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2014, Number 2

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Ann Hepatol 2014; 13 (2)

Increase of ribavirin dose improves sustained virological response in HCV-genotype 1 patients with a partial response to peg-interferon and ribavirin

Conti F, Vukotic R, Lorenzini S, Riili A, Cursaro C, Scuteri A, Loggi E, Galli S, Furlini G, Bernardi M, Andreone P

Language: English
References: 24
Page: 196-203
PDF size: 134.37 Kb.


ABSTRACT

Background and aim. In patients with chronic hepatitis C receiving Peg interferon/ribavirin (PEG-IFN/RBV) who do not achieve ≥ 2log-reduction in HCV-RNA at week 12 (null responders, NR) and in those with ≥ 2log-decrease but detectable at week 24 (partial responders, PR) the probability to achieve the sustained virological response (SVR) is almost null. The aim of this study was to investigate the efficacy of individualized schedule of progressively increased RBV doses in the setting of PEG-IFN/RBV treatment. Material and methods. PR or NR to PEG-IFN/RBV instead of discontinuing treatment were enrolled to receive increasing doses of RBV until a target theoretical concentration ([tRBV]) of ≥ 15 µmol/L (by pharmacokinetic formula based on glomerular filtration rate). HCV-RNA was assessed every 4 weeks and, if detectable, RBV dose was gradually increased until negativization. Twelve weeks later, patients with detectable HCV-RNA discontinued therapy while those with undetectable HCV-RNA continued for further 48 weeks. Results. Twenty genotype-1 patients (8 NR and 12 PR) were enrolled. After 12 weeks 9 (45%) were still HCV-RNA positive and were discontinued, while remaining 11 had undetectable HCV-RNA. One stopped treatment for side effects. Ten completed treatment. Five (all PR) achieved SVR. Side effects incidence was similar to that observed during PEG-IFN/RBV. Conclusions. In conclusion, RBV high doses, according to individualized schedule, increase SVR in PR on a similar extent to that of triple therapy but without increase of side effects. Such treatment should be considered in PR with no access or intolerant to protease inhibitors (PI).


REFERENCES

  1. Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Gonçales FL Jr, Häussinger D, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 2002; 347: 975-82.

  2. Hadziyannis SJ, Sette H Jr, Morgan TR, Balan V, Diago M, Marcellin P, Ramadori G, et al. Peginterferonalpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med 2004; 140: 346-55.

  3. Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, Goodman ZD, et al. Peginterferon alfa- 2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 2001; 358: 958-65.

  4. Craxì A, Pawlotsky JM, Wedemeyer H, Bjoro K, Flisiak R, Forns X, Mondelli M, et al. European Association for the Study of the Liver EASL Clinical Practice Guidelines: Management of hepatitis C virus infection. J Hepatol 2011; 55: 245-64.

  5. Poordad F, McCone J Jr, Bacon BR, Bruno S, Manns MP, Sulkowski MS, Jacobson IM, et al. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med 2011; 364: 1195-206.

  6. Bacon BR, Gordon SC, Lawitz E, Marcellin P, Vierling JM, Zeuzem S, Poordad F, et al. Boceprevir for previously treated chronic HCV genotype 1 infection. N Engl J Med 2011; 364: 1207-17.

  7. Sherman KE, Flamm SL, Afdhal NH, Nelson DR, Sulkowski MS, Everson GT, Fried MW, et al. Response-Guided Telaprevir Combination Treatment for Hepatitis C Virus Infection. N Engl J Med 2011; 365: 1014-24.

  8. Zeuzem S, Andreone P, Pol S, Lawitz E, Diago M, Roberts S, Focaccia R, et al. Telaprevir for Retreatment of HCV Infection. N Engl J Med 2011; 364: 2417-28.

  9. Jen JF, Glue P, Gupta S, Zambas D, Hajian G. Population pharmacokinetic and pharmacodynamic analysis of ribavirin in patients with chronic hepatitis C. Ther Drug Monit 2000; 22: 555-65.

