A multicenter, randomized trial of daily high-dose interferon-alfa 2b for the treatment of chronic hepatitis C: Pretreatment stratification by viral burden and genotype
A multicenter, randomized trial of daily high-dose interferon-alfa 2b for the treatment of chronic hepatitis C: Pretreatment stratification by viral burden and genotype
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DOI：
10.1111/j.1572-0241.2000.03433.x
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发表时间：
2000-11-01
影响因子：
9.8
通讯作者：
Nolte, FS
中科院分区：
文献类型：
--
作者：
Fried, MW;Shiffman, M;Nolte, FS
目的：本研究的目的是前瞻性地确定是否强化方案的每日，高剂量的干扰素将改善慢性丙型肝炎患者的治疗反应率不利的virological characteristics.METHODS：共104例慢性丙型肝炎患者随机在8个中心接受干扰素α-2b的剂量为5万单位（MU），每天或3 MU，每周三次。共24周。患者按病毒负荷高低进行前瞻性随机分组，并按基因型分层。HCV RNA定量聚合酶链反应测定，和反应率之间的剂量regiments.RESULTS：HCV RNA水平下降更迅速，以较低的水平，每天5 MU的治疗组进行了比较。在该组中，第12周的初始病毒学应答（IR）和第24周的治疗结束应答（ETR）是用标准干扰素治疗的患者的两倍（66%对33%和48%对34%，p < 0.01）。两个剂量组的持续缓解率均较低（14% vs 4%，p = 0.08）。在标准剂量组中存在初始应答率的基因型相关差异（63%非1基因型vs 24%基因型1; p = 0.005），但在每日5 MU治疗组中不存在（66% vs 67%，p = NS）。使用多变量分析，只有干扰素剂量与IR和ETR相关（p = 0.002）。结论：与三次免疫治疗相比，每日高剂量干扰素快速降低HCV RNA，并增加初始和治疗结束应答率。养生法这种效应与病毒负荷和基因型无关，表明具有不利病毒特征的患者可能受益于促进快速病毒清除的强化方案。这些数据支持进一步研究使用高剂量诱导方案。然而，持续反应率的改善将需要额外的治疗策略，如延长治疗或连续使用利巴韦林。(C)2000年，我Cell.胃肠病学
OBJECTIVES: The aim of this study was to determine prospectively whether an intensive regimen of daily, high-dose interferon would improve the response rate for the treatment of chronic hepatitis C in patients with unfavorable virological characteristics.METHODS: A total of 104 patients with chronic hepatitis C were randomized at eight centers to receive interferon alfa-2b at a dose of 5 million units (MU) daily or 3 MU t.i.w.. for a period of 24 wk. Patients were prospectively randomized by low or high viral burden and stratified by genotype. HCV RNA was measured by quantitative polymerase chain reaction, and response rates were compared between the dosage regimens.RESULTS: HCV RNA levels dropped more rapidly to lower levels in the group treated with 5 MU daily. In this group, the initial virological response (IR) at wk 12 and the end-of-treatment response (ETR) at wk 24 were double that of patients treated with standard interferon (66% vs 33% and 48% vs 34%, p < 0.01). Sustained response rates were low for both dose groups (14% vs 4%, p = 0.08). Genotype-related differences in initial response rates were present in the standard dose group (63% non-1 genotype vs 24% genotype 1; p = 0.005) but not in those treated with 5 MU daily (66% vs 67%, p = NS). Using multivariate analysis, only the interferon dose was associated with IR and ETR (p = 0.002).CONCLUSIONS: Daily, high dose interferon rapidly dropped HCV RNA and increased initial and end-of-treatment response rates when compared to t.i.w. regimens. This effect, independent of viral burden and genotype, suggests that patients with unfavorable viral characteristics might benefit from an intensive regimen that promotes rapid viral clearance. These data support further study of the use of high dose induction regimens. However, improvements in sustained response rates will require additional therapeutic maneuvers such as prolonged therapy or the adjunctive use of ribavirin. (C) 2000 by Am. Cell. of Gastroenterology.