Advertisement

Drugs & Aging

, Volume 35, Issue 9, pp 843–857 | Cite as

Effectiveness and Safety of Direct-Acting Antiviral Combination Therapies for Treatment of Hepatitis C Virus in Elderly Patients: Results from the German Hepatitis C Registry

  • Georg DultzEmail author
  • Tobias Müller
  • Jörg Petersen
  • Stefan Mauss
  • Tim Zimmermann
  • Marion Muche
  • Karl-Georg Simon
  • Thomas Berg
  • Stefan Zeuzem
  • Dietrich Hüppe
  • Klaus Böker
  • Heiner Wedemeyer
  • Tania M. Welzel
  • Leberstiftungs-GmbH Deutschland
Original Research Article

Abstract

Background

With the aging of the hepatitis C virus (HCV)-infected patient cohort and the availability of highly effective and tolerable treatment regimens, an increasing number of elderly patients are now eligible for HCV therapy. This study investigated clinical and epidemiologic characteristics of elderly HCV-infected patients as well as the effectiveness and safety of available therapies.

Methods

Patients were enrolled into the German Hepatitis C Registry (DHC-R), a prospective, multicenter, real-world cohort study. Patients were treated at the discretion of the physician, and data were collected by a web-based system.

Results

Of 7133 patients who initiated treatment, 686 (9.6%) were > 70 years of age. In patients > 70 years, intent-to-treat (ITT) SVR12 was 92.6% (514/555) compared to 90.7% (4521/4985) in patients ≤ 70 years of age. Overall, adverse events (AEs) were reported in 374 (54.5%) and 3435 patients (53.3%) > 70 or ≤ 70 years of age; 7.6% (52) and 3.6% (235) in the respective age groups had a serious AE. Twenty-two (3.2%) and 62 (1.0%) of the patients > 70 or ≤ 70 years discontinued treatment due to AEs. Death was reported in 34 patients, of whom eight were > 70 years of age. Frequent comorbidities in patients > 70 years of age were cardiac disease, renal disease and diabetes. Psychiatric disorders, substance abuse and viral co-infection were more frequent in younger patients.

Conclusion

Direct-acting antiviral therapies were well tolerated in patients older than 70 years. SVR12 rates in the elderly patient group were similar to those observed in younger patients. Differences in the prevalence of comorbidities between age groups warrant individualized attention with respect to drug–drug interactions and therapy adherence.

The study was registered in the German Clinical Trials Register, DRKS-ID: DRKS00009717.

Notes

Acknowledgements

Data acquisition was conducted by DHC-R investigators. All authors made substantial contributions to the design of the analysis, writing, and/or interpretation of data in this publication. All authors critically revised the manuscript and approved this publication. All authors had access to all relevant data. Data were derived from the German Hepatitis C Registry (Deutsches Hepatitis C Register), a project of the German Liver Foundation (Deutsche Leberstiftung), managed by Leberstiftungs-GmbH Deutschland in cooperation with the Association of German Gastroenterologists in Private Practice (bng), with financial support from the German Center for Infection Research (DZIF) and the companies AbbVie Deutschland GmbH & Co. KG, Bristol-Myers Squibb GmbH & Co. KGaA, Gilead Sciences GmbH, Janssen-Cilag GmbH, MSD Sharp & Dohme GmbH as well as Roche Pharma AG (financial support until 2017-07-14). We thank all DHC-R investigators, study nurses and Leberstiftungs-GmbH Deutschland, in particular, Bianka Wiebner and Dr. Yvonne Serfert. Statistical analysis support was provided by Heike Pfeiffer-Vornkahl from e.factum GmbH (Butzbach, Germany).

Collaborators: Rainer Günther, Holger Hinrichsen, Renate Heyne, Johannes Roth, Tobias Goeser, Rainer Ullrich, Christine John, Wolf Peter Hofmann, Gerlinde Teuber, Hjördis Möller, Axel Baumgarten, Jeannette Schwenzer, Anita Pathil, Michael R. Kraus, Andreas Weber, Maria-Christina Jung, Guido Gerken, Christoph Antoni, Margareta Frank Doss, Andreas Schober, Martin Hoffstadt, Armand v. Lucadou, Hermann Steffens, Hartwig Klinker, Andreas Geier, Gerd Klausen, Peter Buggisch, Markus Cornberg, Christoph Sarrazin, Michael P. Manns, Claus Niederau, Ulla Protzer, Peter Schirmacher.

