Skip to main content

Advertisement

SpringerLink
Log in

High prevalence of occult hepatitis C virus infection in injection drug users with HIV infection

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

Abstract

One of the pathological forms of chronic hepatitis C is occult HCV infection (OCI), in which there is no detectable HCV RNA in plasma specimens but HCV RNA is present in PBMCs and liver biopsy specimens. The aim of this study is to estimate the prevalence of OCI in HIV-positive people who are injection drug users (IDUs). From April 2015 to August 2018, 161 Iranian IDUs with HIV infection enrolled in the study. Viral RNA was extracted from plasma and PBMC samples of participants, and the presence of HCV RNA was examined using RT nested PCR with primers from two conserved regions (5´-UTR and NS5B). HCV genotyping was performed using RFLP and sequencing methods. Of the 161 patients, 134 (83.2%) were positive for anti-HCV antibodies. All 27 patients who were negative for anti-HCV were also negative for HCV RNA in plasma, but five of them (18.5%) were positive for HCV RNA in PBMCs. Importantly, 9 out of 50 patients (18.0%) who apparently had recovered from HCV infection (i.e., were anti-HCV positive and HCV RNA negative) were positive for HCV RNA in PBMCs. Overall, 18.1% of the patients who had no signs of previous HCV infection or had apparently recovered from the disease had OCI. The HCV genotypes of the cases with OCI were as follows: five patients (35.7%) were infected with subtype 1a, eight patients (57.1%) were infected with subtype 3a, and one patient (7.1%) was infected with genotype 4. Thus, it seems that the prevalence of OCI in HIV-positive IDUs is extremely significant in Iran and is likely to delay the global eradication of HCV infection until 2030.

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. Kuehlkamp VM, Schuelter-Trevisol F (2013) Prevalence of human immunodeficiency virus/hepatitis C virus co-infection in Brazil and associated factors: a review. Braz J Infect Dis 17(4):455–463

    Article  PubMed  Google Scholar 

  2. World Health Organization Global Health (2018) HCV [online]. http://www.who.int/news-room/fact-sheets/detail/hepatitis-c. Accessed 1 Feb 2019

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Khodabandehloo M, Roshani D, Sayehmiri K (2013) Prevalence and trend of hepatitis C virus infection among blood donors in Iran: a systematic review and meta-analysis. J Res Med Sci 18(8):674–682

    PubMed  PubMed Central  Google Scholar 

  5. Castillo I, Pardo M, Bartolome J, Ortiz-Movilla N, Rodriguez-Inigo E, de Lucas S 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  PubMed  Google Scholar 

  6. 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  CAS  PubMed  Google Scholar 

  7. Vidimliski PD, Nikolov I, Geshkovska NM, Dimovski A, Rostaing L, Sikole A (2014) Review: occult hepatitis C virus infection: still remains a controversy. J Med Virol 86(9):1491–1498

    Article  PubMed  Google Scholar 

  8. Gad YZ, Ahmad NA, Mousa N, Farag RE, Abdel-Aziz AA, Abousmra NM et al (2012) Occult hepatitis C infection: the prevalence and profile of its immunoregulatory cytokines. Egypt Liver J 2(4):108–112

    Article  Google Scholar 

  9. Mousa N, Eldars W, Eldegla H, Fouda O, Gad Y, Abousamra N et al (2014) Cytokine profiles and hepatic injury in occult hepatitis C versus chronic hepatitis C virus infection. Int J Immunopathol Pharmacol 27(1):87–96

    Article  CAS  PubMed  Google Scholar 

  10. Amin J, Kaye M, Skidmore S, Pillay D, Cooper DA, Dore GJ (2004) HIV and hepatitis C coinfection within the CAESAR study. HIV Med 5(3):174–179

    Article  CAS  PubMed  Google Scholar 

  11. Mohammadi M, Talei G, Sheikhian A, Ebrahimzade F, Pournia Y, Ghasemi E et al (2009) Survey of both hepatitis B virus (HBsAg) and hepatitis C virus (HCV-Ab) coinfection among HIV positive patients. Virol J 6:202

