| Background:Allogeneic hematopoietic stem cell transplantation(allo-HSCT)plays an important role in the treatment of hematological diseases.China has a large number of hepatitis B virus(HBV)infection and a high prevalence rate of HBV infection.Allo-HSCT donors are mainly from relatives who have blood relationship,and HBV is mostly transmitted in families,so the donor and recipient of transplantation are most likely to be hepatitis B surface antigen(HBsAg)positive.The host mainly relies on its immune system to fight HBV.The immune function of Allo-HSCT recipients is inhibited for a long time due to preconditioning and the use of anti-rejection drugs.It takes more than 1 year for the recipients to recover their immune function after transplantation.During this period,the recipients are prone to HBV infection.Hepatitis B surface antibody(HBsAb)titers gradually decline to lose,resulting in a large number of HBV replication,which leads to immune related hepatitis and even death.Mortality in allo-HSCT recipients without HBV therapy ranges from 5% to22%.Hepatitis B surface antibody is very important for the prevention of HBV infection and HBVr.However,the rate of HBsAb loss in HBsAb-positive recipients within 6 months after allo-HSCT was up to 50%.The HBsAb positive donor can transfuse the anti-HBV immune power to the recipient through allo-HSCT,and the donor’ HBsAb has a significant protective effect on the loss of the recipient’ HBsAb.More importantly,HBsAb-positive donors can eliminate HBsAg in recipients after transplantation through adoptive immunity and achieve functional cure.Objective:To analyze the changes of HBV immune markers and it’s influencing factors after allo-HSCT,to explore the relationship between the changes and donors,and to analyze the characteristics of adoptive immunization of HBV in allo-HSCT,in order to provide reference for the clinical management of HBV in allo-HSCT recipients and the cure of HBV by immunotherapy.Methods:Clinical data of patients who were undergoing allo-HSCT in The First Affiliated Hospital of Guangzhou Medical University from April 2015 to December 2021 were collected,and 91 cases were finally enrolled.Donors’ HBV serologic markers,HBV DNA data,and recipients’ HBV serum markers,HBV DNA,liver biochemical indexes data during the pre-transplant to post-transplant follow-up time were collected.The changes of HBV serological markers and their influencing factors after transplantation were analyzed,and the relationship between the changes and donors was analyzed.SPSS 25.0 software was used to carry out the meta-analysis.The measurement data were expressed by median and interquartile interval or mean ±standard deviation.The comparison was made by independent t test or Mann-Whitney U test.The count data were expressed by volume and percentage.The comparison was made by chi-square test.Chi-square test and Logistic regression analysis were used to analyze the influencing factors of HBsAb loss,HBsAg clearance and HBV reactivation.P<0.05 indicated that the difference was statistically significant.Results:1.Hematopoietic reconstruction and survivalNinety-one allo-HSCT recipients were followed up for a median of 25.0(9.3-41.0)months,with a median of 13.0(12.0-16.0)days for hematopoietic reconstitution.23(25.3%)patients died during follow-up.The median survival time was 30.4(7.3-42.5)months in 13 HBsAg-positive and 24.5(10.2-41.2)in 78 HBsAg-negative recipients.The median time for hematopoietic reconstitution in HBsAg-positive recipients was 14.0(12.0-15.0)days and 13.0(11.0-16.0)days in HBsAg-negative recipients.HBsAg positive recipients had no effect on survival time and hematopoietic reconstitution after transplantation(P > 0.05).The patients were divided into 6 groups according combination mode of donorand recipient with different hepatitis B serological markers before transplantation:group 1(donor HBsAb-and recipient HBsAb-)1patients,group 2(donor HBsAb+and recipient HBsAb-)5 patients,Group 3(donor HBsAb-and recipient HBsAb+)22 patients,group 4(donor