肝炎,乙型,慢性%肝炎e抗原,乙型%干扰素α-2a%拉米夫定,阿德福韦酯%药物耐受
肝炎,乙型,慢性%肝炎e抗原,乙型%榦擾素α-2a%拉米伕定,阿德福韋酯%藥物耐受
간염,을형,만성%간염e항원,을형%간우소α-2a%랍미부정,아덕복위지%약물내수
Hepatitis B,chronic%Hepatitis B e antigens%Interferon alpha-2a%Lamivudine%Adefovir dipivoxil%Drug resistance
目的 观察rtN236T位点变异的阿德福韦酯(ADV)耐药HBeAg阳性的慢性乙型肝炎(CHB)患者,ADV分别联合聚乙二醇干扰素(Peg-IFN) α-2a及拉米夫定(LAM)进行治疗的疗效及安全性,并分析影响疗效的因素.方法 收集rtN236T位点变异的ADV耐药HBeAg阳性CHB患者65例,随机分为A组(33例)和B组(32例),A组ADV联合Peg-IFN α-2a治疗,连续48周后停用.B组ADV联合LAM治疗,连续48周后,继续使用24周.在治疗前、治疗后24、48周及随访24周,比较两组HBV DNA载量下降≥2log10拷贝/ml和HBV DNA≤500拷贝/ml患者数及HBeAg阴转率、HBeAg血清学转换率、ALT复常率.比较两组行肝穿刺活组织检查患者治疗前后的肝脏炎症分级、纤维化分期及肝组织学活动指数(HAI)评分.根据数据类型用t检验或x2检验进行统计分析.结果 治疗后24、48周及随访24周时,HBV DNA载量下降≥2log10拷贝/ml的患者,A组分别为81.8％、90.9％、75.8％,B组分别为53.1％、56.2％、59.4％;HBV DNA≤500拷贝/ml的患者,A组分别为48.5％、60.6％、42.4％,B组分别为31.3％、34.4％、31.3％;HBeAg阴转率,A组分别为39.4％、60.6％、54.5％,B组分别为12.5％、37.5％、37.5％;HBeAg血清学转换率,A组分别为27.3％、54.5％、48.5％,B组分别为6.3％、15.6％、18.8％;ALT复常率,A组分别为72.7％、84.8％、78.8％,B组分别为46.9％、56.3％、46.9％;A组均明显高于B组,差异有统计学意义(P值均＜0.05).治疗48周后,A组的肝组织HAI积分、炎症分级及纤维化分期改善情况均明显优于B组(P值均＜ 0.05).除肌酐升高发生率差异无统计学意义外,A组的不良反应发生率均高于B组(P值均＜ 0.05),但未发生终止治疗或危及患者安全的不良反应.A组停药随访24周,5例患者HBVDNA升高≥2log10拷贝/ml,其中4例治疗期间HBV DNA≤500拷贝/ml,此4例患者均发生ALT升高,且均未发生HBeAg血清学转换.结论 rtN236T位点变异的ADV耐药HBeAg阳性CHB患者,ADV联合Peg-IFN α-2a的疗效优于联合LAM,但不良反应发生率更高;未发生HBeAg血清学转换的患者,停药后易出现病毒反跳及ALT升高.
