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

Original article

Vol. 150 No. 3132 (2020)

Management of hepatitis C in opioid agonist therapy patients of the Swiss canton Aargau within and outside the cohort study

DOI
https://doi.org/10.4414/smw.2020.20317
Cite this as:
Swiss Med Wkly. 2020;150:w20317
Published
06.08.2020

Summary

BACKGROUND

Hepatitis C virus (HCV) treatment reduces hepatic and extrahepatic morbidity and mortality and prevents further transmissions. Since October 2017, direct-acting antivirals (DAAs) have been reimbursed in Switzerland for all patients. Intravenous drug use accounts for the majority of HCV infections in Switzerland. Between July 2013 and July 2015, 205 of the 631 opioid agonist therapy (OAT) patients in the Swiss canton Aargau were enrolled into a cohort study, the Argovian OAT cohort study. In March 2019, the Federal Office of Public Health (FOPH) published guidelines for the HCV management in drug users.

AIM

To describe current HCV management in OAT patients of the Swiss canton Aargau in view of the FOPH guidelines and to compare the management of patients within and outside the cohort study.

METHODS

Between July 2013 and August 2018, 330 patients were enrolled into the Argovian OAT cohort study offering human immunodeficiency virus (HIV)/HCV antibody rapid testing, noninvasive liver fibrosis assessment (Fibroscan®) and, since August 2017, capillary HCV RNA rapid testing with the GeneXpert®. To assess HCV management, all information available before 1 September 2018 was considered. In September 2018, 592 of the then 809 OAT patients were not yet enrolled into the cohort study. For them, the cantonal physician sent a questionnaire regarding HCV, HIV, and hepatitis A and B viruses (HAV and HBV) to the OAT prescriber. Up to September 2019, we had received 182 (31%) questionnaires; 160 were eligible for analysis.

RESULTS

In the HCV cascade, the four diagnostic gaps, but not the two treatment-related gaps, were significantly larger in non-cohort compared with cohort patients: (1) never HCV antibody screened: 14% (22/160) versus 0.3% (1/330); (2) no HCV RNA test, if HCV antibody positive: 36% (21/58) versus 11% (19/167) if ever chronically infected; (3) liver fibrosis stage unknown: 51% (19/37) versus 3% (4/120); (4) HCV genotype unknown: 41% (15/37) versus 18% (21/120); (5) never received HCV treatment: 24% (9/37) versus 30% (36/120); (6) no treatment success, if treated and outcome known: 7% (1/14) versus 6% (5/84). HCV treatment outcome was unknown by the OAT prescriber in 50% of non-cohort patients. Adequate HCV management (HCV antibody test ≤1 year ago if HCV antibody negative or last HCV RNA test negative, and ≤1 year ago if HCV antibody positive) was less frequent in non-cohort than in cohort patients: 28% (44/160) versus 69% (229/330).

CONCLUSION

With regard to HCV elimination in OAT patients by 2030, case finding and regular screening for new and re-infections remain a challenge, especially for non-cohort patients in a decentralised setting. Documentation of the HCV sero- and RNA status of each OAT patient by the cantonal physician and a yearly HCV screening reminder sent to the OAT prescriber combined with capillary HCV antibody and HCV RNA testing by the OAT prescriber, general practitioner or the pharmacy might facilitate the implementation of the FOPH guidelines. DAA prescription directly by the OAT prescriber could increase awareness and improve linkage to care.

