Little is known about the distribution of hepatitis C virus (HCV) genotypes among people who inject drugs (PWID) in North African countries, including Tunisia. This study aims to describe HCV genotypes circulating among Tunisian PWID. A cross-sectional study was conducted, and 128 HCV-positive PWID were recruited between 2018 and 2019 from community-based harm reduction centers. After informed consent, sociodemographic characteristics and risk behavior data were obtained using an interviewer-administrated questionnaire. Blood samples were collected for further serological and molecular testing. Overall, five women and 123 men were included. The median age was 39.5 years. The majority of PWID (56.3%) had less than a secondary level of education, were single (57%), were unemployed (65.6%), were incarcerated at least once (93.0%), and had a history of residency in at least one foreign country (50.8%). During the previous 12 months, 82.0% reported having reused syringes at least once, 43.8% shared syringes at least once, while 56.2% had at least one unprotected sexual relation, and 28.1% had more than two different sexual partners. Tattooing was reported among 60.2%. All positive results for HCV-infection by rapid testing were confirmed by enzyme-linked immunosorbent assay (ELISA). HCV-RNA was detectable in 79.7%. Genotyping showed a predominance of genotype 1 (52%) followed by genotype 3 (34%) and genotype 4 (10%). Four patients (4%) had an intergenotype mixed infection. Subtyping showed the presence of six different HCV subtypes as follows: 1a (53.2%), 1b (6.4%), 3a (33.0%), 4a (3.2%), and 4d (4.3%). This is the first study describing circulating HCV genotypes among PWID in Tunisia. The distribution of HCV genotypes is distinct from the general population with a predominance of subtypes 1a and 3a. These findings can be used to guide national efforts aiming to optimize the access of PWID to relevant HCV prevention and treatment measures including pangenotypic regimens for patients infected with HCV genotype 3.

Association Tunisienne d'Information et d'Orientation sur le SIDA et la Toxicomanie Tunis Tunisia

Institute of Parasitology Biology Centre Czech Academy of Sciences Ceske Budejovice Czechia

Laboratory of Clinical Virology WHO Reference Laboratory for Poliomyelitis and Measles in the Eastern Mediterranean Region Pasteur Institute of Tunis Tunis El Manar University Tunis Tunisia

Science Shop Institut Pasteur de Tunis Tunis Tunisia

Zobrazit více v PubMed

Alashek W. A., Altagdi M. (2008). Risk factors and genotypes of hepatitis C virus infection in libyan patients. Libyan J. Med. 3 162–165. 10.4176/080425 PubMed DOI PMC

Ampuero J., Romero-Gómez M., Reddy K. R. (2014). Review article: HCV Genotype 3 – the new treatment challenge. Aliment. Pharmacol. Ther. 39 686–698. 10.1111/apt.12646 PubMed DOI

Ara A. K., Paul J. P. (2015). New direct-acting antiviral therapies for treatment of chronic hepatitis C virus infection. Gastroenterol. Hepatol. 11 458–466. PubMed PMC

Barbosa J. R., Colares J. K. B., Flores G. L., Cortes V. F., Miguel J. C., Portilho M. M. (2017). Performance of rapid diagnostic tests for detection of Hepatitis B and C markers in HIV infected patients. J. Virol. Methods 248 244–249. 10.1016/j.jviromet.2017.08.001 PubMed DOI

Bettaieb J., Chouikha A., Khedhiri M., Kharroubi G., Badreddine M., Bel Hadj, et al. (2019). Hepatitis C virus epidemiology in central-west tunisia: a population-based cross-sectional study. Arch. Virol. 164 2243–2253. 10.1007/s00705-019-04308-8 PubMed DOI

Bielen R., Moreno C., Van Vlierberghe H., Bourgeois S., Mulkay J. P., Vanwolleghem T. (2017). Belgian experience with direct acting antivirals in people who inject drugs. Drug Alcohol. Depend. 177 214–220. 10.1016/j.drugalcdep.2017.04.003 PubMed DOI