目的 觀察rtN236T位點變異的阿德福韋酯(ADV)耐藥HBeAg暘性的慢性乙型肝炎(CHB)患者,ADV分彆聯閤聚乙二醇榦擾素(Peg-IFN) α-2a及拉米伕定(LAM)進行治療的療效及安全性,併分析影響療效的因素.方法 收集rtN236T位點變異的ADV耐藥HBeAg暘性CHB患者65例,隨機分為A組(33例)和B組(32例),A組ADV聯閤Peg-IFN α-2a治療,連續48週後停用.B組ADV聯閤LAM治療,連續48週後,繼續使用24週.在治療前、治療後24、48週及隨訪24週,比較兩組HBV DNA載量下降≥2log10拷貝/ml和HBV DNA≤500拷貝/ml患者數及HBeAg陰轉率、HBeAg血清學轉換率、ALT複常率.比較兩組行肝穿刺活組織檢查患者治療前後的肝髒炎癥分級、纖維化分期及肝組織學活動指數(HAI)評分.根據數據類型用t檢驗或x2檢驗進行統計分析.結果 治療後24、48週及隨訪24週時,HBV DNA載量下降≥2log10拷貝/ml的患者,A組分彆為81.8％、90.9％、75.8％,B組分彆為53.1％、56.2％、59.4％;HBV DNA≤500拷貝/ml的患者,A組分彆為48.5％、60.6％、42.4％,B組分彆為31.3％、34.4％、31.3％;HBeAg陰轉率,A組分彆為39.4％、60.6％、54.5％,B組分彆為12.5％、37.5％、37.5％;HBeAg血清學轉換率,A組分彆為27.3％、54.5％、48.5％,B組分彆為6.3％、15.6％、18.8％;ALT複常率,A組分彆為72.7％、84.8％、78.8％,B組分彆為46.9％、56.3％、46.9％;A組均明顯高于B組,差異有統計學意義(P值均＜0.05).治療48週後,A組的肝組織HAI積分、炎癥分級及纖維化分期改善情況均明顯優于B組(P值均＜ 0.05).除肌酐升高髮生率差異無統計學意義外,A組的不良反應髮生率均高于B組(P值均＜ 0.05),但未髮生終止治療或危及患者安全的不良反應.A組停藥隨訪24週,5例患者HBVDNA升高≥2log10拷貝/ml,其中4例治療期間HBV DNA≤500拷貝/ml,此4例患者均髮生ALT升高,且均未髮生HBeAg血清學轉換.結論 rtN236T位點變異的ADV耐藥HBeAg暘性CHB患者,ADV聯閤Peg-IFN α-2a的療效優于聯閤LAM,但不良反應髮生率更高;未髮生HBeAg血清學轉換的患者,停藥後易齣現病毒反跳及ALT升高.
목적 관찰rtN236T위점변이적아덕복위지(ADV)내약HBeAg양성적만성을형간염(CHB)환자,ADV분별연합취을이순간우소(Peg-IFN) α-2a급랍미부정(LAM)진행치료적료효급안전성,병분석영향료효적인소.방법 수집rtN236T위점변이적ADV내약HBeAg양성CHB환자65례,수궤분위A조(33례)화B조(32례),A조ADV연합Peg-IFN α-2a치료,련속48주후정용.B조ADV연합LAM치료,련속48주후,계속사용24주.재치료전、치료후24、48주급수방24주,비교량조HBV DNA재량하강≥2log10고패/ml화HBV DNA≤500고패/ml환자수급HBeAg음전솔、HBeAg혈청학전환솔、ALT복상솔.비교량조행간천자활조직검사환자치료전후적간장염증분급、섬유화분기급간조직학활동지수(HAI)평분.근거수거류형용t검험혹x2검험진행통계분석.결과 치료후24、48주급수방24주시,HBV DNA재량하강≥2log10고패/ml적환자,A조분별위81.8％、90.9％、75.8％,B조분별위53.1％、56.2％、59.4％;HBV DNA≤500고패/ml적환자,A조분별위48.5％、60.6％、42.4％,B조분별위31.3％、34.4％、31.3％;HBeAg음전솔,A조분별위39.4％、60.6％、54.5％,B조분별위12.5％、37.5％、37.5％;HBeAg혈청학전환솔,A조분별위27.3％、54.5％、48.5％,B조분별위6.3％、15.6％、18.8％;ALT복상솔,A조분별위72.7％、84.8％、78.8％,B조분별위46.9％、56.3％、46.9％;A조균명현고우B조,차이유통계학의의(P치균＜0.05).치료48주후,A조적간조직HAI적분、염증분급급섬유화분기개선정황균명현우우B조(P치균＜ 0.05).제기항승고발생솔차이무통계학의의외,A조적불량반응발생솔균고우B조(P치균＜ 0.05),단미발생종지치료혹위급환자안전적불량반응.A조정약수방24주,5례환자HBVDNA승고≥2log10고패/ml,기중4례치료기간HBV DNA≤500고패/ml,차4례환자균발생ALT승고,차균미발생HBeAg혈청학전환.결론 rtN236T위점변이적ADV내약HBeAg양성CHB환자,ADV연합Peg-IFN α-2a적료효우우연합LAM,단불량반응발생솔경고;미발생HBeAg혈청학전환적환자,정약후역출현병독반도급ALT승고.
