慢性乙型肝炎患者干扰素α受体1基因启动子多态性和干扰素应答的关系

目的 探讨慢性乙型肝炎患者的Ⅰ型干扰素受体1(IFNAR1)基因启动子多态性和IFN-α治疗应答之间的关系.方法 选择接受IFN-α治疗的慢性乙型肝炎患者61例,采用重组IFN-α2b 500万U,隔天肌内注射,疗程48周,观察应答情况,对入选患者的IFNAR1基因启动子区进行测序,计量资料采用t检验,计数资料采用卡方检验.结果 治疗的慢性乙型肝炎患者中,完全应答22例,部分应答8例,无应答31例.IFNAR1基因启动子区一408C/T、-3C/T、-77GT双核苷酸重复序列[-77(GT),]存在基因多态性,这三个位点基因多态性存在连锁,形成-408C/-77(GT)5/-3C等基因单体型.IFNAR1启动子区基因型为-408C/-77(GT)5/-3C及-408C/-77(GT)5/-3C的,基因型为-408C/-77(GT)5/-3C和非-408C/-77(GT)5/-3C的慢性乙型肝炎患者对IFN-α的应答率为61.0%,高于基因型为非-408C/-77(GT)5/-3C,非-408C/-77(GT)5/-3C患者的25.0%(X2=6.961,P=0.008).结论 IFNAR1启动子基因型为-408C/-77(GT)5/-3C及-408C/-77(GT)5/-3C的,-408C/-77(GT)5/-3C和非-408C/-77(GT)5/-3C的慢性乙型肝炎患者对IFN-α治疗应答较好,IFNAR1基因启动子多态性与慢性乙型肝炎患者的干扰素应答有关.     

干扰素联用苦参素治疗慢性乙型肝炎的疗效观察

目的观察干扰素联用苦参素治疗慢性乙型肝炎的疗效。方法设置观察组和对照组，观察组用塞诺金（a2b干扰素）和博尔泰力联用，对照组单用干扰素。结果治疗6个月和1年后复查，观察组HBV-DNA及HBeAg阴转率均明显高于对照组（P〈0．01）。结论提示干扰素联用苦参素治疗慢性乙型肝炎有协同作用，值得在临床推广使用。     

聚乙二醇化干扰素α-2a治疗慢性乙型肝炎的临床研究

目的评价聚乙二醇化干扰素（PEG-IFN）α-2a治疗慢性乙型肝炎（CHB）的疗效和安全性。方法72例CHB患者随机分配到治疗组和对照组。治疗组（30例）予PEG-IFN α-2a 180μg皮下注射，每周1次，疗程48周。对照组（42例）予普通干扰素500 MU，皮下注射，隔日1次，疗程48周，治疗结束后随访48周。结果治疗12周时，治疗组乙型肝炎e抗原（HBeAg）的阴转率达到30％，明显高于对照组，x^2=4．162，P〈0．05，HBeAg定量及乙型肝炎病毒（HBV DNA）定量对数值明显低于治疗前水平，t值分别为2．689、4．080，P〈0．01，而对照组治疗12周时与治疗前相比，差异无统计学意义，t值分别为1．229、1．009，P〉0．05；治疗24周时，治疗组乙型肝炎e抗原（HBeAg）阴转率明显高于对照组，x^2=6．190，P〈0．05，HBeAg定量和HBV DNA定量的对数值均明显低于对照组，t值分别为2．215、2．122，P〈0．05；治疗48周时，治疗组除上述观察指标优于对照组外，HBeAg／抗-HBe血清转换率、丙氨酸氨基转移酶的复常率及完全应答率也明显高于对照组，x^2值分别为5．771、5、617、5、308，P〈0.05；治疗结束后随访48周时，治疗组HBeAg的阴转率、HBeAg定量、HBV DNA定量对数值、HBeAg／抗-HBe血清转换率、丙氨酸氨基转移酶的复常率及完全应答率均明显优于对照组，分别为x^2=11．943、t=3、439、f=6、111、x^2=9．930、x^2=9、522、x^2=7．920，P值均〈0．01，而且保持持续应答，而对照组的应答率则有所下降；治疗组9例患者于治疗前后做2次肝活组织检查，治疗前肝组织中的乙型肝炎表面抗原及核心抗原阳性率分别为88、89％和66、67％，治疗结束时分别为22．22％和33、33％，乙型肝炎表面抗原较治疗前明显减少，x^2=8、001，P〈0、01；治疗前后肝组织的炎症活动度、纤维化程度及胶原表达无明显差异。治疗组有3例出现HBsAg阴转，阴转率为10％，其中2例出现在治疗后32周，1例出现在治疗结束后24周，对照组无一例阴转。PEG-IFNα-2a的不良反应与对照组相似。结论PEG-IFNα-2a治疗慢性乙型肝炎能有效地抑制其病毒复制，且能持续应答，治疗48周内安全且耐受性良好。     