Compliance with Ethical Standards

Conflict of interest

GD: Speaker for AbbVie. TM: Consultancies: MERZ, AbbVie, MSD, Roche, BMS, Bayer, Intercept, and Gilead; speaker: MERZ; grants: Deutsche Forschungsgemeinschaft, Falk Foundation, and Intercept. JP: Grant/research support: BMS, Novartis, and Roche; clinical studies: AbbVie, Arrowhead, BMS, Eisai, Falk, Gilead, Hepatera, Hologic, Intercept, Janssen, Merck, MSD, Roche, Siemens, and Vertex; consultant/advisor: Abbott, AbbVie, Arrowhead, Assembly Pharma, BMS, Contravir, Gilead, GSK, Kedrion, Janssen, Merck, MSD, Novira, and Roche; sponsored lectures: Abbott, BMS, Boehringer, Gilead, Kedrion, Janssen, Merck, Merz, MSD, Novartis, and Roche. SM: Advisory committees or review panels: AbbVie, and MSD; speaker: AbbVie, Janssen, Gilead, and MSD. TZ: Received lecturer, consultant fees and/or travel support from AbbVie, BMS, Gilead, Janssen, MSD and Roche; grant: BMS. MM: Advisory committees: Bayer; speaker: Intercept and BMS; travel grants: AbbVie, Gilead, MSD, and Roche. KGS: Consultancies: AbbVie, Janssen, BMS, and MSD; speaker: Falk, AbbVie, Gilead, BMS, Janssen, Norgine, Merz, and MSD. TB: Speaker: AbbVie, Alexion, Bayer, BMS, Gilead, Intercept, Janssen, MSD/Merck, Merz, Novartis, Sirtex and Sequana Medical; grants: AbbVie, BMS, Gilead, Intercept, Janssen, MSD/Merck, Merz, Novartis, and Sequana Medical; adviser: AbbVie, Alexion, Bayer, BMS, Gilead, Intercept, Janssen, MSD/Merck, Merz, Novartis, and Sequana Medical. SZ: Consultancies/speaker for AbbVie, BMS, Gilead, Janssen, and Merck/MSD. DH: Advisor: Novartis, Gilead, BMS, Janssen, AbbVie, Roche, and MSD. KB: Speaker: MSD, Gilead, BMS and Roche. HW: Advisor: Falk, AbbVie, Novartis, Roche Diagnostics, Eiger, Janssen, GSK, Transgene, MSD, Roche, Gilead, Abbott, and BMS; consultancies: MyrGmbH; grants: Roche Diagnostics, Novartis, Gilead, Roche, Abbott, and MSD; speaker: AbbVie, Gilead, BMS, MSD, Novartis, and ITF. TMW: Consultancies/speaker for AbbVie, Bristol-Myers Squibb, Gilead, and Janssen.

