Observational Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 14, 2018; 24(6): 752-762
Published online Feb 14, 2018. doi: 10.3748/wjg.v24.i6.752
High prevalence of hepatitis B-antibody loss and a case report of de novo hepatitis B virus infection in a child after living-donor liver transplantation
Palittiya Sintusek, Nawarat Posuwan, Piyaporn Wanawongsawad, Suttiruk Jitraruch, Yong Poovorawan, Voranush Chongsrisawat
Palittiya Sintusek, Suttiruk Jitraruch, Yong Poovorawan, Voranush Chongsrisawat, Division of Gastroenterology and Hepatology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
Nawarat Posuwan, Yong Poovorawan, Center of Excellence in Clinical Virology, Chulalongkorn University, Bangkok10330, Thailand
Piyaporn Wanawongsawad, Excellence Center of Organ Transplantation, King Chulalongkorn Memorial Hospital, Bangkok 10330, Thailand
Author contributions: Sintusek P, Poovorawan Y and Chongsrisawat V contributed to study conception and design; Sintusek P and Wanawongsawad P contributed to data acquisition; Sintusek P and Posuwan N were responsible for data analysis and interpretation; Sintusek P wrote the article; Sintusek P, Jitraruch S, Poovorawan Y and Chongsrisawat V contributed to editing, reviewing and final approval of the article.
Supported by the Development of New Faculty Staff, Ratchadaphiseksomphot Endowment Fund to Sintusek P; The Special Task Force for Activating Research in Immune Response in Children with Chronic Liver Diseases and Children after Liver Transplantation, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand to Sintusek P; the Research Chair Grant from the National Science and Technology Development Agency, No. P-15-50004 to Poovorawan Y; and The Center of Excellence in Clinical Virology, Chulalongkorn Unversity and King Chulalongkorn Memorial Hospital, No. GCE 5900930-005 to Poovorawan Y.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee, Faculty of Medicine, Chulalongkorn University (IRB number 614/60).
Informed consent statement: All study participants, or their legal guardian, provided verbal consent prior to study enrolment.
Conflict-of-interest statement: None of the authors has any potential conflict to declare.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at voranush.c@chula.ac.th. Consent was not obtained but the presented data are anonymized and the risk of identification is low.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Voranush Chongsrisawat, MD, Associated Professor, Chief, Division of Gastroenterology and Hepatology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, 1873 Rama 4 Road, Pathumwan, Bangkok 10330, Thailand. voranush.c@chula.ac.th
Telephone: +66-2-2564951 Fax: +66-2-2564911
Received: December 5, 2017
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
Processing time: 62 Days and 8.8 Hours
ARTICLE HIGHLIGHTS
Research background

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.

Research motivation

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.

Research objectives

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.

Research methods

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.

Research results

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.

Research conclusions

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.

Research perspectives

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.