HCV prevalence and predominant genotype in IV drug users

Document Type: Review

Authors

1 Department of Infectious and Tropical Disease, Mashhad University of Medical Sciences, Mashhad, Iran

2 Department of Immunology, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Hepatitis C virus (HCV) causes 308000 deaths due to liver cancer and 758000 deaths due to cirrhosis every year. Almost 170 million people have HCV infection around the world. Information regarding this virus helps us to determine the prevalence of other hepatitis C genotypes in population, especially in intravenous drug users. It is assumed that some genotypes are more common in certain areas or groups of people. A recent study strongly confirms the central role of injecting network traits, not only as a transmission factor but also as a predictor of HCV genotype and phylogenetic determination in different communities. Hepatitis C genotypes and subtypes have different prevalence considering the country. Risk factors such as transfusion, hemodialysis, root of acquisition and etc, are detected in intravenous drug users. Several conducted studies have investigated the prevalence, risk factors, and predominance of HCV genotypes infection in different parts of Iran.

Keywords


Introduction
According to World Health Organization (WHO) reports, hepatitis C causes 308000 deaths due to liver cancer and 758000 deaths due to cirrhosis every year (1). Totally, 170 million people have HCV which is not considered a malignant infectious disease while compared to its annual mortality rate (2,3). Hepatitis C virus (HCV) is belonging to flaviviridae virus family, initially known as non-A non-B hepatitis virus. It causes chronic hepatitis that may progress to cirrhosis and hepatocellular carcinoma(4,5). It is estimated that about 80% of HCV infected victims will develop chronic hepatitis. About 3-11% of those will progress to liver cirrhosis during 20-year time interval and the risk of liver failure and hepatocellular carcinoma increase as a life-threatening factor (6-8). HCV hepatitis is estimated to be the leading cause of liver transplantation in the world (9). The main route for HCV transmission is blood-borne including contaminated blood transfusion or blood products, needle or syringe sharing among members of intravenous drug parties or undergoing a needle stick by health workers. Other risk factors are high-risk sexual behaviors, tattooing, shaving in contaminated barber, reused and unsterilized dental and surgical instruments, and carelessly prepared laboratory equipment (10-12). Currently, the major contributor and driving risk factor for localized and universal spreading of HCV infection are injection drug users (IDUs). According to the 5’-end sequence of genome, HCV is classified to six distinct genotypes (genotype 1 to genotype 6). Every main genotype consists of some subtypes named a, b, c, etc (13,14). Determination of molecular genotyping of HCV in patients is necessary, for proposing therapeutic protocols (2). It is assumed that some genotypes are more common in certain areas or groups of people. For instance, genotype 3 and subtype 1a are widespread in IDUs of western countries (15-18), but 1b version is common among IDU population of Prague (19) and genotype 4 is responsible for most of the infections in IDUs of north-eastern of Poland (20). Whether social networks mitigate the HCV transmission or not is a fact of controversy. While some authors denied the role of these networks in HCV spreading (21-23), a recent study strongly confirmed the central role of injecting network traits, not only as a transmission factor but also as a predictor of HCV genotype in different communities (24).
According to results of this study, the network characteristics like behavior of members, epidemiologic characteristic of members, the size of network population and socioeconomic class of members and so on, will define the rate of HCV transmission among IDUs (25). Recognition and control of these networks in targeted community care program, can improve the quality of HCV transmission in IDUs (24). Worldwide estimation of anti-HCV positivity ranges from 60-80% of injection drug users that presents the positive anti-HCV in about 10 million IDUs (26). China, USA, and federation of Russia are three leading countries for having most infected population. The prevalence of human immunodeficiency virus (HIV) positive is lower than anti-HCV positive among injecting addicted persons (26).

