Skip to main content

Advertisement

SpringerLink
Log in

Prevalence of occult hepatitis C virus infection in beta-thalassemia major patients in Ahvaz, Iran

  • Original Article
  • Published:
Archives of Virology Aims and scope Submit manuscript

Abstract

Occult hepatitis C virus infection (OCI) is defined by the presence of HCV RNA in peripheral blood mononuclear cells (PBMCs) and liver tissue cells despite the absence of HCV RNA in plasma. Currently, OCI is classified into two types: seropositive OCI (anti-HCV positive and serum HCV RNA negative) and seronegative OCI (anti-HCV and serum HCV RNA negative). Beta-thalassemia is described as a blood disorder that decreases the synthesis of hemoglobin. Repeated blood transfusion is the standard treatment for patients with beta-thalassemia major (BTM), and this increases the risk of exposure to infectious agents. The aim of this study was to investigate the prevalence of OCI among BTM patients. Plasma and PBMCs were collected from 90 BTM patients who were referred to Shafa Hospital in the city of Ahvaz and were screened for HCV antibody using a commercial ELISA kit as the first step. Next, nested RT-PCR was performed on extracts of plasma and PBMCs. HCV RNA from positive PBMCs was sequenced, the sequences were aligned, and a phylogenetic tree was constructed to determine their relationship to reference sequences retrieved from the GenBank database. Seventy-nine out of 90 patients (87.8%) were negative for HCV Ab (seronegative), while 11 patients (12.2%) were seropositive. HCV RNA was found in PBMCs of four patients (66.7%) who were negative for HCV Ab (seronegative) and two patients (33.3%) who were positive for HCV Ab (seropositive). HCV RNA was not detected in plasma samples from these six patients. Six out of 90 BTM patients (6.7%) had OCI. HCV genotyping revealed that all six patients were infected with HCV subtype 3a. We found a high frequency of OCI in BTM patients, which warrants more attention, considering the importance of this infection. Further studies are needed to determine the actual prevalence of OCI in BTM patients in Iran.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Smith DB, Bukh J, Kuiken C, Muerhoff AS, Rice CM, Stapleton JT et al (2014) Expanded classification of hepatitis C virus into 7 genotypes and 67 subtypes: updated criteria and genotype assignment web resource. Hepatology 59(1):318–327

    Article  Google Scholar 

  2. Hedskog C, Parhy B, Chang S, Zeuzem S, Moreno C, Shafran SD et al eds (2019) Identification of 19 novel hepatitis C virus subtypes—further expanding HCV classification. Open Forum Infectious Diseases, Oxford University Press US

  3. Borgia SM, Hedskog C, Parhy B, Hyland RH, Stamm LM, Brainard DM et al (2018) Identification of a novel hepatitis C virus genotype from Punjab, India: expanding classification of hepatitis C virus into 8 genotypes. J Infect Dis 218(11):1722–1729

    Article  Google Scholar 

  4. Alter MJ (2007) Epidemiology of hepatitis C virus infection. World J Gastroenterol: WJG 13(17):2436

    Article  Google Scholar 

  5. Andalibalshohada A, Rezaii SA, Abedi F (2014) HCV prevalence and predominant genotype in IV drug users. Reviews in Clinical Medicine. 1(4):200–206

    Google Scholar 

  6. Rusyn I, Lemon SM (2014) Mechanisms of HCV-induced liver cancer: what did we learn from in vitro and animal studies? Cancer Lett 345(2):210–215

    Article  CAS  Google Scholar 

  7. Petruzziello A, Marigliano S, Loquercio G, Cozzolino A, Cacciapuoti C (2016) Global epidemiology of hepatitis C virus infection: an up-date of the distribution and circulation of hepatitis C virus genotypes. World J Gastroenterol 22(34):7824

    Article  Google Scholar 

  8. Merat S, Rezvan H, Nouraie M, Jafari E, Abolghasemi H, Radmard AR et al (2010) Seroprevalence of hepatitis C virus: the first population-based study from Iran. Int J Infect Dis 14:e113–e116

    Article  Google Scholar 

  9. Rezaee AR, Banoei MM, Khalili E, Houshmand M (2012) Beta-Thalassemia in Iran: new insight into the role of genetic admixture and migration. Sci World J 2012:5

    Article  Google Scholar 

  10. Hamed EM, Meabed MH, Aly UF, Hussein RR (2019) Recent progress in gene therapy and other targeted therapeutic approaches for beta thalassemia. Curr Drug Targets 20(16):1603–1623

    Article  CAS  Google Scholar 

  11. Borgna-Pignatti C, Rugolotto S, De Stefano P, Zhao H, Cappellini MD, Del Vecchio GC et al (2004) Survival and complications in patients with thalassemia major treated with transfusion and deferoxamine. Haematologica. 89(10):1187–93