干扰素治疗慢性乙型肝炎的疗效预测及影响因素

IFNα是目前国际公认的治疗CHB的有效药物之一。CHB患者在IFNα治疗6～12个月后,ALT复常率为34%～45%,HBeAg消失和(或)抗-HBe出现率为15%～37%,HBV DNA阴转率(<105拷贝/ml)为37%,HBsAg阴转率为1%～8%。导致CHB患者在IFN治疗后取得持续性应答、部分应答或者无应答的原因是临床和基础研究非常关心的问题,现就IFN疗效的预测和影响因素作简要综述。     

干扰素中和抗体对干扰素治疗慢性乙型肝炎效果的影响

在慢性病毒性肝炎治疗中,正广泛应用干扰素,并取得了较好的疗效,但仍有相当部分患者无应答,影响干扰素抗病毒疗效的因素很多,干扰素抗体的作用也是因素之一.在干扰素治疗慢性病毒性肝炎的过程中,干扰素能刺激机体产生干扰素中和抗体,为了探讨中和抗体的产生率及其临床意义,我们采用中和生物法检测了接受干扰素治疗的慢性乙型肝炎患者血清干扰素中和抗体,探讨了干扰素中和抗体对干扰素疗效的影响.     

干扰素治疗慢性乙型肝炎的影响因素及疗效预测

我国批准用于抗乙型肝炎病毒(HBV)治疗的药物共有两大类.包括普通干扰素(IFN)、聚乙二醇干扰素(PEG-IFN)以及数种核苷(酸)类似物(NAs).     

干扰素治疗慢性乙型肝炎的影响因素及疗效预测

我国批准用于抗乙型肝炎病毒(HBV)治疗的药物共有两大类.包括普通干扰素(IFN)、聚乙二醇干扰素(PEG-IFN)以及数种核苷(酸)类似物(NAs).     

聚乙二醇干扰素α－2a 治疗 HBeAg 阴性慢性乙型肝炎的疗效及影响因素

目的：观察聚乙二醇干扰素（PEG －IFN）α－2a 治疗 HBeAg 阴性慢性乙型肝炎（CHB）患者的疗效及其影响因素。方法收集2009年5月－2012年12月在南方医科大学南方医院感染内科就诊的 HBeAg 阴性的 CHB 患者103例,给予 PEG －IFNα－2a 135μg 治疗,平均疗程为13个月,治疗后随访48周,在治疗及随访期间每3个月检查肝功能、HBV DNA 定量。组间频数比较采用χ2检验,均数比较采用 t 检验,采用二分类多元 Logistic 回归法分析疗效的影响因素。结果103例患者治疗结束时,取得联合应答者84例,联合应答率为81．6％。随访过程中复发33例,复发率为39．3％,治疗后随访1年持续应答患者49例,持续应答率47．6％。经单因素和多因素分析,抗－HBe 阳性是唯一的与持续应答相关的独立影响因素（OR ＝3．69,P ＝0．013）,HBV DNA 定量、HBV 基因型、前 C ／BCP 区变异、肝脏病理等其他治疗前基线特征与持续应答无相关性。结论PEG －IFNα－2a 治疗 HBeAg 阴性 CHB 能够取得较好的疗效,但复发率较高;抗－HBe 阳性患者的持续应答率较高。     

