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
ARTICLE HIGHLIGHTS
Case characteristics

A 74-year-old patient with previous hepatitis B infection presented 11 years after kidney transplantation with diarrhea, loss of appetite, and icterus.

Clinical diagnosis

The main clinical finding was acute liver dysfunction.

Differential diagnosis

The differentials of acute liver dysfunction in this patient were acute hepatitis caused by hepatitis B virus (HBV) reactivation or hepatitis D virus (HDV) superinfection or infection with another hepatotropic virus, sepsis, obstruction of bile ducts, cholangitis, tumor, abscess, or thrombosis.

Laboratory diagnosis

Laboratory results revealed acute hepatitis caused by highly replicative HBV subgenotype F3 with immune escape mutations.

Imaging diagnosis

A computed tomography (CT) scan excluded bile duct obstruction, tumor, abscess, and thrombosis.

Pathological diagnosis

Histologic examinations showed acute hepatitis with multiple disseminated acidophilic single cell necroses and pericentral lipofuscinosis, vacuolar lipid droplets, and minimal periportal fibrosis suggesting additional chronic toxic damage.

Treatment

Acute hepatitis B was treated with an antiviral medication, the nucleoside reverse transcriptase inhibitor (NRTI) entecavir (ETV).

Related reports

HBV reactivation has been reported in immunosuppressed patients, patients with de novo infection, and in successfully vaccinated persons (caused by vaccine escape mutations or subgenotype F).

Term explanation

Vaccine or immune escape describes the ability of the HBV to reinfect or reactivate in the presence of neutralizing antibodies that cannot neutralize the virus.

Experiences and lessons

Acute hepatitis caused by hepatitis B infection may occur in a successfully vaccinated patient if the virus escapes antibody neutralization. Escape may be caused by escape mutations that change surface antigens or by a virus genotype that is distantly related to the virus genotype that the second-generation HBV vaccine is based on.