    Article  PubMed  PubMed Central  Google Scholar 

  12. SeyedAlinaghi S, Jam S, Mehrkhani F, Fattahi F, Sabzvari D, Kourorian Z et al (2011) Hepatitis-C and hepatitis-B co-infections in patients with human immunodeficiency virus in Tehran, Iran. Acta Medica Iranica 49(4):252

    PubMed  Google Scholar 

  13. Malekinejad M, Navadeh S, Lotfizadeh A, Rahimi-Movaghar A, Amin-Esmaeili M, Noroozi A (2015) High hepatitis C virus prevalence among drug users in Iran: systematic review and meta-analysis of epidemiological evidence (2001–2012). Int J Infect Dis 40:116–130

    Article  PubMed  PubMed Central  Google Scholar 

  14. Platt L, Easterbrook P, Gower E, McDonald B, Sabin K, McGowan C et al (2016) Prevalence and burden of HCV co-infection in people living with HIV: a global systematic review and meta-analysis. Lancet Infect Dis 16(7):797–808

    Article  PubMed  Google Scholar 

  15. Kim AY, Onofrey S, Church DR (2013) An epidemiologic update on hepatitis C infection in persons living with or at risk of HIV infection. J Infect Dis 207(suppl_1):S1–S6

    Article  PubMed  PubMed Central  Google Scholar 

  16. Pohjanpelto P, Lappalainen M, Widell A, Asikainen K, Paunio M (1996) Hepatitis C genotypes in Finland determined by RFLP. Clin Diagn Virol 7(1):7–16

    Article  CAS  PubMed  Google Scholar 

  17. Ji H, Kozak RA, Biondi MJ, Pilon R, Vallee D, Liang BB et al (2015) Next generation sequencing of the hepatitis C virus NS5B gene reveals potential novel S282 drug resistance mutations. Virology 477:1–9

    Article  CAS  PubMed  Google Scholar 

  18. Zaghloul H, El-Sherbiny W (2010) Detection of occult hepatitis C and hepatitis B virus infections from peripheral blood mononuclear cells. Immunol Investig 39(3):284–291

    Article  CAS  Google Scholar 

  19. Idrees M, Lal A, Malik FA, Hussain A, Rehman I, Akbar H et al (2011) Occult hepatitis C virus infection and associated predictive factors: the Pakistan experience. Infect Genet Evol 11(2):442–445

    Article  PubMed  Google Scholar 

  20. Keyvani H, Bokharaei-Salim F, Monavari SH, Esghaei M, Nassiri Toosi M, Fakhim S et al (2013) Occult hepatitis C virus infection in candidates for liver transplant with cryptogenic cirrhosis. Hepat Mon 13(8):e11290

    Article  PubMed  PubMed Central  Google Scholar 

  21. Bastani MN, 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. Arch Virol 161(7):1899–1906

    Article  CAS  PubMed  Google Scholar 

  22. 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  PubMed  Google Scholar 

  23. Barril G, Castillo I, Arenas MD, Espinosa M, Garcia-Valdecasas J, Garcia-Fernandez N et al (2008) Occult hepatitis C virus infection among hemodialysis patients. J Am Soc Nephrol 19(12):2288–2292

    Article  PubMed  PubMed Central  Google Scholar 

  24. El-shishtawy S, Sherif N, Abdallh E, Kamel L, Shemis M, Saleem AAA et al (2015) Occult hepatitis C virus infection in hemodialysis patients; Single Center Study. Electron Physician 7(8):1619–1625

    Article  PubMed  PubMed Central  Google Scholar 

  25. Naghdi R, Ranjbar M, Bokharaei-Salim F, Keyvani H, Savaj S, Ossareh S et al (2017) Occult hepatitis C infection among hemodialysis patients: a prevalence study. Ann Hepatol 16(4):510–513

    Article  CAS  PubMed  Google Scholar 

  26. Baid-Agrawal S, Berg T (2014) Reply to: “underestimation of occult hepatitis C virus infection in chronic haemodialysis and kidney transplant patients”. J Hepatol 61(5):1185–1186

    Article  PubMed  Google Scholar 

  27. Castillo I, Martinez-Ara J, Olea T, Bartolomé J, Madero R, Hernández E et al (2014) High prevalence of occult hepatitis C virus infection in patients with primary and secondary glomerular nephropathies. Kidney Int 86(3):619–624