Bochud P. Y., Cai T., Overbeck K., Bochud M., Dufour J. F., Müllhaupt B. (2009). Genotype 3 is associated with accelerated fibrosis progression in chronic Hepatitis C. J. Hepatol. 51 655–666. 10.1016/j.jhep.2009.05.016 PubMed DOI

Bourlière M., Barberin J. M., Rotily M., Guagliardo V., Portal I., Lecomte L. (2002). Epidemiological changes in hepatitis C virus genotypes in france: evidence in intravenous drug users. J. Viral Hepat. 9 62–70. 10.1046/j.1365-2893.2002.00319.x PubMed DOI

Chaabna K., Cheema S., Abraham A., Alrouh H., Lowenfels A. B., Maisonneuve P. (2018). Systematic overview of Hepatitis C infection in the middle East and North Africa. World J. Gastroenterol. 24 3038–3054. 10.3748/wjg.v24.i27.3038 PubMed DOI PMC

Chouikha A., Khedhiri M., Triki H., Hammemi W., Sadraoui A., Touzi H. (2021). Focus on Hepatitis C virus genotype distribution in tunisia prior to elimination: a 16-year retrospective study. Arch. Virol. 166 501–510. 10.1007/s00705-020-04918-7 PubMed DOI

Cooper C. (2017). Rapid HCV RNA testing: removing the final obstacle to elimination. Lancet Gastroenterol. Hepatol. 2 468–469. 10.1016/s2468-1253(17)30086-9 PubMed DOI

Cunningham E. B., Applegate T. L., Lloyd A. R., Dore G. J., Grebely J. (2015). Mixed HCV infection and reinfection in people who inject drugs–impact on therapy. Nat. Rev. Gastroenterol. Hepatol. 12 218–230. 10.1038/nrgastro.2015.36 PubMed DOI

Degenhardt L., Peacock A., Colledge S., Leung J., Grebely J., Vickerman P. (2017). Global prevalence of injecting drug use and sociodemographic characteristics and prevalence of HIV, HBV, and HCV in people who inject drugs: a multistage systematic review. Lancet Global Health 5 e1192–e1207. PubMed PMC

Djebbi A., Bahri O., Langar H., Sadraoui A., Mejri S., Triki H. (2008). Genetic variability of Genotype 1 Hepatitis C virus isolates from Tunisian haemophiliacs. New Microbiol. 31 473–480. PubMed

Djebbi A., Mejri S., Thiers V., Triki H. (2004). Phylogenetic analysis of Hepatitis C virus isolates from Tunisian patients. Eur. J. Epidemiol. 19 555–562. 10.1023/b:ejep.0000032348.83087.01 PubMed DOI

Djebbi A., Triki H., Bahri O., Cheikh I., Sadraoui A., Ben Ammar A., et al. (2003). Genotypes of Hepatitis C virus circulating in Tunisia. Epidemiol. Infect. 130 501–505. 10.1017/s095026880300846x PubMed DOI PMC

Edmunds B. L., Miller E. R., Tsourtos G. (2019). The distribution and socioeconomic burden of Hepatitis C Virus in South Australia: a cross-sectional study 2010–2016. BMC Public Health 19:527. PubMed PMC

European Association for the Study of the Liver (2018). EASL Recommendations on treatment of Hepatitis C 2018. J. Hepatol. 69 461–511. 10.1016/j.jhep.2018.03.026 PubMed DOI

Ezzikouri S., Pineau P., Benjelloun S. (2013). Hepatitis C virus Infection in the maghreb region. J. Med. Virol. 85 1542–1549. 10.1002/jmv.23643 PubMed DOI

Fadlalla F. A., Mohamoud Y. A., Mumtaz G. R., Abu-Raddad L. J. (2015). The epidemiology of Hepatitis C Virus in the maghreb region: systematic review and meta-analyses. PLoS One 10:e0121873. 10.1371/journal.pone.0121873 PubMed DOI PMC

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(Suppl.), S45–S57. PubMed

Grassi A., Ballardini G. (2017). Hepatitis C in injection drug users: it is time to treat. World J. Gastroenterol. 23 3569–3571. 10.3748/wjg.v23.i20.3569 PubMed DOI PMC

