干扰素α-2b与聚乙二醇干扰素α-2a治疗慢性乙型肝炎患者疗效比较研究*

目的 观察干扰素α-2b与聚乙二醇干扰素α-2a（PEG-IFNα-2a）治疗慢性乙型肝炎（CHB）患者的临床疗效。方法 将116例CHB患者分成两组,每组58例。给予对照组普通干扰素α-2b治疗,给予观察组PEG-IFNα-2a,疗程均为48 w。检测血清层黏连蛋白（LN）、透明质酸（HA）、Ⅳ型胶原（Ⅳ-C）、Ⅲ型前胶原肽（PⅢP）及血清白介素4（IL-4）、白介素6（IL-6）、白介素10（IL-10）和干扰素γ（IFN-γ）变化。结果 在治疗结束时,观察组HBV DNA转阴率、HBeAg转阴率、HBeAg血清转换率和ALT复常率分别为75.9%、29.3%、22.4%和70.7%,显著高于对照组的51.7%、19.0%、10.3%和55.2%（P<0.05）;观察组血清LN为（148.5±46.0） μg/L,显著低于对照组【（162.6±26.7） μg/L,P<0.05】,血清HA为（158.7±67.9）μg/L,显著低于对照组【（201.4±55.1） μg/L,P<0.05】,血清Ⅳ-C为（108.3±33.4） μg/L,显著低于对照组【（119.2±62.4） μg/L,P<0.05】,血清PⅢP为（145.8±47.2） μg/L,显著低于对照组【（155.3±36.7）μg/L,P<0.05】;观察组血清IL-4水平为（1.5±0.6） pg/ml,显著低于对照组【（3.9±1.6） pg/ml,P<0.05】,而IL-6水平为（6.9±1.3） pg/ml,显著高于对照组【（3.6±0.9） pg/ml,P<0.05】,IL-10水平为（22.6±13.4） pg/ml,显著低于对照组【（17.3±11.4） pg/ml,P<0.05】,IFN-γ水平为（37.2±10.2） pg/ml,显著高于对照组【（28.3±10.5） pg/ml,P<0.05】;观察组血小板计数减少发生率为51.7%,显著高于对照组的12.1%（P<0.05）。结论 PEG-IFNα-2a治疗CHB患者临床疗效优于普通干扰素α-2b,能持久有效地抑制HBV复制,改善血清肝纤维化指标,但不良反应较大,应及时处理。     

IL28B基因多态性对聚乙二醇干扰素α治疗HBeAg阳性慢性乙型肝炎患者疗效的影响

目的 探讨IL28B基因单核甘酸多态性（SNP）对聚乙二醇干扰素α（Peg-IFNα）治疗的HBeAg阳性慢性乙型肝炎（CHB）患者疗效的影响。方法 2014年8月~2016年10月我院收治的HBeAg阳性CHB患者143例,给予Peg-IFNα治疗24~144 w,随访52 w。采集外周血,提取DNA,检测IL28B 基因SNP位点rsl2979860、rs8099917和rsl2980275多态性分布。应用二分类多变量Logistic回归分析IL28B 基因SNP位点对病毒学应答率的影响。结果 在治疗和随访结束时,应答58例（40.6%）,无应答者85例;在143例CHB患者中,rsl2979860位点CT型占9.1%,TT型占0.7%,CC型占90.21%, rs8099917位点GT型占9.1%,TT型占90.9%,rsl2980275位点AG型占10.5%,AA型占89.51%;应答者rsl2979860 CC基因型为94.8%,显著高于未应答者的87.1% （P<0.05）,rs8099917 TT基因型为96.6%,显著高于未应答者的87.1% （P<0.05）,rsl2980275 AA基因型为94.8%,显著高于未应答者的85.9%（P<0.05）; 校正基线资料后,经二分类多变量Logistic回归分析显示,L28B基因rsl2979860位点为病毒学应答的独立影响因子（P<0.05）。结论 IL28B基因的SNP位点与Peg-IFNα治疗HBeAg阳性的CHB患者病毒学应答密切相关,临床医生在决定给予抗病毒治疗前,可以根据检测的血IL28B基因多态性分布情况,预测Peg-IFNα的最终治疗效果,而作出合理的治疗方案。     