    Article  CAS  PubMed  Google Scholar 

  28. 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  PubMed  Google Scholar 

  29. Helaly GF, Elsheredy AG, El Basset Mousa AA, Ahmed HK, Oluyemi AE (2017) Seronegative and occult hepatitis C virus infections in patients with hematological disorders. Arch Virol 162(1):63–69

    Article  CAS  PubMed  Google Scholar 

  30. Youssef SS, Nasr AS, El Zanaty T, El Rawi RS, Mattar MM (2012) Prevalence of occult hepatitis C virus in egyptian patients with chronic lymphoproliferative disorders. Hepat Res Treat 2012:429784

    PubMed  PubMed Central  Google Scholar 

  31. Roque Cuéllar M, García Lozano J, Sánchez B, Carrillo Cruz E, De la Cruz Vicente F (2017) Occult hepatitis C virus infection in Spanish patients with lymphoproliferative disorders. J Emerg Dis Virol 3(2):2473 (1846.134)

    Google Scholar 

  32. Farahani M, Bokharaei-Salim F, Ghane M, Basi A, Meysami P, Keyvani H (2013) Prevalence of occult hepatitis C virus infection in Iranian patients with lymphoproliferative disorders. J Med Virol 85(2):235–240

    Article  CAS  PubMed  Google Scholar 

  33. Abdelrahim SS, Khairy R, Esmail MAM, Ragab M, Abdel-Hamid M, Abdelwahab SF (2016) Occult hepatitis C virus infection among Egyptian hemodialysis patients. J Med Virol 88(8):1388–1393

    Article  CAS  PubMed  Google Scholar 

  34. De Marco L, Gillio-Tos A, Fiano V, Ronco G, Krogh V, Palli D et al (2009) Occult HCV infection: an unexpected finding in a population unselected for hepatic disease. PloS One. 4(12):e8128

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. De Marco L, Manzini P, Trevisan M, Gillio-Tos A, Danielle F, Balloco C et al (2012) Prevalence and follow-up of occult HCV infection in an Italian population free of clinically detectable infectious liver disease. PloS One. 7(8):e43541

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Lin H, Chen X, Zhu S, Mao P, Zhu S, Liu Y et al (2016) Prevalence of occult hepatitis C virus infection among blood donors in Jiangsu, China. Intervirology 59(4):204–210

    Article  CAS  PubMed  Google Scholar 

  37. Gatserelia L, Sharvadze L, Karchava M, Dolmazashvili E, Tsertsvadze T (2014) Occurrence of occult HCV infection among HIV infected patients in Georgia. Georgian Med News 226:37–41

    Google Scholar 

  38. Bokharaei-Salim F, Keyvani H, Esghaei M, Zare-Karizi S, Dermenaki-Farahani S-S, Hesami-Zadeh K et al (2016) Prevalence of occult hepatitis C virus infection in the Iranian patients with human immunodeficiency virus infection. J Med Virol 88(11):1960–1966

    Article  CAS  PubMed  Google Scholar 

  39. Sheikh M, Bokharaei-Salim F, Monavari SH, Ataei-Pirkooh A, Esghaei M, Moradi N et al (2019) Molecular diagnosis of occult hepatitis C virus infection in Iranian injection drug users. Arch Virol 164(2):349–357

    Article  CAS  PubMed  Google Scholar 

  40. Vento S, Cainelli F, Longhi MS (2002) Reactivation of replication of hepatitis B and C viruses after immunosuppressive therapy: an unresolved issue. Lancet Oncol 3(6):333–340

    Article  CAS  PubMed  Google Scholar 

  41. Melisko ME, Fox R, Venook A (2004) Reactivation of hepatitis C virus after chemotherapy for colon cancer. Clin Oncol 16(3):204–205

    Article  CAS  Google Scholar 

  42. Lin A, Thadareddy A, Goldstein MJ, Lake-Bakaar G (2008) Immune suppression leading to hepatitis C virus re-emergence after sustained virological response. J Med Virol 80(10):1720–1722

    Article  PubMed  Google Scholar 

  43. Bartolome J, Lopez-Alcorocho JM, Castillo I, Rodriguez-Inigo E, Quiroga JA, Palacios R et al (2007) Ultracentrifugation of serum samples allows detection of hepatitis C virus RNA in patients with occult hepatitis C. J Virol 81(14):7710–7715

