Advertisement

International Journal of Clinical Pharmacy

, Volume 39, Issue 6, pp 1304–1311 | Cite as

Adverse effects of direct acting antiviral-based regimens in chronic hepatitis C patients: a Brazilian experience

  • Thalia Medeiros
  • Camila de Morais Salviato
  • Natalia Fonseca do Rosário
  • Geórgia do Nascimento Saraiva
  • Eliane Bordalo Cathalá Esberard
  • Jorge Reis Almeida
  • Analúcia Rampazzo Xavier
  • Andrea Alice da Silva
Research Article

Abstract

Background Direct-acting antivirals (DAA) are currently used for the treatment of chronic hepatitis C (HCV). However, few studies describe the adverse effects (AE) associated with DAA therapy in “real-word” cohorts. Aim To evaluate AE in Brazilian chronic HCV patients after DAA-therapy. Setting A reference center for hepatitis treatment in Rio de Janeiro, Brazil. Methods An observational “real-world” study was conducted with 102 chronic HCV patients undergoing DAA therapy for 12 or 24 weeks. The self-reported AE were correlated with cirrhosis status, genotype, age, current therapeutic schemes and comorbidities. Serious AE were also investigated. Main outcome measure Frequency of AE during DAA therapy. Results Overall, mean ± SD age was 60.9 ± 9.4 years, 67% were females, HCV-genotype 1 was the most prevalent (81%) and 74% were cirrhotic. Moreover, all patients reached sustained virological response. About 90% of patients reported at least one AE associated with current treatment, with a mean of 2.7 symptoms per patient. The most frequently reported AE were fatigue (43%), headache (42%), neuropsychiatric symptoms (30%) and nausea (26%). Furthermore, hemoglobin < 12 mg/dL was the most frequent (38%) laboratory abnormality observed. Neuropsychiatric symptoms were the only AE significantly different in treatment-experienced group when compared to naïve patients (41.7 vs. 12.5, P = 0.002). The higher frequency of AE did not correlate with the presence of previous treatment, cirrhosis, genotype, age, current therapeutic schemes with DAA or comorbidities. Conclusion DAA-based therapeutic regimens demonstrated safety in a Brazilian “real-world” cohort of chronic hepatitis C patients.

Keywords

Adverse effects Brazil Chronic hepatitis C Direct-acting antiviral Sofosbuvir 

Abbreviations

AE

Adverse effects

DAA

Direct-acting antivirals

DCV

Daclatasvir

EoT

End of treatment

HCV

Hepatitis C virus

IFN

Interferon

Peg-IFN

Pegylated interferon

RBV

Ribavirin

SAE

Serious adverse effects

SMV

Simeprevir

SOF

Sofosbuvir

SVR

Sustained virological response

Notes

Acknowledgements

The authors thank to the Unidade de Pesquisa Clínica and the Serviço de Patologia Clínica (UFF) by technical support.

Funding

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES): T. Medeiros, N.F. Rosário, G.N. Saraiva are students fellow.

Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro/FAPERJ (JCNE/E-26/102.173/2013): A.A. Silva is a research fellow.

Conflicts of interest

The authors declare that they have no conflicts of interest.

