中华肝脏病杂志
中華肝髒病雜誌
중화간장병잡지
CHINESE JOURNAL OF HEPATOLOGY
2012年
11期
801-806
,共6页
郑琦%朱月永%陈靖%刘豫瑞%游佳%曾达武%林苏%江家骥
鄭琦%硃月永%陳靖%劉豫瑞%遊佳%曾達武%林囌%江傢驥
정기%주월영%진정%류예서%유가%증체무%림소%강가기
肝炎,乙型,慢性%肝炎抗原,乙型%T淋巴细胞%调节性T细胞%自然杀伤细胞
肝炎,乙型,慢性%肝炎抗原,乙型%T淋巴細胞%調節性T細胞%自然殺傷細胞
간염,을형,만성%간염항원,을형%T림파세포%조절성T세포%자연살상세포
Hepatitis B,chronic%HBeAg%Tlymphocyte%Regulate Tlymphocyte%Natural kill cell
目的 动态观察阿德福韦酯治疗HBeAg阳性慢性乙型肝炎患者外周血HBV特异性T淋巴细胞功能和非特异性免疫细胞的改变,探讨其与HBeAg血清学阴转的相关性；以进一步探讨抗病毒治疗的免疫机制. 方法 20例HBeAg阳性慢性乙型肝炎患者予以阿德福韦酯治疗48周,酶联免疫斑点试验检测分泌干扰素γ的HBV特异性CD4+T淋巴细胞频数,流式细胞术检测调节性T淋巴细胞(Treg)数量和自然杀伤细胞活化受体NKG2D的表达.根据资料不同采用t检验或Mann-Whitney U检验进行统计学分析. 结果 治疗48周时有6例(占30％)患者出现HBeAg的阴转,分为HBeAg阴转组(n=6)和HBeAg未阴转组(n=14).伴随病毒载量的下降,HBeAg阴转组治疗后HBcAg特异性CD4+T淋巴细胞分泌IFN γ和细胞增殖的能力均较治疗前增强,同时也较HBeAg未阴转组增强,48周时(外周血单核细胞中的斑点形成细胞数)的(661.25±281.97)×10-6对比0周时的(280.75±104.33)×10-6,P=0.045,差异有统计学意义;而HBeAg未阴转组治疗前后无改变.同时Treg数量逐渐下降,4周后趋于稳态；而NKG2D在治疗后12周开始持续上升,48周较基线值显著增加(P=0.000).Treg和NKG2D的表达趋势在HBeAg阴转组和未阴转组间差异无统计学意义. 结论 阿德福韦酯抗病毒治疗过程,伴随病毒负荷下降,部分患者HBV特异性T淋巴细胞功能呈一过性增强,与HBeAg阴转密切相关；进一步证实HBV特异性T淋巴细胞功能的恢复是清除病毒,促进HBeAg血清学转换的重要因素.
目的 動態觀察阿德福韋酯治療HBeAg暘性慢性乙型肝炎患者外週血HBV特異性T淋巴細胞功能和非特異性免疫細胞的改變,探討其與HBeAg血清學陰轉的相關性；以進一步探討抗病毒治療的免疫機製. 方法 20例HBeAg暘性慢性乙型肝炎患者予以阿德福韋酯治療48週,酶聯免疫斑點試驗檢測分泌榦擾素γ的HBV特異性CD4+T淋巴細胞頻數,流式細胞術檢測調節性T淋巴細胞(Treg)數量和自然殺傷細胞活化受體NKG2D的錶達.根據資料不同採用t檢驗或Mann-Whitney U檢驗進行統計學分析. 結果 治療48週時有6例(佔30％)患者齣現HBeAg的陰轉,分為HBeAg陰轉組(n=6)和HBeAg未陰轉組(n=14).伴隨病毒載量的下降,HBeAg陰轉組治療後HBcAg特異性CD4+T淋巴細胞分泌IFN γ和細胞增殖的能力均較治療前增彊,同時也較HBeAg未陰轉組增彊,48週時(外週血單覈細胞中的斑點形成細胞數)的(661.25±281.97)×10-6對比0週時的(280.75±104.33)×10-6,P=0.045,差異有統計學意義;而HBeAg未陰轉組治療前後無改變.同時Treg數量逐漸下降,4週後趨于穩態；而NKG2D在治療後12週開始持續上升,48週較基線值顯著增加(P=0.000).Treg和NKG2D的錶達趨勢在HBeAg陰轉組和未陰轉組間差異無統計學意義. 結論 阿德福韋酯抗病毒治療過程,伴隨病毒負荷下降,部分患者HBV特異性T淋巴細胞功能呈一過性增彊,與HBeAg陰轉密切相關；進一步證實HBV特異性T淋巴細胞功能的恢複是清除病毒,促進HBeAg血清學轉換的重要因素.