Grebely J., Dore G. J., Morin S., Rockstroh J. K., Klein M. B. (2017a). Elimination of HCV as a public health concern among people who inject drugs by 2030 - what will it take to get there? J. Int. AIDS Soc. 20:22146. 10.7448/IAS.20.1.22146 PubMed DOI PMC

Grebely J., Lamoury F. M. J., Hajarizadeh B., Mowat Y., Marshall A. D., Bajis S. (2017b). Evaluation of the Xpert HCV viral load point-of-care assay from venepuncture-collected and finger-stick capillary whole-blood samples: a cohort study. Lancet Gastroenterol. Hepatol. 2 514–520. 10.1016/s2468-1253(17)30075-4 PubMed DOI

Grebely J., Larney S., Peacock A., Colledge S., Leung J., Hickman M. (2019). Global, regional, and country-level estimates of Hepatitis C infection among people who have recently injected drugs. Addiction 114 150–166. 10.1111/add.14393 PubMed DOI PMC

Heijnen M., Mumtaz G. R., Abu-Raddad L. J. (2016). Status of HIV and Hepatitis C virus infections among prisoners in the middle East and North Africa: review and synthesis. J. Int. AIDS Soc. 19:20873. 10.7448/ias.19.1.20873 PubMed DOI PMC

Kamarulzaman A., Reid S. E., Schwitters A., Wiessing L., El-Bassel N., Dolan K. (2016). Prevention of transmission of HIV, Hepatitis B Virus, Hepatitis C Virus, and Tuberculosis in prisoners. Lancet 388 1115–1126. 10.1016/s0140-6736(16)30769-3 PubMed DOI

Kanwal F., Kramer J. R., Ilyas J., Duan Z., El-Serag H. B. (2014). HCV Genotype 3 is associated with an increased risk of cirrhosis and hepatocellular cancer in a national sample of U.S. Veterans with HCV. Hepatology 60 98–105. 10.1002/hep.27095 PubMed DOI PMC

Kumar S., Stecher G., Tamura K. (2016). MEGA7: molecular evolutionary genetics analysis Version 7.0 for bigger datasets. Mol. Biol. Evol. 33 1870–1874. 10.1093/molbev/msw054 PubMed DOI PMC

Larney S., Kopinski H., Beckwith C. G., Zaller N. D., Jarlais D. D., Hagan H. (2013). Incidence and prevalence of Hepatitis C in prisons and other closed settings: results of a systematic review and meta-analysis. Hepatology 58 1215–1224. 10.1002/hep.26387 PubMed DOI PMC

Larney S., Peacock A., Leung J., Colledge S., Hickman M., Vickerman P. (2017). Global, regional, and country-level coverage of interventions to prevent and manage HIV and Hepatitis C among people who inject drugs: a systematic review. Lancet Global Health 5 e1208–e1220. PubMed PMC

MacArthur G. J., van Velzen E., Palmateer N., Kimber J., Pharris A., Hope V. (2014). Interventions to prevent HIV and Hepatitis C in people who inject drugs: a review of reviews to assess evidence of effectiveness. Int. J. Drug Policy 25 34–52. 10.1016/j.drugpo.2013.07.001 PubMed DOI

Mane A., Sacks J., Sharma S., Singh H., Tejada-Strop A., Kamili S. (2019). Evaluation of five rapid diagnostic tests for detection of antibodies to Hepatitis C Virus (HCV): a step towards scale-up of HCV screening efforts in India. PLoS One 14:e0210556. 10.1371/journal.pone.0210556 PubMed DOI PMC

Martin N. K., Hickman M., Hutchinson S. J., Goldberg D. J., Vickerman P. (2013). Combination interventions to prevent HCV transmission among people who inject drugs: modeling the impact of antiviral treatment, needle and syringe programs, and opiate substitution therapy. Clin. Infect. Dis. 57(Suppl. 2), S39–S45. PubMed PMC

