血清鞘脂联合定量HBsAg对核苷(酸)类似物经治慢性乙型肝炎患者加用聚乙二醇干扰素α后HBsAg阴转的预测价值  

Predictive value of serum sphingolipids combined with HBsAg quantification in HBsAg clearance of chronic hepatitis B patients treated with nucleos(t)ide analog add-on pegylated interferonα

作　　者：任艳[1] 卞丹丹 梁晨 蒋莹莹[1] 王扬[1] 赵景[1] 陈煜[1] 段钟平[1] 陈新月[1] 郑素军[1] REN Yan;BIAN Dandan;LIANG Chen;JIANG Yingying;WANG Yang;ZHAO Jing;CHEN Yu;DUAN Zhongping;CHEN Xinyue;ZHENG Sujun(Liver Disease Center,Beijing You'an Hospital,Capital Medical University,Beijing 100069,China;Department of Infectious Diseases,Electric Power Teaching Hospital,Capital Medical University,Beijing 100073,China)

机构地区：[1]首都医科大学附属北京佑安医院肝病中心,北京100069 [2]首都医科大学电力教学医院感染性疾病科,北京100073

出　　处：《转化医学杂志》2023年第1期15-21,共7页Translational Medicine Journal

基　　金：国家“艾滋病和病毒性肝炎等重大传染病防治”科技重大专项“十三五”计划(2017ZX10202203-006,2017ZX10302201-004);2019年度院内中青年人才孵育项目(BJYAYY-CY2019-03);北京市医院管理中心重点医学专业发展计划(扬帆计划)(ZYLX202125);北京市自然科学基金(7202068)。

摘　　要：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。Objectives As sphingolipids are involved in the hepatitis B virus(HBV)life cycle and affect interferon’s antiviral effect,we examined serum sphingolipids in patients with chronic hepatitis B treated with nucleos(t)ide analogue(NAs)and pegylated interferonα(peg-IFNα)for 48 weeks to screen out markers of sphingolipids that can predict HBsAg clearance.Methods This single-centre,prospective cohort study enrolled HBeAg-negative or HBeAg-seroconversion CHB patients treated with NAs antiviral therapy for more than 1 year with undetectable HBV-DNA and HBsAg<1500 IU/ml.Patients were treated with peg-IFNα-2a or peg-IFNα-2b for 48 weeks on the basis of NAs therapy.Serum sphingolipid levels were measured at baseline,12 weeks,and 24 weeks by ultra high performance liquid chromatography-tandem mass spectrometric(UPLC-MS/MS).The primary study endpoint was the predictive value of serum sphingolipids on HBsAg clearance.Results Forty-eight of 53 CHB patients completed 48-week peg-IFNαcombined NAs therapy,and 29.2%(14/48)achieved HBsAg clearance.There were significant differences in serum Cerd18:2/22:0and SMd 18:2/26:1 at baseline,12,and 24 weeks between HBsAg clearance and HBsAg no-clearance groups(P<0.05).Low HBsAg level at baseline(OR(95%CI)=0.993(0.987-0.999),P=0.030),high serum SMd18:2/26:1 level at 12weeks(OR(95%CI)=30.366(1.119-823.914),P=0.043),and the decline degree of HBsAg quantification at 24 weeks(OR(95%CI)=4.696(1.218-18.062),P=0.025)were independent predictors of HBsAg clearance.Serum Cerd 18:2/22:0combined with HBsAg quantification at baseline and 12 weeks respectively had a higher predictive value for 48-week HBsAg clearance than HBsAg quantification alone(AUC at baseline:0.895 vs 0.828;AUC at 12 weeks:0.893 vs0.861).Conclusions Serum Cerd18:2/22:0 combined with HBsAg quantification may be a good indicator for early prediction of HBsAg clearance in CHB patients treated with NAs add-on peg-IFN-αfor 48 weeks.

关 键 词：慢性乙型肝炎 聚乙二醇干扰素Α 核苷(酸)类似物 鞘脂 神经酰胺 乙型肝炎表面抗原 

分 类 号：R575.1[医药卫生—消化系统]