中华传染病杂志
中華傳染病雜誌
중화전염병잡지
CHINESE JOURNAL OF INFECTIOUS DISEASES
2008年
10期
597-603
,共7页
陈新月%马丽娜%陶明玲%吴亚松%马冰%张立洁%李海英%黄云丽%张永宏%汪俊韬%李宁
陳新月%馬麗娜%陶明玲%吳亞鬆%馬冰%張立潔%李海英%黃雲麗%張永宏%汪俊韜%李寧
진신월%마려나%도명령%오아송%마빙%장립길%리해영%황운려%장영굉%왕준도%리저
肝炎e抗原,乙型%肝炎,乙型,慢性%干扰素类%聚乙二醇类%核苷酸类%抗病毒药%肝炎表面抗原,乙型
肝炎e抗原,乙型%肝炎,乙型,慢性%榦擾素類%聚乙二醇類%覈苷痠類%抗病毒藥%肝炎錶麵抗原,乙型
간염e항원,을형%간염,을형,만성%간우소류%취을이순류%핵감산류%항병독약%간염표면항원,을형
HBeAg%Hepatitis B,chronic%Interferons%Polyethylene glycols%Nucleosides%Antiviral agents%HBsAg
目的 探讨使用IFN和核苷(酸)类似物联合治疗HBeAg阳性慢性乙型肝炎获得HBsAg血清转换患者的临床特点和作用机制.方法 收集2001年1月至2007年5月使用IFN和拉米夫定或阿德福韦酯联合治疗后出现HBsAg转换的慢性乙型肝炎患者共32例,转阴后定期随访并分析其临床特点.结果 HBV DNA于治疗后3～6个月转阴,初治和复治(包括拉米夫定耐药)患者治疗2年均未见病毒学反弹或新的临床耐药出现.HBsAg转换后平均随访13.2个月,2例出现HBsAg复阳,其中1例抗病毒治疗重新获得HBsAg转换,另1例未再治疗,维持在HBeAg转换状态.余30例患者均维持在HBsAg转换状态.7例治疗后(其中3例治疗前、后两次)行肝穿刺病理和免疫组织化学检查.6例肝内HBsAg及HBcAg均阴性,1例HBsAg免疫组织化学阳性者复发;3例治疗前、后对比肝组织炎性反应和纤维化程度均减轻,其中1例由G2S4变为G1S2～3,该例停用IFN后ALT仍异常,余4例有轻度炎性反应和纤维化.转阴模式有三种,转阴顺序为HBV DNA→HBeAg→HBsAg,占59%(19/32例);HBeAg和HBsAg同步转阴,占31%(10/32例);HBsAg先于HBeAg转阴,占9%(3/32例).治疗1年时血清HBsAg滴度71.4%(15/21例)<100 COI;63.6%(7/11例)<250 IU/L.联合治疗的不良反应基本上同IFN单药治疗.结论 联合治疗和延长疗程是获得HBsAg血清转换的关键.肝组织内HBsAg阳性和血清抗-HBs低水平者易复发.疗程1年时血清HBsAg滴度<100 COI或<250 IU/L可能是HBsAg易转阴的预测指标.
目的 探討使用IFN和覈苷(痠)類似物聯閤治療HBeAg暘性慢性乙型肝炎穫得HBsAg血清轉換患者的臨床特點和作用機製.方法 收集2001年1月至2007年5月使用IFN和拉米伕定或阿德福韋酯聯閤治療後齣現HBsAg轉換的慢性乙型肝炎患者共32例,轉陰後定期隨訪併分析其臨床特點.結果 HBV DNA于治療後3～6箇月轉陰,初治和複治(包括拉米伕定耐藥)患者治療2年均未見病毒學反彈或新的臨床耐藥齣現.HBsAg轉換後平均隨訪13.2箇月,2例齣現HBsAg複暘,其中1例抗病毒治療重新穫得HBsAg轉換,另1例未再治療,維持在HBeAg轉換狀態.餘30例患者均維持在HBsAg轉換狀態.7例治療後(其中3例治療前、後兩次)行肝穿刺病理和免疫組織化學檢查.6例肝內HBsAg及HBcAg均陰性,1例HBsAg免疫組織化學暘性者複髮;3例治療前、後對比肝組織炎性反應和纖維化程度均減輕,其中1例由G2S4變為G1S2～3,該例停用IFN後ALT仍異常,餘4例有輕度炎性反應和纖維化.轉陰模式有三種,轉陰順序為HBV DNA→HBeAg→HBsAg,佔59%(19/32例);HBeAg和HBsAg同步轉陰,佔31%(10/32例);HBsAg先于HBeAg轉陰,佔9%(3/32例).治療1年時血清HBsAg滴度71.4%(15/21例)<100 COI;63.6%(7/11例)<250 IU/L.聯閤治療的不良反應基本上同IFN單藥治療.結論 聯閤治療和延長療程是穫得HBsAg血清轉換的關鍵.肝組織內HBsAg暘性和血清抗-HBs低水平者易複髮.療程1年時血清HBsAg滴度<100 COI或<250 IU/L可能是HBsAg易轉陰的預測指標.
