中华传染病杂志
中華傳染病雜誌
중화전염병잡지
CHINESE JOURNAL OF INFECTIOUS DISEASES
2013年
10期
608-612
,共5页
房建婷%纪永健%李菲菲%孙希珍%任万华
房建婷%紀永健%李菲菲%孫希珍%任萬華
방건정%기영건%리비비%손희진%임만화
肝炎,乙型,慢性%腺嘌呤%干扰素α-2a%聚乙烯二醇类%DNA,环状%DNA,病毒%肝炎e抗原,乙型
肝炎,乙型,慢性%腺嘌呤%榦擾素α-2a%聚乙烯二醇類%DNA,環狀%DNA,病毒%肝炎e抗原,乙型
간염,을형,만성%선표령%간우소α-2a%취을희이순류%DNA,배상%DNA,병독%간염e항원,을형
Hepatitis B,chronic%Adenine%Interferon alfa-2a%Polyethylene glycols%DNA,circular%DNA,viral%Hepatitis B e antigens
目的 探讨阿德福韦酯长期单药治疗后仍处于HBeAg低效价的慢性乙型肝炎患者,加用聚乙二醇干扰素α-2a治疗48周的疗效.方法 本研究为随机、开放、前瞻性的临床试验.将阿德福韦酯单药治疗72～144周仍处于低HBeAg效价(5 S/CO＜ HBeAg＜ 50 S/CO),且血清HBsAg定量＜5000 IU/mL的患者按随机数字表法分为单药组和加药组,单药组继续阿德福韦酯单药治疗48周,加药组加用聚乙二醇干扰素α-2a治疗48周,比较两组治疗前后血清HBeAg效价下降程度、阴转率、血清学转换率和肝组织HBV DNA、HBV共价闭合环状脱氧核糖核酸(cccDNA)载量的下降程度,对两种治疗方案进行疗效评估.患者治疗前后比较采用配对样本t检验,组间比较采用独立样本t检验,组间率的比较采用x2检验.结果 共纳入55例慢性乙型肝炎患者,单药组27例,加药组28例,两组患者年龄分布、性别比例、ALT、AST、TBil、血清HBeAg和HBsAg、肝组织HBV DNA和HBV cccDNA载量在基线水平比较差异均无统计学意义(均P＞0.05).治疗48周后,单药组完成试验25例,加药组26例.加药组HBeAg阴转率、血清转换率均高于单药组(x2值分别为5.38、4.69,均P＜0.05).两组HBeAg效价均较基线值下降(t值分别为8.43和8.50,均P＜0.01)；加药组HBeAg效价低于单药组(t＝5.60,P＜0.01).加药组治疗48周HBV DNA和HBV cccDNA载量分别为(6.93±0.52) lg IU/mg和(5.63±0.54)1g IU/mg,与基线值比较差异均有统计学意义(t值分别=7.12和6.67,均P＜0.01).单药组治疗48周HBV DNA载量为(7.09±0.43)1g IU/mg,与基线值比较差异有统计学意义(t=2.67,P＝0.02)；治疗后48周,加药组与单药组HBV cccDNA载量比较差异有统计学意义(t=2.87,P＝0.00).结论 经阿德福韦酯长期治疗后仍处于HBeAg低效价的慢性乙型肝炎患者,加用聚乙二醇干扰素α-2a,有利于提高血清HBeAg的阴转率和血清学转换率,并加速肝组织HBV DNA、HBV cccDNA的清除.
目的 探討阿德福韋酯長期單藥治療後仍處于HBeAg低效價的慢性乙型肝炎患者,加用聚乙二醇榦擾素α-2a治療48週的療效.方法 本研究為隨機、開放、前瞻性的臨床試驗.將阿德福韋酯單藥治療72～144週仍處于低HBeAg效價(5 S/CO＜ HBeAg＜ 50 S/CO),且血清HBsAg定量＜5000 IU/mL的患者按隨機數字錶法分為單藥組和加藥組,單藥組繼續阿德福韋酯單藥治療48週,加藥組加用聚乙二醇榦擾素α-2a治療48週,比較兩組治療前後血清HBeAg效價下降程度、陰轉率、血清學轉換率和肝組織HBV DNA、HBV共價閉閤環狀脫氧覈糖覈痠(cccDNA)載量的下降程度,對兩種治療方案進行療效評估.患者治療前後比較採用配對樣本t檢驗,組間比較採用獨立樣本t檢驗,組間率的比較採用x2檢驗.結果 共納入55例慢性乙型肝炎患者,單藥組27例,加藥組28例,兩組患者年齡分佈、性彆比例、ALT、AST、TBil、血清HBeAg和HBsAg、肝組織HBV DNA和HBV cccDNA載量在基線水平比較差異均無統計學意義(均P＞0.05).治療48週後,單藥組完成試驗25例,加藥組26例.加藥組HBeAg陰轉率、血清轉換率均高于單藥組(x2值分彆為5.38、4.69,均P＜0.05).兩組HBeAg效價均較基線值下降(t值分彆為8.43和8.50,均P＜0.01)；加藥組HBeAg效價低于單藥組(t＝5.60,P＜0.01).加藥組治療48週HBV DNA和HBV cccDNA載量分彆為(6.93±0.52) lg IU/mg和(5.63±0.54)1g IU/mg,與基線值比較差異均有統計學意義(t值分彆=7.12和6.67,均P＜0.01).單藥組治療48週HBV DNA載量為(7.09±0.43)1g IU/mg,與基線值比較差異有統計學意義(t=2.67,P＝0.02)；治療後48週,加藥組與單藥組HBV cccDNA載量比較差異有統計學意義(t=2.87,P＝0.00).結論 經阿德福韋酯長期治療後仍處于HBeAg低效價的慢性乙型肝炎患者,加用聚乙二醇榦擾素α-2a,有利于提高血清HBeAg的陰轉率和血清學轉換率,併加速肝組織HBV DNA、HBV cccDNA的清除.