聚乙二醇干扰素α-2b治疗慢性乙型肝炎患者外周血T淋巴细胞亚群和血清细胞因子水平变化*

目的 研究聚乙二醇干扰素α-2b治疗慢性乙型肝炎患者外周血T淋巴细胞亚群和血清细胞因子水平的变化。 方法 2014年1月~2016年1月我院收治的184例慢性乙型肝炎患者,92例接受聚乙二醇干扰素α-2b联合恩替卡韦治疗48 w,另92例只接受恩替卡韦治疗。使用流式细胞仪检测外周血T淋巴细胞亚群,采用放射免疫法检测血清IL-6、INF-ɑ、IL-4,采用酶联免疫吸附法检测血清IL-17、TGF-β1和HBV标记物,采用荧光定量PCR法检测血清HBV DNA、核转录因子RORγt、Foxp3、IL-17mRNA。 结果 在停药随访24 w,联合组与恩替卡韦组血清HBV DNA阴转率分别为86.96%和84.78%（P>0.05）;联合组血清HBeAg阴转率为28.89%（13/45）,与恩替卡韦组的15.22%（7/46）比,无显著性差异（P>0.05）;联合组血清ALT水平为（34.6±11.6） U/L,显著低于恩替卡韦组【（64.6±20.5） U/L,P<0.05】;联合组外周血CD3+、CD4+细胞和CD4+/CD8+比值分别为（75.6±14.5）%、（42.7±10.3）%和（1.4±0.6）,显著高于恩替卡韦组【（66.8±14.4）%、（36.7±8.5）%和（1.0±0.5）,P<0.05】,CD8+细胞百分比为（29.3±7.3） %,显著低于恩替卡韦组【（34.8±8.5） %,P<0.05】,两组NK细胞百分比比较无显著性差异（P>0.05）;治疗前两组血清IL-6、IL-17、IL-4、INF-ɑ、TGF-β1水平比较无显著性差异（P>0.05）,治疗后联合组血清IL-6水平为（6.8±1.2）pg/ml,显著高于恩替卡韦组【（3.5±0.8） pg/ml,P<0.05】,IL-17水平为（0.7±0.3） pg/ml,显著低于恩替卡韦组【（2.8±0.9） pg/ml,P<0.05】,IL-4水平为（1.4±0.5）pg/ml,显著低于恩替卡韦组【（3.8±1.5）pg/ml,P<0.05】,INF-ɑ水平为（4.0±1.3） pg/ml,显著高于恩替卡韦组【（2.6±0.9）pg/ml,P<0.05】,两组血清TGF-β1水平比较无显著性差异（P>0.05）;治疗前两组血清Foxp3、IL-17和RORγt mRNA水平比较无显著性差异（P>0.05）,治疗后联合组血清RORγt水平为（0.86±0.31）,显著低于恩替卡韦组【（1.56±0.43）,P>0.05】,而两组血清Foxp3和IL-17mRNA水平比较无显著性差异（P>0.05）。 结论 聚乙二醇干扰素α-2b能通过调控细胞因子和核转录因子水平,从多个环节调控慢性乙型肝炎患者免疫功能,发挥抗病毒作用。     

聚乙二醇干扰素α-2a联合恩替卡韦治疗拉米夫定耐药的慢性乙型肝炎患者疗效分析*

目的 探讨聚乙二醇干扰素α-2a联合恩替卡韦治疗拉米夫定耐药的HBeAg阳性慢性乙型肝炎患者的疗效。方法 随机将85例拉米夫定耐药患者分为两组,给予45例CHB患者恩替卡韦治疗,40例患者接受恩替卡韦和聚乙二醇干扰素α-2a治疗。结果 在治疗24 w末,两组血清ALT和AST水平均较治疗前下降,在治疗48 w末,联合组血清ALT和AST水平较恩替卡韦治疗组显著降低,差异有统计学意义（P<0.05）;联合组血清HBeAg阴转和血清转换率均显著高于恩替卡韦治疗组（P<0.05）。结论 应用聚乙二醇干扰素α-2a联合恩替卡韦治疗拉米夫定耐药的HBeAg慢性乙型肝炎患者可提高HBeAg转阴率和血清转换率,治疗安全。     