肝脂肪变对聚乙二醇干扰素α-2a治疗慢性乙型肝炎疗效的影响

目的 探讨肝脂肪变对慢性乙型肝炎(CHB)患者应用聚乙二醇干扰素α-2a(PEG-IFNα-2a)抗病毒疗效的影响.方法 对2005年至2009年经肝组织病理学检查确诊的应用PEG-IFNα-2a抗病毒治疗且资料齐全的50例CHB患者进行回顾性分析,依据病理学检测结果将其分为无脂变组(28例)、脂变组(轻度脂肪变21例、中度脂肪变1例).检测血常规、肝肾功能、空腹血糖、血脂,荧光定量PCR法检测HBV DNA载量(下限为500拷贝/rnl),采用电化学发光法检测HBV标志物(HBsAg、抗-HBs、HBeAg、抗-HBe)及甲状腺功能;分析比较两组患者治疗48周时的抗病毒疗效、不良反应情况.对数据中的计量资料采用t检验、计数资料采用x2检验进行统计学分析. 结果 无脂变组HBV DNA阴转率(＜500拷贝/ml)为42.9％,HBeAg/抗-HBe血清学转换率为31.6％,完全应答率39.3％;脂变组HBV DNA阴转率为40.9％,HBeAg/抗-HBe血清学转换率为33.3％,完全应答率40.9％,经x2检验(x2值分别为0.012,0.019,0.014,P值分别为0.600,0.560,0.568),未发现两组患者抗病毒治疗48周时的疗效差异存在统计学意义.两组患者抗病毒治疗后甘油三酯均较治疗前升高(无脂变组t=-2.164,P＜0.05;脂变组t=-2.863,P＜0.05);治疗后两组甘油三酯差异有统计学意义(t=2.412,P＜0.05). 结论 本研究未发现轻度肝脂肪变对CHB患者应用PEG-IFNα-2a抗病毒治疗48周时的疗效有明显影响.     

干扰素治疗慢性乙型肝炎时e抗原血清学转换的相关因素

目的探讨HBeAg阳性慢性乙型肝炎在聚乙二醇干扰素α-2a（PEG-IFN α-2a）治疗过程中HBeAg血清学转换和病毒学应答的相关因素，HBeAg血清学转换与HBV DNA应答的相关性。方法患者采用PEG-IFNα-2a每次180μg，皮下注射，每周1次，共治疗48周，治疗结束后随访24周。用Abbott公司生产的第三代HBV血清学检测试剂和AXSYM自动酶标检测仪检测血清HBeAg、抗-HBe，实时荧光定量PCR检测HBVDNA载量，分析不同治疗阶段和随访结束的病毒学应答率（HBV DNA〈1．0×10^5拷贝／ml），HBeAg血清转换率及变化规律和影响病毒学应答和HBeAg血清转换的因素。结果治疗12周和随访结束时HBeAg血清转换组和非转换组的ALT水平比较，差异有统计学意义。病毒学应答无论在治疗期还是随访结束时，应答组与非应答组之间的ALT水平差异均有统计学意义。HBeAg血清学转换与非转换组之间的HBV DNA载量之间在治疗12周、治疗结束和随访结束时，差异无统计学意义。治疗期间病毒学应答与非应答组的HBV DNA载量之间的差异有统计学意义，但持续病毒学应答与HBV DNA载量无显著相关性。治疗12、24周和48周获得病毒学应答组的HBeAg血清转换率分别为43．8％、21．4％和18．9％。治疗12、24周和48周时病毒学应答组，在随访结束时的HBeAg的血清转换率分别为42．9％、33．3％和27．6％。多因素分析显示，治疗72周的HBeAg血清转换与治疗结束时的HBV DNA阴转显著相关（OR=2．15，95．0％CI=1．744-2．664，P〈0．01）。结论治疗12周和持续HBeAg血清学转换以及病毒学应答均与ALT基线水平相关，HBeAg血清学转换与基础HBV DNA载量无关，但与治疗过程中病毒学应答相关。     

