Prevalence of occult hepatitis B virus infection in Egypt: a systematic review with meta-analysis

Azzam et al. Journal of the Egyptian Public Health Association https://doi.org/10.1186/s42506-023-00138-4 (2023) 98:13 Journal of the Egyptian Public Health Association Open Access REVIEW Prevalence of occult hepatitis B virus infection in Egypt: a systematic review with meta‑analysis Ahmed Azzam1*, Heba Khaled2, Esraa S. El‑kayal3, Fathy A. Gad4 and Sarah Omar5 Abstract Background Occult hepatitis B virus (HBV) infection (OBI) is a major public health problem. The clinical importance of OBI stems from the fact that it can be transmitted to healthy individuals at extremely low viral load levels. Addition‑ ally, immunosuppression has the potential to trigger viral replication, which can result in life-threatening liver decom‑ pensation. Despite several studies examining the prevalence of OBI, the pooled prevalence of OBI in Egypt remains unknown, particularly among blood donors and high-risk individuals, to whom intervention should be targeted. Methods A comprehensive literature search of the following databases was conducted from inception to October 2022 using the following keywords: occult hepatitis B virus infection or occult HBV infection or OBI and Egypt in MED‑ LINE [PubMed], Scopus, Google Scholar, and Web of Science. The review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. I-squared and Cochran’s Q were used to measure the heterogeneity between the studies, and based on the random effects model, results were reported as proportions (%) with a 95% confidence interval (CI). Analyses of subgroup analyses were conducted based on the target population. Sensitivity analyses were conducted using the leave-one-out approach to test the robust‑ ness of the results. Results A total of 50 studies with 62 estimations of OBI were included, 19 in patients who were HBsAg-negative and anti-HBc-positive and 43 in patients who were HBsAg-negative. The highest prevalence (41%) was among multitransfused patients according to studies that report occult hepatitis B virus prevalence in an HBsAg-negative popula‑ tion, while the pooled prevalence of OBI among patients on hemodialysis, patients with chronic hepatitis C infection, patients with hepatocellular carcinoma (HCC), and patients with liver cirrhosis was 17%, 10%, 24%, and 13%, respec‑ tively. On the other hand, among studies that report OBI prevalence in HBsAg-negative and anti-HBc-positive indi‑ viduals, the pooled prevalence of OBI among blood donors, patients with chronic hepatitis C infection, and patients with HCC was 12%, 15%, and 31%, respectively. Also, the majority of studies examining the genetic background of OBI have found that genotype D is the most prevalent. Conclusion  This study highlights the high prevalence in OBI among blood donors and high-risk populations in Egypt. The implementation of HBV nucleic acid amplification testing (NAT) may increase the safety of blood trans‑ fusions by excluding all HBV DNA-positive donations. However, the cost-effectiveness of these tests should be investigated. Keywords Prevalence, Epidemiology, Occult hepatitis B, OBI, Hepatitis B virus, HBV, Meta-analysis, Genotype D, Egypt *Correspondence: Ahmed Azzam Full list of author information is available at the end of the article © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Azzam et al. Journal of the Egyptian Public Health Association (2023) 98:13 1 Introduction Hepatitis B virus (HBV) is a partially double-stranded DNA virus belonging to the genus Orthohepadnavirus and the virus family Hepadnaviridae [1]. Chronic HBV infection affects between 257 and 400 million people worldwide [2–4]. Globally, approximately 29% of cirrhosis-related deaths are attributed to HBV [5]. Hepatitis B now ranks as the 15th leading cause of global mortality worldwide [6]. According to the European Association for the Study of the Liver (EASL), HBV infection is classified into five phases: (I) HBeAg-positive chronic infection, (II) HBeAg-positive chronic hepatitis, (III) HBeAg-negative chronic infection, (IV) HBeAg-negative chronic hepatitis, and (V) HBsAg-negative phase or occult HBV infection [7]. Occult HBV infection was defined by a panel of experts as the presence of HBV DNA in the liver (with detectable or undetectable HBV DNA in the blood) in those who tested negative for HBsAg using currently available diagnostics [8]. For HBV testing, the current WHO clinical guidelines recommend an initial HBsAg test. This approach is also applicable to high-risk populations, such as people infected with the hepatitis C virus, those on hemodialysis, and those with advanced chronic liver disease of unknown etiology [9]. Unfortunately, this strategy poses the risk of overlooking OBI. OBI can be categorized as seropositive or seronegative, defined by serum markers of HBV infection. The majority of cases are seropositive [10]. Seropositive OBI is characterized by the detection of anti-HBc antibodies with or without anti-HBs, while seronegative OBI is characterized by undetectable antibodies, both anti-HBc and anti-HBs [11]. The clinical impact of OBI includes the following: First, it plays a significant role in the progression of liver diseases, including hepatocellular carcinoma and liver cirrhosis; second, it can spread to healthy individuals even at extremely low viral load levels. Third, immunosuppressive therapies in patients with OBI may trigger HBV reactivation [12]. Globally, the overall prevalence of OBI was 0.2% (95% CI: 0.1–0.4) in HBsAg-negative blood donors [13]. The prevalence of OBI was generally higher in countries with low economic status; for instance, in Africa, OBI prevalence in HBsAg-negative blood donors was 5% (95% CI: 0.7–12.6) [13]. Regardless of the endemicity, OBI prevalence was high in high-risk groups: 5.5% (95% CI 2.9–8.7) in low-endemicity countries, 5.2% (2.5–8.6) in intermediate-endemicity countries, and 12% (3.4–24.7) in highendemicity countries [14]. Despite several studies addressing the prevalence of OBI, the pooled prevalence of OBI in Egypt remains unknown, especially in specific subpopulations such Page 2 of 16 as blood donors, thos (...truncated)