干扰素α2b联合拉米夫定治疗慢性乙型肝炎患者血清HBeAg阴转和肝功能的变化*

目的分析抗病毒治疗对慢性乙型肝炎患者HBeAg阴转及肝功能的影响。方法选择2013年2月至2013年11月在本院进行治疗的慢性乙型肝炎患者130例,随机分为观察组和对照组各65例。给予对照组患者干扰素α2b治疗,观察组在此基础上联合拉米夫定治疗。采用ELISA法检测血清乙型肝炎病毒标记物;采用实时荧光定量PCR法检测HBV DNA,分别在治疗6个月和12个月观察患者肝功能、HBV DNA阴转率和HBeAg转阴率的变化。结果在治疗6个月时,观察组谷丙转氨酶和谷草转氨酶水平分别为（45.7±23.8） U/L和（62.3±23.7） U/L,显著低于对照组的[（55.8±25.3） U/L和（73.2±25.3） U/L,P<0.05];在治疗12个月时,观察组谷丙转氨酶和谷草转氨酶水平分别为（32.7±19.4） U/L和（46.4±6.3） U/L,显著低于对照组的[（44.6±17.3） U/L和（52.8±5.2） U/L,P<0.05];两组患者血清HBV DNA阴转率和HBeAg阴转率的差异无统计学差异（P>0.05）。结论抗病毒治疗能够有效地改善慢性乙型肝炎患者肝功能,促进HBeAg阴转,使用干扰素α2b联合拉米夫定治疗的效果更为显著,且安全性较高。     

Y型聚乙二醇干扰素α-2b注射液治疗HCV基因2/3型慢性丙型肝炎患者疗效和安全性的多中心随机对照试验研究*

目的 以标准剂量的聚乙二醇干扰素（PegIFN）α-2a联合利巴韦林作为阳性对照,评价新型试验药物Y型PegIFNα-2b注射液联合利巴韦林治疗2型/3型慢性丙型肝炎（CHC）患者的疗效和安全性。方法 采用多中心、随机开放、阳性药对照的Ⅲ期临床试验,筛选符合要求的2型/3型CHC患者,按照2:1的比例随机分配到Y型PegIFNα-2b组和PegIFNα-2a组,同时口服利巴韦林,疗程24 w,停药随访24 w。采用Abbott RealTime HCV Genotype II检测HCV基因型,采用Cobas TaqMan实时定量PCR法检测血清HCV RNA水平。详细记录不良事件。主要疗效指标为持续病毒学应答（SVR）,并进行非劣效检验。结果 本试验实际入组2型/3型CHC患者255例,实际治疗241例。全分析集（FAS）数据显示,158例试验组和83例对照组患者SVR分别为85.4%（95% CI 79.94%~90.94%）和79.5%（95% CI 70.84%~88.20%,P=0.2402）;对符合方案分析集（PPS）人群分析显示,试验组和对照组患者SVR分别为87.9%（95% CI 82.45%~93.27%）和85.9%（95% CI 77.82%~94.01%,P=0.7060）,率差的95%可置信区间均符合非劣效标准;对PPS人群分析显示,85.8%受试者获得了早期病毒学应答（RVR）,RVR的阳性预测值为90.1%;试验组和对照组不良事件发生率相似,分别为95.6%和95.2%,严重不良事件发生率分别为3.8%和3.6%。结论 应用PegIFNα联合利巴韦林治疗2型/3型CHC患者,新型试验药物Y型PegIFNα-2b具有与对照药物PegIFNα-2a相似的疗效和安全性。     

国产聚乙二醇化干扰素α治疗HBeAg阳性慢性乙型肝炎患者疗效研究

目的 观察国产聚乙二醇化干扰素α-2b（peg-IFN-α-2b）治疗血清HBeAg阳性的慢性乙型肝炎（CHB）患者的效果。方法 2015年1月~2017年12月纳入血清HBeAg阳性的CHB患者500例,被分为A组150例,给予国产peg-IFN-α-2b治疗,和B组350例,给予peg-IFN-α-2a治疗。两组均治疗24~48 w。在治疗结束后,随访24 w。结果 治疗前,A组血清HBV DNA定量为（6.1±0.7） lg cps/ml、谷丙转氨酶（ALT）为（81.1±29.8）u/l、体质指数为（22.1±2.9）、血清HBeAg定量为（3.1±0.6） lg s/co和HBsA定量为（4.4±0.6） IU/ml,与B组的（6.2±0.67） lg cps/ml、（80.7±27.9） U/L、（21.9±2.9）、（3.1±0.1） lg s/co和（4.4±0.5） IU/ml比,差异均无统计学意义（P>0.05）;在随访24 w结束时,A组血清ALT复常率为64.0%,血清HBV DNA阴转率为60.0%,与B组的66.9%和62.9%比,差异均无统计学意义（P>0.05）;两组不良反应发生率也无显著性相差（P>0.05）。结论 应用国产peg-IFN-α-2b治疗血清HBeAg阳性的CHB患者能获得与peg-IFN-α-2a治疗相似的疗效,但价格便宜,具有临床应用价值。     

