Skip to main navigation menu Skip to main content Skip to site footer

Original article

Vol. 147 No. 4748 (2017)

Management of hepatitis C in decentralised versus centralised drug substitution programmes and minimally invasive point-of-care tests to close gaps in the HCV cascade

  • Andrea Bregenzer
  • Anna Conen
  • Jürg Knuchel
  • Andrée Friedl
  • Franz Eigenmann
  • Martin Näf
  • Peter Ackle
  • Martin Roth
  • Christoph Andreas Fux
Cite this as:
Swiss Med Wkly. 2017;147:w14544



In Switzerland, intravenous drug use accounts for the majority of hepatitis C virus (HCV) infections. Early HCV treatment prevents further transmissions and reduces morbidity and mortality due to decompensated liver cirrhosis and hepatocellular carcinoma. Nevertheless, patients in drug substitution programmes are often insufficiently screened and treated.


The aim was to compare the current state of HCV management in centralised and decentralised drug substitution programmes of the canton Aargau. Objectives were human immunodeficiency virus (HIV) and HCV prevalence, compliance with guidelines and gaps in the HCV cascade, as well as feasibility/acceptance/validity of HIV/HCV rapid tests on finger-prick blood and noninvasive liver fibrosis assessment with Fibroscan®.


For the cross-sectional study, in June 2013, questionnaires and free rapid tests for HIV (Determine®) and HCV (OraQuick®) that used capillary blood (finger-stick) were sent to 161 physicians providing drug substitution treatment for 631 patients. Free liver fibrosis assessment with Fibroscan® by a member of the study team was offered to all patients. Additionally, patients were directly recruited by the study team in the heroin substitution programme and several addiction clinics visited every 4–6 months, as well as in the Infectious Diseases Outpatient Clinic (questionnaire, rapid tests and Fibroscan® in the same session).


Between July 2013 and July 2015, 205 (32.5%) of the 631 patients receiving opioid substitution in the canton Aargau were enrolled, 192 (93.7%) with HIV/HCV rapid tests and 167 (81.5%) with Fibroscan®. Acceptance of Fibroscan® was higher when offered in the same session (94.1 vs 69.2%). Overall, 77.8% had ever used intravenous drugs. HCV seroprevalence was 53.7% (109/203), HCV RNA prevalence 27.8%. Overall, 7.4% (15/202) were HIV infected, all of whom were HCV co-infected and under antiretroviral treatment. Of the 205 patients included, 104 (50.7%) were recruited in a decentralised setting (family practice / pharmacy) and 101 (49.3%) in a centralised setting (heroin programme, addiction clinic, Infectious Diseases Outpatient Clinic). Compliance with guidelines (regular HIV/HCV screening, workup of HCV-positive patients, availability of HAV/HBV serology) was consistently lower in the decentralised setting, characterised by a higher proportion of females, longer median time in the programme, lower percentage of daily attendance, ever-use of intravenous drugs and HIV and HCV infections. We identified several gaps in the HCV cascade: 23.9% (49/205) had never been HCV screened; 18.9% (18/95) of the HCV positive patients had no HCV RNA test. Of the 61 patients developing chronic HCV infection, 19.7% (12) were not HCV genotyped, 52.5% (32) had no liver fibrosis assessment (liver biopsy) and 54.1% (33) never received treatment; 25.0% (7/28) did not achieve a sustained virological response with interferon-based treatment. The 192 HCV rapid tests showed a sensitivity of 90.4% (94/104; 95% confidence interval 84.7–96.1%) and a specificity of 100% (88/88), and provided 14 new HCV diagnoses. Eight of ten patients with a false-negative HCV rapid test were HCV RNA negative (2 unknown). Among the 88.6% (39/44) currently HCV RNA-positive individuals with valid Fibroscan® results, 24 (61.5%) had a liver stiffness <7.5 kPa. Both HIV co-infection and alcohol overconsumption doubled the risk of severe fibrosis/cirrhosis in HCV positive patients.