McMahon B. J., Bruden D., Townshend-Bulson L., Simons B., Spradling P., Livingston S. (2017). Infection with Hepatitis C Virus Genotype 3 is an independent risk factor for end-stage liver disease, Hepatocellular Carcinoma, and liver-related death. Clin. Gastroenterol. Hepatol. 15 431–437.e2. PubMed PMC

Mejri S., Ben Salah A., Triki H., Ben Alaya N., Djebbi A., Dellagi K. (2005). Contrasting patterns of Hepatitis C Virus infection in two regions from Tunisia. J. Med. Virol. 76 185–193. 10.1002/jmv.20342 PubMed DOI

Midgard H., Weir A., Palmateer N., Lo, Re V., Pineda J. A., et al. (2016). HCV epidemiology in high-risk groups and the risk of reinfection. J. Hepatol. 65(Suppl.), S33–S45. PubMed

Mirzoyan L., Berendes S., Jeffery C., Thomson J., Ben Othman H., Danon L. (2013). New evidence on the HIV epidemic in libya: why countries must implement prevention programs among people who inject drugs. J. Acquir. Immune Defic. Syndr. 62 577–583. 10.1097/qai.0b013e318284714a PubMed DOI

Mosbah H. B., Ghorbel A., Hedhili A. (2018). Illicit use of high-dosage buprenorphine in Tunisia. Afr. J. Drug Alcohol Stud. 17 39–51.

Nkontchou G., Ziol M., Aout M., Lhabadie M., Baazia Y., Mahmoudi A., et al. (2011). HCV genotype 3 is associated with a higher hepatocellular carcinoma incidence in patients with ongoing viral C cirrhosis. J. Viral. Hepat. 18, e516–e522. 10.1111/j.1365-2893.2011.01441.x PubMed DOI

Omland L. H., Osler M., Jepsen P., Krarup H., Weis N., Christensen P. B. (2013). Socioeconomic status in HCV infected patients - risk and prognosis. Clin. Epidemiol. 5 163–172. 10.2147/clep.s43926 PubMed DOI PMC

Palmateer N., Kimber J., Hickman M., Hutchinson S., Rhodes T., Goldberg D. (2010). 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. 105, 844–859. 10.1111/j.1360-0443.2009.02888.x PubMed DOI

Poiteau L., Soulier A., Rosa I., Roudot-Thoraval F., Hézode C., Pawlotsky J. M. (2016). Performance of rapid diagnostic tests for the detection of antibodies to Hepatitis C Virus in whole blood collected on dried blood spots. J. Viral Hepat. 23 399–401. 10.1111/jvh.12501 PubMed DOI

Rashti R., Sharafi H., Alavian S. M., Moradi Y., Mohamadi Bolbanabad A., Moradi G. (2020). Systematic review and meta-analysis of global prevalence of HBsAg and HIV and HCV antibodies among people who inject drugs and female sex workers. Pathogens 9:432. 10.3390/pathogens9060432 PubMed DOI PMC

Rich J. D., Beckwith C. G., Macmadu A., Marshall B. D. L., Brinkley-Rubinstein L. (2016). Clinical care of incarcerated people with HIV, viral Hepatitis, or Tuberculosis. Lancet 388 1103–1114. 10.1016/s0140-6736(16)30379-8 PubMed DOI PMC

Robaeys G., Bielen R., Azar D. G., Razavi H., Nevens F. (2016). Global Genotype Distribution of Hepatitis C Viral Infection among People Who Inject Drugs. J. Hepatol. 65 1094–1103. 10.1016/j.jhep.2016.07.042 PubMed DOI

Ruta S., Cernescu C. (2015). Injecting drug use: a vector for the introduction of new Hepatitis C virus genotypes. World J. Gastroenterol. 21 10811–10823. 10.3748/wjg.v21.i38.10811 PubMed DOI PMC

Saludes V., Antuori A., Lazarus J. V., Folch C., González-Gómez S., González N. (2020). Evaluation of the Xpert HCV VL fingerstick point-of-care assay and dried blood spot HCV-RNA testing as simplified diagnostic strategies among people who inject drugs in Catalonia, Spain. Int. J. Drug Policy 80:102734. 10.1016/j.drugpo.2020.102734 PubMed DOI

