¹Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Saudi Arabia
²Central Blood Bank, Dawadmi General Hospital, Riyadh, Saudi Arabia

*Corresponding Author: Yahya S Altotaibi, Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Saudi Arabia.

Received: May 08, 2025; Published: May 19, 2025

Abstract

Hepatitis E virus (HEV) is an emerging public health concern in Saudi Arabia, yet its molecular epidemiology remains poorly characterized. The current study aims to investigate HEV genotypes circulating in the West Riyadh region through phylogenetic analysis of clinical samples. Molecular epidemiological study was conducted over a two-year 2023-2024 at the Blood Donation Center of Dawadmi General Hospital (BDCDGH). Randomly 100 out of 1100 samples that tested positive for either IgM or IgG antibodies against HEV were selected for further molecular analysis. Only 2% (2/100) of ELISA-positive samples were confirmed HEV RNA-positive by PCR. This 2% PCR positivity likely reflects the natural resolution of most HEV infections in immunocompetent hosts, with only acute cases detectable by PCR, while ELISA captures both past and present exposures. Sequencing identified 2 distinct genotypes, HEV-1a (Dawadmi_Isolate_02) showing 99.7% nucleotide identity with Burmese reference strains, suggesting imported transmission, and HEV-3b (from an Indian worker) closely related (98.06%) to Japanese/Nepalese strains, indicating potential zoonotic or travel-associated exposure. The HEV-1a isolate contained characteristic neutralization epitopes (⁴⁵⁷SGPSLTPF⁴⁶⁴) and proline-rich domains, while the HEV-3b strain harbored subtype-specific mutations (S563L, V617A). Demographic analysis revealed a male-dominated (96%), middle-aged (88% aged 41-60 years) cohort, with unexpected occupational distribution (70% clerks). These findings demonstrate the co-circulation of non-endemic HEV strains in Saudi Arabia, highlighting gaps in current surveillance systems. The study underscores the need for enhanced screening of high-risk groups, zoonotic monitoring, and genomic surveillance to guide prevention strategies in alignment with Saudi Vision 2030 health objectives.

 Keywords: Hepatitis E Virus; Molecular Epidemiology; Saudi Arabia; Genotype; Phylogenetic Analysis; Zoonotic Transmission; HEV-1a; HEV-3b

References

1. World Health Organization (WHO). “Hepatitis E” (2025).
2. Purdy MA., et al. “ICTV Virus Taxonomy Profile: Hepeviridae”. Journal of General Virology12 (2022): 001778.
3. Kenney SP and Meng XJ. “Hepatitis E virus genome structure and replication strategy”. Cold Spring Harbor Perspectives in Medicine9.1 (2019): a031724.  
4. World Health Organization (WHO). “Hepatitis E: Fact Sheet” (2023).
5. Alexandrova R., et al. “Hepatitis E Virus (HEV) infection among immunocompromised individuals: a brief narrative review”. Infection and Drug Resistance (2024): 1021-1040.
6. Adlhoch C., et al. “Hepatitis E virus: Assessment of the epidemiological situation in humans in Europe, 2014/15”. Journal of Clinical Virology 82 (2016): 9-16.
7. El-Daly MM., et al. “Hepatitis E virus (HEV) in Makkah, Saudi Arabia: A population-based seroprevalence study”. Viruses15.2 (2023): 484.
8. Qashqari FS. “Seroprevalence of hepatitis E virus infection in Middle Eastern Countries: A systematic review and meta-analysis”. Medicina58.7 (2022): 905.
9. Shiota T., et al. “The hepatitis E virus capsid C-terminal region is essential for the viral life cycle: Implication for viral genome encapsidation and particle stabilization”. Journal of Virology11 (2013): 6031–6036. 
10. Khan N., et al. “Genetic substructure and host‐specific natural selection trend across vaccine‐candidate ORF‐2 capsid protein of hepatitis‐E virus. Journal of Viral Hepatitis31.9 (2019): 524-534.
11. León-Janampa N., et al. “Relevance of tacrolimus trough concentration and hepatitis E virus genetic changes in kidney transplant recipients with chronic hepatitis E”. Kidney International Reports9.5 (2024): 1333-1342.
12. Antonopoulou N., et al. “Testing Hepatitis E Seroprevalence among HIV-Infected Patients in Greece: THE SHIP Study”. Pathogens7 (2024): 536.
13. Damiris K., et al. “Hepatitis E in immunocompromised individuals”. World Journal of Hepatology14.3 (2022): 482.
14. Mirzaev UK., et al. “Diagnostic accuracy of hepatitis E virus antibody tests: A comprehensive meta‐analysis”. Hepatology Research 55.3 (2025): 346-362.
15. General Authority for Statistics, Kingdom of Saudi Arabia. Labor Force Survey (2023).
16. Montalvo Villalba MC., et al. “Hepatitis E virus in Cuba: A cross‐sectional serological and virological study in pigs and people occupationally exposed to pigs”. Zoonoses and Public Health, 70.1 (2023): 58-68.
17. Haase JA., et al. “Transmission patterns of hepatitis E virus”. Current Opinion in Virology70 (2025): 101451.
18. Saade MC., et al. “The burden of Hepatitis E virus in the Middle East and North Africa region: a systematic review”. The Journal of Infection in Developing Countries5 (2022): 737-744.
19. Lean FZ., et al. “Subclinical hepatitis E virus infection in laboratory ferrets in the UK. Journal of General Virology103.11 (2022): 001803.
20. Pallerla SR., et al. “Hepatitis E virus infection: circulation, molecular epidemiology, and impact on global health”. Pathogens9.10 (2020): 856.
21. Baylis SA., et al. “An evaluation of hepatitis E virus molecular typing methods”. Clinical Chemistry68.1 (2022): 181-191.
22. Kobayashi T., et al. “Production and Characterization of Self-Assembled Virus-like Particles Comprising Capsid Proteins from Genotypes 3 and 4 Hepatitis E Virus (HEV) and Rabbit HEV Expressed in Escherichia coli”. Viruses16.9 (2024): 1400.
23. Purdy MA., et al. “Genetic variability and evolution of hepatitis E virus”. Virus Research1 (2012): 195–202. 
24. Zhang W., et al. “Detection and isolation of genotype 3 subtype b hepatitis E viruses from wild boars in Japan”. Journal of Veterinary Medical Science86.5 (2024): 524-528.
25. Lee GH., et al. “Chronic infection with camelid hepatitis E virus in a liver transplant recipient who regularly consumes camel meat and milk”. Gastroenterology2 (2016): 355–357. 
26. Smith DB., et al. “Update: Proposed reference sequences for subtypes of hepatitis E virus (species Orthohepevirus A)”. Journal of General Virology7 (2020): 692–698. 
27. Lin K and Purdy MA. “Hepatitis E Virus: Isolation, Propagation, and Quantification”. Current Protocols3 (2023): e642.

Citation

Citation: Yahya S Altotaibi., et al. “Genotypic Diversity of Hepatitis E Virus in Clinical Cases from West Riyadh Region, Saudi Arabia”.Acta Scientific Medical Sciences 9.6 (2025): 65-72.

Copyright

Copyright: © 2025 Yahya S Altotaibi., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.