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Órgano Oficial de la Asociación Mexicana de Hepatología

2011, Number 4

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Ann Hepatol 2011; 10 (4)

Danazol improves thrombocytopenia in HCV patients treated with peginterferon and ribavirin

Cabrera ÁG, Gómez-Galicia D, Rodríguez-Fragoso L, Madrid MV, Cañedo DL, Sánchez-Alemán M, Méndez-Sánchez N, Reyes EJ

Language: English
References: 38
Page: 458-468
PDF size: 745.98 Kb.


ABSTRACT

Background. Thrombocytopenia is a common hematologic disorder observed in patients with chronic hepatitis C virus (HCV) infection. Combined peginterferon (PEG-INF) and ribavirin treatment may exacerbate thrombocytopenia in patients with HCV. Objective. The aim of this pilot clinical trial was to assess the efficacy, tolerability and safety of Danazol in thrombocytopenia associated with PEG-INF and ribavirin treatment in patients with HCV. Material and methods. We included patients whose platelets were ‹ 90,000/mm3 and who were undergoing antiviral treatment. Danazol (300-600 mg/day) was administered during and until the end of antiviral therapy [7.6 months (2 to 11 months)]. The monitoring was performed through platelet analysis and liver function tests. A viral load test was done at the beginning and end of treatment. Fortynine patients receiving a combined therapy of PEG-INF, ribavirin and Danazol increased their platelet levels to 121,081/mm3 (46,000-216,000/mm3); 10.6% of patients gained › 100,000 platelets/mm3, and 71% of patients maintained their initial platelet levels. Sustained viral response (SVR) was achieved in 63% of patients. SVR rates were high in patients with genotype non 1 (78.7%) and decreased in patients with genotype 1 (60.1%). The increase in platelet levels was associated to an increase in fibrinogen levels and a decrease in the activity of ALT. By contrast, patients without SVR presented a delayed response to increased platelet levels and showed no significant improvement in liver function when they received Danazol. Conclusion. Danazol can be used along with PEG-INF and ribavirin to treat thrombocytopenia in patients with HCV.


REFERENCES

  1. Modi AA, Liang TJ. Hepatitis C: a clinical review. Oral Dis 2008; 14: 10-4.

  2. 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.

  3. Negro F. Adverse effects of drugs in the treatment of viral hepatitis, Best Pract Res Clin Gastroenterol 2010; 24: 183-92.

  4. Soza A, Everhart JE, Ghany MG, et al. Neutropenia during combination therapy of interferon alfa and ribavirin for chronic hepatitis C. Hepatology 2002; 36: 1273-9.

  5. Peck-Radosavljevic M, Wichlas M, Homoncik-Kraml M, et al. Rapid suppression of hematopoiesis by standard or pegylated interferon alpha. Gastroenterology 2002; 123: 41-51.

  6. Peck-Radosavljevic M, Wichlas M, Pidlich J, et al. Blunted thrombopoietin response to interferon alfa-induced thrombocytopenia during treatment for hepatitis C. Hepatology 1998; 28: 1424-9.

  7. Wenzel F, Gruber W, Giers G. Alteration of serum thrombopoietin levels in patients with chronic hepatitis C under interferon therapy. Clin Hemorheol Microcir 2010; 44(2): 137-44.

  8. Maloisel F, Andrès E, Zimmer J, et al. Danazol therapy in patients with chronic idiopathic thrombocytopenic purpura: long-term results. Am J Med 2004; 116: 590-4.

  9. Stasi R, Provan D. Management of immune thrombocytopenic purpura in adults. Mayo Clin Proc 2004; 79: 504-22.

  10. Ahn YS, Rocha R, Mylvaganam R, et al. Long-term danazol therapy in autoimmune thrombocytopenia: unmaintained remission and age-dependent response in women. Ann Intern Med 1989; 111: 723-9.

  11. Mylvaganam R, Ahn YS, Garcia RO, et al. Very low dose danazol in idiopathic thrombocytopenic purpura and its role as an immune modulator. Am J Med Sci 1989; 298: 215 20.

  12. Nakhoul IN, Kozuch P, Varma M. Management of adult idiopathic thrombocytopenic purpura. Clin Adv Hematol Oncol 2006; 4: 136-44.

  13. Andrés E, Zimmer J, Noel E, et al. Idiopathic thrombocyopenic purpura. A retrospective analysis in 139 patients of the influence of age on the response to corticosteroids, splenectomy and danazol. Drugs Aging 2003; 20: 841-6.

  14. Cabrera-Álvarez G, Madrid-Marina V, Jimenez-Mendez R, et al. Combined therapy with danazol, pegilated interferon, and ribavirin improves thrombocytopenia and liver injury in rats with fibrosis. Ann Hepatol 2007; 6: 233-41.