References

  1. WHO. Fact-sheet Hepatitis C (9 July 2019). Available from: https://www.who.int/news-room/fact-sheets/detail/hepatitis-c (Accessed: 2020 January 13)
  2. 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:.https://doi.org/10.1002/hep.26639
  3. Evon DM, Stewart PW, Amador J, Serper M, Lok AS, Sterling RK, et al. A comprehensive assessment of patient reported symptom burden, medical comorbidities, and functional well being in patients initiating direct acting antiviral therapy for chronic hepatitis C: Results from a large US multi-center observational study. PLoS One. 2018;13(8):e0196908. doi:.https://doi.org/10.1371/journal.pone.0196908
  4. 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:.https://doi.org/10.1002/hep.22375
  5. Edlin BR. Perspective: test and treat this silent killer. Nature. 2011;474(7350):S18–9. doi:.https://doi.org/10.1038/474S18a
  6. Aaron S, McMahon JM, Milano D, Torres L, Clatts M, Tortu S, et al. Intranasal transmission of hepatitis C virus: virological and clinical evidence. Clin Infect Dis. 2008;47(7):931–4. doi:.https://doi.org/10.1086/591699
  7. Degenhardt L, Peacock A, Colledge S, Leung J, Grebely J, Vickerman P, et al. 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 Glob Health. 2017;5(12):e1192–207. doi:.https://doi.org/10.1016/S2214-109X(17)30375-3
  8. Zahnd C, Brezzi M, Bertisch B, Giudici F, Keiser O. Analyse de Situation des Hépatites B et C en Suisse. 2017. Available from: https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=2&ved=2ahUKEwiC_KLc0YLnAhXDb1AKHWdQAW0QFjABegQIBxAC&url=https%3A%2F%2Fwww.bag.admin.ch%2Fdam%2Fbag%2Fde%2Fdokumente%2Fmt%2Fforschungsberichte%2Fsituationsanalyse-hepatitis-bericht.pdf.download.pdf%2Fsituationsanalyse-hepatitis-bericht-de.pdf&usg=AOvVaw03m8hsizPqQkqZgnEfZfY_
  9. 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: https://www.iumsp.ch/Publications/pdf/rds234b_de.pdf
  10. Richard JL, Schaetti C, Basler S, Mäusezahl M. The epidemiology of hepatitis C in Switzerland: trends in notifications, 1988-2015. Swiss Med Wkly. 2018;148:w14619. doi:.https://doi.org/10.4414/smw.2018.14619
  11. Bundesamt für Gesundheit BAG. (1 July 2019). Substitutionsgestützte Behandlungen bei Opioidabhängigkeit. Available from: https://www.bag.admin.ch/bag/de/home/gesund-leben/sucht-und-gesundheit/suchtberatung-therapie/substitutionsgestuetzte-behandlung.html
  12. Bruggmann P, Blach S, Deltenre P, Fehr J, Kouyos R, Lavanchy D, et al. Hepatitis C virus dynamics among intravenous drug users suggest that an annual treatment uptake above 10% would eliminate the disease by 2030. Swiss Med Wkly. 2017;147:w14543.
  13. Zeuzem S. Hepatitis-C-Therapie: State of the Art 2018 [Treatment of Hepatitis C: State of the Art 2018]. Dtsch Med Wochenschr. 2018;143(24):1784–8. Article in German. doi:.https://doi.org/10.1055/a-0591-5916
  14. Lawitz E, Mangia A, Wyles D, Rodriguez-Torres M, Hassanein T, Gordon SC, et al. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med. 2013;368(20):1878–87. doi:.https://doi.org/10.1056/NEJMoa1214853
  15. Bregenzer A, Bruggmann P, Castro E, Moriggia A, Rothen M, Thurnheer MC, et al. Schweizer OAT-Programme auf ihrem Weg zur HCV-Elimination – Die SAMMSU-Kohorte. Suchtmedizin. 2019;21(2):75–90.
  16. Christensen S, Buggisch P, Mauss S, Böker KHW, Schott E, Klinker H, et al. Direct-acting antiviral treatment of chronic HCV-infected patients on opioid substitution therapy: Still a concern in clinical practice? Addiction. 2018;113(5):868–82. doi:.https://doi.org/10.1111/add.14128
  17. Gayam V, Tiongson B, Mandal AK, Garlapati P, Pan C, Mohanty S. Real-world study of hepatitis C treatment with direct-acting antivirals in patients with drug abuse and opioid agonist therapy. Scand J Gastroenterol. 2019;54(5):646–55. doi:.https://doi.org/10.1080/00365521.2019.1617893
  18. Hajarizadeh B, Cunningham EB, Reid H, Law M, Dore GJ, Grebely J. Direct-acting antiviral treatment for hepatitis C among people who use or inject drugs: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2018;3(11):754–67. doi:.https://doi.org/10.1016/S2468-1253(18)30304-2
  19. Grebely J, Dalgard O, Conway B, Cunningham EB, Bruggmann P, Hajarizadeh B, et al.; SIMPLIFY Study Group. Sofosbuvir and velpatasvir for hepatitis C virus infection in people with recent injection drug use (SIMPLIFY): an open-label, single-arm, phase 4, multicentre trial. Lancet Gastroenterol Hepatol. 2018;3(3):153–61. doi:.https://doi.org/10.1016/S2468-1253(17)30404-1
