Archives of Virology

, Volume 164, Issue 10, pp 2493–2504 | Cite as

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

  • Tahereh Donyavi
  • Farah Bokharaei-SalimEmail author
  • Khadijeh Khanaliha
  • Maryam Sheikh
  • Mohammad-Navid Bastani
  • Najmeh Moradi
  • Roghayeh Babaei
  • Zahra Habib
  • Atousa Fakhim
  • Maryam Esghaei
Original Article


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.



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


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

Compliance with ethical standards

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.


  1. 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):455–463CrossRefGoogle Scholar
  2. 2.
    World Health Organization Global Health (2018) HCV [online]. Accessed 1 Feb 2019
  3. 3.
    Taherkhani R, Farshadpour F (2015) Epidemiology of hepatitis C virus in Iran. World J Gastroenterol 21(38):10790–10810CrossRefGoogle Scholar
  4. 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):674–682Google Scholar
  5. 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):7–14CrossRefGoogle Scholar
  6. 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):76–84CrossRefGoogle Scholar
  7. 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):1491–1498CrossRefGoogle Scholar
  8. 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):108–112CrossRefGoogle Scholar
  9. 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):87–96CrossRefGoogle Scholar
  10. 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):174–179CrossRefGoogle Scholar
  11. 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 6:202CrossRefGoogle Scholar
  12. 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):252Google Scholar
  13. 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 40:116–130CrossRefGoogle Scholar
  14. 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):797–808CrossRefGoogle Scholar
  15. 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–S6CrossRefGoogle Scholar
  16. 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):7–16CrossRefGoogle Scholar
  17. 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 477:1–9CrossRefGoogle Scholar
  18. 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):284–291CrossRefGoogle Scholar
  19. 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):442–445CrossRefGoogle Scholar
  20. 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):e11290CrossRefGoogle Scholar
  21. 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):1899–1906CrossRefGoogle Scholar
  22. 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):107–114CrossRefGoogle Scholar
  23. 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):2288–2292CrossRefGoogle Scholar
  24. 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):1619–1625CrossRefGoogle Scholar
  25. 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):510–513CrossRefGoogle Scholar
  26. 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):1185–1186CrossRefGoogle Scholar
  27. 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):619–624CrossRefGoogle Scholar
  28. 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):251CrossRefGoogle Scholar
  29. 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):63–69CrossRefGoogle Scholar
  30. 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 2012:429784Google Scholar
  31. 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. 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):235–240CrossRefGoogle Scholar
  33. 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):1388–1393CrossRefGoogle Scholar
  34. 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):e8128CrossRefGoogle Scholar
  35. 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):e43541CrossRefGoogle Scholar
  36. 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):204–210CrossRefGoogle Scholar
  37. 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 226:37–41Google Scholar
  38. 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):1960–1966CrossRefGoogle Scholar
  39. 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):349–357CrossRefGoogle Scholar
  40. 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):333–340CrossRefGoogle Scholar
  41. 41.
    Melisko ME, Fox R, Venook A (2004) Reactivation of hepatitis C virus after chemotherapy for colon cancer. Clin Oncol 16(3):204–205CrossRefGoogle Scholar
  42. 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):1720–1722CrossRefGoogle Scholar
  43. 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):7710–7715CrossRefGoogle Scholar
  44. 44.
    Kopko PM, Holland PV (2000) Universal leukocyte reduction. Curr Opin Hematol 7(6):397–401CrossRefGoogle Scholar
  45. 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–e116CrossRefGoogle Scholar
  46. 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):77–87CrossRefGoogle Scholar
  47. 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–S57CrossRefGoogle Scholar
  48. 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):e40357CrossRefGoogle Scholar
  49. 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):10811–10823CrossRefGoogle Scholar
  50. 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):2195–2199CrossRefGoogle Scholar
  51. 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):258–265CrossRefGoogle Scholar
  52. 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):195–207CrossRefGoogle Scholar
  53. 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):e94791CrossRefGoogle Scholar
  54. 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):808–815CrossRefGoogle Scholar
  55. 55.
    Sy T, Jamal MM (2006) Epidemiology of hepatitis C virus (HCV) infection. Int J Med Sci 3(2):41–46CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2019

Authors and Affiliations

  • Tahereh Donyavi
    • 1
  • Farah Bokharaei-Salim
    • 1
    • 2
    Email author
  • Khadijeh Khanaliha
    • 3
  • Maryam Sheikh
    • 2
  • Mohammad-Navid Bastani
    • 2
  • Najmeh Moradi
    • 1
  • Roghayeh Babaei
    • 1
  • Zahra Habib
    • 2
  • Atousa Fakhim
    • 4
  • Maryam Esghaei
    • 2
  1. 1.Iran University of Medical SciencesTehranIran
  2. 2.Department of Virology, School of MedicineIran University of Medical SciencesTehranIran
  3. 3.Research Center of Pediatric Infectious Diseases, Institute of Immunology and Infectious DiseasesIran University of Medical SciencesTehranIran
  4. 4.Department of Architectural Engineering, Faculty of EngineeringIslamic Azad University, South Tehran BranchTehranIran

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