HCV in Iran
Several conducted studies have investigated the prevalence, risk factors, and predominance of genotypes of HCV infection in different parts of Iran. Health care standards including blood checking for HIV, hepatitis B virus (HBV) and HCV are elevated since 1996. New policies against drug abusing patients in health care approaches have changed the problems of blood-borne viral infections including HCV (27). It is conservatively estimated that there are about 180000 IDUs in Iran (28). Currently, IDUs are the main fuel for driving HCV transmission in Iran and HCV prevalence has reached to 50-75% among IDUs, (29-37). As described before, there is a correlation between certain groups and predominant HCV genotypes. 3a and 1b are prevailing genotypes in European IDUs and post-transfusion victims respectively (38,39). Preponderant genotype is not definitely recognized in Iranian IDUs but 1a is reported as the commonest genotype in post-transfusion subjects (40-42). The predominant HCV genotype varies geographically among IDUs in Iran according to different performed studies. The frequency and distribution of common HCV genotype in Iran are summarized in Table 1.
It has been demonstrated that HCV genotype prevalence is changing continuously in different population and social networks (24).
Based on evidences obtained from blood donor screening, overall prevalence of HCV infection was 0.12%-0.59% among blood volunteers in Iran; ten times lower compaed to reported positive Hepatits B virus seroprevalence in a conducted study by Abedi et al (48-50). While much higher rates of HCV infection (31.5% to 47%) is demonstrated among IDUs inmate in jails, parks, or other public residential places (32,35,51). This wide discrepancy in HCV prevalence, directly results from higher frequency of high risk behaviors like injecting drugs and homosexuality especially among prisoners and tattooing among IDUs. In addition, incarceration duration solely increases the likelihood of HCV infection (52).
Although similar to many other countries the main mode of HCV spreading in Iran is drug injecting, it seems that tattooing performance is more effective in HCV transmission than drug injecting inside the prison 33. This is in harmony with other performed studies in different times and places (51,53,54).
In another study attending to estimate co-infection rate among Iranian IDUs, it is showed that HCV infection is more common than HIV infection among IDUS (34.5% vs. 10.7%) and HCV infection is more common among HIV positive rather than in HIV negative IDUs (80.6% vs. 28.7%, P<0.0001) (11).

HCV around the world
According to WHO records, 3% of population is infected by HCV throughout the world (55). A quarter of million deaths are caused by HCV infection in any way. About 10 million HCV positive IDUs are living throughout the world with maximum burden in Eastern Europe, East and South East Asia (26). All reported articles showed that the primary and essential rout of HCV transmission is blood contact mainly occurs in injecting drug users followed by unsafe sex practices, occupational exposures, and mother to child transmission. There is no consistent rhythm on HCV genotype distribution throughout the world. Table 2 shows the HCV prevalence and localized predominant genotype in every country. IDU network as the main source of HCV and probably other blood-borne viral infection like HIV and HBV need to be managed and controlled. Preventive and therapeutic programs for infected and non-infected IDUs are necessary to stop rapid progression of HCV. Unfortunately, educational steps and elevation of knowledge about drug injection consequences had little outcomes among IDUs (65). Other effective practical interventions are recognition and medical treatment of infected IDUs. Medications are too expensive to cover all patients, so prevention of paying several times, encouragement the patients to join to therapeutic programs, and easy access to medication should be established. HBV vaccination should be performed specially among HCV infected IDUs because co-infection causes higher complication and mortality rates. In addition, co-infection can increase the HCV transmission and rapid elevation of HCV disease burden among IDUs and non-IDUs (66). Alcohol consumption should be encouraged to be limited or even discontinued and patients should be evaluated for other disabling liver diseases management(67, 68). Needle and syringe should be provided feasibly for IDUs, harm reduction centers should be organized to maintain the patients on safer drug use conditions(69). Strategies are required to stop the universal rapid increasing growth rate of HCV infection and its related consequences.

Acknowledgement
We would like to thank Clinical Research Development Unit of Ghaem Hospital for their assistant in this manuscript. This study was supported by a grant from the Vice Chancellor for Research of the Mashhad University of Medical Sciences for the research project as a medical student thesis with approval number of 920247.

Conflict of Interest
 The authors declare no conflict of interest.

