Krogsgaard K, Bindslev N, Christensen E, Craxi A, Schlichting P, Schalm S, Carreno V, Trepo C, Gerken G, Thomas H C
Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Denmark.
J Hepatol. 1994 Oct;21(4):646-55. doi: 10.1016/s0168-8278(94)80114-2.
Alpha interferon induces HBeAg seroconversion in about one third of treated patients and has become an established treatment of chronic hepatitis B. A number of smaller studies have suggested that response to treatment is more likely to occur in patients with higher levels of transaminases, with recent (adult) onset, a history of acute hepatitis, low levels of HBV DNA and in heterosexual males. The aim of this European co-operative study was to estimate the effect of alpha interferon more accurately and to evaluate the influence of host pre-treatment variables on the effect of interferon. Individual data were collected from 751 patients from 10 controlled clinical trials on alpha interferon (lymphoblastoid or recombinant) treatment for chronic hepatitis B. Alpha interferon was administered to 496 patients, while 255 were untreated controls. Individual patient data were analysed by survival analysis (log rank test and Cox regression analysis), stratified by trial, with the disappearance of HBeAg as the major endpoint. The results showed that the HBeAg disappearance rate with or without interferon treatment was higher in patients with high aminotransferase levels, with a history of acute hepatitis and in male heterosexual patients disregarding HIV status. If HIV-positive patients were excluded, the effect of sexual orientation was not significant. Therapy with alpha interferon increased the a priori HBeAg disappearance rate by a factor of 1.76; the relative treatment effect of alpha interferon was independent of the tested pretreatment host variables, but dependent on the total (intended) interferon dose (low dose < or = 200 MU/m2 increased HBeAg disappearance by a factor 1.37; medium/high dose > or = 200 MU/m2 increased HBeAg disappearance by a factor 2.05). In conclusion, this meta-analysis suggests that the effect of alpha interferon is less than previously assumed and independent of pretreatment host variables tested. It confirms the higher therapeutic benefit of a total dose exceeding 200 MU/m2 and of selection of patients based on disease activity and immune reactivity. Although all patient seem to have the same relative benefit, the absolute benefit of alpha interferon treatment seems to be greatest in patients with high transaminase levels and with a history of acute hepatitis.
α干扰素可使约三分之一接受治疗的患者发生HBeAg血清学转换，已成为慢性乙型肝炎的一种既定治疗方法。一些规模较小的研究表明，转氨酶水平较高、近期（成人）发病、有急性肝炎病史、HBV DNA水平较低的患者以及异性恋男性对治疗更可能产生反应。这项欧洲合作研究的目的是更准确地评估α干扰素的疗效，并评估宿主治疗前变量对干扰素疗效的影响。从10项关于α干扰素（淋巴母细胞型或重组型）治疗慢性乙型肝炎的对照临床试验中的751例患者收集了个体数据。496例患者接受了α干扰素治疗，255例为未治疗的对照。通过生存分析（对数秩检验和Cox回归分析）对个体患者数据进行分析，按试验分层，以HBeAg消失作为主要终点。结果显示，无论有无干扰素治疗，转氨酶水平高、有急性肝炎病史的患者以及异性恋男性（无论HIV状态如何）的HBeAg消失率更高。如果排除HIV阳性患者，性取向的影响不显著。α干扰素治疗使HBeAg预先设定的消失率提高了1.76倍；α干扰素的相对治疗效果与所检测的治疗前宿主变量无关，但取决于总的（预定的）干扰素剂量（低剂量≤200 MU/m2使HBeAg消失率提高1.37倍；中/高剂量≥200 MU/m2使HBeAg消失率提高2.05倍）。总之，这项荟萃分析表明，α干扰素的疗效低于先前的假设，且与所检测的治疗前宿主变量无关。它证实了总剂量超过200 MU/m2以及根据疾病活动和免疫反应性选择患者具有更高的治疗益处。虽然所有患者似乎都有相同的相对益处，但α干扰素治疗的绝对益处似乎在转氨酶水平高和有急性肝炎病史的患者中最大。
