Krogsgaard K, Christensen E, Bindslev N, Schalm S, Andersen P K, Ring-Larsen H
Department of Infectious Diseases, Hvidovre Hospital, Copenhagen, Denmark.
J Hepatol. 1996 Dec;25(6):795-802. doi: 10.1016/s0168-8278(96)80281-9.
BACKGROUND/AIMS: Alpha interferon (IFN) is an established treatment of chronic hepatitis B. The effect has been shown to be dose related, recommended dose regimens being associated with a doubling of the spontaneous, baseline HBeAg to anti-HBe seroconversion rate. However, the efficacy of IFN treatment in relation to the dose of IFN actually received remains to be established. The aim of this study was to estimate the relative efficacy of IFN as a function of the cumulative IFN dose. In addition we determined if and when a patient returns to his baseline chance of seroconversion after stopping IFN therapy.
Individual patient data from 10 clinical controlled trials were available for the present analysis, in all, 746 patients, of whom 491 received IFN and 255 were untreated controls. The data were analyzed performing a time-dependent Cox regression analysis of the relative efficacy of IFN using the cumulative IFN dose administered up to any given time during the observation period and the time after termination of therapy as explanatory variables.
In the proposed model, the chance of HBeAg disappearance for a treated patient relative to no therapy was estimated to 2.1 at a cumulative dose of 100 MU and leveled out at about 2.8 at a cumulative dose of 500 MU. The effect of IFN was shown to decay rapidly after discontinuation and after 3 months a patient could be considered to be back to his baseline chance of HBeAg disappearance. These findings show that IFN administered at a dose of 15-30 MU/week should be considered effective (relative efficacy approximately 2) already after 1-2 months of treatment.
The present findings do not lend any support to the concept that IFN treatment becomes less effective when a certain total dose of IFN has been administered or that the treatment effect reaches beyond 3 months after stopping IFN.
背景/目的：α干扰素（IFN）是慢性乙型肝炎的一种既定治疗方法。已证明其效果与剂量相关，推荐的剂量方案可使自发的基线HBeAg至抗-HBe血清转换率翻倍。然而，IFN治疗的疗效与实际接受的IFN剂量之间的关系仍有待确定。本研究的目的是评估IFN作为累积IFN剂量函数的相对疗效。此外，我们还确定了患者在停止IFN治疗后是否以及何时恢复到基线血清转换机会。
本分析可获得来自10项临床对照试验的个体患者数据，总共746例患者，其中491例接受IFN治疗，255例为未治疗的对照。使用观察期内任何给定时间给予的累积IFN剂量和治疗终止后的时间作为解释变量，通过对IFN的相对疗效进行时间依赖性Cox回归分析来分析数据。
在提出的模型中，治疗患者相对于未治疗患者的HBeAg消失机会在累积剂量为100 MU时估计为2.1，在累积剂量为500 MU时稳定在约2.8。IFN的作用在停药后迅速衰减，3个月后患者可被认为恢复到HBeAg消失的基线机会。这些发现表明，以15 - 30 MU/周的剂量给予IFN在治疗1 - 2个月后就应被认为是有效的（相对疗效约为2）。
目前的研究结果不支持以下观点，即当给予一定总量的IFN后IFN治疗效果会降低，或者治疗效果在停止IFN治疗后超过3个月仍存在。