목적 탐토아덕복위지장기단약치료후잉처우HBeAg저효개적만성을형간염환자,가용취을이순간우소α-2a치료48주적료효.방법 본연구위수궤、개방、전첨성적림상시험.장아덕복위지단약치료72～144주잉처우저HBeAg효개(5 S/CO＜ HBeAg＜ 50 S/CO),차혈청HBsAg정량＜5000 IU/mL적환자안수궤수자표법분위단약조화가약조,단약조계속아덕복위지단약치료48주,가약조가용취을이순간우소α-2a치료48주,비교량조치료전후혈청HBeAg효개하강정도、음전솔、혈청학전환솔화간조직HBV DNA、HBV공개폐합배상탈양핵당핵산(cccDNA)재량적하강정도,대량충치료방안진행료효평고.환자치료전후비교채용배대양본t검험,조간비교채용독립양본t검험,조간솔적비교채용x2검험.결과 공납입55례만성을형간염환자,단약조27례,가약조28례,량조환자년령분포、성별비례、ALT、AST、TBil、혈청HBeAg화HBsAg、간조직HBV DNA화HBV cccDNA재량재기선수평비교차이균무통계학의의(균P＞0.05).치료48주후,단약조완성시험25례,가약조26례.가약조HBeAg음전솔、혈청전환솔균고우단약조(x2치분별위5.38、4.69,균P＜0.05).량조HBeAg효개균교기선치하강(t치분별위8.43화8.50,균P＜0.01)；가약조HBeAg효개저우단약조(t＝5.60,P＜0.01).가약조치료48주HBV DNA화HBV cccDNA재량분별위(6.93±0.52) lg IU/mg화(5.63±0.54)1g IU/mg,여기선치비교차이균유통계학의의(t치분별=7.12화6.67,균P＜0.01).단약조치료48주HBV DNA재량위(7.09±0.43)1g IU/mg,여기선치비교차이유통계학의의(t=2.67,P＝0.02)；치료후48주,가약조여단약조HBV cccDNA재량비교차이유통계학의의(t=2.87,P＝0.00).결론 경아덕복위지장기치료후잉처우HBeAg저효개적만성을형간염환자,가용취을이순간우소α-2a,유리우제고혈청HBeAg적음전솔화혈청학전환솔,병가속간조직HBV DNA、HBV cccDNA적청제.
Objective To investigate the efficacy of sequential add-on of pegylated interferon α-2a (PEGIFN-α-2a) for 48 weeks in chronic hepatitis B (CHB) patients with low serum hepatitis B e antigen (HBeAg) titer after long term adefovir dipivoxil (ADV) monotherapy.Methods This was a randomized,open and prospective clinical trial.Patients who had been treated with ADV for 72 to 144 weeks,with undetectable serum hepatitis B virus (HBV) DNA level,low HBeAg titer (5 S/CO＜ HBeAg＜50 S/CO) and serum hepatitis B surface antigen (HBsAg) ＜5000 IU/mL were included.The patients were categorized into ADV monotherapy group and ADV plus PEGIFN-a-2a combination therapy group by random number table.Patients in ADV group continued ADV monotherapy and patients in combination therapy group added PEGIFN-α-2a to ADV for 48 weeks.After the treatment,efficacy of the two therapies were assessed by comparing the reduction of serum HBeAg reduction,HBeAg loss rate,HBeAg seroconversion rate,and reduction of intrahepatic HBV DNA and HBV covalently closed circular DNA (cccDNA).Pre-and post-treatment results were compared by paired samples t test.Comparison between groups was performed using indepedent samples t test.Comparison of rates between groups was performed using x2 test.Results The trial enrolled 55 CHB patients,and there were 27 patients in ADV monotherapy group,28 patients in combination therapy group.Baseline characteristics including age distribution,sex ratio,alanine aminotransferase (ALT),aspartate aminotransferase (AST),total bilirubin (TBil),serum HBeAg and HBsAg,hepatic HBV DNA and HBV cccDNA were all comparable (all P＞0.05).Twenty-five patients in ADV monotherapy group and 26 patients in combination therapy group completed 48 weeks treatment.HBeAg loss rates and seroconversion rates of combination therapy group were higher than those of ADV monotherapy group (x2 =5.38 and 4.69,respectively,both P＜0.05).HBeAg titers of both groups were significantly lower than those of baseline (t=8.43 and 8.50,respectively,both P＜0.05).The HBeAg titer of combination therapy group was lower than that of monotherapy group (t=5.60,P＜ 0.01).HBV DNA and HBV cccDNA in liver tissue of combination therapy group was (6.934±0.52) lg IU/mg and (5.63±0.54) lg IU/mg post-treatment,respectively,which were both lower than baseline (t＝7.12.6.67,respectively,both P＜0.01).HBV DNA in liver tissue of monotherapy group was (7.09＝0.43) lg IU/mg post-treatment,which was lower than baseline (t=2.67,P=0.02).After treatment,HBV cccDNA in liver tissue of combination therapy group was lower than that of monotherapy group (t =2.87,P=0.00).Conclusions Compared with ADV monotherapy,sequential add-on of PEGIFN-a-2a in combination with ADV can achieve higher serum HBeAg loss rate and seroconversion rate and facilitate the clearance of hepatic HBV DNA and HBV cccDNA in CHB patients with low HBeAg titer after long-term ADV monotherapy.