聚乙二醇干扰素-α-2a治疗血清低水平HBsAg阳性的慢性乙型肝炎患者临床结局预测研究*

目的 分析聚乙二醇干扰素-α-2a (Peg-IFNα-2a)治疗低水平HBsAg阳性的慢性乙型肝炎（CHB）患者的临床结局及其血清HBsAg水平对疗效的预测价值。方法 2014年4月~2016年4月我院就诊的低水平HBsAg 阳性的CHB患者80例,采用随机数字表法将其分成两组,每组40例。患者入组前经核苷（酸）类似物（NAs）治疗获得病毒学应答。给予对照组恩替卡韦治疗,观察组接受恩替卡韦和Peg-IFNα-2a联合治疗48 w。采用受试者工作特征曲线（ROC）下面积（AUC）评估基线HBsAg水平预测HBsAg清除的效能。结果 在治疗48 w末,观察组血清HBsAg和HBV DNA水平分别为（1.5±0.3） lg U/ml和（0.1±0.1） lg U/ml,显著低于对照组的（2.0±0.2）lg U/ml和（1.3±0.3） lg U/ml（P<0.05）,观察组HBsAg清除率和HBV DNA转阴率分别为32.5%和92.5%,显著高于对照组的6.3%和55.0%（P<0.05）;基线HBsAg水平是HBsAg清除的独立相关因素（OR:0.337,95%CI:0.026~0.652, P<0.05）;经ROC曲线分析,以基线HBsAg水平等于2.0 lg U/mL为截断点,基线HBsAg水平预测治疗48 w血清HBsAg清除的AUC为0.77,敏感度为0.85,特异度为0.68,阳性预测值为67.2%,阴性预测值为85.3%,正确性为72.5%。结论 应用peg-IFN-α-2a治疗已经NAs治疗获得低水平HBsAg阳性的CHB患者可进一步提高临床疗效,且基线HBsAg水平能预测治疗结束时血清HBsAg清除情况。     

IFNL4和IL-28B基因多态性检测评估慢性乙型肝炎患者抗病毒治疗应答价值分析

目的探讨检测血干扰素λ4(IFNL4)和白介素-28B(IL-28B)基因多态性对慢性乙型肝炎(CHB)患者抗病毒治疗后应答的评估价值。方法 2015年3月～2017年3月收治的CHB患者140例,均接受聚乙二醇干扰素α-2a治疗12个月。应用市售试剂盒检测外周血IFNL4和IL-28B基因多态性。结果在治疗结束时,在140例CHB患者中,108例(77.1%)获得应答,32例(22.9%)无应答;应答组IL-28Brsrs8099917位点基因TT型占比为88.9%,显著高于无应答组的68.8%(P0.05);应答组血清ALLT、AST和HBV DNA水平分别为(35.4±3.2) U/L、(38.6±2.1) U/L和(3.8±2.1) lg copies/ml,均显著低于无应答组的(61.5±4.8) U/L、(73.5±3.0) U/L和(5.2±3.1)lg copies/ml (P0.05);125例IFNL4 TT/TT型患者血清ALT、AST和HBV DNA水平分别为(47.1±2.5) U/L、(49.1±1.6) U/L和(4.5±1.2) lg copies/ml,与15例TT/△G型患者的(48.0±2.1) U/L、(59.4±1.5) U/L和(4.7±1.3)lg copies/ml比,无显著性差异(P0.05);118例IL-28B TT型患者血清ALT、AST和HBV DNA水平分别为(36.4±2.1) U/L、(38.9±2.7) U/L和(4.0±1.7) lg copies/ml,显著低于22例TG型患者[分别为(59.0±1.4) U/L、(72.1±1.1) U/L和(6.0±2.1) lg copies/ml(P0.05)。结论 CHB患者IFNL4rs368234815位点基因以TT/TT型和IL-28Brs8099917位点基因以TT型居多,检测IFNL4基因多态性可能对预测抗病毒疗效无明显指导意义,而检测IL-28B基因多态性可能对抗病毒疗效有一定的预测价值。     