  20. Cunningham EB, Amin J, Feld JJ, Bruneau J, Dalgard O, Powis J, et al.; SIMPLIFY study group. Adherence to sofosbuvir and velpatasvir among people with chronic HCV infection and recent injection drug use: The SIMPLIFY study. Int J Drug Policy. 2018;62:14–23. doi:.https://doi.org/10.1016/j.drugpo.2018.08.013
  21. Bundesamt für Gesundheit BAG. (27 April 2017.) BAG erweitert Vergütung von Medikamenten gegen Hepatitis C. Available from: https://www.bag.admin.ch/bag/de/home/das-bag/aktuell/medienmitteilungen.msg-id-66508.html
  22. Bundesamt für Gesundheit BAG. (25 September 17.) Hepatitis C: Uneingeschränkte Vergütung der neuen Arzneimittel für alle Betroffenen. Available from: https://www.bag.admin.ch/bag/de/home/das-bag/aktuell/medienmitteilungen.msg-id-68158.html
  23. World Health Organization. (May 2016.) Combating hepatitis B and C to reach elimination by 2030 - Advocacy brief. Available from: http://apps.who.int/iris/bitstream/10665/206453/1/WHO_HIV_2016.04_eng.pdf (Cited 2020 January 14.)
  24. Swiss Hepatitis Strategy 2014-2030. Available from: https://www.hepatitis-schweiz.ch/files/Dokumente/PDF/Process_Paper_14_02_2019.pdf (Cited 2020 January 14.)
  25. Bundesamt für Gesundheit BAG. (03/2019) Hepatitis C bei Drogenkonsumierenden: Richtlinien mit settingspezifischen Factsheets. Available from: https://www.bag.admin.ch/dam/bag/de/dokumente/mt/infektionskrankheiten/hepatitis-c/richtlinien-hepatitis-c-drogen.pdf.download.pdf/richtlinien-hepatitis-c-drogen-de.pdf (Cited 2020 January 14.)
  26. 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. doi:https://doi.org/10.4414/smf.2007.06330
  27. 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:.https://doi.org/10.1016/j.drugpo.2015.07.005
  28. Bregenzer A, Conen A, Knuchel J, Friedl A, Eigenmann F, Näf M, et al. 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. Swiss Med Wkly. 2017;147:w14544.
  29. Bregenzer A, Warmann N, Ottiger C, Fux CA. Rapid point-of-care HCV RNA quantification in capillary whole blood for diagnosing chronic HCV infection, monitoring treatment and detecting reinfection. Swiss Med Wkly. 2019;149:w20137. doi:.https://doi.org/10.4414/smw.2019.20137
  30. Offizielle Website der nationalen Substitutionsstatistik, 2016-2020). Available from: https://www.substitution.ch/de/jahrliche_statistik.html&year=2018&canton=ag (Cited: 2020 June 14.)
  31. 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:.https://doi.org/10.1016/j.jviromet.2010.12.009
  32. 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:.https://doi.org/10.1136/jech-2014-204451
  33. European Centre for Disease Prevention and Control. Hepatitis B and C testing strategies in healthcare and community settings in the EU/EEA –A systematic review. Stockholm: ECDC; 2018
  34. Fourati S, Feld JJ, Chevaliez S, Luhmann N. Approaches for simplified HCV diagnostic algorithms. J Int AIDS Soc. 2018;21(Suppl 2):e25058. doi:.https://doi.org/10.1002/jia2.25058
  35. Chevaliez S. Strategies for the improvement of HCV testing and diagnosis. Expert Rev Anti Infect Ther. 2019;17(5):341–7. doi:.https://doi.org/10.1080/14787210.2019.1604221
  36. Bundesamt für Gesundheit BAG. (April 2020) Analysenliste vom 30.04.2020. Available from: https://www.bag.admin.ch/dam/bag/de/dokumente/kuv-leistungen/leistungen-und-tarife/Analysenliste/analysenliste-gesamt-01042020.pdf.download.pdf/Analysenliste%20vom%2001.04.2020.pdf (Cited: 2020 June 14.)
  37. Orasure (21 January 2013) Product information: OraQuick® HCV Rapid Antibody Test, Available from: https://www.orasure.com/products-infectious/products-infectious-oraquick-hcv.asp (Cited: 2020 June 14.)
  38. Pawlotsky J-M, Negro F, Aghemo A, Berenguer M, Dalgard O, Dusheiko G, et al.; European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu; European Association for the Study of the Liver. EASL Recommendations on Treatment of Hepatitis C 2018. J Hepatol. 2018;69(2):461–511. doi:.https://doi.org/10.1016/j.jhep.2018.03.026
  39. Ghany MG, Morgan TR ; AASLD-IDSA Hepatitis C Guidance Panel. Hepatitis C Guidance 2019 Update: American Association for the Study of Liver Diseases-Infectious Diseases Society of America Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection. Hepatology. 2020;71(2):686–721. doi:.https://doi.org/10.1002/hep.31060