목적 탐토사용IFN화핵감(산)유사물연합치료HBeAg양성만성을형간염획득HBsAg혈청전환환자적림상특점화작용궤제.방법 수집2001년1월지2007년5월사용IFN화랍미부정혹아덕복위지연합치료후출현HBsAg전환적만성을형간염환자공32례,전음후정기수방병분석기림상특점.결과 HBV DNA우치료후3～6개월전음,초치화복치(포괄랍미부정내약)환자치료2년균미견병독학반탄혹신적림상내약출현.HBsAg전환후평균수방13.2개월,2례출현HBsAg복양,기중1례항병독치료중신획득HBsAg전환,령1례미재치료,유지재HBeAg전환상태.여30례환자균유지재HBsAg전환상태.7례치료후(기중3례치료전、후량차)행간천자병리화면역조직화학검사.6례간내HBsAg급HBcAg균음성,1례HBsAg면역조직화학양성자복발;3례치료전、후대비간조직염성반응화섬유화정도균감경,기중1례유G2S4변위G1S2～3,해례정용IFN후ALT잉이상,여4례유경도염성반응화섬유화.전음모식유삼충,전음순서위HBV DNA→HBeAg→HBsAg,점59%(19/32례);HBeAg화HBsAg동보전음,점31%(10/32례);HBsAg선우HBeAg전음,점9%(3/32례).치료1년시혈청HBsAg적도71.4%(15/21례)<100 COI;63.6%(7/11례)<250 IU/L.연합치료적불량반응기본상동IFN단약치료.결론 연합치료화연장료정시획득HBsAg혈청전환적관건.간조직내HBsAg양성화혈청항-HBs저수평자역복발.료정1년시혈청HBsAg적도<100 COI혹<250 IU/L가능시HBsAg역전음적예측지표.
Objective To study clinical features and mechanism in patients suffered from chronic hepatitis B achieving seroconversion of HBsAg by combination treatment with interferon (IFN) and nucleoside analogue (NA). Methods Thirty-two cases with chronic HBV hepatitis were enrolled into this retrospective study. All of them received combination treatment with IFN and Lamivudine/Adefovir, as well as achieved seroconversion of HBsAg from June, 2001 to May, 2007. All the cases in this study were followed up. Results Generally, serum HBV DNA fell below the detection limit 3 to 6 months after starting combination treatment. Virological breakthrough/relapse or new clinical resistant had not been found in all enrolments after combination treatment, including patients with previous resistant to Lamivudine, although the average length of treatment was over 2 years. The average period of following up after seroconversion of HBsAg was 13.2 months. Two cases transfered back to HBsAg positive, one of them achieved seroconversion of HBsAg again by the anti-virus treatment, and the other one gave up treatment and remained anti-HBe positive and HBeAg negative.The other 30 eases kept at the stage of seroconversion of HBsAg. Seven patients underwent liver biopsy after seroconversion of HBsAg, and 3 of them had taken liver biopsy before combination therapy too. Biopsy specimens were scored for fibrosis and neeroinflammation according to the Knodell histological activity index. Six cases showed HBsAg and HBcAg negative by immunohistochemistry,and only 1 case with HBsAg positive in liver tissue experienced relapse. Inflammation and fibrosis grade of the 3 cases who had taken liver biopsy twice were lowered after HBsAg seroconversion,although the ALT level of 1 case who had turned from G2S4 to GIS2-3 remained abnormal after HBsAg seroconversion. According to the sequence and character of HBsAg seroconversion, there were three models of HBsAg conversion. The sequence of transition was HBV DNA→HBeAg→HBsAg,which was dominant one, accounting for 59%(19/32 cases). HBV DNA negative, and the titer of HBeAg wandering at a low level, after then HBeAg and HBsAg change to negative in the same time,31% (10/32 cases). The titer of HBsAg decreased rapidly after the HBV DNA clearance, and the HBsAg clearance was earlier than HBeAg, 9% (3/32 cases). After 1 year of combination therapy,there were 15 of 21 cases (71.4%) whose titer HBsAg showed less than 100 COI by agent from Roche, and 7 of 11 cases (63.6%) whose titer HBsAg showed less than 250 IU/L by agent from Abbott. The frequency of adverse reaction was similar with that induced by IFN monotherapy, and no new adverse reaction was found. Conclusions Combination therapy and long course treatment might be the key to achieve the HBsAg seroconversion. Those with HBsAg in liver tissue and (or) low serum anti-HBs are more likely to relapse. The titer of HbsAg<100 COI (Roche, Germany) or<250 IU/L (Abbott, USA) after one year treatment may be regarded as a predict index of HBsAg seroconversion.