聚乙二醇化干扰素α-2a联合利巴韦林治疗代偿期丙型肝炎肝硬化患者临床疗效研究*

目的 探讨应用聚乙二醇化干扰素α-2a联合利巴韦林治疗代偿期丙型肝炎肝硬化患者的临床疗效。方法 2003年1月~2016年12月我院就诊的代偿期丙型肝炎肝硬化患者122例,采用随机数字表法分成两组,每组61例。给予对照组常规护肝治疗,给予观察组聚乙二醇化干扰素α-2a联合利巴韦林治疗24~48 w。随访两组24 w。采用实时荧光定量RT-PCR法检测血清HCV RNA,采用全自动生化分析仪检测血生化指标,采用化学发光法检测血清层粘连蛋白（LN）、Ⅲ型前胶原（PC Ⅲ）、透明质酸（HA）,常规使用Fibroscan行肝脏硬度检测（LSM）。结果 在治疗结束时,观察组血清HCV RNA水平为（2.0±0.4） lg IU/ml,显著低于对照组【（3.8±1.3）lg IU/ml,P<0.05】;血清AST和ALT水平分别（46.03±24.05） U/L和（36.32±20.1） U/L,显著低于对照组【（78.7±21.1） U/L和（51.2±20.9） U/L,P<0.05）;观察组血清LN、PCⅢ和HA水平分别为（126.3±29.0）μg/L、（212.3±43.8）μg/L和（211.4±42.0）μg/L,均显著低于对照组【（140.3±32.1）μg/L、（267.5±39.8）μg/L和（329.6±68.4）μg/L,P<0.05】;观察组LSM为（13.6±2.4） kPa,显著低于对照组【（17.6±5.2）kPa,P<0.05】;在随访时发现,观察组血清ALT复常率和持续病毒学应答率（SVR）均显著高于对照组（分别为93.4%对45.9%和72.1%对9.8%,P<0.05）,而疾病进展发生率为3.3%,显著低于对照组的13.1%（P<0.05）。结论 应用聚乙二醇化干扰素α-2a联合利巴韦林抗病毒治疗代偿期丙型肝炎肝硬化患者可显著提高SVR,延缓肝纤维化进展,稳定肝功能指标。     

重组干扰素α-2a,α-2b治疗慢性乙型肝炎疗效比较

探讨不同亚型α干扰素（IFNα-2α,IFNα-2b）治疗慢性乙型肝炎的疗效差异。110例慢性乙型肝炎（CHB）患者被随机分为IFNα-2α,治疗组（52例）和IFNα-2b治疗组（58例）。IFNα-2α治疗组采用IFNα-2a（因特芬）每日3MU肌注,IFNα-2b治疗组采用IFNα-2b（隆化诺）每日3MU肌注,30天后改隔日3MU肌注,疗程6月。观察两组用药3月,6月后血清ALT昨常率,HBeAg阴转率,HBV－DNA阴转率和治疗反应率。ALT复常率两组无明显差异（P＞0．05）。HBeAg阴转率：IFNα－2b治疗组（51.7%,67.2%),明显优于IFNα－2a治疗组（32.7%,44.2%),两组差异明显（P＜0．05）。HBV DNA阴转率：6月后IFNα－2b治疗组（58．6％）,明显优于IFNα-2α治疗组（34．6％）,两组差异明显（P＜0．05）。治疗后完全反应率：IFNα－2b治疗组（46．6％） ,明显优于IFNα-2α治疗组（21．2％）,两组间有极显著差异（P＜0．01）。干扰素α-2b亚型治疗慢性乙型肝炎疗效明显优于干扰素α-2α,亚型。     

Hepatitis B surface antigen clearance in inactive hepatitis B surface antigen carriers treated with peginterferon alfa-2a

AIM: To examine the association between interferon(IFN) therapy and loss of hepatitis B surface antigen(HBs Ag) in inactive HBs Ag carriers. METHODS: This was a retrospective cohort study in inactive HBs Ag carriers, who were treatment-naive, with a serum HBs Ag level 100 IU/m L and an undetectable hepatitis B virus(HBV) DNA level( 100 IU/m L). All the 20 treated patients received subcutaneous PEG-IFN alfa-2a 180 μg/wk for 72 wk and were then followed for 24 wk. There were 40 untreated controls matched with 96 wk of observation. Serum HBs Ag, HBV DNA, and alanine aminotransferases were monitored every 3 mo in the treatment group and every 3-6 mo in the control group. RESULTS: Thirteen(65.0%) of 20 treated patients achieved HBs Ag loss, 12 of whom achieved HBs Ag seroconversion. Mean HBs Ag level in treated patients decreased to 6.69 ± 13.04 IU/m L after 24 wk of treatment from a baseline level of 26.22 ± 33.00 IU/m L. Serum HBV DNA level remained undetectable( 100 IU/m L) in all treated patients during the study. HBs Ag level of the control group decreased from 25.72 ± 25.58 IU/m L at baseline to 17.11 ± 21.62 IU/m L at week 96(P = 0.108). In the control group, no patient experienced HBs Ag loss/seroconversion, and two(5.0%) developed HBV reactivation.CONCLUSION: IFN treatment results in HBs Ag loss and seroconversion in a considerable proportion of inactive HBs Ag carriers with low HBs Ag concentrations.     

