Copyright
©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
Characteristics of escape mutations from occult hepatitis B virus infected patients with hematological malignancies in South Egypt
Abeer Elkady, Sayuki Iijima, Sahar Aboulfotuh, Elsayed Mostafa Ali, Douaa Sayed, Nashwa M Abdel-Aziz, Amany M Ali, Shuko Murakami, Masanori Isogawa, Yasuhito Tanaka
Abeer Elkady, Department of Clinical and Chemical Pathology, Medical School of South Valley University, Qena 83523, Egypt
Abeer Elkady, Sayuki Iijima, Shuko Murakami, Masanori Isogawa, Yasuhito Tanaka, Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan
Sahar Aboulfotuh, Department of Clinical and Chemical Pathology, Medical School of Sohag University, Sohag 82524, Egypt
Elsayed Mostafa Ali, Department of Medical Oncology, Medical School of Sohag University, Sohag 82524, Egypt
Douaa Sayed, Department of Clinical and Chemical Pathology, South Egypt Cancer Institute, Assuti 71515, Egypt
Nashwa M Abdel-Aziz, Amany M Ali, Department of Medical Oncology, South Egypt Cancer Institue, Assuit 71515, Egypt
Author contributions: Elkady A and Iijima S contributed equally to this work; Elkady A, Iijima S and Tanaka Y designed the study, directed its implementation, supervised all of the field activities and contributed to the analysis and interpretation of the data as well as to the redaction of the manuscript; Aboulfotuh S, Mostafa Ali E, Sayed D, Abdel-Aziz NM and Ali AM contributed to the collection of the materials and patient data; Murakami S and Isogawa M read the draft and approved the data.
Supported by Japan Society for the Promotion of Science, No. 15H05289.
Institutional review board statement: The study was reviewed and approved by the South Egypt Cancer Institute (Egypt).
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: Authors do not have any financial or personal relationship with other people or organizations that could inappropriately influence their work.
Data sharing statement: No additional data are available.
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: Yasuhito Tanaka, MD, PhD, Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, 467-8601 Kawasumi, Mizuho, Nagoya 467-8601, Japan.
ytanaka@med.nagoya-cu.ac.jp
Telephone: +81-52-8538191 Fax: +81-52-8420021
Received: June 8, 2016
Peer-review started: June 13, 2016
First decision: July 20, 2016
Revised: September 19, 2016
Accepted: December 13, 2016
Article in press: December 14, 2016
Published online: March 28, 2017
Processing time: 288 Days and 11.6 Hours
AIM
To investigate the prevalence and virological characteristics of occult hepatitis B virus (HBV) infections in patients with hematological malignancies in South Egypt.
METHODS
Serum samples were collected from 165 patients with hematological malignancies to monitor titers of HBV DNA, hepatitis B surface antigen (HBsAg), and antibodies to HBV core (anti-HBc) and surface antigens. Serum samples negative for HBsAg and positive for anti-HBc were subjected to nucleic acid extraction and HBV DNA detection by real-time polymerase chain reaction. DNA sequences spanning the S region were analyzed in cases with occult HBV infection. In vitro comparative study of constructed 1.24-fold wild type and S protein mutant HBV genotype D clones was further performed.
RESULTS
HBV DNA was detected in 23 (42.6%) of 54 patients with hematological malignancies who were HBsAg negative, but anti-HBc positive, suggesting the presence of occult HBV infection. The complete HBV genome was retrieved from 6 occult HBV patients, and P120T and S143L were detected in 3 and 2 cases, respectively. Site directed mutagenesis was done to produce 1.24-fold genotype D clones with amino acid mutations T120 and L143. The in vitro analyses revealed that a lower level of extracellular HBsAg was detected by chemiluminescence enzyme immunoassay (CLEIA) with the clone containing T120 mutation, compared with the wild type or the clone with S143L mutation despite the similar levels of extracellular and intracellular HBsAg detected by Western blot. Southern blot experiments showed that the levels of intracellular HBV DNA were not different between these clones.
CONCLUSION
Occult HBV infection is common in patients with hematological malignancies and associated with P120T and S143L mutations. 120T mutation impairs the detection of HBsAg by CLEIA.
Core tip: The present study was conducted to investigate the prevalence and virological characteristics of occult hepatitis B virus (HBV) infections in patients with hematological malignancies in Egypt. Serum samples were collected from 165 patients with different hematological malignancies and screened for occult HBV infection. In the present study, occult HBV infection was detected in 23 (42.6%) of 54 patients with hematological malignancies who were hepatitis B surface antigen (HBsAg) negative, but antibodies to HBV core (anti-HBc) positive. Based on in vitro study of clones inserted with 120T and 143L, it was found that the 120T mutation could impair HBsAg detection by changing its conformation. Patients with hematological malignancies should be screened and closely monitored for anti-HBc and HBV DNA.