목적 동태관찰아덕복위지치료HBeAg양성만성을형간염환자외주혈HBV특이성T림파세포공능화비특이성면역세포적개변,탐토기여HBeAg혈청학음전적상관성；이진일보탐토항병독치료적면역궤제. 방법 20례HBeAg양성만성을형간염환자여이아덕복위지치료48주,매련면역반점시험검측분비간우소γ적HBV특이성CD4+T림파세포빈수,류식세포술검측조절성T림파세포(Treg)수량화자연살상세포활화수체NKG2D적표체.근거자료불동채용t검험혹Mann-Whitney U검험진행통계학분석. 결과 치료48주시유6례(점30％)환자출현HBeAg적음전,분위HBeAg음전조(n=6)화HBeAg미음전조(n=14).반수병독재량적하강,HBeAg음전조치료후HBcAg특이성CD4+T림파세포분비IFN γ화세포증식적능력균교치료전증강,동시야교HBeAg미음전조증강,48주시(외주혈단핵세포중적반점형성세포수)적(661.25±281.97)×10-6대비0주시적(280.75±104.33)×10-6,P=0.045,차이유통계학의의;이HBeAg미음전조치료전후무개변.동시Treg수량축점하강,4주후추우은태；이NKG2D재치료후12주개시지속상승,48주교기선치현저증가(P=0.000).Treg화NKG2D적표체추세재HBeAg음전조화미음전조간차이무통계학의의. 결론 아덕복위지항병독치료과정,반수병독부하하강,부분환자HBV특이성T림파세포공능정일과성증강,여HBeAg음전밀절상관；진일보증실HBV특이성T림파세포공능적회복시청제병독,촉진HBeAg혈청학전환적중요인소.
Objective To observe the changes in hepatitis B virus (HBV)-specific and non-specific cellular immunity that accompany viral load decline during adefovir dipivoxil (ADV) treatment in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B,and to explore the antiviral immunity mechanism underlying the treatment response.Methods Serial analysis of cellular immunological parameters was performed in HBeAg-positive patients (n =20) throughout the 48-week course of ADV therapy (10 mg/d).HBV-specific T cell reactivity to HBV core antigen (HBcAg) was assessed by enzymelinked immunosorbent spot assay and cell proliferation assay at pre-treatment (baseline) and post-treatment weeks 4,12,24,36,and 48.Percentage of regulatory T cells (Tregs),as well as activated peripheral natural killer (NK) cells (expressing the NKG2D receptor),was measured by flow cytometry.Comparisons of means were performed by the two-tailed t-test or the Mann-Whitney rank sum test.Results After 48 weeks of ADV therapy,HBeAg loss was observed in six of the 20 (30％) patients and 14 patients remained HBeAg-positive.In the patients with HBeAg loss,the viral load reduction was accompanied by a significantly enhanced response rate of HBV-specific interferon (IFN)-gamma-producing CD4+ T cells [measured as (spot forming cells/peripheral blood mononuclear cells); baseline:(661.25 ± 281.97) × 10-6 vs.week 48:(280.75 ± 104.33) ×10-6,P =0.045].In contrast,patients without HBeAg loss showed no significant differences in T cell response rates.The patient groups with and without HBeAg loss showed similar proportions of peripheral blood Tregs during the treatment course,which included a trend of gradual decrease from baseline to week 4 with steady levels thereafter.In addition,both groups showed a similar increase in NKG2D expression that began at week 12 and peaked at week 48.Conclusion HBV-specific T cell reactivity temporally increases in some ADV-treated chronic hepatitis B patients,and this trend is strongly associated with HBeAg loss.Furthermore,recovery of HBV-specific T cell reactivity promotes viral clearance and HBeAg seroconversion.
