In vivo immunization by vaccine therapy following virus suppression by lamivudine: a novel approach for treating patients with chronic hepatitis B
In vivo immunization by vaccine therapy following virus suppression by lamivudine: a novel approach for treating patients with chronic hepatitis B
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DOI：
10.1016/j.jcv.2004.07.004
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发表时间：
2005-02-01
影响因子：
8.8
通讯作者：
Onji, M
中科院分区：
文献类型：
--
作者：
Horiike, N;Akbar, SMF;Onji, M
背景：乙肝病毒及其宿主对乙肝病毒的免疫应答在慢性乙型肝炎的发病机制中起着重要作用。拉米夫定是一种免疫调节剂能力最小的有效抗病毒药物。此外，拉米夫定在慢性乙型肝炎患者中会引起严重的副作用，如HBVDNA突破和突破性肝炎。另一方面，疫苗疗法是一种新近发展起来的免疫疗法，对慢性乙肝患者表现出强大的免疫调节潜力和几乎没有副作用，但几乎没有抗病毒能力。目的：本临床试验的目的是评价拉米夫定和疫苗联合治疗慢性乙型肝炎患者的疗效。研究设计：72例慢性乙型肝炎患者(HBe抗原阳性，40例；抗HBe抗体阳性，32例)。所有患者均服用拉米夫定，每日100毫克，疗程12个月。15例(HBeAg+，9例；抗-HBe+，6例)口服拉米夫定，皮内注射乙肝表面抗原20 g，每2周1次，共12次(联合治疗)。结果：联合治疗12个月后，9例(100%)HBeAg+CHB患者血清HBVdna转阴率为100%，31例单纯拉米夫定治疗HBeAg+CHB患者15例(48%)血清HBVDNA转阴(P<；0.05)。在接受联合治疗的患者中，从HBeAg到抗-HBe的血清转换率也显著更高(56%比拉米夫定单一治疗的16%，P<；0.05)。在接受拉米夫定单一治疗的57例患者中，10例发现HBVDNA突破，4例发现突破性肝炎；然而，任何接受联合治疗的患者都没有发现这些。结论：联合治疗慢性乙型肝炎是一种较好的治疗方案，并发症少。(C)2004爱思唯尔B.V.保留所有权利。
Background: Both the hepatitis B virus (HBV) and the immune response of the hosts to HBV play important roles in the pathogenesis of chronic hepatitis B (CHB). Lamivudine is a potent antiviral agent with minimal immune modulator capacity. Moreover, lamivudine causes severe side effects like breakthrough of HBV DNA and breakthrough hepatitis in patients with CHB. On the other hand, vaccine therapy, a recently-developed immune therapy, exhibits potent immune modulatory potentials and almost no side effects, but possesses little antiviral capacity in patients with CHB.Objectives: The aim of this clinical trial is to evaluate the efficacy of a combination therapy of lamivudine and vaccine in patients with CHB.Study design: Seventy-two patients with CHB (hepatitis B e antigen (HBeAg)-positive, 40; antibody to HBeAg (anti-HBe)-positive, 32). All patients received lamivudine at a dose of 100 mg daily for 12 months. Fifteen patients (HBeAg+, 9; anti-HBe+, 6) receiving oral lamivudine were also given a vaccine containing 20 jig of hepatitis B surface antigen, intradermally, once every 2 weeks for 12 times (combination therapy).Results: Twelve months after the start of therapy, serum HBV DNA became negative in 9 of 9 (100%) HBeAg+ CHB patients receiving combination therapy and in 15 of 31 (48%) HBeAg+ CHB patients receiving lamivudine monotherapy (P < 0.05). The rate of seroconversion from HBeAg to anti-HBe was also significantly higher in patients receiving combination therapy (56% versus lamivudine monotherapy, 16%, P < 0.05). Of the 57 patients receiving lamivudine monotherapy, breakthrough of HBV DNA was found in 10 and breakthrough hepatitis was found in 4; however, these were not seen in any patient receiving combination therapy. Conclusions: Combination therapy represents a better therapeutic regimen with few complications in patients with CHB. (C) 2004 Elsevier B.V. All rights reserved.