目的 评估替比夫定与阿德福韦酯联合治疗优化阿德福韦酯单药治疗应答不佳的阳性慢性乙型肝炎患者的疗效。 方法 选择2008年6月－2009年8月间共26例阿德福韦酯治疗至少12个月且病毒学应答不佳的乙型肝炎病毒e抗原（HBeAg），阳性的慢性乙型肝炎患者，在10 mg阿德福韦酯治疗的基础上，加用600 mg替比夫定。肝功能和乙型肝炎病毒（HBV） DNA每3个月评估1次，乙型肝炎两对半和腹部B型超声每半年评估1次。 结果 在第1年的治疗期间，所有患者血清HBV DNA水平均呈进行性下降，其中24例（92.3%）血清HBV DNA水平在联合治疗12个月时低于检测值下限，有25例（96.2%）患者丙氨酸转氨酶水平复常。治疗6个月时，分别有7例（26.9%）和2例（7.7%）患者发生HBeAg消失和血清学转换；治疗12个月时，分别有11例（42.3%）和8例（30.8%）患者发生HBeAg消失和血清学转换。整个治疗期间，26例患者均未出现病毒学突破。 结论 阿德福韦酯单药治疗应答不佳时，加用替比夫定可有效控制病毒，使患者获得较好的病毒学、生化学和免疫学应答。Objective To evaluate the curative efficacy of telbivudine combined with defovir dipivoxil on positive-HBeAg chronic hepatitis B patients with suboptimal response to adefovir dipivoxil. Methods A total of 26 HBeAg-positive patients with suboptimal response to adefovir dipivoxil (treated with adefovir dipivoxil for more than 12 months) were treated with adefovir dipivoxil 10 mg in addition to telbivudine 600 mg between June 2008 and August 2009. Liver function and serum hepatitis B virus (HBV) DNA tests were assessed at the baseline and 3-month intervals, whereas HBV serological markers and abdominal ultrasonography were carried out every 6 months. Results During the first year of treatment, all patients showed a progressive decline of serum HBV DNA levels; while undetectable serum HBV DNA and normalization of alanine aminotransferase was achieved in 24(92.3%) and 25 (96.2%) patients, respectively, at the end of the first year of treatment. The 6- and 12-month cumulative rates of HBeAg loss were 26.9% (7/26) and 42.3% (11/26), respectively; and corresponding cumulative rates of HBeAg/anti-HBe seroconversion were 7.7% (2/26) and 30.8 (8/26), respectively. During the observation period, no virological breakthrough was detected. Conclusion Telbivudine combined with defovir dipivoxil may be a good choice for patients with suboptimal response to adefovir dipivoxil, which could induce effective viral inhibition and help patients obtain more virological, biochemical and immunological responses.
【摘要】 目的 观察阿德福韦酯联合拉米夫定治疗阿德福韦酯治疗48周后应答不佳，HBeAg阳性慢性乙型肝炎的疗效和安全性。 方法 选择2006年1月-2010年12月间阿德福韦酯治疗48周后乙型肝炎病毒 DNAgt;104 copies/mL的26例慢性乙型肝炎患者，给与拉米夫定（100 mg，1次/d）联合治疗。观察治疗12周，24周时的应答情况。 结果 所有纳入26例患者在联合拉米夫定优化治疗24周后，无论是病毒学应答还是血清学应答都获得显著的改善，无一例患者观察到有耐药以及药物不良反应发生。 结论 联合拉米夫定是对阿德福韦酯应答不佳慢性乙型肝炎患者安全有效的干预策略之一。【Abstract】 Objective To observe the effect and safety of adefovir dipivoxil (ADV) combined with lamnivudine (LAM) in treating HBeAg-positive chronic hepatitis B (CHB) patients with poor response to ADV monotherapy for 48 weeks. Methods Twenty-six HBeAg-positive CHB patients received initial treatment of ADV from January 2006 to December 2010, and their serum HBV-DNA still maintained over or equal to 1.0×104 copies/mL after 48 weeks. These patients received the optimized treatment of ADV (10 mg, one time per day) combined with LAM (100 mg, one time per day). Patients′ responses to the treatment at the 12th and 24th week were observed. Results Compared with baseline, ADV plus LAM had an improved response rate of virological response, biochemical response and HBeAg/HBeAb seroconversion. No LAM-resistant or ADV-resistant mutations were detected. In all the 26 patients, no adverse reactions were observed. Conclusion Optimized therapy combining LAM and ADV can be a good choice for patients with hepatitis B who have a poor response to ADV monotherapy.