Sellami R., Feki I., Zahaf A., Masmoudi J. (2016). The profile of drug users in tunisia: implications for prevention. La Tunisie Medicale 94 531–534. PubMed

Sereno S., Perinelli P., Laghi V. (2009). Changes in the prevalence of Hepatitis c virus genotype among italian injection drug users—relation to period of injection started. J. Clin. Virol. 45 354–357. 10.1016/j.jcv.2009.04.022 PubMed DOI

Sharafi H., Poustchi H., Azimian F., Tamadoni B., Ramezani R., Gouya M. M. (2019). Performance of a rapid diagnostic test for screening of Hepatitis C in a real-life prison setting. J. Clin. Virol. 113 20–23. 10.1016/j.jcv.2019.02.005 PubMed DOI

Shivkumar S., Peeling R., Jafari Y., Joseph L., Pant Pai N. (2012). Accuracy of rapid and point-of-care screening tests for Hepatitis C: a systematic review and meta-analysis. Ann. Intern. Med. 157 558–566. 10.7326/0003-4819-157-8-201210160-00006 PubMed DOI

Société Tunisienne de Pathologie Infectieuse and Société Tunisienne de Gastro-entérologie. (2015). Actualisation des Recommandations du Traitement de L’hépatite Virale C en Collaboration Entre la STGE et la STPI. Available online at: https://infectiologie.org.tn/pdf_ppt_docs/recommandations/1536342624.pdf

Trimbitas R.-D., Serghini F. Z., Lazaar F., Baha W., Foullous A., Essalhi M. (2014). The ‘hidden’ epidemic: a snapshot of moroccan intravenous drug users. Virol. J. 11:43. 10.1186/1743-422x-11-43 PubMed DOI PMC

Wang Q. Q., Zhang J., Hu J. S., Chen H. T., Du L., Wu L. Q. (2011). Rapid detection of Hepatitis C Virus RNA by a reverse transcription loop-mediated isothermal amplification assay. FEMS Immunol. Med. Microbiol. 63 144–147. PubMed

Wiessing L., Ferri M., Grady B., Kantzanou M., Sperle I., Cullen K. J. (2014). Hepatitis C virus infection epidemiology among people who inject drugs in europe: a systematic review of data for scaling up treatment and prevention. PLoS One 9:e103345. 10.1371/journal.pone.0103345 PubMed DOI PMC

World Health Organization (2012). MENAHRA–The Middle East and North Africa Harm Reduction Association Best Practices in Strengthening Civil Society’s Role in Delivering Harm Reduction Services. Geneva: WHO.

World Health Organization (2016). Global Health Sector Strategy on Viral Hepatitis 2016-2021. Towards Ending Viral Hepatitis. Geneva: World Health Organization.

World Health Organization (2017). Global Hepatitis Report 2017. Geneva: World Health Organization.

World Health Organization (2018a). Guidelines for the Care and Treatment of Persons Diagnosed with Chronic Hepatitis C Virus Infection. Geneva: WHO. PubMed

World Health Organization (2018b). Progress Report on Access to Hepatitis C Treatment: Focus on Overcoming Barriers in Low-and Middle-Income Countries. Geneva: World Health Organization.

Zhou B., Cai G. F., Lv H. K., Xu S. F., Wang Z. T., Jiang Z. G. (2019). Factors correlating to the development of Hepatitis C virus infection among drug users-findings from a systematic review and meta-analysis. Int. J. Environ. Res. Public Health 16:2345. 10.3390/ijerph16132345 PubMed DOI PMC

Zoratti M. J., Siddiqua A., Morassut R. E., Zeraatkar D., Chou R., van Holten J. (2020). Pangenotypic direct acting antivirals for the treatment of chronic Hepatitis C virus infection: a systematic literature review and meta-analysis. EClinicalMedicine 18:100237. 10.1016/j.eclinm.2019.12.007 PubMed DOI PMC