  15. World Health Organization. Declaration of Helsinki. Bull World Health Organizat 2001; 79: 373-4.

  16. World Health Organization. Guidelines for good clinical practice (GCP) for trials on pharmaceutical products. WHO Technical Reports Series 1995; 850.

  17. Melero J, Berenguer M. Antiviral therapy in patients with HCV-cirrhosis. Ann Hepatol 2009; 8: 292-7.

  18. Cheng WS, Roberts SK, McCaughan G, et al; on behalf of the CHARIOT Study Group. Low virological response and high relapse rates in hepatitis C genotype 1 patients with advanced fibrosis despite adequate therapeutic dosing. J Hepatol 2010; 53: 616-23.

  19. Lacobellis A, Ippolito A, Andriulli A. Antiviral therapy in hepatitis C virus cirrhotic patients in compensated and decompensated condition. World J Gastroenterol 2008; 14: 6467-72.

  20. Demirturk N, Cevik F, Demirdal T, et al. Autoimmune thrombocytopenia induced by PEG-IFN-alpha plus ribavirin in hepatitis C. Platelets 2006; 17: 340-3.

  21. Medeiros BC, Seligman PA, Everson GT, et al. Possible autoimmune thrombocytopenia associated with pegylated interferon-alpha2a plus ribavirin treatment for hepatitis C. J Clin Gastroenterol 2004; 38: 84-6.

  22. Weitz IC. Treatment of immune thrombocytopenia associated with interferon therapy of hepatitis C with the anti-CD20 monoclonal antibody, rituximab. Am J Hematol 2005; 78: 138-41.

  23. Danish FA, Koul SS, Subhani FR, Rabbani AE, Yasmin S. Considerations in the management of hepatitis C virus-related thrombocytopenia with eltrombopag. Saudi J Gastroenterol 2010; 16: 51-6.

  24. Cook L, Cooper N. Eltrombopag-a novel approach for the treatment of chronic immune thrombocytopenic purpura: review and safety considerations. Drug Design Develop Ther 2010; 4: 139-45.

  25. Bussel JB, Cheng G, Saleh MN, et al. Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura. N Engl J Med 2007; 357: 2237-47.

  26. McHutchison JG, Dusheiko G, Shiffman ML, Rodriguez-Torres M, Sigal S, Bourliere M, et al.; TPL102357 Study Group. Eltrombopag for thrombocytopenia in patients with cirrhosis associated with hepatitis C. N Engl J Med 2007; 357: 2227-36.

  27. Alavian SM, Tabatabaei SV. Meta-analysis of factors associated with sustained viral response in patients on hemodialysis treated with standard or pegylated interferon for hepatitis C infection. Iran J Kidney Dis 2010; 4: 181-94.

  28. Narciso-Schiavon JL, Schiavon LL, Carvalho-Filho RJ, et al. Gender influence on treatment of chronic hepatitis C genotype 1. Rev Soc Bras Med Trop 2010; 43: 217-23.

  29. Bashour FN, Teran JC, Mullen KD. Prevalence of peripheral blood cytopenias (hypersplenism) in patients with nonalcoholic chronic liver disease. Am J Gastroenterol 2000; 95: 2936-9.

  30. Kobayashi M, Ikeda K, Hosaka T, et al. Natural history of compensated cirrhosis in the Child-Pug Class A compared between 490 patients with hepatitis C and 167 with B virus infections. J Med Virol 2006; 78: 459-65.

  31. Peck-Radosavljevic M. Thrombocytopenia in liver disease. Can J Gastroenterol 2000; 14: 60D-66D.

  32. Sallah S, Bobzien W. Bleeding problems in patients with liver disease. Ways to manage the many hepatic effects on coagulation. Postgrad Med 1999; 106: 187-195.

  33. Davis GL, Estevan-Mur R, Rustgi V, et al. Interferon Alfa- 2b alone or in combination with ribavirin for the treatment of relapse of chronic hepatitis C. N Engl J Med 1998; 339: 1493-9.

  34. Afdhal N, McHutchison J, Brown R, et al. Thrombocytopenia associated with chronic liver diseases. J Hepatol 2008; 48: 1000-7.

  35. Wekler BB. The pathophysiology of thrombocytopenia in hepatitis C virus infection and chronic liver disease. Aliment Pharmacol Ther 2007; 26: 13-9.

  36. Ahn YS, Horstman LL. Idiopathic thrombocytopenic purpura: pathophysiology and management. Int J Hematol 2002; 76: 123-31.

  37. Masuzaki R, Yoshida H, Omata M. Interferon reduces the risk of hepatocellular carcinoma in hepatitis C virus-related chronic hepatitis/liver cirrhosis. Oncology 2010; 78: 17-23.

  38. McHutchinson 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.




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