Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
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
Research background

Occult hepatitis C virus (HCV) infection (OCI) is defined as the presence of HCV genome in the liver samples or peripheral blood mononuclear cells despite a negative test for serum viral RNA. OCI, a common condition worldwide, might be associated with significant morbidities such as liver cirrhosis or hepatocellular carcinoma. No review has yet been performed to provide a pooled estimate for the OCI prevalence rate in the Middle East and Eastern Mediterranean (M and E) countries, a region with the highest rates of HCV infection in the world.

Research motivation

In this systematic review and meta-analysis, we tried to characterize a clear feature of OCI epidemiology in 26 countries of the M and E region based on documents found by searching international and regional electronic sources as well as some local grey literature. We hope our findings help researchers to perform more investigations on diagnosis, management, and control of OCI, particularly in high-risk populations such as patients with chronic liver disease, multi-transfused patients, those infected with HIV, injecting drug users, etc.

Research objectives

The main objective of this review is to provide pooled mean estimates of the OCI rate and assess the contribution of potential variables on the between-study heterogeneity in the M and E region. The results would help professionals, investigators and policy makers to organize suitable activities regarding OCI, particularly in high-risk patients.

Research methods

A systematic review and meta-analysis was performed following PRISMA guidelines. A comprehensive search of electronic databases was conducted up to June 2020 in the Web of Science, PubMed, SCOPUS, ScienceDirect, ProQuest, the Index Medicus for the Eastern Mediterranean Region, Scientific Information Database, Iranian Database of publication (Magiran), and Iranian Databank of Medical Literature. Also some conference abstracts and all references from bibliographies of retrieved articles were manually reviewed. Forest plots were applied to demonstrate the point prevalence rates and the 95% confidence intervals, and subgroup and meta-regression analyses were applied to identify the factors contributing to heterogeneity between surveys.

Research results

Thirty-seven studies involving 5200 participants from Egypt, Iran, Pakistan, Saudi Arabia, and Turkey were analyzed. The overall pooled prevalence rate of OCI was 10.04%. The pooled rate among healthy populations was 4.79%, but the rate was much higher among patients with hematologic disorders (19.57%), HIV-positive subjects (12.95%), patients with chronic liver diseases (12.04%), and multi-transfused patients (8.71%). The rate of OCI was not significantly related to the country, disease subpopulations, year of study, the method of HCV RNA detection, sample size, patients’ HCV serostatus and sex, and no significant change was detected in the OCI rate over time (P > 0.05).

Research conclusions

This review and meta-analysis demonstrates high rates of OCI prevalence, especially across risk populations in the M and E region. Some appropriate OCI screening programs are recommended to target individuals who are at risk of HCV infection.

Research perspectives

According to this systematic review and meta-analysis, further investigations are required in order to collect more data on the OCI frequency in M and E countries other than Egypt and Iran, two nations with the highest and lowest rates of chronic HCV infection in the region, respectively. Moreover, large scale studies are needed to evaluate OCI prevalence among less studied populations such as injecting drug users, HBV-infected patients, and thalassemia and hemophilia patients.