The Investigation Of HBV Reinfection And Active Immunization Strategy In Liver Recipients Of Hepatitis B Virus Related Liver Diseases

Background：Hepatitis B immune globulins (HBIG) in combination with nucleosideor nucleotide analogues (NUCs) are the recommended prophylactics for treatinghepatitis B virus (HBV) recurrence following liver transplantation (LT). However,HBIG treatment is expensive. Active immunization with hepatitis B vaccine would bea preferable alternative HBIG treatment. However, the overall response rate tostandard vaccination (given at months0,1, and6) is relatively low inimmunocompromised patients.Aims: To compare the immunogenicity of two modified HBV vaccination schedulesin liver transplant recipients.Methods: Two cohorts of114subjects were immunized with recombinant HBVvaccine containing S-antigen. The patients in the rapid response group wereimmunized with40μ g HBV vaccine at months0,1,2,3, and with20μ g at months4,5, and6. The patients in the accelerated response group were immunized with40μ gof HBV vaccine at days0,7,14,28, and20ug at months2,3, and4.Results: The overall response rate was16.7%(19/114) and all responding subjectsdiscontinued HBIG treatment without HBV recurrence. The response rate was24.6%(14/57) and8.8%(5/57) in the rapid vaccination and the accelerated vaccinationschedules, respectively (P=0.024). The multivariate analysis was carried out for the95patients with complete baseline information. There were no statistically relevantcorrelations between response rate and sex, age, body mass index (BMI), indicationfor OLT, donor type and post-OLT antiviral regimen. HBV recurrence and survivalbetween vaccination and control group during the follow-up period showed nodifference. Conclusion: HBV vaccination may induce endogenous anti-HBs to replace HBIG inselected patients. Vaccination schedules may influence vaccine response, andindividual optimization may improve such responses. AimIn china，the hepatitis B virus related liver diseases were the leading indication forliver transplantation. Due to the previous exposure to HBV, the prevalence of HBsAgnegative/anti-HBc positive donors were estimated over50%in some areas. However,the risk of HBV recurrence was not reported to be high in previous studies and thedonor’s anti-HBc status has not been found to affect survival of the patients andallograft. The presence of HBV deoxyribonucleic acid (HBVDNA) in the long timesurvivors transplanted for HBV related liver disease without biochemical andserological evidence of HBV recurrence were reported recent year.The aim of this monocenter study was to analyze patients’ clinical and histologicalcharacteristics of allograft from anti-HBc-positive donors post-transplantationwithout HBV recurrence.Methods: In March2012, this study identified159patient transplanted for HBVrelated diseases, and27patients received a liver from an anti-HBc-positive donor inoutpatient clinic.45patients were excluded for inadequate follow-up period post LT,10patients were excluded for HBV recurrence. Finially,84patients fufilled theinclusion cretieria and19patients eligible for the study were agreed to receive liverbiopsy. The intrahepatic HBVDNA and HBV cccDNA was detected with thereal-time polymerase chain reaction. The histological characteristics were analyzed.All the information of pre-and post-liver transplantation was reviewed.Result:9patients were HBVDNA positive in liver, and7of the9were recipientsreceived anti-HBc donor. The rate of the HBVDNA positivity in liver was87.5%and 18.2%respectively in the anti-HBc positive group and anti-HBc negative group(P=0.003). The HBVcccDNA were not detected in all the biopsies.We also analyzerisk factor affecting the intrahepatic HBVDNA positivity by univariate model. Theresult demonstrates that the donor anti-HBc status was the unique predictor ofHBVDNA positivity in allograft. The histological characteristics were displayed nosignificant difference between the allograft from the anti-HBc positive donor withthose from anti-HBc negative donor.Conclusion:The prevalence of occult infection is much higher in the allograft from the anti-HBcpositive donor than that from anti-HBc negative donor.Despite the persistence ofHBVDNA in liver, there is no biochemical and histological evidence of liver damage.