Janssen Harry L A, van Zonneveld Monika, Senturk Hakan, Zeuzem Stefan, Akarca Ulus S, Cakaloglu Yilmaz, Simon Christopher, So Thomas M K, Gerken Guido, de Man Robert A, Niesters Hubert G M, Zondervan Pieter, Hansen Bettina, Schalm Solko W
Department of Gastroenterology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands.
Lancet. 2005;365(9454):123-9. doi: 10.1016/S0140-6736(05)17701-0.
Treatment of HBeAg-positive patients with chronic hepatitis B is not effective in most. A combination of immunomodulatory pegylated interferon alfa-2b and antiviral lamivudine might improve the rate of sustained response.
307 HBeAg-positive patients with chronic hepatitis B were assigned combination therapy (100 microg/week pegylated interferon alfa-2b and 100 mg/day lamivudine) or monotherapy (100 microg/week pegylated interferon alfa-2b and placebo) for 52 weeks. During weeks 32-52 the pegylated interferon dose was 50 microg/week in both treatment groups. The analyses were based on the modified intention-to-treat population after exclusion of 24 patients from one centre withdrawn for misconduct, ten who lost HBeAg before the study start, and seven who received no study medication. All included patients were followed up for 26 weeks after treatment.
49 (36%) of 136 patients assigned monotherapy and 46 (35%) of 130 assigned combination therapy had lost HBeAg at the end of follow-up (p=0.91). More of the combination-therapy than of the monotherapy group had cleared HBeAg at the end of treatment (57 [44%] vs 40 [29%]; p=0.01) but relapsed during follow-up. Patterns were similar when response was assessed by suppression of serum hepatitis B virus (HBV) DNA or change in concentrations of alanine aminotransferase. Response rates (HBeAg loss) varied by HBV genotype (p=0.01): A, 42 (47%) patients; B, ten (44%); C, 11 (28%); and D, 26 (25%).
Treatment with pegylated interferon alfa-2b is effective for HBeAg-positive chronic hepatitis B. Combination with lamivudine in the regimen used is not superior to monotherapy. HBV genotype is an important predictor of response to treatment.
大多数情况下，对HBeAg阳性的慢性乙型肝炎患者进行治疗效果不佳。免疫调节性聚乙二醇化干扰素α-2b与抗病毒药物拉米夫定联合使用可能会提高持续应答率。
307例HBeAg阳性的慢性乙型肝炎患者被分配接受联合治疗（每周100μg聚乙二醇化干扰素α-2b和每日100mg拉米夫定）或单药治疗（每周100μg聚乙二醇化干扰素α-2b和安慰剂），为期52周。在第32至52周期间，两个治疗组的聚乙二醇化干扰素剂量均为每周50μg。分析基于排除了24例因行为不端从一个中心退出的患者、10例在研究开始前失去HBeAg的患者以及7例未接受研究药物治疗的患者后的改良意向性治疗人群。所有纳入的患者在治疗后随访26周。
在随访结束时，136例接受单药治疗的患者中有49例（36%）、130例接受联合治疗的患者中有46例（35%）失去了HBeAg（p=0.91）。联合治疗组在治疗结束时清除HBeAg的患者比单药治疗组更多（57例[44%]对40例[29%]；p=0.01），但在随访期间复发。当通过血清乙型肝炎病毒（HBV）DNA抑制或丙氨酸氨基转移酶浓度变化评估应答时，模式相似。应答率（HBeAg消失）因HBV基因型而异（p=0.01）：A型，42例（47%）患者；B型，10例（44%）；C型，11例（28%）；D型，26例（25%）。
聚乙二醇化干扰素α-2b治疗对HBeAg阳性的慢性乙型肝炎有效。在所使用的方案中与拉米夫定联合并不优于单药治疗。HBV基因型是治疗应答的重要预测指标。