    PubMed  Google Scholar 

  12. El-Faramawy AAM, El-Rashidy OF, Tawfik PH, Hussein GH (2012) Transfusion transmitted hepatitis: Where do we stand now? A one center study in upper Egypt. Hepat Mon 12(4):286

    Article  Google Scholar 

  13. Din G, Malik S, Ali I, Ahmed S, Dasti JI (2014) Prevalence of hepatitis C virus infection among thalassemia patients: a perspective from a multi-ethnic population of Pakistan. Asian Pac J Trop Med 7:S127–S133

    Article  Google Scholar 

  14. Ataei B, Hashemipour M, Kassaian N, Hassannejad R, Nokhodian Z, Adibi P (2012) Prevalence of anti HCV infection in patients with Beta-thalassemia in isfahan-iran. Int J Prev Med 3(Suppl1):S118

    PubMed  PubMed Central  Google Scholar 

  15. Abolghasemi H, Amid A, Zeinali S, Radfar MH, Eshghi P, Rahiminejad MS et al (2007) Thalassemia in Iran: epidemiology, prevention, and management. J Pediatr Hematol Oncol 29(4):233–238

    Article  Google Scholar 

  16. Behzadifar M, Gorji HA, Bragazzi NL (2018) The prevalence of hepatitis C virus infection in thalassemia patients in Iran from 2000 to 2017: a systematic review and meta-analysis. Arch Virol 163(5):1131–1140

    Article  CAS  Google Scholar 

  17. Ghaderi-Zefrehi H, Gholami-Fesharaki M, Sharafi H, Sadeghi F, Alavian SM (2016) The distribution of hepatitis C virus genotypes in middle eastern countries: a systematic review and meta-analysis. Hepatitis Mon 16:9

    Google Scholar 

  18. Cha RR, Lee SS, Lee CM, Ji SB, Jung HC, Cho HC et al (2016) Clinical features and outcomes of patients with genotype 3 hepatitis C virus infection in Korea: a retrospective observational study. Medicine 95:6

    Google Scholar 

  19. Blackard JT, Smeaton L, Hiasa Y, Horiike N, Onji M, Jamieson DJ et al (2005) Detection of hepatitis C virus (HCV) in serum and peripheral-blood mononuclear cells from HCV-monoinfected and HIV/HCV–coinfected persons. J Infect Dis 192(2):258–265

    Article  Google Scholar 

  20. Laskus T, Radkowski M, Wang L-F, Nowicki M, Rakela J (2000) Uneven distribution of hepatitis C virus quasispecies in tissues from subjects with end-stage liver disease: confounding effect of viral adsorption and mounting evidence for the presence of low-level extrahepatic replication. J Virol 74(2):1014–1017

    Article  CAS  Google Scholar 

  21. Lerat H, Rumin S, Habersetzer F, Berby F, Trabaud M-A, Trépo C et al (1998) In vivo tropism of hepatitis C virus genomic sequences in hematopoietic cells: influence of viral load, viral genotype, and cell phenotype. Blood J Am Soc Hematol 91(10):3841–9

    CAS  Google Scholar 

  22. Di Liberto G, Roque-Afonso AM, Kara R, Ducoulombier D, Fallot G, Samuel D et al (2006) Clinical and therapeutic implications of hepatitis C virus compartmentalization. Gastroenterology 131(1):76–84

    Article  Google Scholar 

  23. Salim FB, Keyvani H, Amiri A, Sefidi FJ, Shakeri R, Zamani F (2010) Distribution of different hepatitis C virus genotypes in patients with hepatitis C virus infection. World J Gastroenterol 16(16):2005

    Article  CAS  Google Scholar 

  24. Dehghani-Dehej F, Sarvari J, Esghaei M, Hosseini SY, Garshasbi S, Kalantari S et al (2018) Presence of different hepatitis C virus genotypes in plasma and peripheral blood mononuclear cell samples of Iranian patients with HIV infection. J Med Virol 90(8):1343–1351

    Article  CAS  Google Scholar 

  25. Gong G-Z, Lai L-Y, Jiang Y-F, He Y, Su X-S (2003) HCV replication in PBMC and its influence on interferon therapy. World J Gastroenterol: WJG 9(2):291

    Article  Google Scholar 

  26. Mohd Hanafiah K, Groeger J, Flaxman AD, Wiersma ST (2013) Global epidemiology of hepatitis C virus infection: new estimates of age-specific antibody to HCV seroprevalence. Hepatology 57(4):1333–1342

    Article  Google Scholar 

  27. Sefidi FJ, Keyvani H, Monavari SH, Alavian SM, Fakhim S, Bokharaei-Salim F (2013) Distribution of hepatitis C virus genotypes in Iranian chronic infected patients. Hepatitis Mon 13:1

    Google Scholar 

  28. Bastani M-N, Bokharaei-Salim F, Keyvani H, Esghaei M, Monavari SH, Ebrahimi M et al (2016) Prevalence of occult hepatitis C virus infection in Iranian patients with beta thalassemia major. Adv Virol 161(7):1899–1906

