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Anemia Predicts Sustained Virological Response in Cirrhotic and Noncirrhotic Patients with Chronic Hepatitis C Treated with Peginterferon Alfa-2a and Ribavirin

  • Management of the Cirrhotic Patient (NS Reau and A Cardenas, Section Editors)
  • Published:
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Abstract

The aim of this post hoc analysis from four prospective clinical trials was to determine if the association between anemia and increased SVR occurs in patients with cirrhosis treated with peginterferon alfa-2a/ribavirin. The results suggest that rates of anemia were similar in patients with and without cirrhosis (hemoglobin ≤10 g/dL 17.9 vs 18.5 %; ≥3 g/dL decrease in hemoglobin 74.3 vs 70.6 %, respectively). SVR rates were consistently higher in noncirrhotic patients with and without anemia; however, within each cohort, SVR rates were considerably higher in patients who experienced a ≥3.0 g/dL drop in hemoglobin level. Among patients with cirrhosis, SVR rates with and without a ≥3.0 g/dL drop in hemoglobin were 30.6 and 17.7 %. SVR rates were similar in cirrhotic patients with or without hemoglobin levels dropping to ≤10.0 g/dL (29.9 vs 26.7 %). This analysis confirmed that SVR rates are higher in patients who experience a >3.0 g/dL drop in hemoglobin during treatment with peginterferon alfa-2a/ribavirin and, for the first time, showed that this phenomenon occurs in patients with cirrhosis.

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References

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  1. McHutchison JG, Manns MP, Brown Jr RS, Reddy KR, Shiffman ML, Wong JB. Strategies for managing anemia in hepatitis C patients undergoing antiviral therapy. Am J Gastroenterol. 2007;102:880–9.

    Article  CAS  PubMed  Google Scholar 

  2. Lindahl K, Stahle 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.

    Article  CAS  PubMed  Google Scholar 

  3. Poordad F, McCone Jr J, Bacon BR, et al. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med. 2011;364:1195–206.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. McHutchison JG, Lawitz EJ. Shiffman MLet al. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med. 2009;361:580–93.

    Article  CAS  PubMed  Google Scholar 

  5. Jacobson IM, McHutchison JG. Dusheiko Get al. Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med. 2011;364:2405–16.

    Article  CAS  PubMed  Google Scholar 

  6. Hammond K, Jimmerson L, MacBrayne C et al. Increased plasma and intracellular ribavirin concentrations associated with telaprevir use [Abstract 34]. 20th Conference on Retroviruses and Opportunistic Infections;3–6 March 2013; Atlanta, GA.

  7. Bruno S, Shiffman ML, Roberts SK, et al. Efficacy and safety of peginterferon alfa-2a (40KD) plus ribavirin in hepatitis C patients with advanced fibrosis and cirrhosis. Hepatology. 2010;51:388–97.

    Article  CAS  PubMed  Google Scholar 

  8. Fontaine H, Hézode C, Dorival C, et al. SVR12 rates and safety of triple therapy including telaprevir or boceprevir in 485 cirrhotic non responders treated in the French Early Access Program (ANRS CO20-CUPIC). J Hepatol. 2013;58(suppl):S27–8.

    Article  Google Scholar 

  9. Reau N, Hadziyannis SJ, Messinger D, Fried MW, Jensen DM. Early predictors of anemia in patients with hepatitis C genotype 1 treated with peginterferon alfa-2a (40KD) plus ribavirin. Am J Gastroenterol. 2008;103:1981–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. McHutchison JG, Manns M, Patel K, et al. Adherence to combination therapy enhances sustained response in genotype-1-infected patients with chronic hepatitis C. Gastroenterology. 2002;123:1061–9.

    Article  CAS  PubMed  Google Scholar 

  11. Reddy KR, Shiffman ML, Morgan TR, et al. Impact of ribavirin dose reductions in hepatitis C virus genotype 1 patients completing peginterferon alfa-2a/ribavirin treatment. Clin Gastroenterol Hepatol. 2007;5:124–9.

    Article  CAS  PubMed  Google Scholar 

  12. Ghany MG, Strader DB, Thomas DL, Seeff LB. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology. 2009;49:1335–74.

    Article  CAS  PubMed  Google Scholar 

  13. Sulkowski MS, Shiffman ML, Afdhal NH, et al. Hepatitis C virus treatment-related anemia is associated with higher sustained virologic response rate. Gastroenterology. 2010;139:1602–11.

    Article  PubMed  Google Scholar 

  14. Sulkowski MS, Poordad F, Manns MP, et al. Anemia during treatment with peginterferon alfa-2b/ribavirin and boceprevir: analysis from the serine protease inhibitor therapy 2 (SPRINT-2) trial. J Hepatol. 2013;57:974–84. This study showed that patients who developed anemia while being treated on a triple therapy HCV drug regimen had higher SVR rates than those who did not.

    Article  CAS  Google Scholar 

  15. Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347:975–82.

    Article  CAS  PubMed  Google Scholar 

  16. Hadziyannis SJ, Sette Jr H, Morgan TR, et al. Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med. 2004;140:346–55.

