Case Report
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jul 27, 2018; 10(7): 509-516
Published online Jul 27, 2018. doi: 10.4254/wjh.v10.i7.509
Hepatitis B virus subgenotype F3 reactivation with vaccine escape mutations: A case report and review of the literature
Stefan Schlabe, Kathrin van Bremen, Souhaib Aldabbagh, Dieter Glebe, Corinna M Bremer, Tobias Marsen, Walter Mellin, Veronica Di Cristanziano, Anna M Eis-Hübinger, Ulrich Spengler
Stefan Schlabe, Kathrin van Bremen, Souhaib Aldabbagh, Anna M Eis-Hübinger, Ulrich Spengler, German Center of Infectious Diseases Research (DZIF), Partner-Site Cologne-Bonn, Bonn-Cologne35392, Germany
Stefan Schlabe, Kathrin van Bremen, Ulrich Spengler, Department of Internal Medicine I, University Hospital of Bonn, Bonn 53127, Germany
Souhaib Aldabbagh, Anna M Eis-Hübinger, Institute of Virology, University Hospital of Bonn, Bonn 53127, Germany
Dieter Glebe, Corinna M Bremer, Institute of Medical Virology, Justus Liebig University Giessen, National Reference Center for Hepatitis B and D Viruses, Biomedical Research Center Seltersberg, Giessen 35392, Germany
Dieter Glebe, Corinna M Bremer, German Center of Infectious Diseases Research (DZIF), Partner-Site Giessen, Giessen 35392, Germany
Tobias Marsen, Practice of Nephrology and Dialysis, Nephrological Center Cologne-Lindenthal, Cologne 50937, Germany
Walter Mellin, Practice of Pathology and Cytology, Cologne 50931, Germany
Veronica Di Cristanziano, Institute of Virology, University Hospital of Cologne, Cologne 50935, Germany
Author contributions: Schlabe S and van Bremen K wrote the manuscript; Marsen T wrote the nephrological medical history, including transplantation and HBV management before transplantation; Mellin W discussed pathological findings of HBV reactivation; Eis-Hübinger AM, Aldabbagh S, Bremer CM, and Glebe D characterized the resistant virus and performed deep sequencing; Di Cristanziano V, Schlabe S, van Bremen K, Marsen T and Spengler U took care of the patient; escape mechanism and impact of second and third-generation vaccines were discussed and revised by Schlabe S, Spengler U, Eis-Hübinger AM, and Glebe D; the phylogenetic analysis and alignment were done by Eis-Hübinger AM and Aldabbagh S; all authors read and approved the final manuscript.
Informed consent statement: The patient gave informed consent for the publication of his medical history. Identifying details were omitted or anonymized.
Conflict-of-interest statement: Spengler U has consulted for AbbVie and has received a royalty from UpToDate for another study. Marsen T has received speakers honoraria from GHD Gesundheits GmbH and Fresenius Medical Care Nephrology for another study. Schlabe S has received sponsoring for educational events from Janssen for another study. All other authors state no conflict of interest.
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: Stefan Schlabe, MD, Doctor, Resident, Department of Internal Medicine I, University Hospital of Bonn, Sigmund-Freud-Str. 25, Bonn 53127, Germany.stefan.schlabe@ukbonn.de
Telephone: +49-163-7477199
Received: April 6, 2018
Peer-review started: April 7, 2018
First decision: April 23, 2018
Revised: May 8, 2018
Accepted: June 7, 2018
Article in press: June 8, 2018
Published online: July 27, 2018
Processing time: 112 Days and 19.4 Hours
Abstract

Hepatitis B represents a global health threat because its chronic course and sequelae contribute to a high morbidity and mortality. Hepatitis B virus (HBV) infection can be controlled by vaccines, antiviral treatment, and by interrupting transmission. Rare vaccine escape mutants are serious because they eliminate vaccine protection. Here, we present a 74-year-old vaccinated patient with HBV reactivation 11 years after kidney transplantation. The patient was HBV-positive but HBsAg-negative prior to vaccination 6 years before transplantation. The reactivated virus was HBV genotype F3 with vaccine escape mutations G145R, P120Q, and Q129P. The patient was successfully treated with entecavir. The epidemiological reasons for this subgenotype, which is extremely rare in Western Europe, were unclear. This case illustrates that second-generation vaccines are not always effective in a specific group of patients.

Keywords: Entecavir; Hepatitis B virus; Subgenotype F3; Kidney transplantation; Vaccine escape mutant G145R

Core tip:We report the first documented case of hepatitis B virus (HBV) subgenotype F3 reactivation with vaccine escape mutations in a patient after kidney transplantation. We successfully treated this patient with entecavir. This case illustrates a specific clinical situation in which the current World Health Organization HBV vaccine may be unsuccessful, and third generation vaccines should be considered.