In contrast to HIV, HCV transmission among intravenous drug users is still ongoing. The management of hepatitis C in drug substitution patients needs improvement, especially in family practices. Minimally invasive “point-of-care” diagnostics such as the HCV antibody rapid test using capillary blood and mobile Fibroscan® can close some of the gaps in the HCV cascade. HCV RNA determination in capillary blood is still an unmet need. A “one-stop strategy” might improve linkage to care. Restricting the new, highly efficient (90–100% sustained virological response for all genotypes) direct-acting antivirals to patients with at least stage F2 fibrosis withholds treatment from two thirds of the chronically infected and prevents us from reaching the WHO goal of 80% treatment uptake necessary to eliminate hepatitis C by 2030.


  1. Nelson PK, Mathers BM, Cowie B, Hagan H, Des Jarlais D, Horyniak D, et al. Global epidemiology of hepatitis B and hepatitis C in people who inject drugs: results of systematic reviews. Lancet. 2011;378(9791):571–83. doi:.
  2. Bruggmann P, Grebely J. Prevention, treatment and care of hepatitis C virus infection among people who inject drugs. Int J Drug Policy. 2015;26(Suppl 1):S22–6. doi:.
  3. Cominetti F, Simonson T, Dubois-Arber F, Gervasoni JP, Schaub M, Monnat M. Analyse der Hepatitis-C-Situation bei den drogenkonsumierenden Personen in der Schweiz. Lausanne: Institut universitaire de médecine sociale et préventive; 2015. (Raisons de santé 234b) Available from:
  4. Steffen T, Blättler R, Gutzwiller F, Zwahlen M. HIV and hepatitis virus infections among injecting drug users in a medically controlled heroin prescription programme. Eur J Public Health. 2001;11(4):425–30. doi:.
  5. Bundesamt für Gesundheit (BAG). Substitutionsgestützte Behandlungen bei Opioidabhängigkeit Revision July 2013
  6. Bundesamt für Gesundheit (BAG). Substitutionsgestützte Behandlungen bei Opioidabhängigkeit (revised: 28 Dec. 2016), (Accessed: 24 Jan. 2017)
  7. Grebely J, Page K, Sacks-Davis R, van der Loeff MS, Rice TM, Bruneau J, et al.; InC3 Study Group. The effects of female sex, viral genotype, and IL28B genotype on spontaneous clearance of acute hepatitis C virus infection. Hepatology. 2014;59(1):109–20. doi:.
  8. Edlin BR. Perspective: test and treat this silent killer. Nature. 2011;474(7350):S18–9. doi:.
  9. Thein HH, Yi Q, Dore GJ, Krahn MD. Estimation of stage-specific fibrosis progression rates in chronic hepatitis C virus infection: a meta-analysis and meta-regression. Hepatology. 2008;48(2):418–31. doi:.
  10. Westbrook RH, Dusheiko G. Natural history of hepatitis C. J Hepatol. 2014;61(1, Suppl):S58–68. doi:.
  11. Wiley TE, McCarthy M, Breidi L, McCarthy M, Layden TJ. Impact of alcohol on the histological and clinical progression of hepatitis C infection. Hepatology. 1998;28(3):805–9. doi:.
  12. Hézode C, Roudot-Thoraval F, Nguyen S, Grenard P, Julien B, Zafrani ES, et al. Daily cannabis smoking as a risk factor for progression of fibrosis in chronic hepatitis C. Hepatology. 2005;42(1):63–71. doi:.
  13. Ishida JH, Peters MG, Jin C, Louie K, Tan V, Bacchetti P, et al. Influence of cannabis use on severity of hepatitis C disease. Clin Gastroenterol Hepatol. 2008;6(1):69–75. doi:.
