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World J Hepatol. Feb 27, 2021; 13(2): 242-260
Published online Feb 27, 2021. doi: 10.4254/wjh.v13.i2.242
Occult hepatitis C virus infection in the Middle East and Eastern Mediterranean countries: A systematic review and meta-analysis
Mohammad Reza Hedayati-Moghaddam, Hossein Soltanian, Sanaz Ahmadi-Ghezeldasht
Mohammad Reza Hedayati-Moghaddam, Hossein Soltanian, Sanaz Ahmadi-Ghezeldasht, Blood Borne Infections Research Center, Academic Center for Education, Culture and Research (ACECR), Razavi Khorasan Branch, Mashhad 91779-49367, Iran
Author contributions: Hedayati-Moghaddam MR conception and design of the study, analysis and interpretation of data, drafting the paper, revising the article, and final approval; Soltanian H acquisition of data, and final approval; Ahmadi-Ghezeldasht S acquisition of data, drafting the paper, and final approval.
Conflict-of-interest statement: The authors deny any conflict of interest.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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:
Corresponding author: Mohammad Reza Hedayati-Moghaddam, MD, Associate Professor, Blood Borne Infections Research Center, Academic Center for Education, Culture and Research (ACECR), Razavi Khorasan Branch, Ferdowsi University campus, Azadi sq, Mashhad 91779-49367, Iran.
Received: October 5, 2020
Peer-review started: October 5, 2020
First decision: November 16, 2020
Revised: November 25, 2020
Accepted: December 8, 2020
Article in press: December 8, 2020
Published online: February 27, 2021

The presence of hepatitis C virus (HCV) RNA in liver tissue or peripheral blood mononuclear cells with no identified virus genome in the serum has been reported worldwide among patients with either normal or elevated serum liver enzymes. The characterization of occult HCV infection (OCI) epidemiology in the Middle East and Eastern Mediterranean (M and E) countries, a region with the highest incidence and prevalence rates of HCV infection in the world, would be effective for more appropriate control of the infection.


To estimate the pooled prevalence of OCI in M and E countries using a systematic review and meta-analysis.


A systematic literature search was performed using international, regional and local electronic databases. Some conference proceedings and references from bibliographies were also reviewed manually. The search was carried out during May and June 2020. Original observational surveys were considered if they assessed the prevalence of OCI among the population of M and E countries by examination of HCV nucleic acid in peripheral blood mononuclear cells in at least 30 cases selected by random or non-random sampling methods. The meta-analysis was performed using Comprehensive Meta-analysis software based on heterogeneity assessed by Cochran’s Q test and I-square statistics. Data were considered statistically significant at a P value < 0.05.


A total of 116 non-duplicated citations were found in electronic sources and grey literature. A total of 51 non-overlapping original surveys were appraised, of which 37 met the inclusion criteria and were included in the analysis. Data were available from 5 of 26 countries including Egypt, Iran, Pakistan, Saudi Arabia, and Turkey. The overall prevalence rate of OCI was estimated at 10.04% (95%CI: 7.66%-13.05%). The lowest OCI rate was observed among healthy subjects (4.79%, 95%CI: 2.86%-7.93%). The higher rates were estimated for patients suffering from chronic liver diseases (12.04%, 95%CI: 5.87%-23.10%), and multi-transfused patients (8.71%, 95%CI: 6.05%-12.39%). Subgroup analysis indicated that the OCI rates were probably not associated with the studied subpopulations, country, year of study, the detection method of HCV RNA, sample size, patients’ HCV serostatus, and sex (all P > 0.05). Meta-regression analyses showed no significant time trends in OCI rates among different groups.


This review estimated high rates of OCI prevalence in M and E countries, especially among multi-transfused patients as well as patients with chronic liver diseases.

Keywords: Occult hepatitis C, Prevalence, Review, Meta-analysis, Middle East, Eastern Mediterranean region

Core Tip: No comprehensive reported data are available in the literature regarding the estimated prevalence rate of occult hepatitis C virus (HCV) infection in the Middle East and Eastern Mediterranean countries. This is the first systematic review and meta-analysis to calculate occult HCV infection rate in this region. We estimated the overall rate as well as the rates among both healthy and high-risk populations such as those infected with human immunodeficiency virus, patients with end-stage renal diseases, cryptogenic liver diseases, cleared or treated HCV infection, lymphoproliferative disorders, and multi-transfused patients.