儿童异基因造血干细胞移植术后乙型肝炎病毒免疫标记的变化

目的 了解儿童异基因造血干细胞移植（allo-HSCT）前后乙型肝炎病毒（HBV）免疫标记的变化情况,探讨供受者allo-HSCT前不同HBV免疫状态与allo-HSCT后受者HBV免疫标记变化的关系.方法 回顾性分析2010年1月-2012年6月在我院接受allo-HSCT治疗的130例儿童血液病患儿移植前后HBV免疫标记物（HBsAg、HBsAb、HBeAg、HBeAb及HBcAb）、HBV-DNA等临床资料,移植后随访中位时间18（6 ～36）个月.结果 （1）allo-HSCT前：HBsAg阴性患儿126例,阳性4例；HBsAb阳性患儿92例；HBsAg阳性供者6例,余均为HBsAg阴性供者.（2）allo-HSCT后：16例移植前HBsAb阴性受者移植后转为HBsAb阳性：66例移植前HBsAb阳性受者接受HBsAb阳性供者移植后,47例仍为HBsAb阳性,18例为HBsAb阴性,1例发生HBV再激活；21例移植前HBsAb阳性受者接受HBsAb阴性供者移植后,13例转为HBsAb阴性.（3）移植前供者HBsAb阳性,输注CD34＋细胞＞7.24×106/kg、移植前受者HBsAb滴度高低对移植后受者HBsAb转为阴性有显著影响,P值分别为0.005、0.040和0.000.（4）2例移植前合并HBV感染患儿移植后发生HBV再激活,2例移植前无HBV感染患儿接受大三阳供者移植后继发HBV感染.结论 HBsAb阴性患儿接受HBsAb阳性供者allo-HSCT后,在造血和免疫功能重建的同时,其体内可产生针对HBV的保护性抗体；移植后受者HBsAb随时间逐渐丢失,丢失的比例与移植前受者HBsAb滴度高低、输注CD34＋细胞数高低、供者HBsAb阳性与否明显相关.因此,移植前对供受者进行针对HBV的免疫接种及移植后免疫重建后对受者再次免疫接种有利于预防移植后HBV激活及感染.

The changes of hepatitis B virus in children underwent allogeneic hematopoietic stem cell transplantation

Objective To evaluate the changes of hepatitis B virus （HBV） related immune markers after allogeneic hematopoietic stem cell transplantation （allo-HSCT）,and to investigate the relationship between the donors＇ immunity before allo-HSCT and HBV-related immune markers after allo-HSCT.Methods A total of 130 children undergone allo-HSCT at our center from Jan 2010 to Jun 2012 was reviewed retrospectively; their donors were analyzed as well.HBV-related immune markers including HBsAg,HBsAb,HBeAg,HBeAb and HBcAb were detected in both recipients and donors before and after allo-HSCT.Results （1） Among all recipients,126 cases were HBsAg negative （HBsAg-） and 4 cases were HBsAg positive （HBsAg ＋） before allo-HSCT; 92 cases were HBsAb ＋ ; 6 were HBsAg ＋.The median follow-up time was 18 months （ranged from 6 to 36 months）.（2）The seroconversion rate from HBsAg-to HBsAg＋ after transplantation was 48.5% （16 of 33）.（3） Among 66 HBsAb＋ recipients undergone allo-HSCT from HBsAb＋ donors,18 cases turned to HBsAb-after allo-HSCT,47 cases remained HBsAb＋,and one recipient occurred HBV reactivation.Among 21 HBsAb＋ recipients undergone allo-HSCT from HBsAb-donors,13 cases turned to HBsAb-.Moreover,Donors＇ HBsAb positive rate before transplantation,the infusion counts of CD34 ＋ cells 〉 7.24 × 106/kg and the higher recipients HBsAb titers before transplantation had significant effects on the negative conversion rates of HBsAb of the recipients after transplantation.The P values were 0.005,0.040 and 0.000 respectively.（4） Two recipients complicated with HBV infection before allo-HSCT occurred HBV reactivation; another 2 recipients without HBV infection developed to HBV infection after allo-HSCT from HBsAg＋ donors.Conclusions Anti-HBs antibodies were generated in HBsAb-recipients after allo-HSCT from HBsAb＋ donors.Anti-HBs antibodies in recipients after transplantation lost gradually with the time passed by.There were obvious correlations among loss ratio of HBsAb,HBsAb titer,CD34 ＋ cells and HBsAb status of donors.Therefore,HBV vaccination for both recipients and donors before allo-HSCT and secondary vaccination after allo-HSCT are necessary for the patients to prevent HBV reactivation and infection.