  14. Missiha SB, Ostrowski M, Heathcote EJ. Disease progression in chronic hepatitis C: modifiable and nonmodifiable factors. Gastroenterology. 2008;134(6):1699–714. doi:.
  15. Martin-Carbonero L, Benhamou Y, Puoti M, Berenguer J, Mallolas J, Quereda C, et al. Incidence and Predictors of Severe Liver Fibrosis in Human Immunodeficiency Virus–Infected Patients with Chronic Hepatitis C: A European Collaborative Study. Clin Infect Dis. 2004;38(1):128–33. doi:.
  16. Martinez-Sierra C, Arizcorreta A, Diaz F, Roldan R, Martin-Herrera L, Perez-Guzman L, et al. Progression of chronic hepatitis C to liver fibrosis and cirrhosis in patients coinfected with hepatitis C virus and Human Immunodeficiency Virus. Clin Infect Dis. 2003;36:491–8. doi:.
  17. Müllhaupt B, Fehr J, Moradpour D, Rauch A. Treatment of Chronic Hepatitis C – August 2017 Update - SASL - SSI Expert Opinion Statement. (Accessed: 21 Sept. 2017)
  18. European Association for the Study of the Liver. EASL Recommendations on Treatment of Hepatitis C 2015. J Hepatol. 2015;63(1):199–236. doi:.
  19. AASLD/IDSA HCV Guidance Panel. Hepatitis C guidance: AASLD-IDSA recommendations for testing, managing, and treating adults infected with hepatitis C virus. Hepatology. 2015;62(3):932–54. doi:.
  20. Boglione L, Mornese Pinna S, De Nicolò A, Cusato J, Cariti G, Di Perri G, et al. Treatment with direct-acting antiviral agents of hepatitis C virus infection in injecting drug users: A prospective study. J Viral Hepat. 2017;24(10):850–7; Epub ahead of print. doi:.
  21. Kaan IA, Jones T, McCaughan GW. Have we significantly underestimated the capacity in the Australian health system to treat chronic hepatitis C infection in an interferon-free era? Intern Med J. 2017;47(3):269–74. doi:.
  22. Janjua NZ, Islam N, Wong J, Yoshida EM, Ramji A, Samji H, et al. Shift in disparities in hepatitis C treatment from interferon to DAA era: A population-based cohort study. J Viral Hepat. 2017;24(8):624–30; Epub ahead of print. doi:.
  23. Marshall AD, Nielsen S, Cunningham EB, Aghemo A, Alho H, Backmund M, et al. Restrictions for reimbursement of interferon-free direct acting antiviral therapies for HCV infection in Europe (LBP-505). The International Liver Congress 2017 April 19-23, Amsterdam, The Netherlends
  24. Bundesamt für Gesundheit (BAG). Stellungnahme des Bundesamtes für Gesundheit zum Bericht Situationsanalyse Hepatitis B und C. (06 Apr. 2017), (Accessed: 23 May 2017)
  25. Hepatitis Schweiz [Website]. Keine Limitatio mehr (12 Dec. 2017), (Accessed: 21 Sept. 2017)
  26. Broers B, Helbling B, François A, Schmid P, Chuard C, Hadengue A, et al.; Swiss Association for the Study of the Liver (SASL 18). Barriers to interferon-α therapy are higher in intravenous drug users than in other patients with acute hepatitis C. J Hepatol. 2005;42(3):323–8. doi:.
  27. Belfiori B, Ciliegi P, Chiodera A, Bacosi D, Tosti A, Baldelli F, et al. Peginterferon plus Ribavirin for chronic hepatitis C in opiate addicts on methadone/buprenorphine maintenance therapy. Dig Liver Dis. 2009;41(4):303–7. doi:.
  28. Grebely J, deVlaming S, Duncan F, Viljoen M, Conway B. Current approaches to HCV infection in current and former injection drug users. J Addict Dis. 2008;27(2):25–35. doi:.