一种新的HBeAg阴性慢性乙型肝炎病毒变异机制

Objective To investigate mutation patterns in core promoter(CP)region of hepatitis B virus(HBV).Methods HBV DNA was extracted from sera of patients with chronic HBV infection.The CP sequence was amplified by polymerase chain reaction(PCR)and cloned into pMD19 T vector.The positive clones were then sequenced.The sequences were compared with known HBV genome in GenBank to identify the mutation sites and patterns of patients with chronic HBV infection.Results There were 74 clones from 21 patients with chronic HBV infection which were sequenced.The sequence comparisons showed that there was a 234-nucleotide deletion in CP region of HBV genome in 54 clones and a 245-nucleotide deletion in one clone.These deletion regions included CP,HBeAg initiation codon and direct repeat sequence(DR)Ⅰ regions,which named CP deletion(CPD).A1585T replacement mutation was also found in HBV strain with CPD,which indicated that there was linkage between these two mutations.Conclusions A novel mechanism of HBeAg negative chronic hepatitis B is observed,which includes deletions of CP and HBeAg initiation codon.Meanwhile,a simple and useful PCR method is developed to detect CPD.     

一种新的HBeAg阴性慢性乙型肝炎病毒变异机制

Objective To investigate mutation patterns in core promoter(CP)region of hepatitis B virus(HBV).Methods HBV DNA was extracted from sera of patients with chronic HBV infection.The CP sequence was amplified by polymerase chain reaction(PCR)and cloned into pMD19 T vector.The positive clones were then sequenced.The sequences were compared with known HBV genome in GenBank to identify the mutation sites and patterns of patients with chronic HBV infection.Results There were 74 clones from 21 patients with chronic HBV infection which were sequenced.The sequence comparisons showed that there was a 234-nucleotide deletion in CP region of HBV genome in 54 clones and a 245-nucleotide deletion in one clone.These deletion regions included CP,HBeAg initiation codon and direct repeat sequence(DR)Ⅰ regions,which named CP deletion(CPD).A1585T replacement mutation was also found in HBV strain with CPD,which indicated that there was linkage between these two mutations.Conclusions A novel mechanism of HBeAg negative chronic hepatitis B is observed,which includes deletions of CP and HBeAg initiation codon.Meanwhile,a simple and useful PCR method is developed to detect CPD.     

一种新的HBeAg阴性慢性乙型肝炎病毒变异机制

Objective To investigate mutation patterns in core promoter(CP)region of hepatitis B virus(HBV).Methods HBV DNA was extracted from sera of patients with chronic HBV infection.The CP sequence was amplified by polymerase chain reaction(PCR)and cloned into pMD19 T vector.The positive clones were then sequenced.The sequences were compared with known HBV genome in GenBank to identify the mutation sites and patterns of patients with chronic HBV infection.Results There were 74 clones from 21 patients with chronic HBV infection which were sequenced.The sequence comparisons showed that there was a 234-nucleotide deletion in CP region of HBV genome in 54 clones and a 245-nucleotide deletion in one clone.These deletion regions included CP,HBeAg initiation codon and direct repeat sequence(DR)Ⅰ regions,which named CP deletion(CPD).A1585T replacement mutation was also found in HBV strain with CPD,which indicated that there was linkage between these two mutations.Conclusions A novel mechanism of HBeAg negative chronic hepatitis B is observed,which includes deletions of CP and HBeAg initiation codon.Meanwhile,a simple and useful PCR method is developed to detect CPD.     