  1. Mathers C, Fat DM, Organization WH, Boerma JT. The Global Burden of Disease: 2004 Update. World Health Organization, Geneva, Switzerland; 2008.
  2. Longo D, Fauci A, Kasper D, et al. Harrison’s principles of internal medicine. 18th ed. New York, NY: McGraw-Hill; 2011.
  3. Zanetti AR. Global surveillance and control of hepatitis C. Report of a WHO Consultation organized in collaboration with the Viral Hepatitis Prevention Board, Antwerp, Belgium. J  Viral Hepat. 1999;6:35-47.
  4. Choo Q-L, Kuo G, Weiner AJ, et al. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science. 1989;244:359-362.
  5. Lindenbach B, Rice C. Flaviviridae: the viruses and their replication. In: Knipe D, Howley P, editors. Fields virology. 4th ed. Philadelphia: Lippincott-Raven Publishers; 2001. p. 991-1041.
  6. Te HS, Jensen DM. Epidemiology of hepatitis B and C viruses: a global overview. Clin Liver Dis. 2010;14:1-21.
  7. Dore GJ, Freeman AJ, Law M, et al. Is severe liver disease a common outcome for people with chronic hepatitis C? J Gastroenterol Hepatol. 2002;17:423-430.
  8. Limburg W. Natural history, treatment and prevention of hepatitis C in injecting drug users: an overview. In: Jager J, Limburg W, Kretzschmar M, Postma M, Wiessing L,editors. Hepatitis C and injecting drug use: impact, costs and policy options. Lisbon: European Monitoring Centre for Drugs and Drug Addiction; 2004 p.21-38.
  9. Verna EC, Brown RS Jr. Hepatitis C virus and liver transplantation. Clin Liver Dis. 2006;10:919-940.
  10. Samimi-Rad K, Toosi MN, Masoudi-nejad A, et al. Molecular epidemiology of hepatitis C virus among injection drug users in Iran: a slight change in prevalence of HCV genotypes over time. Arch Virol. 2012;157:1959-1965.
  11. Rahimi-Movaghar A, Razaghi EM, Sahimi-Izadian E, et al. HIV, hepatitis C virus, and hepatitis B virus co-infections among injecting drug users in Tehran, Iran. Int J Infect Dis. 2010;14:e28-e33.
  12. Imani R, Karimi A, Rouzbahani R, et al. Seroprevalence of HBV, HCV and HIV infection among intravenous drug users in Shahr-e-Kord, Islamic Republic of Iran. East Mediterr Health J. 2008;14:1136-1141.
  13. Holmes E. Sequence variability in the 5’non-coding region of hepatitis C virus: identification of a new virus type and restrictions on sequence diversity. J Gen Virol. 1993;74:661-668.
  14. Lindebach B, Rice C. The hepatitis C viruses. In: Knipe D, McMahon J, Pouget E, Tortu S, editors. Individual and Couple-Level Risk F PM. 4th ed. Philadelphia: Lippincott Williams & Wilkins; 2002. p. 602-613.
  15. Woodfield DG, Harness M, Rix-Trott K, et al. Identification and genotyping of hepatitis C virus in injectable and oral drug users in New Zealand. Aust N Z J Med. 1994;24:47-50.
  16. Harris KA, Gilham C, Mortimer PP, et al. The most prevalent hepatitis C virus genotypes in England and Wales are 3a and 1a. J Med Virol. 1999;58:127-131.
  17. Freeman AJ, Zekry A, Whybin LR, et al. Hepatitis C prevalence among Australian injecting drug users in the 1970s and profiles of virus genotypes in the 1970s and 1990s. Med J Aust. 2000;172:588-591.
  18. Zein NN. Clinical significance of hepatitis C virus genotypes. Clin Microbiol Rev. 2000;13:223-235.
  19. Krekulova L, Rehak V, Madrigal N, et al. Genotypic and epidemiologic characteristics of hepatitis C virus infections among recent injection drug user and nonuser populations. Clin Infect Dis. 2001;33:1435-1438.
  20. Chlabicz S, Flisiak R, Kowalczuk O, et al. High prevalence of genotype 4 among hepatitis C virus-infected intravenous drug users in north-eastern Poland. J Med Virol. 2008;80:615-618.
  21. Aitken CK, McCaw RF, Bowden DS, et al. Molecular epidemiology of hepatitis C virus in a social network of injection drug users. J Infect Dis. 2004;190:1586-1595.
  22. Brewer DD, Hagan H, Sullivan DG, et al. Social structural and behavioral underpinnings of hyperendemic hepatitis C virus transmission in drug injectors. J Infect Dis. 2006;194:764-772.
  23. Pilon R, Leonard L, Kim J, et al. Transmission patterns of HIV and hepatitis C virus among networks of people who inject drugs. PLoS One. 2011;6:e22245.
  24. Sacks-Davis R, Daraganova G, Aitken C, et al. Hepatitis C virus phylogenetic clustering is associated with the social-injecting network in a cohort of people who inject drugs. PLoS One. 2012;7:e47335.