References

  1. 1.
    EASL. Clinical Practice Guidelines: management of hepatitis C virus infection. J Hepatol. 2014;60(2):392–420.CrossRefGoogle Scholar
  2. 2.
    Hepatitis C guidance. AASLD-IDSA recommendations for testing, managing, and treating adults infected with hepatitis C virus. Hepatology. 2015;62(3):932–54.CrossRefGoogle Scholar
  3. 3.
    Sarrazin C, Berg T, Buggisch P, Dollinger MM, Hinrichsen H, Hofer H, et al. Aktuelle Empfehlung zur Therapie der chronischen Hepatitis C. Z Gastroenterol. 2015;53(4):320–34.CrossRefPubMedGoogle Scholar
  4. 4.
    Zeuzem S. Treatment options in Hepatitis C. Dtsch Arztebl Int. 2017;114(1–02):11–21.PubMedPubMedCentralGoogle Scholar
  5. 5.
    Höner Zu Siederdissen C, Buggisch P, Böker K, Schott E, Klinker H, Pathil A, et al. Treatment of hepatitis C genotype 1 infection in Germany: effectiveness and safety of antiviral treatment in a real-world setting. United Eur Gastroenterol J. 2018;6(2):213–24.  https://doi.org/10.1177/2050640617716607.CrossRefGoogle Scholar
  6. 6.
    Buggisch P, Vermehren J, Mauss S, Günther R, Schott E, Pathil A et al. Real-world effectiveness of 8 weeks treatment with ledipasvir/sofosbuvir in chronic hepatitis C. J Hepatol 2017.Google Scholar
  7. 7.
    Welzel TM, Hinrichsen H, Sarrazin C, Buggisch P, Baumgarten A, Christensen S, et al. Real-world experience with the all-oral, interferon-free regimen of ombitasvir/paritaprevir/ritonavir and dasabuvir for the treatment of chronic hepatitis C virus infection in the German Hepatitis C Registry. J Viral Hepat. 2017;24(10):840–9.CrossRefPubMedGoogle Scholar
  8. 8.
    Mücke MM, Mücke VT, Lange CM, Zeuzem S. Special populations: treating hepatitis C in patients with decompensated cirrhosis and/or advanced renal impairment. Liver Int. 2017;37(Suppl 1):19–25.CrossRefPubMedGoogle Scholar
  9. 9.
    Rockstroh JK. Optimal therapy of HIV/HCV co-infected patients with direct acting antivirals. Liver Int. 2015;35(Suppl 1):51–5.CrossRefPubMedGoogle Scholar
  10. 10.
    Vespasiani-Gentilucci U, Galati G, Gallo P, de Vincentis A, Riva E, Picardi A. Hepatitis C treatment in the elderly: new possibilities and controversies towards interferon-free regimens. World J Gastroenterol. 2015;21(24):7412–26.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Yang Z, Zhuang L, Yang L, Liu C, Lu Y, Xu Q, et al. Efficacy and safety of peginterferon plus ribavirin for patients aged ≥ 65 years with chronic hepatitis C: a systematic review and meta-analysis. Clin Res Hepatol Gastroenterol. 2014;38(4):440–50.CrossRefPubMedGoogle Scholar
  12. 12.
    Nudo CG, Wong P, Hilzenrat N, Deschênes M. Elderly patients are at greater risk of cytopenia during antiviral therapy for hepatitis C. Can J Gastroenterol. 2006;20(9):589–92.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Honda T, Katano Y, Shimizu J, Ishizu Y, Doizaki M, Hayashi K, et al. Efficacy of peginterferon-alpha-2b plus ribavirin in patients aged 65 years and older with chronic hepatitis C. Liver Int. 2010;30(4):527–37.CrossRefPubMedGoogle Scholar
  14. 14.
    Poynard T, Ratziu V, Charlotte F, Goodman Z, McHutchison J, Albrecht J. Rates and risk factors of liver fibrosis progression in patients with chronic hepatitis c. J Hepatol. 2001;34(5):730–9.CrossRefPubMedGoogle Scholar
  15. 15.
    Pradat P, Voirin N, Tillmann HL, Chevallier M, Trépo C. Progression to cirrhosis in hepatitis C patients: an age-dependent process. Liver Int. 2007;27(3):335–9.CrossRefPubMedGoogle Scholar
  16. 16.
    Younossi Z, Park H, Henry L, Adeyemi A, Stepanova M. Extrahepatic manifestations of hepatitis C: a meta-analysis of prevalence, quality of life, and economic burden. Gastroenterology. 2016;150(7):1599–608.CrossRefPubMedGoogle Scholar
  17. 17.
    van der Meer AJ, Berenguer M. Reversion of disease manifestations after HCV eradication. J Hepatol. 2016;65(1 Suppl):S95–108.CrossRefPubMedGoogle Scholar
  18. 18.
    Hassoun Z, Willems B, Deslauriers J, Nguyen BN, Huet P. Assessment of fatigue in patients with chronic hepatitis C using the Fatigue Impact Scale. Dig Dis Sci. 2002;47(12):2674–81.CrossRefPubMedGoogle Scholar
