临床肝胆病杂志
臨床肝膽病雜誌
림상간담병잡지
CHINESE JOURNAL OF CLINICAL HEPATOLOGY
2015年
4期
530-533
,共4页
王少扬%林涛发%刘海周%马卫闽%谢志红
王少颺%林濤髮%劉海週%馬衛閩%謝誌紅
왕소양%림도발%류해주%마위민%사지홍
肝炎,乙型,慢性%细胞因子类%杀伤细胞%恩替卡韦
肝炎,乙型,慢性%細胞因子類%殺傷細胞%恩替卡韋
간염,을형,만성%세포인자류%살상세포%은체잡위
hepatitis B,chronic%cytokines%killer cells%entecavir
目的:观察自体细胞因子诱导的杀伤细胞(CIK)治疗慢性乙型肝炎(CHB)患者的疗效及安全性,探索CHB治疗的新策略。方法收集2009年12月1日至2012年12月1日南京军区福州总医院收治的84例CHB患者,称为CIK治疗组,采集其外周血单个核细胞,在体外经干扰素γ、白细胞介素2、抗CD3单克隆抗体等细胞因子诱导成CIK,分次自体回输,观察治疗前及治疗后12、24、48周患者肝功能、HBV血清标志物变化及HBV DNA水平;50例接受恩替卡韦(ETV)治疗的患者作为对照组,称为ETV治疗组。将两组HBeAg阳性和HBeAg阴性患者分组进行比较分析,同时对不良反应和肾功能进行评估。计量资料组间比较采用t检验,计数资料组间比较采用χ2检验。结果随着观察时间延长,CIK治疗组无论是HBeAg阳性患者还是HBeAg阴性患者,其ALT水平均降低,其中HBeAg阳性患者治疗12、24周时与ETV治疗组相比,两组差异均具有统计学意义(t值分别为5.03、4.72,P值均<0.01);CIK治疗组在不同时间点的HBeAg阴转率和血清转换率均高于ETV治疗组,其中治疗24周和48周时两组间的HBeAg阴转率差异均有统计学意义(χ2值分别为6.85、4.83,P值均<0.05)。无论是HBeAg阳性还是HBeAg阴性,在治疗12、24、48周后,CIK治疗组的HBV DNA阴转率均低于ETV组,尤其两组HBeAg阳性患者的HBV DNA阴转率差异均有统计学意义(χ2值分别为45.62、26.89、12.54,P值均<0.01),但随着观察时间延长,CIK治疗组HBV DNA阴转率逐渐升高。结论 CIK治疗CHB后在48周随访观察期内是安全有效的。虽然与ETV治疗相比,HBV DNA下降水平较低,但治疗后随着观察时间的延长,HBeAg阴转率和血清转换率明显高于ETV治疗组,提示CIK治疗后可能存在持久的免疫应答效应。
目的:觀察自體細胞因子誘導的殺傷細胞(CIK)治療慢性乙型肝炎(CHB)患者的療效及安全性,探索CHB治療的新策略。方法收集2009年12月1日至2012年12月1日南京軍區福州總醫院收治的84例CHB患者,稱為CIK治療組,採集其外週血單箇覈細胞,在體外經榦擾素γ、白細胞介素2、抗CD3單剋隆抗體等細胞因子誘導成CIK,分次自體迴輸,觀察治療前及治療後12、24、48週患者肝功能、HBV血清標誌物變化及HBV DNA水平;50例接受恩替卡韋(ETV)治療的患者作為對照組,稱為ETV治療組。將兩組HBeAg暘性和HBeAg陰性患者分組進行比較分析,同時對不良反應和腎功能進行評估。計量資料組間比較採用t檢驗,計數資料組間比較採用χ2檢驗。結果隨著觀察時間延長,CIK治療組無論是HBeAg暘性患者還是HBeAg陰性患者,其ALT水平均降低,其中HBeAg暘性患者治療12、24週時與ETV治療組相比,兩組差異均具有統計學意義(t值分彆為5.03、4.72,P值均<0.01);CIK治療組在不同時間點的HBeAg陰轉率和血清轉換率均高于ETV治療組,其中治療24週和48週時兩組間的HBeAg陰轉率差異均有統計學意義(χ2值分彆為6.85、4.83,P值均<0.05)。無論是HBeAg暘性還是HBeAg陰性,在治療12、24、48週後,CIK治療組的HBV DNA陰轉率均低于ETV組,尤其兩組HBeAg暘性患者的HBV DNA陰轉率差異均有統計學意義(χ2值分彆為45.62、26.89、12.54,P值均<0.01),但隨著觀察時間延長,CIK治療組HBV DNA陰轉率逐漸升高。結論 CIK治療CHB後在48週隨訪觀察期內是安全有效的。雖然與ETV治療相比,HBV DNA下降水平較低,但治療後隨著觀察時間的延長,HBeAg陰轉率和血清轉換率明顯高于ETV治療組,提示CIK治療後可能存在持久的免疫應答效應。
목적:관찰자체세포인자유도적살상세포(CIK)치료만성을형간염(CHB)환자적료효급안전성,탐색CHB치료적신책략。방법수집2009년12월1일지2012년12월1일남경군구복주총의원수치적84례CHB환자,칭위CIK치료조,채집기외주혈단개핵세포,재체외경간우소γ、백세포개소2、항CD3단극륭항체등세포인자유도성CIK,분차자체회수,관찰치료전급치료후12、24、48주환자간공능、HBV혈청표지물변화급HBV DNA수평;50례접수은체잡위(ETV)치료적환자작위대조조,칭위ETV치료조。장량조HBeAg양성화HBeAg음성환자분조진행비교분석,동시대불량반응화신공능진행평고。계량자료조간비교채용t검험,계수자료조간비교채용χ2검험。결과수착관찰시간연장,CIK치료조무론시HBeAg양성환자환시HBeAg음성환자,기ALT수평균강저,기중HBeAg양성환자치료12、24주시여ETV치료조상비,량조차이균구유통계학의의(t치분별위5.03、4.72,P치균<0.01);CIK치료조재불동시간점적HBeAg음전솔화혈청전환솔균고우ETV치료조,기중치료24주화48주시량조간적HBeAg음전솔차이균유통계학의의(χ2치분별위6.85、4.83,P치균<0.05)。무론시HBeAg양성환시HBeAg음성,재치료12、24、48주후,CIK치료조적HBV DNA음전솔균저우ETV조,우기량조HBeAg양성환자적HBV DNA음전솔차이균유통계학의의(χ2치분별위45.62、26.89、12.54,P치균<0.01),단수착관찰시간연장,CIK치료조HBV DNA음전솔축점승고。결론 CIK치료CHB후재48주수방관찰기내시안전유효적。수연여ETV치료상비,HBV DNA하강수평교저,단치료후수착관찰시간적연장,HBeAg음전솔화혈청전환솔명현고우ETV치료조,제시CIK치료후가능존재지구적면역응답효응。
