Occult hepatitis C virus infection in the Middle East and Eastern Mediterranean countries: A systematic review and meta-analysis

BACKGROUND: 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. AIM: To estimate the pooled prevalence of OCI in M and E countries using a systematic review and meta-analysis. METHODS: 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. RESULTS: 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. CONCLUSION: 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.