Peginterferon alpha-2b is safe and effective in HBeAg-positive chronic hepatitis B patients with advanced fibrosis
Peginterferon alpha-2b is safe and effective in HBeAg-positive chronic hepatitis B patients with advanced fibrosis
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DOI：
10.1002/hep.21723
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发表时间：
2007-08-01
期刊：
影响因子：
13.5
通讯作者：
Janssen, Harry L. A.
中科院分区：
文献类型：
--
作者：
Buster, Erik H. C. J.;Hansen, Bettina E.;Janssen, Harry L. A.
慢性B型肝炎（CH B）晚期肝纤维化患者通常不考虑使用聚乙二醇干扰素（PEG-IFN）治疗，因为IFN治疗可能会诱发免疫反应，潜在地诱导肝脏失代偿。我们研究了PEG-IFN-α-2b（100 μ g/周）单独或联合拉米夫定（100 mg/天）治疗52周的B e抗原（HBeAg）阳性CHB患者的疗效和安全性。70例晚期纤维化患者（Ishak纤维化评分4-6）和169例无晚期纤维化患者（均患有代偿性肝病）参加了研究。病毒学应答定义为第78周HBeAg血清转换和B肝炎病毒（HBV）DNA <10，000拷贝/ml，晚期纤维化患者的发生率显著高于无纤维化患者（分别为25%和12%; P = 0.02）。此外，肝硬化患者（n = 24）比无肝硬化患者更频繁地表现出病毒学应答（分别为30%和14%; P = 0.02）。晚期肝纤维化患者的肝纤维化改善率更高（66%对26%，P < 0.001）。HBV基因A型在晚期肝纤维化患者中的发生率高于无肝纤维化患者（57%比24%，P < 0.001）。大多数不良事件，包括严重不良事件，在晚期纤维化患者和非晚期纤维化患者中观察到的频率相同。伴晚期肝纤维化组较无肝纤维化组易发生疲乏、厌食和血小板减少（P < 0.01）。两个患者组的必要剂量降低或治疗中止相当（分别为P = 0.92和P = 0.47）。结论：PEG-IFN治疗HBeAg阳性的晚期肝纤维化患者安全有效。由于PEG-IFN治疗导致高比率的持续停药应答，因此不应将患有晚期纤维化或肝硬化但代偿性肝病的患者排除在PEG-IFN治疗之外。
Chronic hepatitis B (CHB) patients with advanced fibrosis are often not considered for treatment with peginterferon (PEG-IFN) because IFN therapy may precipitate immunological flares, potentially inducing hepatic decompensation. We investigated the efficacy and safety of treating hepatitis B e antigen (HBeAg)-positive CHB patients with 52 weeks of PEG-IFN-alpha-2b (100 mu g weekly) alone or in combination with lamivudine (100 mg daily). Seventy patients with advanced fibrosis (Ishak fibrosis score 4-6) and 169 patients without advanced fibrosis, all with compensated liver disease, participated in the study. Virologic response, defined as HBeAg seroconversion and hepatitis B virus (HBV) DNA < 10,000 copies/ml at week 78, occurred significantly more often in patients with advanced fibrosis than in those without (25% versus 12%, respectively; P = 0.02). Also patients with cirrhosis (n = 24) exhibited a virologic response more frequently than did patients without cirrhosis (30% versus 14%, respectively; P = 0.02). Improvement in liver fibrosis occurred more frequently in patients with advanced fibrosis (66% versus 26%, P < 0.001). HBV genotype A was more prevalent among patients with advanced fibrosis than among those without (57% versus 24%, P < 0.001). Most adverse events, including serious adverse events, were observed equally as frequently in patients with advanced fibrosis and those without. Fatigue, anorexia, and thrombocytopenia occurred more often in patients with advanced fibrosis than in those without (P < 0.01). Necessary dose reduction or discontinuation of therapy was comparable for both patient groups (P = 0.92 and P = 0.47, respectively). Conclusion: PEG-IFN is effective and safe for HBeAg-positive patients with advanced fibrosis. Because PEG-IFN therapy results in a high rate of sustained off-therapy response, patients with advanced fibrosis or cirrhosis but compensated liver disease should not be excluded from PEG-IFN treatment.