Objective To evaluate the safety and efficacy of autologous cytokine-induced killer (CIK)cells in the treatment of patients with chronic hepatitis B (CHB),and to investigate a new therapeutic strategy for CHB.Methods Peripheral blood mononuclear cells were isolated from 84 patients with CHB,and then induced to CIK cells in vitro with cytokines such as interferon-γ,interleukin-2,and mono-clonal antibody against CD3.The autologous CIK cells obtained were infused back into the individual patient.Liver function parameters,se-rum markers,and HBV DNA levels were evaluated before treatment and at 12,24,and 48 weeks after treatment.Fifty patients who received entecavir (ETV)treatment were used as controls.Comparison was made between HBeAg-positive patients and HBeAg-negative patients. Adverse reactions and kidney function were evaluated.Comparison of continuous data between the two groups was made by t test,and com-parison of categorical data was made by chi-square test.Results The alanine aminotransferase (ALT)levels in both HBeAg-positive pa-tients and HBeAg-negative patients in the treatment group decreased as the observation time went on.HBeAg -positive patients in the treatment group had significant lower ALT levels than those in the control group at 12 and 24 weeks after treatment (t=5.03,P<0.01;t=4.72,P<0.01).The treatment group had higher HBeAg clearance rate and seroconversion rate than the control group at each time point. Particularly,there were significant differences in HBeAg clearance rates at 24 and 48 weeks after treatment between the two groups (χ2 =6.85,P<0.05;χ2 =4.83,P<0.05).Both HBeAg-positive patients and HBeAg-negative patients in the treatment group had higher HBV DNA levels and lower incidence rates of undetectable HBV DNA level than those in the control group.However,as the observation time went on,the HBV DNA copy level gradually decreased,and the HBV DNA clearance rate gradually increased in the treatment group.Conclusion The therapy with autologous CIK cells is safe and effective in patients with CHB during 48 weeks after treatment.In spite of a lower HBV DNA clearance rate,this therapy results in higher HBeAg clearance rate and seroconversion rate than ETV therapy as the observation time goes on,which suggests a probably sustainable immune response after treatment with autologous CIK cells.