无应答的患者，应考虑用PegIFN-α-2b和利巴韦林重新治疗至少48周。基线GGT值和RVR对重新治疗结果具有高度预测性。
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