Pericarditis and chronic inflammatory demyelinating polyneuropathy during therapy with pegylated interferon alfa-2a for chronic hepatitis C

We report a case of pericarditis and chronic inflammatory demyelinating polyneuropathy with biological signs of a lupus-like syndrome due to pegylated interferon alfa-2a therapy during treatment for chronic hepatitis C. The patient developed moderate weakness in the lower limbs and dyspnea. He was hospitalized for congestive heart failure. An electrocardiogram showed gradual ST-segment elevation in leads V(1) through V(6) without coronary artery disease. A transthoracic cardiac ultrasonographic study revealed moderate pericardial effusion with normal left ventricular function. Anti-DNA antibody and antids DNA IgM were positive. Neurological examination revealed a symmetrical predominantly sensory polyneuropathy with impairment of light touch and pin prick in globe and stoking-like distribution. Treatment with prednisolone improved the pericarditis and motor nerve disturbance and the treatment with intravenous immunoglobulin improved the sensory nerve disturbance.     

Hepatitis B Virus Genotype B and High Expression of Interferon Alpha Receptor β Subunit are Associated With Better Response to Pegylated Interferon Alpha 2a in Chinese Patients With Chronic Hepatitis B Infection

Background

Hepatitis B virus (HBV) is one of leading causes of various hepatic diseases including acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Hundreds of million people worldwide are infected by HBV, chronically.

Objectives

This study in conducted to investigate the influence of Hepatitis B virus (HBV) genotypes and type I IFN-αreceptor β subunit (IFNAR2) expression in liver on response to treatment with pegylated IFN-α-2a (Peg-IFN-α-2a) for chronic hepatitis B infection.

Patients and Methods

In this study, 65 eligible patients with chronic hepatitis B disease were enrolled. HBV genotypes of these patients were analyzed by using PCR-RFLP of the surface gene of HBV. The expression of IFNAR2 in the liver was immune histochemically investigated using anti-IFNAR2 antibody. All immune histochemical slides were read semi-quantitatively by image analysis. Chronic hepatitis B patients were treated with Peg-IFN-α2a therapy for a 48-week period and followed up for 24 weeks. Baseline characteristics and sustained viral response (SVR) to Peg-IFN-α-2a therapy were evaluated.

Results

55 % of patients exhibited HBV genotype B and 31.7 % patients exhibited HBV genotypes C infections. After treatment with Peg-IFN-α-2a, SVR was achieved in 66.7 % of patients with HBV genotype B and in 26.3 % of patients with HBV genotype C (P = 0.009). Semiquantitative and the image analysis indicated by gray level values revealed a higher IFNAR2 expression in the group with severe inflammation (P < 0.001). Patients’ high IFNAR2 protein expression had a significant impact on SVR to Peg-IFN-α-2a therapy (P = 0.028).

Conclusions

HBV genotype B and high expression of IFNAR2 in the liver of chronic hepatitis B patients are closely associated with better response to Peg-IFN-α-2a therapy in chronic hepatitis B disease.     

Serum proteins in chronic hepatitis B patients treated with peginterferon alfa-2b

AIM: To study the differential protein profile in serum of hepatitis B patients.METHODS: Serum samples were obtained from patients with chronic hepatitis B who were receiving peginterferon alfa-2b.The serum samples were subjected to albumin depletion and analyzed by two-dimensional gel electrophoresis(2-DE).Differentially expressed protein spots were identified by electrospray ionizationquadrupole time-of-flight mass spectrometry.Alpha2-HS-glycoprotein,complement component C3c and CD5 antigen were further analyzed by an enzymelinked immunosorbent assay and immunonephelometry.RESULTS: Nineteen patients with HBeAg-positive chronic hepatitis B(CHB) were studied.These patients were followed for at least 1 year after treatment and were classified according to their treatment response: responders(n = 9) and non-responders(n = 10).2-DE and MS/MS analysis were performed to compare the serum proteins before initiating peginterferon alfa2b.From the quantitative analysis of the 2-D gel,7 proteins were detected between the two groups at different levels before treatment.Among these potential candidates,serum levels of alpha-2-HS-glycoprotein,complement component C3c and CD5 antigen-like precursor were further analyzed.In the validation phase,23 subjects,9 sustained responders and 14 nonresponders,were recruited.Interestingly,the levels of alpha-2-HS-glycoprotein and complement component C3c were elevated in the serum of the non-responders compared to the responders.CONCLUSION: Serum alpha-2-HS-glycoprotein and complement component C3c may be potential serum biomarkers in predicting the treatment response of peginterferon alfa-2b in patients with CHB prior to treatment.     

