CAJ | 학술논문

目的比较拉米夫定应答不佳慢性乙型肝炎(CHB)患者加用阿德福韦酯联合治疗与换用恩替卡韦单药治疗48周疗效.方法采用前瞻性研究方法观察2010年6月-2011年6月在浙江省诸暨市人民医院感染科和浙江大学医学院附属第一医院接受拉米夫定抗病毒治疗24周以上,但HBV DNA仍阳性的住院及门诊CHB患者120例,以随机数字表法将患者分为两组,每组各60例,一组在用拉米夫定的基础上加用阿德福韦酯联合抗病毒治疗,另一组则换用恩替卡韦单药治疗,疗程均为48周.每1～3个月检测患者的肝功能、肾功能、甲胎蛋白、HBV血清学标志物、HBV DNA、凝血酶原时间(PT)、肝脏的超声波或行CT检查.采用x2检验比较治疗48周时两组的病毒学、血清学的应答率和耐药发生率,观察两组的不良反应.结果基线HBV DNA介于3～5 lg拷贝/mL的拉米夫定应答不佳者,加用阿德福韦酯治疗至48周后有86.8％ (33/38)的患者HBV DNA转阴,而换用恩替卡韦单药治疗组有69.2％(27/39)的患者转阴,两组比较差异具有统计学意义(x2=4.578,p＜0.05)；基线HBV DNA＞5lg拷贝/mL的拉米夫定应答不佳者,加用阿德福韦酯的患者HBV DNA转阴率为72.7％ (16/22),而换用恩替卡韦单药治疗患者只有52.4％(11/21),两组差异也具有统计学意义(x2=4.865,P＜0.05).拉米夫定应答不佳者经加用阿德福韦酯联合治疗后48周无一例发生病毒学突破,也无耐药的发生；而换用恩替卡韦治疗组则有5例发生病毒学突破,3例检测到基因突变,其中2例为rtM204V、rtL180M和rtS202G变异,1例为rtM204V、rtL180M和rtT184A,所有发生基因突变的病例均为基线HBV DNA ＞105拷贝/mL者.结论拉米夫定应答不佳CHB患者加用阿德福韦酯比换用恩替卡韦单药治疗更能抑制HBV复制,且可减少病毒耐药的发生.
목적 비교랍미부정응답불가만성을형간염(CHB)환자가용아덕복위지연합치료여환용은체잡위단약치료48주료효.방법 채용전첨성연구방법관찰2010년6월-2011년6월재절강성제기시인민의원감염과화절강대학의학원부속제일의원접수랍미부정항병독치료24주이상,단HBV DNA잉양성적주원급문진CHB환자120례,이수궤수자표법장환자분위량조,매조각60례,일조재용랍미부정적기출상가용아덕복위지연합항병독치료,령일조칙환용은체잡위단약치료,료정균위48주.매1～3개월검측환자적간공능、신공능、갑태단백、HBV혈청학표지물、HBV DNA、응혈매원시간(PT)、간장적초성파혹행CT검사.채용x2검험비교치료48주시량조적병독학、혈청학적응답솔화내약발생솔,관찰량조적불량반응.결과 기선HBV DNA개우3～5 lg고패/mL적랍미부정응답불가자,가용아덕복위지치료지48주후유86.8％ (33/38)적환자HBV DNA전음,이환용은체잡위단약치료조유69.2％(27/39)적환자전음,량조비교차이구유통계학의의(x2=4.578,p＜0.05)；기선HBV DNA＞5lg고패/mL적랍미부정응답불가자,가용아덕복위지적환자HBV DNA전음솔위72.7％ (16/22),이환용은체잡위단약치료환자지유52.4％(11/21),량조차이야구유통계학의의(x2=4.865,P＜0.05).랍미부정응답불가자경가용아덕복위지연합치료후48주무일례발생병독학돌파,야무내약적발생；이환용은체잡위치료조칙유5례발생병독학돌파,3례검측도기인돌변,기중2례위rtM204V、rtL180M화rtS202G변이,1례위rtM204V、rtL180M화rtT184A,소유발생기인돌변적병례균위기선HBV DNA ＞105고패/mL자.결론 랍미부정응답불가CHB환자가용아덕복위지비환용은체잡위단약치료경능억제HBV복제,차가감소병독내약적발생.
Objective To compare the efficacy of add-on adefovir dipivoxil (ADV) therapy and switch-to entecavir (ETV) monotherapy in chronic hepatitis B (CHB) patients with suboptimal response to lamivudine (LAM).Methods A prospective study was performed in 120 CHB patients from Zhuji People' s Hospital and the First Affiliated Hospital of Zhejiang University School of Medicine during June 2010 and June 2011.All patients previously received more than 24 weeks LAM treatment,but HBV DNA was still positive.Patients were randomized assigned to two groups:60 patients received add-on ADV therapy and another 60 switched to ETV monotherapy.Both groups were treated for 48 weeks.Liver and kidney function,alpha-fetal protein (AFP),HBV serum markers,HBV DNA and prothrombin time (PT) were examined,and ultrasonography or CT scan of liver was performed every 1-3 months.x2 test was used to compare the HBV DNA negative rates,HBeAg seroconversion rates,resistance rates and adverse reaction at week 48 between two groups.Results Thirty-three out of 38 patients (86.8％) with baseline HBV DNA 103-105 copies/mL became HBV DNA negative after add-on ADV treatment for 48 weeks,twenty-seven out of 39 patients (69.2％) with baseline HBV DNA 103-105 copies/ml became HBV DNA negative after switch-to ETV treatment.There was a statistical difference between two groups (x2 =4.578,P ＜ 0.05).Sixteen out of 22 patients (72.7％) with baseline HBV DNA ＞ 105 copies/mL became HBV DNA negative after add-on ADV treatment for 48 weeks,while only 52.4％ (11/21) patients achieved HBV DNA negative in the switch-to ETV group.There was also a statistical difference between two groups (x2 =4.865,P ＜0.05).None of patients in add-on group developed virological breakthrough and resistance,while 5 patients in switch-to ETV group developed virogical breakthrough and 3 patients developed genetic mutation.Among them,rtM204V + rtL180M + rtS202G mutation was detected in 2 patients,and rtM204V + rtL180M +rtT184A mutation was detected in 1 patient; all mutations happened in the baseline HBV DNA ＞ 105 copies/mL group.Conclusion The add-on ADV therapy is better in viral inhibition than switch-to ETV therapy for CHB patients with suboptimal response to LAM,and it can reduce the occurrence of drug resistance.