Objective To compare the efficacy and safety of the common antivirals,including adefovir dipivoxil (ADV),pegylated-interferon a-2a (peg-IFN) and lamivudine (LAM),used as combination therapies to treat chronic hepatitis B (CHB) patients with positivity for the hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV) harboring the ADV-resistanee mutation,rtN236T,and to explore the factors associated with curative outcome.Methods Sixty-five adult CHB patients (age range:20-60 years) who were unresponsive to ADV therapy (HBeAg-positive；HBV DNA ≥ 10s copies/ml),LAM-naive,and tested positive for the rtN236T HBV mutation were enrolled in the study and randomly divided into two treatment groups:Group A (n =33),who were administered ADV (10 mg/day,orally) plus peg-IFN (180 μg/week,subcutaneous injection) for 48 weeks；and Group B (n =32 patients),who received the ADV plus LAM (100 mg/day,orally) for 48 weeks followed by continued LAM treatment for an additional 24 weeks.Pre-(baseline),during and post-treatment measurements of HBV viral loads and hepatitis B markers were made by quantitative PCR and electrochemiluminescence assays,respectively.All patients underwent liver biopsies to determine the histological activity index (HAI) and treatment response regarding inflammation and fibrosis stage.The rates of virological response (VR),HBeAg-negativity,HBeAg seroconversion,and alanine aminotransferase (ALT) normalization were calculated,and the significance of differences between groups were assessed by Student's t-test and x2 test.Results There were no significant differences between the two groups in regards to sex,age,or baseline levels of HBV DNA,ALT,and total bilirubin (P ＞ 0.05).At weeks 24 and 48 of treatment and 24 after treatment end,group A showed significantly higher (vs.group B,P ＜ 0.05) rates of reduced HBV DNA viral loads (81.8％,90.9％,and 75.8％ vs.53.1％,56.2％,and 59.4％),VR (48.5％,60.6％,and 42.4％ vs.31.3％,34.4％,and 31.3％),HBeAg-negativity (39.4％,60.6％,and 54.5％ vs.12.5％,37.5％,and 37.5％),HBeAg seroconversion (27.3％,54.5％,and 48.5％ vs.6.3％,15.6％,and 18.8％),and ALT normalization (72.7％,84.8％,and 78.8％ vs.46.9％,56.3％,and 46.9％).After 48 weeks oftreatment,group A showed significantly improved HAI (vs.group B,P ＜ 0.05).With the exception of treatment-related increased creatinine (P ＜ 0.05),group A showed significantly higher rates of adverse reactions；although,none was serious enough to threaten patient safety or necessitate early termination of the treatment regimen.Twenty-four weeks after treatment completion,five patients had HBV viral loads of ≥ 2log10 copies/ml and four had ≤ 500 copies/ml,and ALT was normalized in 28 patients.The four patients in group A with HBV DNA ≤ 500 copies/ml and elevated ALT during treatment did not show HBeAg seroconversion.Conclusion Peg-IFN plus ADV combination therapy produced better outcomes than the ADV plus LAM combination therapy in regards to HBV viral loads,VR rate,HBeAg-negative rate,HBeAg seroconversion rate,ALT normalization rate,and HAI,but was associated with a higher rate of adverse reactions (none of which were severe).Lack of HBeAg seroconversion was associated with higher virus load and ALT levels.