  19. 19.
    Reddy KR, Bourlière M, Sulkowski M, Omata M, Zeuzem S, Feld JJ, et al. Ledipasvir and sofosbuvir in patients with genotype 1 hepatitis C virus infection and compensated cirrhosis: an integrated safety and efficacy analysis. Hepatology. 2015;62(1):79–86.CrossRefPubMedGoogle Scholar
  20. 20.
    Shiffman ML, Rustgi V, Bennett M, Forns X, Asselah T, Vila RP, et al. Corrigendum: safety and efficacy of ombitasvir/paritaprevir/ritonavir plus dasabuvir with or without ribavirin in HCV-infected patients taking concomitant acid-reducing agents. Am J Gastroenterol. 2016;111(7):1077.CrossRefPubMedGoogle Scholar
  21. 21.
    Zeuzem S, Dusheiko GM, Salupere R, Mangia A, Flisiak R, Hyland RH, et al. Sofosbuvir and ribavirin in HCV genotypes 2 and 3. N Engl J Med. 2014;370(21):1993–2001.CrossRefPubMedGoogle Scholar
  22. 22.
    Welzel TM, Petersen J, Herzer K, Ferenci P, Gschwantler M, Wedemeyer H, et al. Daclatasvir plus sofosbuvir, with or without ribavirin, achieved high sustained virological response rates in patients with HCV infection and advanced liver disease in a real-world cohort. Gut. 2016;65(11):1861–70.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Leroy V, Angus P, Bronowicki J, Dore GJ, Hezode C, Pianko S, et al. Daclatasvir, sofosbuvir, and ribavirin for hepatitis C virus genotype 3 and advanced liver disease: a randomized phase III study (ALLY-3 +). Hepatology. 2016;63(5):1430–41.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Vermehren J, Peiffer K, Welsch C, Grammatikos G, Welker M, Weiler N, et al. The efficacy and safety of direct acting antiviral treatment and clinical significance of drug-drug interactions in elderly patients with chronic hepatitis C virus infection. Aliment Pharmacol Ther. 2016;44(8):856–65.CrossRefPubMedGoogle Scholar
  25. 25.
    Conti F, Brillanti S, Buonfiglioli F, Vukotic R, Morelli MC, Lalanne C, et al. Safety and efficacy of direct-acting antivirals for the treatment of chronic hepatitis C in a real-world population aged 65 years and older. J Viral Hepat. 2017;24(6):454–63.CrossRefPubMedGoogle Scholar
  26. 26.
    Toyoda H, Kumada T, Tada T, Shimada N, Takaguchi K, Senoh T, et al. Efficacy and tolerability of an IFN-free regimen with DCV/ASV for elderly patients infected with HCV genotype 1B. J Hepatol. 2017;66(3):521–7.CrossRefPubMedGoogle Scholar
  27. 27.
    Akuta N, Sezaki H, Suzuki F, Kawamura Y, Hosaka T, Kobayashi M, et al. Favorable efficacy of daclatasvir plus asunaprevir in treatment of elderly Japanese patients infected with HCV genotype 1b aged 70 and older. J Med Virol. 2017;89(1):91–8.CrossRefPubMedGoogle Scholar
  28. 28.
    Ogawa E, Furusyo N, Nomura H, Takahashi K, Higashi N, Kawano A, et al. Effectiveness and safety of sofosbuvir plus ribavirin for HCV genotype 2 patients 65 and over with or without cirrhosis. Antiviral Res. 2016;136:37–44.CrossRefPubMedGoogle Scholar
  29. 29.
    Nishida N, Kono M, Minami T, Chishina H, Arizumi T, Takita M, et al. Safety, tolerability, and efficacy of sofosbuvir plus ribavirin in elderly patients infected with hepatitis C virus genotype 2. Dig Dis. 2016;34(6):632–9.CrossRefPubMedGoogle Scholar
  30. 30.
    Lens S, Fernández I, Rodríguez-Tajes S, Hontangas V, Vergara M, Forné M et al. Interferon-free therapy in elderly patients with advanced liver disease. Am J Gastroenterol 2017.Google Scholar
  31. 31.
    Kartashev V, Döring M, Nieto L, Coletta E, Kaiser R, Sierra S. New findings in HCV genotype distribution in selected West European, Russian and Israeli regions. J Clin Virol. 2016;81:82–9.CrossRefPubMedGoogle Scholar
  32. 32.
    Jacobson IM, Davis GL, El-Serag H, Negro F, Trépo C. Prevalence and challenges of liver diseases in patients with chronic hepatitis C virus infection. Clin Gastroenterol Hepatol. 2010;8(11):924–33.CrossRefPubMedGoogle Scholar
  33. 33.
    Poynard T, Bedossa P, Opolon P. Natural history of liver fibrosis progression in patients with chronic hepatitis C. Lancet. 1997;349(9055):825–32.CrossRefPubMedGoogle Scholar