References

  1. 1.
    Brazil. Ministry of health. Clinical protocol and therapeutic guidance for hepatitis C and coinfections. Brasilia; 2015.Google Scholar
  2. 2.
    Masip M, Tuneu L, Pagès N, Torras X, Gallego A, Guardiola JP, et al. Prevalence and detection of neuropsychiatric adverse effects during hepatitis C treatment. Int J Clin Pharm. 2015;37(6):1143–51.CrossRefPubMedGoogle Scholar
  3. 3.
    Aygen B, Yıldız O, Akhan S, Çelen KM, Ural O, Koruk ST, et al. Retreatment of chronic hepatitis C infection with telaprevir: preliminary results in Turkey. Balkan Med J. 2015;32(3):266–72.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Picard O, Cacoub P. Dermatological adverse effects during genotype-1 hepatitis C treatment with the protease inhibitors telaprevir and boceprevir. Patient management. Clin Res Hepatol Gastroenterol. 2012;36(5):437–40.CrossRefPubMedGoogle Scholar
  5. 5.
    Kohjima M, Kurokawa M, Enjoji M, Yoshimuto T, Nakamura T, Ohashi T, et al. Analysis of renal function during telaprevir-based triple therapy for chronic hepatitis C. Exp Ther Med. 2016;11(5):1781–7.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Guglieri-López B, Ventura-Cerdá JM, Gómez-Álvarez S, Climente-Martí M. Incidence, management and costs of adverse effects in chronic hepatitis C patients on triple therapy with telaprevir or boceprevir: first 12 weeks of treatment. Enferm Infecc Microbiol Clin. 2015;33(5):331–6.CrossRefPubMedGoogle Scholar
  7. 7.
    Predescu O, Streba LA, Irimia E, Streba L, Mogoantă L. Adverse effects of peg-Interferon and Ribavirin combined antiviral treatment in a Romanian hepatitis C virus infected cohort. Rom J Morphol Embryol. 2012;53(3):497–502.PubMedGoogle Scholar
  8. 8.
    Yang J-F, Kao Y-H, Dai C-Y, Huang J-F, Hsieh M-Y, Lin Z-Y, et al. Comparison of adverse effects related to pegylated interferon-based therapy for patients with chronic hepatitis B and chronic hepatitis C in Taiwan. Hepatol Int. 2010;4(4):732–40.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Gonçalves C, Amaral K, Sander G, Martins N, Pereira L, Picon P. Effectiveness of alpha interferon (+ ribavirin) in the treatment of chronic viral hepatitis C genotypes 2 and 3 in a Brazilian sample. Arq Gastroenterol. 2012;49(2):150–6.CrossRefPubMedGoogle Scholar
  10. 10.
    Gimeno-Ballester V, Simón M, Trigo C, Mar J, San MiguelR. Sofosbuvir plus simeprevir for the treatment of genotype 1 chronic hepatitis C: a review of evidence. Expert Rev Gastroenterol Hepatol. 2016;10(11):1289–303.CrossRefPubMedGoogle Scholar
  11. 11.
    Werner CR, Schwarz JM, Egetemeyr DP, Beck R, Malek NP, Lauer UM, et al. Second-generation direct-acting-antiviral hepatitis C virus treatment: efficacy, safety, and predictors of SVR12. World J Gastroenterol. 2016;22(35):8050–9.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Ampuero J, Romero-Gómez M. Pharmacogenetics of ribavirin-induced anemia in hepatitis C. Pharmacogenomics. 2016;17(14):1587–94.CrossRefPubMedGoogle Scholar
  13. 13.
    Gaeta GB, Precone DF, Felaco FM, Bruno R, Spadaro A, Stornaiuolo G, et al. Premature discontinuation of interferon plus ribavirin for adverse effects: a multicentre survey in ‘real world’ patients with chronic hepatitis C. Aliment Pharmacol Ther. 2002;16(9):1633–9.CrossRefPubMedGoogle Scholar
  14. 14.
    Osinusi A, Kohli A, Marti MM, Nelson A, Zhang X, Meissner EG, et al. Re-treatment of chronic hepatitis C virus genotype 1 infection after relapse: an open-label pilot study. Ann Intern Med. 2014;161(9):634–8.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Gane EJ, Kowdley KV, Pound D, Stedman CAM, Davis M, Etzkorn K, et al. Efficacy of sofosbuvir, velpatasvir, and GS-9857 in patients with hepatitis C virus genotype 2, 3, 4, or 6 infections in an open-label, phase 2 trial. Gastroenterology. 2016;151(5):902–9.CrossRefPubMedGoogle Scholar
  16. 16.