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Kopko PM, Holland PV (2000) Universal leukocyte reduction. Curr Opin Hematol 7(6):397–401

    Article  CAS  PubMed  Google Scholar 

  45. 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(Suppl 3):e113–e116

    Article  PubMed  Google Scholar 

  46. Messina JP, Humphreys I, Flaxman A, Brown A, Cooke GS, Pybus OG et al (2015) Global distribution and prevalence of hepatitis C virus genotypes. Hepatology 61(1):77–87

    Article  PubMed  Google Scholar 

  47. Gower E, Estes C, Blach S, Razavi-Shearer K, Razavi H (2014) Global epidemiology and genotype distribution of the hepatitis C virus infection. J Hepatol 61(1 Suppl):S45–S57

    Article  PubMed  Google Scholar 

  48. 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. Hepat Mon 16(9):e40357

    Article  PubMed  PubMed Central  Google Scholar 

  49. Ruta S, Cernescu C (2015) Injecting drug use: a vector for the introduction of new hepatitis C virus genotypes. World J Gastroenterol 21(38):10811–10823

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Alavian SM, Miri SM, Keshvari M, Elizee PK, Behnava B, Tabatabaei SV et al (2009) Distribution of hepatitis C virus genotype in Iranian multiply transfused patients with thalassemia. Transfusion 49(10):2195–2199

    Article  CAS  PubMed  Google Scholar 

  51. 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  PubMed  Google Scholar 

  52. Weber R, Ruppik M, Rickenbach M, Spoerri A, Furrer H, Battegay M et al (2013) Decreasing mortality and changing patterns of causes of death in the Swiss HIV cohort study. HIV Med 14(4):195–207

    Article  CAS  PubMed  Google Scholar 

  53. Hsieh MH, Tsai JJ, Hsieh MY, Huang CF, Yeh ML, Yang JF et al (2014) Hepatitis C virus infection among injection drug users with and without human immunodeficiency virus co-infection. PloS One 9(4):e94791

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Thongsawat S, Maneekarn N, Kuniholm MH, Pantip C, Thungsuputi A, Lumlertkul D et al (2008) Occult hepatitis C virus infection during an outbreak in a hemodialysis unit in Thailand. J Med Virol 80(5):808–815

    Article  PubMed  Google Scholar 

  55. Sy T, Jamal MM (2006) Epidemiology of hepatitis C virus (HCV) infection. Int J Med Sci 3(2):41–46

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

All authors would like to thank all of the volunteers who generously enrolled in this study.

Funding

The present study was funded by Research Deputy of Iran University of Medical Sciences (IUMS), Tehran, Iran, Grant number 28820.

Author information

Authors and Affiliations

  1. Iran University of Medical Sciences, Tehran, Iran

    Tahereh Donyavi, Farah Bokharaei-Salim, Najmeh Moradi & Roghayeh Babaei

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

    Farah Bokharaei-Salim, Maryam Sheikh, Mohammad-Navid Bastani, Zahra Habib & Maryam Esghaei

  3. Research Center of Pediatric Infectious Diseases, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran

    Khadijeh Khanaliha

  4. Department of Architectural Engineering, Faculty of Engineering, Islamic Azad University, South Tehran Branch, Tehran, Iran

    Atousa Fakhim

Authors
  1. Tahereh Donyavi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Farah Bokharaei-Salim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Khadijeh Khanaliha
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Maryam Sheikh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mohammad-Navid Bastani
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Najmeh Moradi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Roghayeh Babaei
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Zahra Habib
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Atousa Fakhim
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Maryam Esghaei
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Farah Bokharaei-Salim.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Ethical approval for this research was obtained from the local ethics committee of Iran University of Medical Sciences (IUMS), Tehran, Iran, is accordance with Helsinki declaration. All of the participants were informed about this study prior to their enrollment.

Additional information

Handling Editor: Michael A. Purdy.

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

Donyavi, T., Bokharaei-Salim, F., Khanaliha, K. et al. High prevalence of occult hepatitis C virus infection in injection drug users with HIV infection. Arch Virol 164, 2493–2504 (2019). https://doi.org/10.1007/s00705-019-04353-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00705-019-04353-3

Search

Navigation