  25. De P, Cox J, Boivin JF, et al. The importance of social networks in their association to drug equipment sharing among injection drug users: a review. Addiction. 2007;102:1730-1739.
  26. Nelson PK, Mathers BM, Cowie B, et al. Global epidemiology of hepatitis B and hepatitis C in people who inject drugs: results of systematic reviews. Lancet. 2011;378:571-583.
  27. Rezvan H, Abolghassemi H, Kafiabad SA. Transfusion-transmitted infections among multitransfused patients in Iran: a review. Transfus Med. 2007;17:425-433.
  28. Mathers BM, Degenhardt L, Phillips B, et al. Global epidemiology of injecting drug use and HIV among people who inject drugs: a systematic review. Lancet. 2008;372:1733-1745.
  29. Zamani S, Radfar R, Nematollahi P, et al. Prevalence of HIV/HCV/HBV infections and drug-related risk behaviours amongst IDUs recruited through peer-driven sampling in Iran. Int J Drug Policy. 2010;21:493-500.
  30. Kheirandish P, SeyedAlinaghi S, Jahani M, et al. Prevalence and correlates of hepatitis C infection among male injection drug users in detention, Tehran, Iran. J Urban Health. 2009;86:902-908.
  31. Zamani S, Ichikawa S, Nassirimanesh B, et al. Prevalence and correlates of hepatitis C virus infection among injecting drug users in Tehran. Int J Drug Policy. 2007;18:359-363.
  32. Mohammad Alizadeh AH, Alavian SM, Jafari K, et al. Prevalence of hepatitis C virus infection and its related risk factors in drug abuser prisoners in Hamedan--Iran. World J Gastroenterol. 2005;11:4085-4089.
  33. Mohtasham Amiri Z, Rezvani M, Jafari Shakib R, et al. Prevalence of hepatitis C virus infection and risk factors of drug using prisoners in Guilan province. East Mediterr Health J. 2007;13:250-256.
  34. Rahbar AR, Rooholamini S, Khoshnood K. Prevalence of HIV infection and other blood-borne infections in incarcerated and non-incarcerated injection drug users (IDUs) in Mashhad, Iran. Int J Drug Policy. 2004;15:151-155.
  35. Khani M, Vakili M. Prevalence and risk factors of HIV, hepatitis B virus and hepatitis C virus infections in drug addicts among Zanjan prisoners. Arch Iranian Med. 2003;6:1-4.
  36. Asgari F, Gouya M, Fotouhi K, et al. Hepatitis C virus infection among Iranian prisoners and its relation with addiction, 2001-2005. Hakim. 2008;11:1.
  37. Zali M, Nowroozi A, Amir-rasooly H, et al. Prevalence of anti HCV antibody and routes of hematological transmission addicts of Ghasr prison. Pajouhesh.1998;22:26-32.
  38. Micalessi MI, Gerard C, Ameye L, et al. Distribution of hepatitis C virus genotypes among injecting drug users in contact with treatment centers in Belgium, 2004-2005. J Med Virol. 2008;80:640-645.
  39. Dal Molin G, Ansaldi F, Biagi C, et al. Changing molecular epidemiology of hepatitis C virus infection in Northeast Italy. J Med Virol. 2002;68:352-356.
  40. Samimi-Rad K, Shahbaz B. Hepatitis C virus genotypes among patients with thalassemia and inherited bleeding disorders in Markazi province, Iran. Haemophilia. 2007;13:156-163.
  41. Hosseini-Moghaddam SM, Keyvani H, Kasiri H, et al. Distribution of hepatitis C virus genotypes among hemodialysis patients in Tehran--a multicenter study. J Med Virol. 2006;78:569-573.
  42. Alavian SM, Miri SM, Keshvari M, et al. Distribution of hepatitis C virus genotype in Iranian multiply transfused patients with thalassemia. Transfusion. 2009;49:2195-2199.
  43. Assarehzadegan MA, Shakerinejad G, Noroozkohnejad R, et al. Prevalence of hepatitis C and B infection and HC V genotypes among hemodialysis patients in Khuzestan province, southwest Iran. Saudi J Kidney Dis Transpl. 2009;20:681-684.
  44. Keyvani H, Alizadeh AH, Alavian SM, et al. Distribution frequency of hepatitis C virus genotypes in 2231 patients in Iran. Hepatol Res. 2007;37:101-103.
  45. Kabir A, Alavian SM, Keyvani H. Distribution of hepatitis C virus genotypes in patients infected by different sources and its correlation with clinical and virological parameters: a preliminary study. Comp Hepatol. 2006;5:4.
  46. Mousavi SF, Moosavy SH, Alavian SM, et al. Distribution of hepatitis C virus genotypes among patients with hepatitis C virus infection in hormozgan, iran. Hepat Mon. 2013;13:e14324.
