目的鞘脂参与乙型肝炎病毒(HBV)的生命周期并影响干扰素的抗病毒作用。本研究拟通过分析核苷(酸)类似物(NAs)经治慢性乙型肝炎(CHB)患者加用聚乙二醇干扰素α(peg-IFNα)治疗48周血清鞘脂的变化情况,以期筛选出可预测联合治疗48周HBsAg...目的鞘脂参与乙型肝炎病毒(HBV)的生命周期并影响干扰素的抗病毒作用。本研究拟通过分析核苷(酸)类似物(NAs)经治慢性乙型肝炎(CHB)患者加用聚乙二醇干扰素α(peg-IFNα)治疗48周血清鞘脂的变化情况,以期筛选出可预测联合治疗48周HBsAg阴转的鞘脂标志物。方法该单中心、前瞻性队列研究入组了接受核苷(酸)类似物抗病毒治疗1年以上,HBV-DNA检测不到且HBsAg<1500 IU/mL的HBeAg阴性或已发生HBeAg阴转的CHB患者。入组患者加用peg-IFNα-2a或peg-IFNα-2b抗病毒治疗48周。应用超高效液相色谱-串联质谱方法检测基线、12周、24周血清鞘脂水平。主要研究终点是血清鞘脂对48周HBsAg阴转的预测价值。结果53例CHB患者中有48例完成了48周peg-IFNα联合NAs治疗,其中29.2%(14/48)患者实现了HBsAg阴转。基线、12周、24周血清Cerd18:2/22:0、SMd18:2/26:1在HBsAg阴转组及未阴转组之间存在明显差异(P<0.05)。基线HBsAg低水平(OR(95%CI)=0.993(0.987-0.999),P=0.030)、12周血清SMd18:2/26:1高水平(OR(95%CI)=30.366(1.119-823.914),P=0.043)及24周HBsAg定量下降程度(OR(95%CI)=4.696(1.218-18.062),P=0.025)分别是HBsAg阴转的独立预测因素。基线、12周时血清Cerd18:2/22:0分别联合HBsAg定量较之单独相应随访点HBsAg定量对联合治疗48周时HBsAg阴转的预测价值更高(基线AUC:0.895 vs 0.828;12周AUC:0.893 vs 0.861)。结论血清Cerd18:2/22:0联合HBsAg定量可能是早期预测NAs经治CHB患者加用peg-IFNα治疗48周时HBsAg阴转的良好指标。展开更多
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 we...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.展开更多
文摘目的鞘脂参与乙型肝炎病毒(HBV)的生命周期并影响干扰素的抗病毒作用。本研究拟通过分析核苷(酸)类似物(NAs)经治慢性乙型肝炎(CHB)患者加用聚乙二醇干扰素α(peg-IFNα)治疗48周血清鞘脂的变化情况,以期筛选出可预测联合治疗48周HBsAg阴转的鞘脂标志物。方法该单中心、前瞻性队列研究入组了接受核苷(酸)类似物抗病毒治疗1年以上,HBV-DNA检测不到且HBsAg<1500 IU/mL的HBeAg阴性或已发生HBeAg阴转的CHB患者。入组患者加用peg-IFNα-2a或peg-IFNα-2b抗病毒治疗48周。应用超高效液相色谱-串联质谱方法检测基线、12周、24周血清鞘脂水平。主要研究终点是血清鞘脂对48周HBsAg阴转的预测价值。结果53例CHB患者中有48例完成了48周peg-IFNα联合NAs治疗,其中29.2%(14/48)患者实现了HBsAg阴转。基线、12周、24周血清Cerd18:2/22:0、SMd18:2/26:1在HBsAg阴转组及未阴转组之间存在明显差异(P<0.05)。基线HBsAg低水平(OR(95%CI)=0.993(0.987-0.999),P=0.030)、12周血清SMd18:2/26:1高水平(OR(95%CI)=30.366(1.119-823.914),P=0.043)及24周HBsAg定量下降程度(OR(95%CI)=4.696(1.218-18.062),P=0.025)分别是HBsAg阴转的独立预测因素。基线、12周时血清Cerd18:2/22:0分别联合HBsAg定量较之单独相应随访点HBsAg定量对联合治疗48周时HBsAg阴转的预测价值更高(基线AUC:0.895 vs 0.828;12周AUC:0.893 vs 0.861)。结论血清Cerd18:2/22:0联合HBsAg定量可能是早期预测NAs经治CHB患者加用peg-IFNα治疗48周时HBsAg阴转的良好指标。
基金Supported by The 90th Anniversary of Chulalongkorn University Fund(Ratchadaphiseksomphot Endowment Fund)The Thailand Research Fund,No.RMU5180051+2 种基金The Thailand Research Fund Senior Research Scholarship,No.RTA5380005The Higher Education Research Promotion and National Research University Project of Thailand,Office of the Higher Education Commission,No.HR1163AIntegrated Innovation Academic Center,Chulalongkorn University Centenary Academic Development Project,No.CU56-HR05,The Liver Research Unit,Chulalongkorn University
文摘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.