  40. Wlassow M, Poiteau L, Roudot-Thoraval F, Rosa I, Soulier A, Hézode C, et al. The new Xpert HCV viral load real-time PCR assay accurately quantifies hepatitis C virus RNA in serum and whole-blood specimens. J Clin Virol. 2019;117:80–4. doi:.https://doi.org/10.1016/j.jcv.2019.06.007
  41. Müllhaupt B, Semela D, Ruckstuhl L, Magenta L, Clerc O, Torgler R, et al. Real World Evidence of the Effectiveness and Clinical Practice Use of Glecaprevir plus Pibrentasvir in Patients with Chronic Hepatitis C Genotypes 1 to 6: The MYTHEN Study. SGG-SGVC-SASL-GESKES Annual Meeting. Interlaken. September 12th–13th, 2019. Oral presentation O23. Swiss Med Wkly. 2019;149(Suppl 240):S7. Available from https://smw.ch/fileadmin/content/supplements/SMW_Suppl_240.pdf.
  42. Moradpour D, Fehr J, Semela D, Rauch A, Müllhaupt B. Treatment of Chronic Hepatitis C - August 2018 Update SASL-SSI Expert Opinion Statement. Available from: https://www.sginf.ch/files/sasl-ssi_eos_aug2018.pdf
  43. Brown RS, Jr, Buti M, Rodrigues L, Chulanov V, Chuang WL, Aguilar H, et al. Glecaprevir/pibrentasvir for 8 weeks in treatment-naïve patients with chronic HCV genotypes 1-6 and compensated cirrhosis: The EXPEDITION-8 trial. J Hepatol. 2020;72(3):441–9. doi:.https://doi.org/10.1016/j.jhep.2019.10.020
  44. American Association for the Study of Liver Diseases, Infectious Diseases Society of America. HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C. Available from: www.hcvguidelines.org. Last updated 6 November 2019.
  45. Shaheen AA, Myers RP. Diagnostic accuracy of the aspartate aminotransferase-to-platelet ratio index for the prediction of hepatitis C-related fibrosis: a systematic review. Hepatology. 2007;46(3):912–21. doi:.https://doi.org/10.1002/hep.21835
  46. 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:.https://doi.org/10.1053/j.gastro.2004.11.018
  47. Wade AJ, Doyle JS, Gane E, Stedman C, Draper B, Iser D, et al. Outcomes of treatment for hepatitis C in primary care compared to hospital-based care: a randomised controlled trial in people who inject drugs. Clin Infect Dis. 2020;70(9):1900–6. doi:.https://doi.org/10.1093/cid/ciz546
  48. Coutinho RA. HIV and hepatitis C among injecting drug users. BMJ. 1998;317(7156):424–5. doi:.https://doi.org/10.1136/bmj.317.7156.424
  49. Hagan H, Thiede H, Weiss NS, Hopkins SG, Duchin JS, Alexander ER. Sharing of drug preparation equipment as a risk factor for hepatitis C. Am J Public Health. 2001;91(1):42–6. doi:.https://doi.org/10.2105/AJPH.91.1.42
  50. 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:.https://doi.org/10.1097/AOG.0000000000001507
  51. 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. doi:.https://doi.org/10.4414/smw.2011.13193
  52. Iakunchykova O, Meteliuk A, Zelenev A, Mazhnaya A, Tracy M, Altice FL. Hepatitis C virus status awareness and test results confirmation among people who inject drugs in Ukraine. Int J Drug Policy. 2018;57:11–7. doi:.https://doi.org/10.1016/j.drugpo.2018.03.022
  53. Murtagh R, Swan D, O’Connor E, McCombe G, Lambert JS, Avramovic G, et al. Hepatitis C Prevalence and Management Among Patients Receiving Opioid Substitution Treatment in General Practice in Ireland: Baseline Data from a Feasibility Study. Interact J Med Res. 2018;7(2):e10313. doi:.https://doi.org/10.2196/10313
  54. Litwin AH, Drolet M, Nwankwo C, Torrens M, Kastelic A, Walcher S, et al. Perceived barriers related to testing, management and treatment of HCV infection among physicians prescribing opioid agonist therapy: The C-SCOPE Study. J Viral Hepat. 2019;26(9):1094–104. doi:.https://doi.org/10.1111/jvh.13119
  55. Palmer AY, Wade AJ, Draper B, Howell J, Doyle JS, Petrie D, et al. A cost-effectiveness analysis of primary versus hospital-based specialist care for direct acting antiviral hepatitis C treatment. Int J Drug Policy. 2020;76:102633; Epub ahead of print. doi:.https://doi.org/10.1016/j.drugpo.2019.102633
  56. Loustaud-Ratti V, Debette-Gratien M, Carrier P. European Association for the Study of the Liver and French hepatitis C recent guidelines: The paradigm shift. World J Hepatol. 2018;10(10):639–44. doi:.https://doi.org/10.4254/wjh.v10.i10.639
  57. Wade A, Draper B, Doyle J, Allard N, Grinzi P, Thompson A, et al. A survey of hepatitis C management by Victorian GPs after PBS-listing of direct-acting antiviral therapy. Aust Fam Physician. 2017;46(4):235–40.

Most read articles by the same author(s)

1 2 > >>