    Article  CAS  PubMed  Google Scholar 

  17. Jeffers LJ, Cassidy W, Howell CD, Hu S, Reddy KR. Peginterferon alfa-2a (40 kd) and ribavirin for black American patients with chronic HCV genotype 1. Hepatology. 2004;39:1702–8.

    Article  CAS  PubMed  Google Scholar 

  18. Rodriguez-Torres M, Jeffers LJ, Sheikh MY, et al. Peginterferon alfa-2a and ribavirin in Latino and non-Latino whites with hepatitis C. N Engl J Med. 2009;360:257–67.

    Article  CAS  PubMed  Google Scholar 

  19. Sievert W, Dore GJ, McCaughan GW, et al. Virological response is associated with decline in hemoglobin concentration during pegylated interferon and ribavirin therapy in hepatitis C virus genotype 1. Hepatology. 2011;53:1109–17. This was a retrospective study of patients with GT1 HCV who were treated with pegylated interferon and ribavirin therapy. Their results showed that those who developed anemia or a hemoglobin decline >30 g/L after week 5 of therapy achieved higher SVRs, even after controlling for erythropoietin use.

    Article  CAS  PubMed  Google Scholar 

  20. Brennan BJ, Morcos PN, Wang K, et al. The pharmacokinetics of peginterferon alfa-2a and ribavirin in African American, Hispanic and Caucasian patients with chronic hepatitis C. Aliment Pharmacol Ther. 2012;35:1209–20.

    Article  CAS  PubMed  Google Scholar 

  21. Pegasys package insert. Available at http://www.gene.com/download/pdf/pegasys_prescribing.pdf.

  22. 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.

    Article  CAS  PubMed  Google Scholar 

  23. Loustaud-Ratti V, Alain S, Rousseau A, et al. Ribavirin exposure after the first dose is predictive of sustained virological response in chronic hepatitis C. Hepatology. 2008;47:1453–61.

    Article  CAS  PubMed  Google Scholar 

  24. AASLD/IDSA/IAS–USA. Recommendations for testing, managing, and treating hepatitis C. http://www.hcvguidelines.org. Accessed November 18, 2014.

  25. Kowdley KV, Lawitz E, Crespo I, et al. Sofosbuvir with pegylated interferon alfa-2a and ribavirin for treatment-naive patients with hepatitis C genotype-1 infection (ATOMIC): an open-label, randomised, multicentre phase 2 trial. Lancet. 2013;381:2100–7. This study showed that Sofosbuvir with pegylated interferon and ribavirin had high SVR rates in GT-1 patients and that there was no additional benefit to treating beyond 12 weeks compared with those treated for 24 weeks.

    Article  CAS  PubMed  Google Scholar 

  26. Lawitz E, Lalezari JP, Hassanein T, et al. Sofosbuvir in combination with peginterferon alfa-2a and ribavirin for non-cirrhotic, treatment-naive patients with genotypes 1, 2, and 3 hepatitis C infection: a randomised, double-blind, phase 2 trial. Lancet Infect Dis. 2013;13:401–8. This study showed the safety and tolerability of Sofosbuvir in combination with pegylated interferon and ribavirin.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

Funding for this manuscript was provided by Genentech Inc. and F. Hoffmann-La Roche Ltd. Third-party writing assistance for this manuscript was furnished by Blair Jarvis, MSc, ELS, and Sue Currie, PhD, of Health Interactions and funded by Genentech Inc. and F. Hoffmann-La Roche Ltd. Drs. Reau, Korner, Han, and Jensen were involved in the study concept and design, analysis and interpretation of data, drafting of the manuscript, statistical analyses, and critical revision of the manuscript for important intellectual content.

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Conflict of Interest

Nancy S. Reau reports research support from AbbVie, Boehringer-Ingelheim, BMS, Gilead, Janssen and consultation fees from AbbVie, Gilead, Janssen, BMS. Eli J. Kornerand Jian Hanare employed by Genentech, Inc. Donald Jensen reports personal fees from Abbvie, Boehringer-Ingelheim, BMS, Gilead, Janssen, Genentech and non-financial support from Therapeutic Advances in Gastro as well as grants from Boehringer-Ingelhiem, BMS, Gilead, Janssen, Genentech and Vertex, outside of the submitted work.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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Authors and Affiliations

  1. Center for Liver Diseases, University of Chicago Medical Center, 5841 S. Maryland Avenue MC 7120, Chicago, IL, 60637, USA

    Nancy S. Reau & Donald Jensen

  2. Genentech Inc, 1 DNA Way, South San Francisco, CA, 94080, USA

    Eli J. Korner & Jian Han

Authors
  1. Nancy S. Reau
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  2. Eli J. Korner
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  3. Jian Han
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  4. Donald Jensen
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Correspondence to Nancy S. Reau.

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This article is part of the Topical Collection on Management of the Cirrhotic Patient

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Reau, N.S., Korner, E.J., Han, J. et al. Anemia Predicts Sustained Virological Response in Cirrhotic and Noncirrhotic Patients with Chronic Hepatitis C Treated with Peginterferon Alfa-2a and Ribavirin. Curr Hepatology Rep 14, 53–59 (2015). https://doi.org/10.1007/s11901-015-0257-7

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  • DOI: https://doi.org/10.1007/s11901-015-0257-7

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