  10. Glue P. The clinical pharmacology of ribavirin. Semin Liver Dis 1999; 19(Suppl. 1): 17-24.

  11. Bruchfeld A, Lindahl K, Schvarcz R, Ståhle L. Dosage of ribavirin in patients with hepatitis C should be based on renal function: a population pharmacokinetic analysis. Ther Drug Monit 2002; 24: 701-8.

  12. Lindahl K, Schvarcz R, Bruchfeld A, Ståhle L. Evidence that plasma concentration rather than dose per kilogram body weight predicts ribavirin-induced anaemia. J Viral Hepat 2004; 11: 84-7.

  13. Ogawa E, Furusyo N, Kajiwara E, Takahashi K, Nomura H, Tanabe Y, Satoh T, et al. An inadequate dose of ribavirin is related to virological relapse by chronic hepatitis C patients treated with pegylated interferon alpha-2b and ribavirin. J Infect Chemother 2012; 18: 689-97.

  14. Ackefors M, Gjertsen H, Wernerson A, Weiland O. Concentration- guided ribavirin dosing with darbepoetin support and peg-IFN alfa-2a for treatment of hepatitis C recurrence after liver transplantation. J Viral Hepat 2012; 19: 635-9.

  15. Lindahl K, Ståhle L, Bruchfeld A, Schvarcz R. High-dose ribavirin in combination with standard dose peginterferon for treatment of patients with chronic hepatitis C. Hepatology 2005; 41: 275-9.

  16. METAVIR Cooperative Study Group. An algorithm for the grading of activity in chronic hepatitis. Hepatology 1996; 24: 289-93.

  17. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16: 31-41.

  18. Ramachandran P, Fraser A, Agarwal K, Austin A, Brown A, Foster GR, Fox R, et al. UK consensus guidelines for the use of the protease inhibitors boceprevir and telaprevir in genotype 1 chronic hepatitis C infected patients. Aliment Pharmacol Ther 2012; 35: 647-62.

  19. Sulkowski MS, Poordad F, Manns MP, Bronowicki JP, Rajender Reddy K, Harrison SA, Afdhal NH, et al. Anemia during treatment with peginterferon alfa-2b/ribavirin and boceprevir: analysis from the serine protease inhibitor therapy 2 (SPRINT-2) trial. Hepatology 2013; 57: 974-84.

  20. Shiffman ML, Di Bisceglie AM, Lindsay KL, Morishima C, Wright EC, Everson GT, Lok AS, et al. Peginterferon alfa- 2a and ribavirin in patients with chronic hepatitis C who have failed prior treatment. Gastroenterology 2004; 126: 1015-23.

  21. Taliani G, Gemignani G, Ferrari C, Aceti A, Bartolozzi D, Blanc PL, Capanni M, et al. Pegylated interferon alfa-2b plus ribavirin in the retreatment of interferon-ribavirin nonresponder patients. Gastroenterology 2006; 130: 1098-106.

  22. Jensen DM, Marcellin P, Freilich B, Andreone P, Di Bisceglie A, Brandão-Mello CE, Reddy KR, et al. Re-treatment of patients with chronic hepatitis C who do not respond to peginterferon- alpha2b: a randomized trial. Ann Intern Med 2009; 150: 528-40.

  23. Poynard T, Colombo M, Bruix J, Schiff E, Terg R, Flamm S, Moreno-Otero R, et al. Peginterferon alfa-2b and ribavirin: effective in patients with hepatitis C who failed interferon alfa/ribavirin therapy. Gastroenterology 2009; 136: 1618-28.

  24. Chevaliez S, Hézode C, Soulier A, Costes B, Bouvier-Alias M, Rouanet S, Foucher J, et al. High-Dose Pegylated Interferon- α and Ribavirin in Nonresponder Hepatitis C Patients and Relationship With IL-28B Genotype (SYREN Trial). Gastroenterology 2011; 141: 119-27.




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