    Brazil. Ministry of health. 1° Seminar on participatory management forum of municipal health councils of metropolitan region II. Brasilia; 2007.Google Scholar
  17. 17.
    Wu LS, Jimmerson LC, MacBrayne CE, Kiser JJ, D’Argenio DZ. Modeling ribavirin-induced anemia in patients with chronic hepatitis C virus. CPT Pharmacomet Syst Pharmacol. 2016;5(2):65–73.CrossRefGoogle Scholar
  18. 18.
    Suwanthawornkul T, Anothaisintawee T, Sobhonslidsuk A, Thakkinstian A, Teerawattananon Y. Efficacy of second generation direct-acting antiviral agents for treatment naïve hepatitis C genotype 1: a systematic review and network meta-analysis. PLoS ONE. 2015;10(12):e0145953.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Calleja JL, Crespo J, Rincón D, Ruiz-Antorán B, Fernandez I, Perelló C, et al. Effectiveness, safety and clinical outcomes of direct-acting antiviral therapy in HCV genotype 1 infection: results from a Spanish real-world cohort. J Hepatol. 2017;66(6):1138–48.CrossRefPubMedGoogle Scholar
  20. 20.
    Chen YC, Chiou WY, Hung SK, Su YC, Hwang SJ. Hepatitis C virus itself is a causal risk factor for chronic kidney disease beyond traditional risk factors: a 6-year nationwide cohort study across Taiwan. BMC Nephrol. 2013;14:187.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Lee JJ, Lin MY, Chang JS, Hung CC, Chang JM, Chen HC, et al. Hepatitis C virus infection increases risk of developing end-stage renal disease using competing risk analysis. PLoS ONE. 2014;9(6):e100790.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Sulkowski MS, Flamm S, Kayali Z, Lawitz EJ, Kwo P, McPhee F et al. Short-duration treatment for chronic hepatitis C virus with daclatasvir, asunaprevir, beclabuvir and sofosbuvir (FOURward study). Liver Int. 2017;37(6):836–42.CrossRefPubMedGoogle Scholar
  23. 23.
    Garcia TJ, Lara PH, Morimoto TP, Higasiaraguti M, Perejão AM, Ayub MA. Side effects of the hepatitis C treatment at the ABC application center. Rev Assoc Med Bras. 2012;58(5):543–9.CrossRefPubMedGoogle Scholar
  24. 24.
    Harrington PR, Fleischer R, Connelly SM, Lewis LL, Murray J. Ribavirin reduces absolute lymphocyte counts in hepatitis C virus-infected patients treated with interferon-free. Direct-acting antiviral regimens. Clin Infect Dis. 2015;61(6):974–7.CrossRefPubMedGoogle Scholar
  25. 25.
    Iacobellis A, Cozzolongo R, Minerva N, Valvano MR, Niro GA, Fontana R, et al. Feasibility of pegylated interferon and ribavirin in hepatitis C-related cirrhosis with neutropenia or thrombocytopenia. Dig Liver Dis. 2014;46(7):621–4.CrossRefPubMedGoogle Scholar
  26. 26.
    Gastaldi G, Goossens N, Clément S, Negro F. Current level of evidence on causal association between hepatitis C virus and type 2 diabetes: a review. J Adv Res. 2017;8(2):149–59.CrossRefPubMedGoogle Scholar
  27. 27.
    Rodríguez-Osorio I, Cid P, Morano L, Castro Á, Suárez M, Delgado M, et al. Real life experience with direct-acting antivirals agents against hepatitis C infection in elderly patients. J Clin Virol. 2017;88:58–61.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Thalia Medeiros
    • 1
  • Camila de Morais Salviato
    • 1
  • Natalia Fonseca do Rosário
    • 1
  • Geórgia do Nascimento Saraiva
    • 1
  • Eliane Bordalo Cathalá Esberard
    • 3
  • Jorge Reis Almeida
    • 1
  • Analúcia Rampazzo Xavier
    • 1
    • 2
  • Andrea Alice da Silva
    • 1
    • 2
  1. 1.Laboratório Multiusuário de Apoio à Pesquisa em Nefrologia e Ciências Médicas, Departamento de Medicina Clínica, Faculdade de MedicinaUniversidade Federal FluminenseRio de JaneiroBrazil
  2. 2.Departamento de Patologia, Faculdade de MedicinaUniversidade Federal FluminenseRio de JaneiroBrazil
  3. 3.Centro de Referência de Tratamento em Hepatites/HUAP, Serviço de Gastroenterologia, Departamento de Medicina Clínica, Faculdade de MedicinaUFFRio de JaneiroBrazil

Personalised recommendations