Published online Feb 14, 2018. doi: 10.3748/wjg.v24.i6.752
Peer-review started: December 6, 2017
First decision: December 21, 2017
Revised: January 5, 2018
Accepted: January 20, 2018
Article in press: January 20, 2018
Published online: February 14, 2018
A more rapid decline of anti-HBs antibody was observed in children after liver transplantation compared to healthy children who had been previously immunized. The loss of anti-HBs might not indicate a loss of hepatitis B virus (HBV) immunity in healthy subjects. However, viral reactivation and de novo hepatitis B infection were clearly demonstrated in an HBsAg-negative recipient who received a liver from hepatitis B core antibody-positive or negative donors, suggesting the loss of HBV protection in such immunocompromised subjects. The present study provided strong evidence of HBV immunity loss in 60% of children after liver transplantation and one case of de novo hepatitis B infection. This was despite a high titer of anti-HBs prior to transplantation and the receipt of a hepatitis B core-negative liver. The present study highlighted the importance of developing strategies to re-establish active immunity to HBV following liver transplantation.
HBV infection in patients after liver transplantation can lead to chronic hepatitis, shorter graft survival and graft loss. However, a routine strategy for HBV reimmunization after liver transplantation, and an appropriate cutoff for the prevention of de novo hepatitis B infection, have yet to be elucidated. This study demonstrated a decline of anti-HBs level after liver transplantation and provided valuable data relating to the factors which can affect the rapid loss of anti-HBs and which can be modulated before liver transplantation in order to delay rapid anti-HBs loss. Such factors include booster hepatitis B vaccines and the early administration of albumin. A revaccination program is recommended for children after liver transplantation in order to re-establish active immunity to HBV.
Regular assessment of anti-HBs and revaccination after liver transplantation to maintain an anti-HBs titer level above the protective threshold should be considered to prevent de novo hepatitis B. Further studies should aim to identify the best rationale for a reimmunization program to effectively re-establish active immunity to HBV.
The authors enrolled a total of 50 children who had undergone liver transplantation between May 2001 and June 2017. Demographic data, types of donor and liver transplant, anti-HBs level, time since liver transplantation, complications and immunosuppressant-use were collated and analyzed using SPSS version 24.0.0 software. To this end, the authors reported an observational study of a five-year-old boy who had received full HBV vaccination previously, underwent liver transplantation with his father’s anti-HBc-negative liver, but was then diagnosed with de novo hepatitis B three years after transplantation.
The authors found that the loss of hepatitis B immunity after liver transplantation was unexpectedly common and that 60% of subjects had an anti-HBs level < 10 IU/L after a mean period of 2.53 years after transplantation. The potential factors relating to the loss of HBV immunity were anti-HBs (P = 0.002), serum albumin (P = 0.04), total bilirubin (P = 0.001) and direct bilirubin (P = 0.003) prior to liver transplantation. We also report a case of de novo hepatitis B, who received a hepatitis B core antibody-negative liver from his father, and had a high titer of anti-HBs (> 1000 IU/L) prior to transplantation. Future studies should aim to develop strategies to re-establish active immunity to HBV after liver transplantation.
The new findings of this study are the high prevalence of hepatitis B immunity loss, and a case report of de novo hepatitis B, in a previously immunized recipient who received a liver from a hepatitis B core antibody-negative donor. De novo hepatitis B in a previously immunized recipient who received a liver from a hepatitis B core antibody-negative donor, could have been initiated when exposed to HBV during the period following transplantation coincident with the loss of HBV immunity. High anti-HBs loss after liver transplantation is unexpectedly common. High anti-HBs (> 1000 IU/L) prior to liver transplantation cannot prevent de novo hepatitis. Serum anti-HBs, albumin, total bilirubin and direct bilirubin prior to liver transplantation were the potential factors associated with the loss of HBV immunity after liver transplantation. Anti-HBs levels below the protective level in children after liver transplantation might reflect the loss of immunity or the loss of protection against HBV. A re-immunization program for all liver-transplanted children in order to prevent de novo hepatitis B. Disease severity, nutritional status, immune status and HBV immunity as a result of HBV immunization might represent potential factors to consider for re-establishing active HBV immunity following liver transplantation. De novo hepatitis B could have occurred after liver transplantation at a point when the recipient was likely to have been exposed to HBV.
Re-assessment of anti-HBs levels and vaccination to maintain levels of anti-HBs above the protective level might prevent de novo hepatitis B after liver transplantation. Studying the immunological response of HBsAg-specific T and B cells following HBV exposure in order to establish an appropriate cutoff for the protective level of anti-HBs to prevent HBV infection in children after liver transplantation will be merit. Moreover, setting up an appropriate HBV immunization protocol to re-establish active HBV immunity by assessing cellular and humoral immunity response after HBV immunization protocols over short- and long-term follow-up periods also should be considered.