一种新的HBeAg阴性慢性乙型肝炎病毒变异机制

Objective To investigate mutation patterns in core promoter(CP)region of hepatitis B virus(HBV).Methods HBV DNA was extracted from sera of patients with chronic HBV infection.The CP sequence was amplified by polymerase chain reaction(PCR)and cloned into pMD19 T vector.The positive clones were then sequenced.The sequences were compared with known HBV genome in GenBank to identify the mutation sites and patterns of patients with chronic HBV infection.Results There were 74 clones from 21 patients with chronic HBV infection which were sequenced.The sequence comparisons showed that there was a 234-nucleotide deletion in CP region of HBV genome in 54 clones and a 245-nucleotide deletion in one clone.These deletion regions included CP,HBeAg initiation codon and direct repeat sequence(DR)Ⅰ regions,which named CP deletion(CPD).A1585T replacement mutation was also found in HBV strain with CPD,which indicated that there was linkage between these two mutations.Conclusions A novel mechanism of HBeAg negative chronic hepatitis B is observed,which includes deletions of CP and HBeAg initiation codon.Meanwhile,a simple and useful PCR method is developed to detect CPD.     

一种新的HBeAg阴性慢性乙型肝炎病毒变异机制

Objective To investigate mutation patterns in core promoter(CP)region of hepatitis B virus(HBV).Methods HBV DNA was extracted from sera of patients with chronic HBV infection.The CP sequence was amplified by polymerase chain reaction(PCR)and cloned into pMD19 T vector.The positive clones were then sequenced.The sequences were compared with known HBV genome in GenBank to identify the mutation sites and patterns of patients with chronic HBV infection.Results There were 74 clones from 21 patients with chronic HBV infection which were sequenced.The sequence comparisons showed that there was a 234-nucleotide deletion in CP region of HBV genome in 54 clones and a 245-nucleotide deletion in one clone.These deletion regions included CP,HBeAg initiation codon and direct repeat sequence(DR)Ⅰ regions,which named CP deletion(CPD).A1585T replacement mutation was also found in HBV strain with CPD,which indicated that there was linkage between these two mutations.Conclusions A novel mechanism of HBeAg negative chronic hepatitis B is observed,which includes deletions of CP and HBeAg initiation codon.Meanwhile,a simple and useful PCR method is developed to detect CPD.     

一种新的HBeAg阴性慢性乙型肝炎病毒变异机制

Objective To investigate mutation patterns in core promoter(CP)region of hepatitis B virus(HBV).Methods HBV DNA was extracted from sera of patients with chronic HBV infection.The CP sequence was amplified by polymerase chain reaction(PCR)and cloned into pMD19 T vector.The positive clones were then sequenced.The sequences were compared with known HBV genome in GenBank to identify the mutation sites and patterns of patients with chronic HBV infection.Results There were 74 clones from 21 patients with chronic HBV infection which were sequenced.The sequence comparisons showed that there was a 234-nucleotide deletion in CP region of HBV genome in 54 clones and a 245-nucleotide deletion in one clone.These deletion regions included CP,HBeAg initiation codon and direct repeat sequence(DR)Ⅰ regions,which named CP deletion(CPD).A1585T replacement mutation was also found in HBV strain with CPD,which indicated that there was linkage between these two mutations.Conclusions A novel mechanism of HBeAg negative chronic hepatitis B is observed,which includes deletions of CP and HBeAg initiation codon.Meanwhile,a simple and useful PCR method is developed to detect CPD.     

一种新的HBeAg阴性慢性乙型肝炎病毒变异机制

Objective To investigate mutation patterns in core promoter(CP)region of hepatitis B virus(HBV).Methods HBV DNA was extracted from sera of patients with chronic HBV infection.The CP sequence was amplified by polymerase chain reaction(PCR)and cloned into pMD19 T vector.The positive clones were then sequenced.The sequences were compared with known HBV genome in GenBank to identify the mutation sites and patterns of patients with chronic HBV infection.Results There were 74 clones from 21 patients with chronic HBV infection which were sequenced.The sequence comparisons showed that there was a 234-nucleotide deletion in CP region of HBV genome in 54 clones and a 245-nucleotide deletion in one clone.These deletion regions included CP,HBeAg initiation codon and direct repeat sequence(DR)Ⅰ regions,which named CP deletion(CPD).A1585T replacement mutation was also found in HBV strain with CPD,which indicated that there was linkage between these two mutations.Conclusions A novel mechanism of HBeAg negative chronic hepatitis B is observed,which includes deletions of CP and HBeAg initiation codon.Meanwhile,a simple and useful PCR method is developed to detect CPD.     