  29. Bruggmann P, Falcato L, Dober S, Helbling B, Keiser O, Negro F, et al.; Swiss Hepatitis C Cohort Study. Active intravenous drug use during chronic hepatitis C therapy does not reduce sustained virological response rates in adherent patients. J Viral Hepat. 2008;15(10):747–52. doi:.
  30. Bruggmann P, Broers B, Meili D. Hepatitis C-Therapie bei Patienten unter Opioidsusbstitution. Empfehlungen der Schweizerischen Gesellschaft für Suchtmedizin (SSAM). Schweiz Med Forum. 2007;7:916–9
  31. Prasad L, Spicher VM, Zwahlen M, Rickenbach M, Helbling B, Negro F ; Swiss Hepatitis C Cohort Study Group. Cohort Profile: the Swiss Hepatitis C Cohort Study (SCCS). Int J Epidemiol. 2007;36(4):731–7. doi:.
  32. Mehta SH, Genberg BL, Astemborski J, Kavasery R, Kirk GD, Vlahov D, et al. Limited uptake of hepatitis C treatment among injection drug users. J Community Health. 2008;33(3):126–33. doi:.
  33. Witteck A, Schmid P, Hensel-Koch K, Thurnheer MC, Bruggmann P, Vernazza P ; Swiss Hepatitis C and HIV Cohort Studies. Management of hepatitis C virus (HCV) infection in drug substitution programs. Swiss Med Wkly. 2011;141:w13193.
  34. Meyer JP, Moghimi Y, Marcus R, Lim JK, Litwin AH, Altice FL. Evidence-based interventions to enhance assessment, treatment, and adherence in the chronic Hepatitis C care continuum. Int J Drug Policy. 2015;26(10):922–35. doi:.
  35. McLeod A, Weir A, Aitken C, Gunson R, Templeton K, Molyneaux P, et al. Rise in testing and diagnosis associated with Scotland’s Action Plan on Hepatitis C and introduction of dried blood spot testing. J Epidemiol Community Health. 2014;68(12):1182–8. doi:.
  36. Bruggmann P, Litwin AH. Models of care for the management of hepatitis C virus among people who inject drugs: one size does not fit all. Clin Infect Dis. 2013;57(Suppl 2):S56–61. doi:.
  37. Grebely J, Robaeys G, Bruggmann P, Aghemo A, Backmund M, Bruneau J, et al.; International Network for Hepatitis in Substance Users. Recommendations for the management of hepatitis C virus infection among people who inject drugs. Int J Drug Policy. 2015;26(10):1028–38. doi:.
  38. Lee SR, Kardos KW, Schiff E, Berne CA, Mounzer K, Banks AT, et al. Evaluation of a new, rapid test for detecting HCV infection, suitable for use with blood or oral fluid. J Virol Methods. 2011;172(1-2):27–31. doi:.
  39. Friedrich-Rust M, Ong MF, Martens S, Sarrazin C, Bojunga J, Zeuzem S, et al. Performance of transient elastography for the staging of liver fibrosis: a meta-analysis. Gastroenterology. 2008;134(4):960–74. doi:.
  40. Castéra L, Vergniol J, Foucher J, Le Bail B, Chanteloup E, Haaser M, et al. Prospective comparison of transient elastography, Fibrotest, APRI, and liver biopsy for the assessment of fibrosis in chronic hepatitis C. Gastroenterology. 2005;128(2):343–50. doi:.
  41. Castera L, Forns X, Alberti A. Non-invasive evaluation of liver fibrosis using transient elastography. J Hepatol. 2008;48(5):835–47. doi:.
  42. Roulot D, Czernichow S, Le Clésiau H, Costes JL, Vergnaud AC, Beaugrand M. Liver stiffness values in apparently healthy subjects: influence of gender and metabolic syndrome. J Hepatol. 2008;48(4):606–13. doi:.