    CAS  Google Scholar 

  29. Sadeghi F, Bokharaei-Salim F, Salehi-Vaziri M, Monavari SH, Alavian SM, Salimi S et al (2014) Associations between human TRIM22 gene expression and the response to combination therapy with Peg-IFNα-2a and ribavirin in Iranian patients with chronic hepatitis C. J Med Virol 86(9):1499–1506

    Article  CAS  Google Scholar 

  30. Makvandi M, Khalafkhany D, Rasti M, Neisi N, Omidvarinia A, Mirghaed A et al (2014) Detection of Hepatitis C virus RNA in peripheral blood mononuclear cells of patients with abnormal alanine transaminase in Ahvaz. Indian J Med Microbiol 32(3):251

    Article  CAS  Google Scholar 

  31. Radmehr H, Makvandi M, Samarbafzadeh A, Teimoori A, Neisi N, Rasti M et al (2016) Prevalence of Hepatitis C virus Genotype 3a in patients with Hodgkin and Non-Hodgkin Lymphoma. Iran J Microbiol 8(6):389

    PubMed  PubMed Central  Google Scholar 

  32. Ohno O, Mizokami M, Wu R-R, Saleh MG, Ohba K-I, Orito E et al (1997) New hepatitis C virus (HCV) genotyping system that allows for identification of HCV genotypes 1a, 1b, 2a, 2b, 3a, 3b, 4, 5a, and 6a. J Clin Microbiol 35(1):201–7

    Article  CAS  Google Scholar 

  33. Ayadi A, Nafari AH, Irani S, Mohebbi E, Mohebbi F, Sakhaee F et al (2019) Occult hepatitis C virus infection in patients with beta-thalassemia major: Is it a neglected and unexplained phenomenon? J Cell Biochem 120(7):11908–11914

    Article  CAS  Google Scholar 

  34. Kahyesh-Esfandiary R, Sadigh ZA, Esghaei M, Bastani MN, Donyavi T, Najafi A et al (2019) Detection of HCV genome in peripheral blood mononuclear cells of Iranian seropositive and HCV RNA negative in plasma of patients with beta-thalassemia major: Occult HCV infection. J Med Virol 91(1):107–114

    Article  CAS  Google Scholar 

  35. Taherkhani R, Farshadpour F (2015) Epidemiology of hepatitis C virus in Iran. World J Gastroenterol 21(38):10790–10810

    Article  CAS  Google Scholar 

  36. Keikha M, Eslami M, Yousefi B, Ali-Hassanzadeh M, Kamali A, Yousefi M et al (2020) HCV genotypes and their determinative role in hepatitis C treatment. Virusdisease 2020:1–6

    Google Scholar 

  37. Jafroodi M, Davoudi-Kiakalayeh A, Mohtasham-Amiri Z, Pourfathollah AA, Haghbin A (2015) Trend in prevalence of hepatitis C virus infection among β-thalassemia major patients: 10 years of experience in Iran. Int J Prevent Med 2015:6

    Google Scholar 

  38. Castillo I, Pardo M, Bartolomé J, Ortiz-Movilla N, Rodríguez-Iñigo E, Lucas SD et al (2004) Occult hepatitis C virus infection in patients in whom the etiology of persistently abnormal results of liver-function tests is unknown. J Infect Dis 189(1):7–14

    Article  Google Scholar 

  39. Austria A, Wu GY (2018) Occult hepatitis C virus infection: a review. J Clin Transl Hepatol 6(2):155–160

    Article  Google Scholar 

Download references

Acknowledgements

This paper is issued the thesis from MSc by Sepideh Nasimzadeh with registration number OG-9734 and financially supported by Infectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. The authors give their special thanks to the volunteers who have participated in the current study.

Author information

Authors and Affiliations

  1. Infectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Sepideh Nasimzadeh & Azarakhsh Azaran

  2. Department of Medical Virology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Sepideh Nasimzadeh, Azarakhsh Azaran, Shahram Jalilian & Manoochehr Makvandi

  3. Alimentary Tract Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Seyed Saeid Seyedian

  4. Thalassemia and Hemoglobinopathy Research Center Research Institute of Health, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Bijan keikhaei

  5. Department of biostatistics, Faculty of Health, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Fateme Jahangiri Mehr

Authors
  1. Sepideh Nasimzadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Azarakhsh Azaran
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shahram Jalilian
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Manoochehr Makvandi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Seyed Saeid Seyedian
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Bijan keikhaei
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Fateme Jahangiri Mehr
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Azarakhsh Azaran.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Additional information

Handling Editor: Carolina Scagnolari.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nasimzadeh, S., Azaran, A., Jalilian, S. et al. Prevalence of occult hepatitis C virus infection in beta-thalassemia major patients in Ahvaz, Iran. Arch Virol 166, 2703–2710 (2021). https://doi.org/10.1007/s00705-021-05126-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00705-021-05126-7

Search

Navigation