Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 21, 2016; 22(39): 8720-8734
Published online Oct 21, 2016. doi: 10.3748/wjg.v22.i39.8720
Update on occult hepatitis B virus infection
Manoochehr Makvandi
Manoochehr Makvandi, Health Research Institute, Infectious and Tropical Disease Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz 15794-61357, Iran
Manoochehr Makvandi, Department of Medical Virology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz 15794-61357, Iran
Author contributions: Makvandi M solely wrote this paper.
Conflict-of-interest statement: The author declares that there are no conflicts of interest in the content of this review.
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:
Correspondence to: Dr. Manoochehr Makvandi, Health Research Institute, Infectious and Tropical Disease Research Center, Ahvaz Jundishapur University of Medical Sciences, Boulevard Golestan, Ahvaz 15794-61357, Iran.
Telephone: +98-9166181683 Fax: +98-6113738313
Received: March 28, 2016
Peer-review started: March 29, 2016
First decision: May 30, 2016
Revised: June 13, 2016
Accepted: July 20, 2016
Article in press: July 21, 2016
Published online: October 21, 2016

The event of mutations in the surface antigen gene of hepatitis B virus (HBV) results in undetectable hepatitis B surface antigen with positive/negative anti-hepatitis B core (anti-HBc) antibody status in serum and this phenomenon is named occult hepatitis B infection (OBI). The presence of anti-HBc antibody in serum is an important key for OBI tracking, although about 20% of OBI cases are negative for anti-HBc antibody. The diagnosis of OBI is mainly based on polymerase chain reaction (PCR) and real-time PCR assays. However, real-time PCR is a more reliable method than PCR. OBI is a great issue for the public health problem and a challenge for the clinical entity worldwide. The persistence of OBI may lead to the development of cirrhosis and hepatocellular carcinoma. With regard to OBI complications, the screening of HBV DNA by the highly sensitive molecular means should be implemented for: (1) patients with a previous history of chronic or acute HBV infection; (2) patients co-infected with hepatitis C virus/human immunodeficiency virus; (3) patients undergoing chemotherapy or anti-CD20 therapy; (4) recipients of organ transplant; (5) blood donors; (6) organ transplant donors; (7) thalassemia and hemophilia patients; (8) health care workers; (9) patients with liver related disease (cryptogenic); (10) hemodialysis patients; (11) patients undergoing lamivudine or interferon therapy; and (12) children in time of HBV vaccination especially in highly endemic areas of HBV. Active HBV vaccination should be implemented for the close relatives of patients who are negative for OBI markers. Thus, the goal of this review is to evaluate the rate of OBI with a focus on status of high risk groups in different regions of the world.

Keywords: Nested polymerase chain reaction, Occult hepatitis B infection, Cryptogenic, Real-time polymerase chain reaction

Core tip: Occult hepatitis B infection (OBI) is defined as negative hepatitis B surface antigen and positive/negative anti-hepatitis B core immunoglobulin G status but hepatitis B virus (HBV) DNA is detectable in serum and liver tissue. Genotypes A, C, G, E and D have been found among patients with OBI in different regions of the world. Genotype D is the only dominant genotype among Iranian OBI patients. OBI has been reported among many high risk groups, including blood donors, liver transplant recipients, patients co-infected with hepatitis C virus/human immunodeficiency virus, patients undergoing immunosuppressive therapy or hemodialysis, patients with liver cirrhosis, cryptogenic liver disease, or abnormal alanine transaminase, healthcare workers, patients with lymphoma or rheumatoid arthritis. It is recommended that to manage and reduce OBI and HBV carriage, the screening of HBV DNA be implemented among high risk groups by means of highly sensitive molecular assays periodically. In addition, comprehensive investigations are needed to understand the epidemiology of OBI worldwide.