目的观察恩替卡韦(ETV)联合阿德福韦酯(ADV)治疗拉米夫定(LAM)治疗失败的慢性乙型肝炎(CHB)患者48周的临床疗效和安全性。方法入选我院门诊2008年1月至2014年12月128例LAM治疗失败的CHB患者,选用ETV、ADV挽救治疗,随机分成4组,其中ADV与LAM联用≤12周为A组,共30例;ADV与LAM联用>12周为B组,共35例;单用ETV为C组,共30例;ETV联用ADV为D组,共33例。治疗后每12周检测病毒学指标及肝功能等,治疗48周期间进行安全性评估。结果 D组在治疗12、24、36及48周,HBV DNA转阴率分别为84.8%、93.9%、97.0%、100.0%,各治疗阶段较A组、B组、C组明显提高,差异有统计学意义(P均<0.05);各治疗阶段与A组、B组、C组两两比较差异均有统计学意义(P均<0.008)。而A组、B组、C组各治疗阶段两两比较差异均无统计学意义。D组在治疗12、24、36及48周,ALT复常率均较A组、B组、C组提高,其中12周时与A组、B组、C组两两比较差异均有统计学意义;24、36周时与A组、B组两两比较差异均有统计学意义(P均<0.008);48周时D组ALT转阴率达100%,与A组比较差异有统计学意义(P=0.001);各治疗阶段A组、B组、C组ALT转阴率两两比较,仅36周时A组与C组两两比较差异有统计学意义(P=0.004)。HBe Ag阳性患者中对于HBe Ag转阴率及血清学转换率,各治疗阶段四组应答率均较低,差异无统计学意义(P均>0.05)。未发生与研究药物相关的严重不良反应。结论对于LAM治疗失败的CHB患者ETV联合ADV挽救治疗疗效明显,且安全性好,值得临床推广。 Objective To observe the clinical efficacy and safety of entecavir (ETV) combined with adefovir dipivoxil (ADV) for 48 weeks in patients with chronic hepatitis B (CHB) who failed lamivudine (LAM) treatment. METHODS: One hundred and eighty patients with CHB who failed LAM treatment from January 2008 to December 2014 were enrolled in this study. ETV and ADV were selected and randomly divided into 4 groups. Group A was treated with ADV or LAM for ≤12 weeks For example, ADV combined with LAM was 12 weeks in group B with a total of 35 cases. ETV alone was used in group C with 30 cases in total. ETV combined with ADV was in group D with 33 cases in total. Virological tests and liver function tests were performed every 12 weeks after treatment, and safety evaluations were performed during the 48 weeks of treatment. Results The negative rates of HBV DNA in group D were 84.8%, 93.9%, 97.0% and 100.0% respectively at 12, 24, 36 and 48 weeks after treatment, and were significantly higher than those in groups A, B and C (P <0.05). There was significant difference between each treatment stage and A group, B group and C group (P <0.008). However, there was no significant difference in each treatment stage between groups A, B and C. At 12, 24, 36 and 48 weeks, the ALT normalization rate in group D was significantly higher than that in group A, B and C, and the difference was statistically significant when compared with those in groups A, B and C at 12 weeks (P <0.008). At 48 weeks, the ALT negative rate in group D was 100%, which was significantly different from that in group A at 24 and 36 weeks (P = 0.001). The ALT negative rates in groups A, B and C at each treatment stage were compared with each other at any treatment stage. There was a significant difference between the two groups in the A group and the C group only at 36 weeks (P = 0.004). HBeAg-positive HBeAg-negative rate and seroconversion rate, the response rate of the four treatment groups were lower, the difference was not statistically significant (P all> 0.05). No serious adverse drug reactions have occurred with the study drug. Conclusions ETV combined with ADV salvage therapy for CHB patients failed in LAM treatment has obvious curative effect and good safety, which is worthy of clinical promotion.