Ullerich H, Avenhaus W, Poremba C, Domschke W, Menzel J
Department of Medicine B, University of Muenster, Germany.
Aliment Pharmacol Ther. 2002 Dec;16(12):2107-14. doi: 10.1046/j.1365-2036.2002.01379.x.
Hepatitis C viral kinetic studies have demonstrated the increased anti-viral effect of higher than standard dosages of interferon and of daily treatment schedules.
To compare, in a prospective, randomized, controlled trial, the efficacy and safety of high-dose interferon-alpha therapy vs. standard-dosage interferon-alpha therapy, in a triple therapy combination with ribavirin and amantadine.
Previously untreated patients with chronic hepatitis C were randomized to the standard interferon-alpha group (n = 15), receiving thrice weekly 6 MU interferon-alpha for 12 weeks, followed by 3 MU interferon-alpha for 36 weeks, or the high-dose interferon-alpha group (n = 15), receiving daily 9 MU interferon-alpha for 4 weeks, followed by 6 MU (weeks 5-8), 3 MU (weeks 9-12) and 1.5 MU (weeks 13-48) interferon-alpha. All patients were given ribavirin (1000-1200 mg) and amantadine (200 mg) daily for 48 weeks.
At the end of treatment and after the 24-week follow-up period, serum hepatitis C virus RNA was undetectable in eight (53%) and six (40%) patients treated with standard-dosage interferon-alpha, respectively, compared with 11 (73%) and 10 (67%) treated with high-dose interferon-alpha, respectively (not significant). The safety profile of both treatment regimens was similar. Severe adverse events leading to withdrawal from the study occurred in one patient (7%) in each group, and in both groups one patient (7%) was lost during therapy for unknown reasons.
The findings suggest that, although the difference between the response rates of standard and high-dose interferon-alpha regimens (within a triple anti-viral therapy combination) did not reach statistical significance, there was a clear trend towards a higher response with high-dose interferon-alpha therapy and an equal safety profile.
丙型肝炎病毒动力学研究表明，高于标准剂量的干扰素及每日治疗方案具有增强的抗病毒效果。
在一项前瞻性、随机、对照试验中，比较高剂量α-干扰素疗法与标准剂量α-干扰素疗法，联合利巴韦林和金刚烷胺进行三联疗法的疗效和安全性。
既往未接受过治疗的慢性丙型肝炎患者被随机分为标准α-干扰素组（n = 15），接受每周3次6 MU α-干扰素治疗12周，随后接受3 MU α-干扰素治疗36周；或高剂量α-干扰素组（n = 15），接受每日9 MU α-干扰素治疗4周，随后分别接受6 MU（第5 - 8周）、3 MU（第9 - 12周）和1.5 MU（第13 - 48周）α-干扰素治疗。所有患者均每日给予利巴韦林（1000 - 1200 mg）和金刚烷胺（200 mg），持续48周。
在治疗结束时及24周随访期后，标准剂量α-干扰素治疗的患者中分别有8例（53%）和6例（40%）血清丙型肝炎病毒RNA检测不到，相比之下，高剂量α-干扰素治疗的患者中分别有11例（73%）和10例（67%）血清丙型肝炎病毒RNA检测不到（无显著性差异）。两种治疗方案的安全性相似。每组均有1例患者（7%）因严重不良事件退出研究，两组均有1例患者（7%）在治疗期间因不明原因失访。
研究结果表明，尽管标准剂量和高剂量α-干扰素方案（在三联抗病毒治疗组合中）的应答率差异未达到统计学显著性，但高剂量α-干扰素治疗有明显更高应答率的趋势且安全性相当。