  43. Garfein RS, Vlahov D, Galai N, Doherty MC, Nelson KE. Viral infections in short-term injection drug users: the prevalence of the hepatitis C, hepatitis B, human immunodeficiency, and human T-lymphotropic viruses. Am J Public Health. 1996;86(5):655–61. doi:.
  44. Thorpe LE, Ouellet LJ, Levy JR, Williams IT, Monterroso ER. Hepatitis C virus infection: prevalence, risk factors, and prevention opportunities among young injection drug users in Chicago, 1997-1999. J Infect Dis. 2000;182(6):1588–94. doi:.
  45. Xia YH, Chen W, Tucker JD, Wang C, Ling L. HIV and hepatitis C virus test uptake at methadone clinics in Southern China: opportunities for expanding detection of bloodborne infections. BMC Public Health. 2013;13(1):899. doi:.
  46. Janjua NZ, Kuo M, Yu A, Alvarez M, Wong S, Cook D, et al. The Population Level Cascade of Care for Hepatitis C in British Columbia, Canada: The BC Hepatitis Testers Cohort (BC-HTC). EBioMedicine. 2016;12:189–95. doi:.
  47. Yehia BR, Schranz AJ, Umscheid CA, Lo Re V, 3rd. The treatment cascade for chronic hepatitis C virus infection in the United States: a systematic review and meta-analysis. PLoS One. 2014;9(7):e101554. doi:.
  48. Hajarizadeh B, Grebely J, McManus H, Estes C, Razavi H, Gray RT, et al. Chronic hepatitis C burden and care cascade in Australia in the era of interferon-based treatment. J Gastroenterol Hepatol. 2017;32(1):229–36. doi:.
  49. Vanhommerig JW, Thomas XV, van der Meer JT, Geskus RB, Bruisten SM, Molenkamp R, et al.; MOSAIC (MSM Observational Study for Acute Infection with hepatitis C) Study Group. Hepatitis C virus (HCV) antibody dynamics following acute HCV infection and reinfection among HIV-infected men who have sex with men. Clin Infect Dis. 2014;59(12):1678–85. doi:.
  50. Kee KM, Wang JH, Hung CH, Chen CH, Lee CM, Chang KC, et al. Decreased anti-hepatitis C virus titer and associated factors in chronic hepatitis C patients after sustained virological response: a prospective study. J Gastroenterol Hepatol. 2012;27(6):1106–11. doi:.
  51. Toyoda H, Kumada T, Kiriyama S, Sone Y, Tanikawa M, Hisanaga Y, et al. Changes in hepatitis C virus (HCV) antibody status in patients with chronic hepatitis C after eradication of HCV infection by interferon therapy. Clin Infect Dis. 2005;40(6):e49–54. doi:.
  52. Tuaillon E, Mondain AM, Meroueh F, Ottomani L, Picot MC, Nagot N, et al. Dried blood spot for hepatitis C virus serology and molecular testing. Hepatology. 2010;51(3):752–8.
  53. Cepheid® [Website] Xpert HCV Viral Load Brochure - CE-IVD. (Accessed: 30 Jan. 2017)
  54. Grebely J, Lamoury FMJ, Hajarizadeh B, Mowat Y, Marshall AD, Bajis S, et al.; LiveRLife Study Group. 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. 2017;2(7):514–20. doi:.
  55. Bregenzer A, Warmann N, Ottiger C, Fux CA. Validation of a point-of-care quantitative HCV-RNA test using capillary blood from the finger (Xpert® HCV Viral Load, Cepheid®) (P59). Joint Annual Meeting 2017 August 30 - September 01, Basel, Switzerland, (Accessed: 21 Sept. 2017)
  56. Bottero J, Boyd A, Gozlan J, Carrat F, Nau J, Pauti MD, et al. Simultaneous Human Immunodeficiency Virus-Hepatitis B-Hepatitis C Point-of-Care Tests Improve Outcomes in Linkage-to-Care: Results of a Randomized Control Trial in Persons Without Healthcare Coverage. Open Forum Infect Dis. 2015;2(4):ofv162. doi:.
