Brief Article
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World J Gastroenterol. Oct 7, 2013; 19(37): 6214-6220
Published online Oct 7, 2013. doi: 10.3748/wjg.v19.i37.6214
Incidence and characteristics of HBV reactivation in hematological malignant patients in south Egypt
Abeer Elkady, Sahar Aboulfotuh, Elsayed Mostafa Ali, Douaa Sayed, Nashwa M Abdel-Aziz, Amany M Ali, Shuko Murakami, Sayuki Iijima, Yasuhito Tanaka
Abeer Elkady, Shuko Murakami, Sayuki Iijima, Yasuhito Tanaka, Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan
Abeer Elkady, Department of Clinical and Chemical Pathology, Medical School of South Valley University, Qena 83523, Egypt
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, 71515 Assuit, Egypt
Author contributions: Elkady A 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; Ali EM, Aboulfotuh S, Sayed D, Abdel-Aziz NM, and Ali AM contributed to the collection of the materials and patient data; Murakami S and Iijima S contributed to the analysis and interpretation of the data.
Supported by The Grant for National Center For Global Health and Medicine (22A-9); a Grant-in-Aid form Japan Society for the Promotion of Science (JSPS) Fellows (21.09355) and a Grant-in-Aid form the Ministry of Health, Labour and Welfare of Japan
Correspondence to: Yasuhito Tanaka, MD, PhD, Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan. ytanaka@med.nagoya-cu.ac.jp
Telephone: +81-52-8538191 Fax: +81-52-8420021
Received: April 27, 2013
Revised: July 24, 2013
Accepted: August 4, 2013
Published online: October 7, 2013
Abstract

AIM: To investigate characteristics of hepatitis B virus (HBV) implicated in HBV reactivation in patients with hematological malignancies receiving immunosuppressive therapy.

METHODS: Serum samples were collected from 53 patients with hematological malignancies negative for hepatitis B surface antigen (HBsAg) before the start of and throughout the chemotherapy course. HBV reactivation was diagnosed when the HBsAg status changed from negative to positive after the initiation of chemotherapy and/or when HBV DNA was detected by real-time detection polymerase chain reaction (RTD-PCR). For detecting the serological markers of HBV infection, HBsAg as well as antibodies to the core antigen (anti-HBc) and to the surface antigen were measured in the sera by CEIA. Nucleic acids were extracted from sera, and HBV DNA sequences spanning the S gene were amplified by RTD-PCR. The extracted DNA was further subjected to PCR to amplify the complete genome as well as the specific genomic sequences bearing the enhancer II/core promoter/pre-core/core regions (nt 1628-2364). Amplicons were sequenced directly.

RESULTS: Thirty-five (66%) of the 53 HBsAg-negative patients were found to be negative serologically for anti-HBc, and the remaining 18 (34%) patients were positive for anti-HBc. Five of the 53 (9.4%) patients with hematologic malignancies experienced HBV reactivation. Genotype D1 was detected in all five patients. Four types of mutant strains were detected in the S gene product of HBV strains and were isolated from 3 patients with HBV reactivation: T/S120, L143, and I126. HBV DNA was detected in the pretreatment HBsAg-negative samples in one of the five patients with HBV reactivation. In this patient, sequences encompassing the HBV full genome obtained from sera before the start of chemotherapy and at the time of de novo HBV hepatitis were detected and it showed 100% homology. Furthermore, in the phylogenetic tree, the sequences were clustered together, thereby indicating that this patient developed reactivation from an occult HBV infection.

CONCLUSION: Past infection with HBV is a risk factor for HBV reactivation in Egypt. Mandatory anti-HBc screening prior to chemotherapy in patients with hematological malignancies is recommended.

Keywords: Hepatitis B virus, Occult infection, Reactivation, Hepatitis B surface antigen

Core tip: The study aimed to investigate characteristics of hepatitis B virus (HBV) implicated in HBV reactivation in patients with hematological malignancies receiving immunosuppressive therapy in Egypt. Fifty-three hepatitis B surface antigen (HBsAg)-negative patients treated with chemotherapy were included in the study. The incidence of HBV reactivation was 9.4% among the studied cohort, and all of the affected individuals were positive for HBsAg as well as antibodies to the hepatitis B core antigen. The present study provides further evidence via molecular evolutionary analysis of the development of HBV reactivation from an occult HBV infection. Past infection with HBV is a risk factor for HBV reactivation in Egypt. Mandatory antibodies to the core antigen screening prior to chemotherapy in patients with hematological malignancies is suggested.