一种新的HBeAg阴性慢性乙型肝炎病毒变异机制

Objective To investigate mutation patterns in core promoter(CP)region of hepatitis B virus(HBV).Methods HBV DNA was extracted from sera of patients with chronic HBV infection.The CP sequence was amplified by polymerase chain reaction(PCR)and cloned into pMD19 T vector.The positive clones were then sequenced.The sequences were compared with known HBV genome in GenBank to identify the mutation sites and patterns of patients with chronic HBV infection.Results There were 74 clones from 21 patients with chronic HBV infection which were sequenced.The sequence comparisons showed that there was a 234-nucleotide deletion in CP region of HBV genome in 54 clones and a 245-nucleotide deletion in one clone.These deletion regions included CP,HBeAg initiation codon and direct repeat sequence(DR)Ⅰ regions,which named CP deletion(CPD).A1585T replacement mutation was also found in HBV strain with CPD,which indicated that there was linkage between these two mutations.Conclusions A novel mechanism of HBeAg negative chronic hepatitis B is observed,which includes deletions of CP and HBeAg initiation codon.Meanwhile,a simple and useful PCR method is developed to detect CPD.     

聚乙二醇化干扰素治疗乙型肝炎病毒e抗原阳性慢性乙型肝炎患者乙型肝炎病毒表面抗原消失的相关因素

目的 探讨聚乙二醇化干扰素（PEG-IFN α-2a）治疗HBeAg阳性慢性乙型肝炎(CHB)患者过程中预测HBsAg消失的相关因素。方法 对72例HBeAg阳性CHB患者,应用PEG-IFN α-2a 180 μg,每周1次,共48周。每3个月检测ALT、AST及HBV DNA、HBeAg和H BsAg定量,对48周治疗结束时HBsAg消失与基线、12周、24周的HBV DNA、HBeAg和HBsAg定量的相关关系进行分析。计数资料行Fisher精确检验及受试者工作特征(ROC)曲线分析。结果65例HBeAg阳性CHB患者完成本研究,其中7例HBsAg消失。48周时HBsAg的消失与治疗12周时H BeAg水平有关（Fisher确切概率法,P=0.023）,与治疗24周时HBeAg水平高度相关 （Fisher确切概率法,P=0.004）,与12周或24周时HBsAg＜250 IU/mL相关(Fisher确切概率法,P=0.001,P=0.002)。与12周时HBV DNA阴转相关（Fisher确切概率法,P=0.039）,而与24周时HBV DNA是否阴转无关（Fisher确切概率法,P= 0.130）。经ROC曲线分析显示,12周、24周HBsAg及24周HBeAg曲线下面积(AUC)分别为0.8584(P=0.0021)、0.9606(P=0.001)及0.8350(P=0.040)。结论 联合应用24周HBeAg和HBsAg定量水平可能是预测48周疗程结束时是否发生HBsAg消失的有效指标。     

一种新的HBeAg阴性慢性乙型肝炎病毒变异机制

目的 检测HBV核心启动子区(CP)基因变异方式.方法 自HBV慢性感染患者血清中提取HBV DNA,扩增CP区域序列,克隆入pMD19 T载体,选择阳性克隆进行DNA测序,与已知HBV基因相应序列比较患者体内HBV基因变异位点以及变异形式.结果 自21例患者中共挑选74个克隆测序,54个克隆中病毒基因序列CP区发生大段缺失突变,长度达234个核苷酸,另有1个克隆发生245个核苷酸缺失突变.缺失突变区域包括CP区、HBeAg起始密码子和直接重复序列(DR)Ⅰ区,命名为CP缺失突变,发生CP缺失突变的病毒株同时存在A1585T替换突变,这两个部位的突变具有联动特征.结论 观察到一种导致HBeAg阴性慢性乙型肝炎的新方式,即CP、HBeAg起始密码子缺失突变,并提出一种简明的CP缺失检测方式.