  47. Joukar F, Khalesi AK, Jafarshad R, et al. Distribution of hepatitis C virus genotypes in haemodialysis patients of Guilan, northern Islamic Republic of Iran. East Mediterr Health J. 2012;18:236-240.
  48. Alavian SM, Gholami B, Masarrat S. Hepatitis C risk factors in Iranian volunteer blood donors: a case-control study. J Gastroenterol Hepatol. 2002;17:1092-1097.
  49. Ghavanini AA, Sabri MR. Hepatitis B surface antigen and anti-hepatitis C antibodies among blood donors in the Islamic Republic of Iran. East Mediterr Health J. 2000;6:1114-1116.
  50. Abedi F, Madani H, Asadi A, et al. Significance of blood-related high-risk behaviors and horizontal transmission of hepatitis B virus in Iran. Arch Virol. 2011;156:629-635.
  51. Zali M-R, Aghazadeh R, Nowroozi A, et al. Anti-HCV antibody among Iranian IV drug users: is it a serious problem. Arch Iran Med. 2001;4:115-119.
  52. Alavian S-M, Adibi P, Zali M-R. Hepatitis C virus in Iran: Epidemiology of an emerging infection. Arch Iranian Med. 2005;8:84-90.
  53. Hellard ME, Hocking JS, Crofts N. The prevalence and the risk behaviours associated with the transmission of hepatitis C virus in Australian correctional facilities. Epidemiol Infect. 2004;132:409-415.
  54. Samuel MC, Doherty PM, Bulterys M, et al. Association between heroin use, needle sharing and tattoos received in prison with hepatitis B and C positivity among street-recruited injecting drug users in New Mexico, USA. Epidemiol Infect. 2001;127:475-484.
  55. World Health Organization. Hepatitis C-Revised October 2000. Geneva; 2000 [Accessed on: 8/5/2007]. (Fact Sheet, 164). Available at: http://www.who.int/mediacentre/factsheets/fs164/en/index.html.
  56. Rehman L, Ullah I, Ali I, et al. Active hepatitis C infection and HCV genotypes prevalent among the IDUs of Khyber Pakhtunkhwa. Virol  J. 2011;8:327.
  57. Lopes CL, Teles SA, Espirito-Santo MP, et al. Prevalence, risk factors and genotypes of hepatitis C virus infection among drug users, Central-Western Brazil. Rev Saude Publica. 2009;43 Suppl 1:43-50.
  58. Xia X, Luo J, Bai J, et al. Epidemiology of hepatitis C virus infection among injection drug users in China: systematic review and meta-analysis. Public Health. 2008;122:990-1003.
  59. Judd A, Hutchinson S, Wadd S, et al. Prevalence of, and risk factors for, hepatitis C virus infection among recent initiates to injecting in London and Glasgow: cross sectional analysis. J Viral Hepat. 2005;12:655-662.
  60. Vicknasingam B, Narayanan S, Navaratnam V. Prevalence rates and risk factors for hepatitis C among drug users not in treatment in Malaysia. Drug Alcohol Rev. 2009;28:447-454.
  61. Paintsil E, Verevochkin SV, Dukhovlinova E, et al. Hepatitis C virus infection among drug injectors in St Petersburg, Russia: social and molecular epidemiology of an endemic infection. Addiction. 2009;104:1881-1890.
  62. Muasya T, Lore W, Yano K, et al. Prevalence of hepatitis C virus and its genotypes among a cohort of drug users in Kenya. East Afr Med J. 2008;85:318-325.
  63. Liu JY, Lin HH, Liu YC, et al. Extremely high prevalence and genetic diversity of hepatitis C virus infection among HIV-infected injection drug users in Taiwan. Clin Infect Dis. 2008;46:1761-1768.
  64. Shrestha SM, Shrestha S, Tsuda F, et al. Infection with GB virus C and hepatitis C virus in drug addicts, patients on maintenance hemodialysis, or with chronic liver disease in Nepal. J Med Virol. 1997;53:157-161.
  65. Aspinall EJ, Weir A, Sacks-Davis R, et al. Does informing people who inject drugs of their hepatitis C status influence their injecting behaviour? Analysis of the Networks II study. Int J Drug Policy. 2014;25:179-182.
  66. Amin J, Law MG, Bartlett M, et al. Causes of death after diagnosis of hepatitis B or hepatitis C infection: a large community-based linkage study. Lancet. 2006;368:938-945.
  67. Gibson A, Randall D, Degenhardt L. The increasing mortality burden of liver disease among opioid-dependent people: cohort study. Addiction. 2011;106:2186-2192.
  68. Swan T. The hepatitis C treatment pipeline report. Treatment action group. 2011.
  69. Palmateer N, Kimber J, Hickman M, et al. Evidence for the effectiveness of sterile injecting equipment provision in preventing hepatitis C and human immunodeficiency virus transmission among injecting drug users: a review of reviews. Addiction. 2010;105:844-859.