摘要目的 对替比夫定(LDT)初始单用及联用阿德福韦酯(ADV)治疗HBeAg阳性慢性乙型肝炎(CHB)抗病毒的长期效果、安全性进行回顾性研究. 方法 将140例HBeAg阳性慢性乙型肝炎患者随机分为初始单用组(LDT,75例)和初始联用组(LDT加ADV,65例).初始单用组给予LDT 600 mg,口服,1次/d;初始联用组给予LDT 600 mg联合ADV 10 mg,口服,1次/d.疗程最短96周、最长240周.观察两组疗效、耐药发生率、不良反应情况,检测不同时段HBV血清学标志物、HBV DNA定量、肝功能、肾功能、肌酶等.计量资料比较用t检验;计数资料比较采用x2检验. 结果 12周时HBV DNA下降≥2 log10拷贝/ml的百分比,单用组及联用组分别为86.7％(65/75)、92.3％(60/65),24周HBV DNA阴转率分别为62.7％、61.5％,48周HBV DNA阴转率分别为76.0％、81.5％,96周HBV DNA阴转率分别为80.0％、89.2％,至240周HBV DNA阴转率分别为93.3％、88.9％,两组间比较,各时间点P值均＞0.05,差异均无统计学意义,两组均有较高的早期、快速、持久HBV DNA阴转率;单用组HBV DNA阴转率24周与96周及以上各时间点比较,差异均有统计学意义(x2值分别为5.51、3.86、5.81、9.87,P值均＜0.05),联用组HBV DNA阴转率24周与48周及以上各时间点比较,差异均有统计学意义(x2值分别为6.38、6.38、10.19、4.11,P值均＜0.05).单用组、联用组HBeAg血清学转换率在48周分别为29.3％、30.8％,96周分别为42.7％、40.0％,144周分别为55.0％、43.3％,192周分别为55.8％、66.7％,240周分别为63.3％、66.7％,两组间各时点两两比较差异无统计学意义(P值均＞0.05);两组组内24周与48周比较,差异无统计学意义(P＞ 0.05),但在24周与96周分别比较(x2值分别为11.46、4.31),与144周分别比较(x2值分别为21.05、4.05),与192周分别比较(x2值分别为18.80、9.18),差异均有统计学意义(P值均＜ 0.05).两组间耐药发生率比较差异均无统计学意义(P值均＞0.05),耐药率48周分别为4％、1.5％,96周分别为5.3％、3.1％,144周分别为10％、3.3％,192周分别为11.6％、8.3％,240周分别为13.3％、l1.1％;两组组内各时点随疗程延长耐药发生率差异无统计学意义(P值均＞0.05).少数患者出现肌肉酸痛及CK升高,给予对症处理后消失或复常.结论 LDT具有早期快速强效持久的抑制病毒作用,延长疗程可提高HBV DNA阴转率、HBeAg血清学转换率及持续应答率,尤其以96周以上疗效显著,提示LDT治疗CHB疗程至少应在96周以上.初始联用48周,HBV DNA阴转率优于初始单用,但并不能降低耐药发生率,延长疗程耐药率无差异.

abstractsObjective To prospectively observe the long-term antiviral efficacy and safety of telbivudine (LDT) administered as a monotherapy and as a combination therapy with adefovir dipivoxil (ADV) in patients diagnosed with chronic hepatitis B (CHB) and positivity for hepatitis B e antigen (HBeAg).Methods A total of 140 patients with HBeAg-positive CHB were randomly divided into treatment groups for LDT monotherapy (n =75; 600 mg orally,once daily) and LDT+ADV combination therapy (n =65; LDT 600 mg plus ADV 10 mg orally,once daily).The shortest treatment course was 96 weeks and the longest was 240 weeks.At treatment weeks 12,24,48,96,144,192,and 240 patients were tested for hepatitis B virus (HBV) DNA,HBeAg seroeonversion and ALT normalization time; in addition,the incidence and type of adverse drug reactions were recorded.Data were statistically analyzed to determine the significance of differences observed between groups.Results The rate of patients experiencing ≥ 2 log HBV DNA reduction was higher in the LDT + ADV group (92.3％(60/65) vs.LDT:86.7％(65/75),x2 =1.58).The HBV DNA negative rates of the LDT and LDT + ADV groups were 62.7％ and 61.5％ (x2 =0.01) at week 24,76.0％ and 81.5％ (x2 =0.63) at week 48,80.0％ and 89.2％ (x2 =2.2) at week 96,78.3％ and 93.3％ (x2 =3.24) at week 144,83.7％ and 91.7％ (x2 =0.47) at week 192,and 93.3％ and 88.9％ at week 240 (comparison between two groups for each point P ＞ 0.05); both groups showed higher early and rapid sustained HBV DNA negative rates.For the HBeAg seroconversion,the rates of the LDT and LDT + ADV groups were 17.3％ and 23.1％ (x2 =0.71) at week 24,29.3％ and 30.8％ (x2 =0.03) at week 48,42.7％ and 40.0％ (x2 =0.10) at week 96,55.0％ and 43.3％ (x2 =1.08) at week 144,55.8％ and 66.7％ (x2 =0.45) at week 192,and 63.3％ and 66.7％ at week 240; however,pairwise comparison showed no statistically significant differences between the groups (P ＞ 0.05).Similarly,there was no significant difference between the two groups in incidence of resistance at week 48 (4.0％ and 1.5％),week 96 (5.3％ and 3.1％),week 144 (10.0％ and 3.3％,x2 =1.23),week 192 (11.6％ and 8.3％),and week 240 (13.3％ and 11.1％) (all P ＞ 0.05).Three patients experienced muscle soreness (LDT,n =2; LDT + ADV,n =1) and two patients experienced increased creatine phosphokinase (LDT,n =1; LDT + ADV,n =1); all side effects resolved spontaneously or with symptom-appropriate treatment.Conclusion The long-term efficacy of LDT as a monotherapy or as a combination therapy with ADV was similar and the two different treatment approaches were associated with similar rates of resistance.The long-term safety was good for both treatment approaches.