Efficacy and Tolerability of Peginterferon alpha-2a and Peginterferon alpha-2b in Iranian Patients With Chronic Hepatitis C

Background:

Nearly 0.5% of Iranians are infected with HCV. Peginterferon-alpha-2a and Peginterferon-alpha-2b are the two available types of interferon for the treatment of hepatitis C. Comparing the results of these two treatments is still a challenge.

Objectives:

The aim of this study was to compare the results of Peginterferon-alpha-2a and Peginterferon-alpha-2b in Iranian patients with chronic hepatitis C.

Patients and Methods:

289 patients with chronic hepatitis C attending Tehran Hepatitis Center (THC) and Hepatitis Clinic of Tehran Blood Transfusion Organization (TBTO) from January 2008 to April 2013 and treated with combination of Peginterferon-alpha-2a or Peginterferon-alpha-2b plus Ribavirin were enrolled in this retrospective cross-sectional study. Treatment response and side effects were compared.

Results:

Among all naive patients, 82.0% achieved SVR, 5.4% were resistant to therapy and 11.0% withdrew the treatment. Relapse was seen in 12.2% of naive patients who finished the course of treatment. RVR and EVR were seen in 67.7% and 90.6% of naive patients, respectively. Patients divided into two groups. Group A consists of 247 patients treated with Peginterferon-alpha-2a and group B 42 patients treated with Peginterferon-alpha-2b. No significant difference in treatment response was observed between naive patients of the two groups. The rates of arthralgia/myalgia, alopecia, pruritus, insomnia, dyspnea and anorexia were higher in group A and the rates of dermal problems, coryza and bleeding were higher in group B. In a subgroup analysis, the two kinds of Peginterferon-alpha-2a available in Iran were compared. Rapid and early viral responses and relapse rates were lower in the one made in Iran and the long-term responses were not different. The rates of arthralgia/myalgia, fever, alopecia, pruritus, insomnia, dyspnea, anorexia, cough, headache and abdominal pain were higher and the rates of irritability and coryza were lower in the one made in Iran.

Conclusions:

There was no significant difference in the efficacy of Peginterferon-alpha-2a and Peginterferon-alpha-2b in Iranian patients. Physicians might choose the treatment regimen for every individual concerning the differences in side effects of Peginterferons.     

聚乙二醇干扰素α-2a联合阿德福韦酯治疗HBeAg阳性慢性乙型肝炎疗效预测因素分析

目的 分析聚乙二醇干扰素（PEG-IFNα-2a）联合阿德福韦酯（ADV）治疗HBeAg阳性慢性乙型肝炎（CHB）患者48 w时的疗效及其预测因素。方法 将196例HBeAg阳性CHB患者分为PEG-IFNα-2a治疗64例,ADV治疗66例和PEG-IFNα-2a联合ADV治疗66例,疗程均为48 w。采用ELISA法检测INF-γ和IL-10;采用Achitect（Abbott）微粒子化学发光免疫分析法检测HBeAg定量。结果 在治疗48 w时,联合组HBV DNA阴转率、HBeAg阴转率、HBeAg转换率和ALT复常率分别为74.2%、24.2%、48.5%和80.3%,显著高于干扰素组（53.1%、10.9%、29.7%和54.7%,P<0.05）和阿德福韦组（62.1%、13.6%、9.1%和65.2%,P<0.05）;联合组INF-γ水平为（45.3±11.3） pg/ml,显著高于干扰素组[（37.1±10.3） pg/ml,P<0.05]和阿德福韦组[（36.3±11.5） pg/ml,P<0.05];联合组IL-10水平为（10.3±14.6） pg/ml,显著低于干扰素组[（17.1±11.3） pg/ml,P<0.05]和阿德福韦组[（18.3±10.5） pg/ml,P<0.05];联合组治疗48 w时HBeAg血清学转换与治疗24 w时HBeAg水平下降的百分比有关,即治疗24 w时HBeAg水平较基线下降大于89.1%的阳性预测值为88.7%,阴性预测值（NPV）为81.9%,灵敏度为83.1%,特异度为87.9%。结论 PEG-IFNα-2a联合ADV治疗HBeAg阳性慢性乙型肝炎能增强机体细胞免疫应答,疗效优于单药治疗,其中治疗24 w时HBeAg下降的百分比可预测48 w时的疗效。     