  57. Cooper C. Rapid HCV RNA testing: removing the final obstacle to elimination. Lancet Gastroenterol Hepatol. 2017;2(7):468–9. doi:.
  58. Chahine EB, Sucher AJ, Hemstreet BA. Sofosbuvir/Velpatasvir: The First Pangenotypic Direct-Acting Antiviral Combination for Hepatitis C. Ann Pharmacother. 2016:1060028016668897. [Epub ahead of print].
  59. Bruggmann P. Die Hepatitis-C-Epidemiologie in der Schweiz und die Rolle der Grundversorgung. Praxis (Bern). 2016;105(15):885–9. doi:.
  60. Cadranel JF, Rufat P, Degos F ; For the Group of Epidemiology of the French Association for the Study of the Liver (AFEF). Practices of liver biopsy in France: results of a prospective nationwide survey. Hepatology. 2000;32(3):477–81. doi:.
  61. Stauber R. Nichtinvasive Diagnose der Leberfibrose bei chronischen Hepatopathien. J Gastroenterol Hepatol Erkr. 2009;7(4):12–7. Available at:
  62. Witteck A, Schmid P. Hepatitis C – Update 2010. Schweiz Med Forum. 2010;10(42):729–36.
  63. Grady BP, Schinkel J, Thomas XV, Dalgard O. Hepatitis C virus reinfection following treatment among people who use drugs. Clin Infect Dis. 2013;57(Suppl 2):S105–10. doi:.
  64. National Institute of Health. NIH Consensus Statement on Management of Hepatitis C: 2002. NIH Consens State Sci Statements. 2002;19(3):1–46.
  65. Dhumeaux D, Marcellin P, Lerebours E. Treatment of hepatitis C. The 2002 French consensus. Gut. 2003;52(12):1784–7. doi:.
  66. Overbeck K, Dufour JF, Müllhaupt B, Helbling B, Borovicka J, Malinverni R, et al. Impact of international consensus guidelines on antiviral therapy of chronic hepatitis C patients in Switzerland. Swiss Med Wkly. 2010;140(9-10):146–52.
  67. European Association for the Study of the Liver. EASL Recommendations on Treatment of Hepatitis C 2016. J Hepatol. 2017;66(1):153–94. doi:.
  68. WHO. 05/2016, Combating hepatitis B and C to reach elimination by 2030 - Advocacy brief; (Accessed: 21 Nov. 2016)
  69. Martin NK, Vickerman P, Grebely J, Hellard M, Hutchinson SJ, Lima VD, et al. Hepatitis C virus treatment for prevention among people who inject drugs: Modeling treatment scale-up in the age of direct-acting antivirals. Hepatology. 2013;58(5):1598–609. doi:.
  70. Moradpour D, Müllhaupt B. Hepatitis C: aktuelle Therapie. Schweiz Med Forum. 2015;15(17):366-370
  71. Harris M, Ward E, Gore C. Finding the undiagnosed: a qualitative exploration of hepatitis C diagnosis delay in the United Kingdom. J Viral Hepat. 2016;23(6):479–86. doi:.
  72. Doerrbecker J, Behrendt P, Mateu-Gelabert P, Ciesek S, Riebesehl N, Wilhelm C, et al. Transmission of hepatitis C virus among people who inject drugs: viral stability and association with drug preparation equipment. J Infect Dis. 2013;207(2):281–7. doi:.
  73. Fernandez N, Towers CV, Wolfe L, Hennessy MD, Weitz B, Porter S. Sharing of Snorting Straws and Hepatitis C Virus Infection in Pregnant Women. Obstet Gynecol. 2016;128(2):234–7. doi:.
  74. Karageorgopoulos DE, Allen J, Bhagani S. Hepatitis C in human immunodeficiency virus co-infected individuals: Is this still a “special population”? World J Hepatol. 2015;7(15):1936–52. doi:.

Most read articles by the same author(s)

1 2 > >>