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World J Methodol. May 20, 2022; 12(3): 179-190
Published online May 20, 2022. doi: 10.5662/wjm.v12.i3.179
Global prevalence of occult hepatitis C virus: A systematic review and meta-analysis
Donatien Serge Mbaga, Sebastien Kenmoe, Jacky Njiki Bikoï, Guy Roussel Takuissu, Marie Amougou-Atsama, Etienne Atenguena Okobalemba, Jean Thierry Ebogo-Belobo, Arnol Bowo-Ngandji, Martin Gael Oyono, Jeannette Nina Magoudjou-Pekam, Ginette Irma Kame-Ngasse, Alex Durand Nka, Alfloditte Flore Feudjio, Cromwel Zemnou-Tepap, Elie Adamou Velhima, Juliette Laure Ndzie Ondigui, Rachel Audrey Nayang-Mundo, Sabine Aimee Touangnou-Chamda, Yrene Kamtchueng Takeu, Jean Bosco Taya-Fokou, Chris Andre Mbongue Mikangue, Raoul Kenfack-Momo, Cyprien Kengne-Ndé, Carole Stephanie Sake, Seraphine Nkie Esemu, Richard Njouom, Lucy Ndip, Sara Honorine Riwom Essama
Donatien Serge Mbaga, Jacky Njiki Bikoï, Arnol Bowo-Ngandji, Juliette Laure Ndzie Ondigui, Sabine Aimee Touangnou-Chamda, Jean Bosco Taya-Fokou, Chris Andre Mbongue Mikangue, Carole Stephanie Sake, Sara Honorine Riwom Essama, Department of Microbiology, The University of Yaounde I, Yaounde 00237, Cameroon
Sebastien Kenmoe, Seraphine Nkie Esemu, Lucy Ndip, Department of Microbiology and Parasitology, University of Buea, Buea 00237, Cameroon
Sebastien Kenmoe, Richard Njouom, Department of Virology, Centre Pasteur of Cameroon, Yaounde 00237, Cameroon
Guy Roussel Takuissu, Centre of Research in Food, Food Security and Nutrition, Institute of Medical Research and Medicinal Plants Studies, Yaounde 00237, Cameroon
Marie Amougou-Atsama, Centre de Recherche sur les Maladies Emergentes et Re-Emergentes, Institute of Medical Research and Medicinal Plants Studies, Yaounde 00237, Cameroon
Etienne Atenguena Okobalemba, Faculty of Medicine and Biomedical Science, The University of Yaounde I, Yaounde 00237, Cameroon
Jean Thierry Ebogo-Belobo, Ginette Irma Kame-Ngasse, Elie Adamou Velhima, Yrene Kamtchueng Takeu, Medical Research Centre, Institute of Medical Research and Medicinal Plants Studies, Yaounde 00237, Cameroon
Martin Gael Oyono, Laboratory of Parasitology and Ecology, The University of Yaounde I, Yaounde 00237, Cameroon
Jeannette Nina Magoudjou-Pekam, Alfloditte Flore Feudjio, Cromwel Zemnou-Tepap, Raoul Kenfack-Momo, Department of Biochemistry, The University of Yaounde I, Yaounde 00237, Cameroon
Alex Durand Nka, Virology Laboratory, Chantal Biya International Reference Center for Research on HIV/AIDS Prevention and Management, Yaounde 00237, Cameroon
Rachel Audrey Nayang-Mundo, Department of Microbiology, Protestant University of Central Africa, Yaounde 00237, Cameroon
Cyprien Kengne-Ndé, Epidemiological Surveillance, Evaluation and Research Unit, National Aids Control Committee, Douala 00237, Cameroon
Author contributions: Kenmoe S, Mbaga DS, and Riwom Essama SH were responsible for conception and design of the study as well as project administration; Mbaga DS, Kenmoe S, Njiki Bikoï J, Takuissu GR, Amougou Atsama M, Atenguena Okobalemba E, Ebogo-Belobo JT, Bowo-Ngandji A, Oyono MG, Magoudjou-Pekam JN, Kame-Ngasse GI, Nka AD, Feudjio AF, Zemnou-Tepap C, Velhima EA, Ndzie Ondigui JL, Nayang Mundo RA, Touangnou-Chamda SA, Kamtchueng Takeu Y, Taya-Fokou JB, Mbongue Mikangue CA, Kenfack-Momo R, and Kengne-Nde C were responsible for the data curation and interpretation of results; Kengne-Nde C and Kenmoe S were responsible for statistical analysis; Kenmoe S, Mbaga DS, and Riwom Essama SH were responsible for the project supervision; Kenmoe S and Mbaga DS wrote the original draft; All authors critically reviewed the first draft and approved the final version of the paper for submission, and have read and approved the final manuscript.
Supported by the European Union (EDCTP2 programme), No. TMA2019PF-2705.
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: Sebastien Kenmoe, PhD, Assistant Lecturer, Department of Microbiology and Parasitology, University of Buea, Molyko to Buea town Rd, Buea 00237, Cameroon.
Received: December 9, 2021
Peer-review started: December 9, 2021
First decision: February 15, 2022
Revised: March 3, 2022
Accepted: April 29, 2022
Article in press: April 29, 2022
Published online: May 20, 2022

Occult hepatitis C infection (OCI) is characterized by the presence of hepatitis C virus (HCV) RNA in the liver, peripheral blood mononuclear cells (PBMC) and/or ultracentrifuged serum in the absence of detectable HCV-RNA in serum. OCI has been described in several categories of populations including hemodialysis patients, patients with a sustained virological response, immunocompromised individuals, patients with abnormal hepatic function, and apparently healthy subjects.


To highlight the global prevalence of OCI.


We performed a systematic and comprehensive literature search in the following 4 electronic databases PubMed, EMBASE, Global Index Medicus, and Web of Science up to 6th May 2021 to retrieve relevant studies published in the field. Included studies were unrestricted population categories with known RNA status in serum, PBMC, liver tissue and/or ultracentrifuged serum. Data were extracted independently by each author and the Hoy et al tool was used to assess the quality of the included studies. We used the random-effect meta-analysis model to estimate the proportions of OCI and their 95% confidence intervals (95%CI). The Cochran's Q-test and the I2 test statistics were used to assess heterogeneity between studies. Funnel plot and Egger test were used to examine publication bias. R software version 4.1.0 was used for all analyses.


The electronic search resulted in 3950 articles. We obtained 102 prevalence data from 85 included studies. The pooled prevalence of seronegative OCI was estimated to be 9.61% (95%CI: 6.84-12.73) with substantial heterogeneity [I² = 94.7% (95%CI: 93.8%-95.4%), P < 0.0001]. Seropositive OCI prevalence was estimated to be 13.39% (95%CI: 7.85-19.99) with substantial heterogeneity [I2 = 93.0% (90.8%-94.7%)]. Higher seronegative OCI prevalence was found in Southern Europe and Northern Africa, and in patients with abnormal liver function, hematological disorders, and kidney diseases. Higher seropositive OCI prevalence was found in Southern Europe, Northern America, and Northern Africa.


In conclusion, in the present study, it appears that the burden of OCI is high and variable across the different regions and population categories. Further studies on OCI are needed to assess the transmissibility, clinical significance, long-term outcome, and need for treatment.

Keywords: Occult hepatitis C virus infection, Prevalence, Worldwide, Peripheral blood mononuclear cells, Hepatitis C virus

Core Tip: This study showed that the burden of seropositive and seronegative occult hepatitis C infections (OCIs) is high and variable in different regions and population categories. Patients with hematological disorders, kidney diseases, and abnormal liver function showed the highest OCI prevalence.