Dear Editor

I read with great interest the article by Safarpour and colleagues on the epidemiology of hepatitis D virus (HDV) and its associated factors in southern Iran. The authors reported that, of 137 patients with chronic hepatitis B, 21.2% (n=29) tested positive for HDV using a competitive enzyme immunoassay (ELISA) kit, with a reported sensitivity and specificity of approximately 90% and 100%, respectively. ¹

It is important to note that this study included only patients with low hepatitis B virus (HBV) DNA levels. Although HDV infection typically suppresses HBV replication, this is not universal; up to 19.3% of patients could have HBV DNA levels exceeding 10,000 IU/mL by four logs. ² The viral kinetics of HBV and HDV coinfection could be categorized into three profiles: HDV-dominant (low HBV DNA), HBV-dominant (high HBV DNA), and profiles with equivalent levels of both viruses. ² Furthermore, HBV genotype D, the most prevalent genotype in Iran, might co-infect with HDV, leading to higher HBV DNA levels. ²

This study design has limited power to detect HBV/HDV coinfection compared to HDV superinfection. Many guidelines recommend screening all HBsAg-positive individuals for HDV using reliable serological tests, irrespective of HBV DNA level. ³ This limitation raises concerns about the accuracy of the reported HDV prevalence among the HBV-infected patients in this study.

The effect of age on acquiring HDV infection has been described in many reports. Interestingly, in this series, a history of dental procedures was reported as protective. This finding might be a proxy for greater health awareness and better access to healthcare among those without HDV infection. Therefore, it should be interpreted with caution.

Additionally, the study did not report on coinfection with other viruses, such as the hepatitis C virus (HCV) and human immunodeficiency virus (HIV), which are known to increase the risk of HDV acquisition. For example, a study from Shiraz, Iran, demonstrated a higher prevalence of HDV among HIV/HBV-coinfected patients. ⁴

In conclusion, this report highlighted the need for more comprehensive and accurately designed studies to assess the true prevalence and impact of HDV infection in Iran.

Acknowledgment

No artificial intelligence (AI)-assisted technologies were used in writing this manuscript.

Conflict of Interest

None declared.

References

1. Safarpour AR, Shahedi A, Fattahi MR, Sadeghi E, Akbarzadeh M, Ahmadi L, et al. Epidemiology of Hepatitis D Virus and Associated Factors in Patients Referred to Level Three Hepatitis Clinic, Fars Province, Southern Iran. Iran J Med Sci. 2025; 50:220-8. Publisher Full Text | DOI | PubMed [ PMC Free Article ]
2. Sausen DG, Shechter O, Bietsch W, Shi Z, Miller SM, Gallo ES, et al. Hepatitis B and Hepatitis D Viruses: A Comprehensive Update with an Immunological Focus. Int J Mol Sci. 2022; 23Publisher Full Text | DOI | PubMed [ PMC Free Article ]
3. European Association for the Study of the L. EASL Clinical Practice Guidelines on hepatitis delta virus. J Hepatol. 2023; 79:433-60. DOI | PubMed
4. Motamedifar MP, Taheri MM, Lankarani KBM, Gholami MB, Lari MAM, Faramarzi HM, et al. The Prevalence and Risk Factors of Hepatitis Delta Virus in HIV/HBV Co-Infected Patients in Shiraz, Iran, 2012. Iran J Med Sci. 2015; 40:448-53. Publisher Full Text | PubMed [ PMC Free Article ]