  34. 34.
    Massard J, Ratziu V, Thabut D, Moussalli J, Lebray P, Benhamou Y, et al. Natural history and predictors of disease severity in chronic hepatitis C. J Hepatol. 2006;44(1 Suppl):S19–24.CrossRefPubMedGoogle Scholar
  35. 35.
    Kiser JJ, Burton JR, Everson GT. Drug-drug interactions during antiviral therapy for chronic hepatitis C. Nat Rev Gastroenterol Hepatol. 2013;10(10):596–606.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Smolders EJ, Smit C, Tmm De Kanter C, Dofferhoff A, Arends JE, Brinkman K et al. High need to switch cART or co-medication with the initiation of DAAs in elderly HIV/HCV co-infected patients. J Acquir Immune Defic Syndr 2017.Google Scholar
  37. 37.
    Rice DP, Faragon JJ, Banks S, Chirch LM. HIV/HCV antiviral drug interactions in the era of direct-acting antivirals. J Clin Transl Hepatol. 2016;4(3):234–40.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Smolders EJ, de Kanter CTMM, de Knegt RJ, van der Valk M, Drenth JPH, Burger DM. Drug-drug interactions between direct-acting antivirals and psychoactive medications. Clin Pharmacokinet. 2016;55(12):1471–94.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Badri PS, King JR, Polepally AR, McGovern BH, Dutta S, Menon RM. Dosing recommendations for concomitant medications during 3D anti-HCV therapy. Clin Pharmacokinet. 2016;55(3):275–95.CrossRefPubMedGoogle Scholar
  40. 40.
    Tacke F, Günther R, Buggisch P, Klinker H, Schober A, John C, et al. Treatment of HCV genotype 2 with sofosbuvir and ribavirin results in lower sustained virological response rates in real life than expected from clinical trials. Liver Int. 2017;37(2):205–11.CrossRefPubMedGoogle Scholar
  41. 41.
    Cornberg M, Petersen J, Schober A, Mauss S, Böker KHW, Link R, et al. Real-world use, effectiveness and safety of anti-viral treatment in chronic hepatitis C genotype 3 infection. Aliment Pharmacol Ther. 2017;45(5):688–700.CrossRefPubMedGoogle Scholar
  42. 42.
    Wiese M, Fischer J, Löbermann M, Göbel U, Grüngreiff K, Güthoff W, et al. Evaluation of liver disease progression in the German hepatitis C virus (1b)-contaminated anti-D cohort at 35 years after infection. Hepatology. 2014;59(1):49–57.CrossRefPubMedGoogle Scholar
  43. 43.
    Fabrizi F, Verdesca S, Messa P, Martin P. Hepatitis C virus infection increases the risk of developing chronic kidney disease: a systematic review and meta-analysis. Dig Dis Sci. 2015;60(12):3801–13.CrossRefPubMedGoogle Scholar
  44. 44.
    Younossi Z, Henry L. Systematic review: patient-reported outcomes in chronic hepatitis C—the impact of liver disease and new treatment regimens. Aliment Pharmacol Ther. 2015;41(6):497–520.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Georg Dultz
    • 1
    Email author
  • Tobias Müller
    • 2
  • Jörg Petersen
    • 3
  • Stefan Mauss
    • 4
  • Tim Zimmermann
    • 5
  • Marion Muche
    • 2
  • Karl-Georg Simon
    • 6
  • Thomas Berg
    • 7
  • Stefan Zeuzem
    • 1
  • Dietrich Hüppe
    • 8
  • Klaus Böker
    • 9
  • Heiner Wedemeyer
    • 10
    • 11
    • 12
  • Tania M. Welzel
    • 1
  • Leberstiftungs-GmbH Deutschland
  1. 1.Department of Medicine 1J.W. Goethe University FrankfurtFrankfurt am MainGermany
  2. 2.Charité Campus Virchow-Klinikum (CVK)BerlinGermany
  3. 3.ifi-Institute for Interdisciplinary MedicineHamburgGermany
  4. 4.Center for HIV and HepatogastroenterologyDüsseldorfGermany
  5. 5.University Medical Center of the Johannes Gutenberg University MainzMainzGermany
  6. 6.Hepatologische PraxisLeverkusenGermany
  7. 7.University Hospital LeipzigLeipzigGermany
  8. 8.Hepatologische SchwerpunktpraxisHerneGermany
  9. 9.Hepatologische PraxisHannoverGermany
  10. 10.Department of Gastroenterology and HepatologyUniversity Hospital Essen, University of Duisburg EssenEssenGermany
  11. 11.Department of Gastroenterology, Hepatology and EndocrinologyHannover Medical SchoolHannoverGermany
  12. 12.Leberstiftungs-GmbH DeutschlandHannoverGermany

Personalised recommendations