慢性乙型肝炎患者外周血单个核细胞穿孔素表达与干扰素抗病毒疗效的关系

目的研究慢性乙型肝炎(CHB)患者干扰素(IFN)治疗前、后外周血单个核细胞(PBMC)中穿孔素表达情况,探讨其对IFN抗病毒疗效的影响。方法采用免疫细胞化学技术检测35例CHB患者IFNα-2b治疗前、后PBMC中穿孔索的表达。结果IFNα～2b治疗前、后PBMC穿孔素的表达分别为7．9%±4．6%和15．3%±6．4%,较治疗前明显上升,t=6．53,P＜0．01,差异有统计学意义。IFNα-2b治疗后完全应答者有12例、部分应答者14例、无应答者9例。IFN治疗后完全应答组穿孔索的表达为19．2%±5．2%,部分应答组为14．2%±5．5%,无应答组为11．7%±6．7%,完全应答组与部分应答组比较,t=2．33,P＜0．05；完全应答组与无应答组比较,t=2．89,P＜0．01,差异有统计学意义。结论CHB患者IFN治疗可以使PBMC中穿孔素的表达升高,PBMC中穿孔素的表达可能与IFN抗病毒疗效有密切的关系。     

聚乙二醇干扰素α-2a联合利巴韦林治疗基因1型慢性丙型肝炎病毒学应答对复发率的预测及影响因素

目的:探讨慢性丙型肝炎基因1型患者经聚乙二醇干扰素α-2a(PEG-INFα-2a)联合利巴韦林(RBV)治疗后快速病毒学应答(RVR)、早期完全病毒学应答(cEVR)、早期部分病毒学应答(pEVR)和早期无应答(NonEVR)对复发率的预测及影响病毒应答的因素。方法:应用丙型肝炎病毒基因分型检测芯片检测103例慢性丙型肝炎基因1型患者。所有患者均给予PEG-INFα-2a联合RBV治疗,并分别检测其治疗前及治疗第4、12、48周和随访24周时检测患者的HCVRNA。分析在治疗12周内因药物不良反应而调整PEG-INFα-2a、RBV剂量的情况。结果:PEG-INFα-2a联合RBV治疗患者达RVR者为71例(68.9%)、cEVR为20例(19.4%)、pEVR为7例(6.8%)及NonEVR为5例(4.9%),治疗终点的病毒应答率(EOT)分别为95.8%、95.0%、74.4%及40.0%;持续病毒学应答(SVR)率分别为92.9%、80.0%、42.9%及20.9%;复发率分别为5.9%、15.8%、60.0%及100.0%。12周内PEG-INFα-2a和(或)RBV剂量减少与不同病毒学应答模式明显相关(P<0.05)。结论:PEG-INFα-2a联合RBV治疗慢性丙型肝炎基因1型患者早期病毒学应答不同模式对复发率有一定预测价值。治疗12周内PEG-INFα-2a和(或)RBV减量可能使病毒清除减少,是导致病毒复发率增高的重要因素之一。     

Association of ITPA polymorphism with outcomes of peginterferon-α plus ribavirin combination therapy

AIM:To analyzed the association between inosine triphosphatase(ITPA)(rs1127354) genotypes and sustained virological response(SVR) rates in peginterferon(Peg-IFN)α + ribavirin(RBV) treatment.METHODS:Patients who underwent Peg-IFNα + RBV combination therapy were enrolled(n = 120) and they had no history of other IFN-based treatments.Variation in hemoglobin levels during therapy,cumulative reduction of RBV dose,frequency of treatment withdrawal,and SVR rates were investigated in each ITPA genotype.RESULTS:In patients with ITPA CC genotype,hemoglobin decline was significantly greater and the percentage of patients in whom total RBV dose was < 60% of standard and/or treatment was withdrawn was significantly higher compared with CA/AA genotype.However,SVR rates were equivalent between CC and CA/AA genotypes,and within a subset of patients with Interleukin 28B(IL28B)(rs8099917) TT genotype,SVR rates tended to be higher in patients with ITPA CC genotype,although the difference was not significant.CONCLUSION:ITPA CC genotype was a disadvantageous factor for Peg-IFNα + RBV treatment in relation to completion rates and RBV dose.However,CC genotype was not inferior to CA/AA genotype for SVR rates.When full-length treatment is accomplished,it is plausible that more SVR is achieved in patients with ITPA CC variant,especially in a background of IL28B TT genotype.