HBsAb+ and recipient HBsAb+)50patients,group 5(donor HBsAb+ and recipient HBsAg+)9 patients,group6(donor HBsAb-and recipient HBsAg+)4 patients.2.The changes of HBV immune markers in recipients after allo-HSCT and the effect of donor immunization on them.2.1.Hepatitis B surface antibodies obtained by recipients after allo-HSCTOne patient in group 1 had HBsAb+/HBc Ab+ from 1 month after transplantation to 6 months after transplantation,and the titer of HBsAb was 140.9m IU/ml.In group2,5 recipients(100%)obtained HBsAb after transplantation,the median time was 1.7(1.0-4.8)months,and the median titer of HBsAb was 139.8(39.6-267.8)m IU/ml.2.2.Loss of hepatitis B surface antibody in recipients after allo-HSCT and its influencing factorsIn group 3,HBsAb was negative in donors.HBsAb loss occurred in 5 cases(22.7%)after transplantation,and the median time was 16.0(9.3-32.5)months.The median follow-up time was 7.0(2.0-15.5)months,17 cases(77.3%)maintained HBsAb positive,and the median HBsAb titer was 187.2(57.0-383.4)m IU/ml.In group 4,HBsAb was positive in donors.HBsAb loss occurred in 12 cases(24.0%)after transplantation,the median time of HBsAb loss was 12(10.6-30.8)months.And38 cases(76.0%)were HBsAb positive after follow-up to the median time of 11.5(3.3-21.1)months,and the median titer of HBsAb was 108.7(33.3-217.8)m IU/ml.Univariate analysis showed that there were significant differences in HBsAb titer and acute graft-versus-host disease(a GVHD)before transplantation(p<0.05),but there was no significant difference in age,chronic graft-versus-host disease,antithymoglobulin and donor HBsAb titer(P>0.05).Multivariate analysis showed that low titer of HBsAb(< 304 m IU/ml)before transplantation was a risk factor for HBsAb loss after transplantation(OR= 12.704,95%CI=1.355-119.140,P=0.026),and a GVHD was also a risk factor.2.3.Clearance and influencing factors of hepatitis B surface antigen in recipients after allo-HSCTIn group 5,HBsAb was positive in donors,and 4 cases(44.4%)had negative HBsAg and HBsAb appeared after transplantation.The median time of negative conversion of HBsAg was 11.6(4.0-16.8)months,the median time of HBsAb appearing was 16.0(4.0-23.5)months,and the median titer of HBsAb was 191.5(44.4-457.6)m IU/ml.Mild hepatitis occurred in all 4 recipients except 1 case with no abnormal liver function during HBsAg clearance.In group 6,HBsAb was negative in donors.1 case(25%)of HBsAg turned negative and HBsAb appeared after transplantation,which occurred at 13.6 months after transplantation,and the highest HBsAb titer was more than 1000 m IU/ml.Hepatitis occurred when the recipient was cleared.Univariate analysis showed that there was significant difference in HBsAb titer of donors,but there was no significant difference in whether donors were HBsAb+/HBc Ab+ or not.Multivariate analysis showed that high titer of donor HBsAb(≥88m IU/ml)was beneficial to HBsAg clearance(OR=28,95%CI=1.350-580.591,P = 0.031).2.4.HBV reactivation occurred in patients after allo-HSCTReactivation occurred in 5 cases(6.4%)of 78 HBsAg+/HBc Ab+ or HBsAg-/HBc Ab+ recipients,with a median time of 4.5(2.3-19.2)months.The four recipients were HBsAg+ and one recipient was HBsAb+/HBc Ab+.All of them were not occurring severe hepatitis.The single factor suggested that there were significant difference in the positive rate of HBsAb and HBsAg of recipient before transplantationand the occurrence of a GVHD.Multivariate results suggest that HBsAg-positive before transplantation is a risk factor for HBVr in recipients after transplantation(OR=29,95%CI=2.558-328.713,P =0.007).Conclusion:1.HBsAg positive recipients had no effect on survival time and hematopoietic reconstitution of allo-HSCT recipients.2.The low titer of HBsAb of recipients and the occurrence of a GVHD were the risk factors for HBsAb loss after allo-HSCT.3.Donor’ high titer HBsAb was the protective factor of HBsAg clearance after allo-HSCT.4.HBsAg positive before transplantation was a risk factor for HBVr in patients with allo-HSCT. |
PDF Full Text Request