PATHOGENESIS, PREVENTION, AND MANAGEMENT OF PATIENTS WITH ANEMIA OCCURRING DURING ANTIVIRAL THERAPY WITH BOCEPREVIR FOR CHRONIC HEPATITIS C

Download full text PDF
Issue: 
7
Year: 
2015

E. Burnevich (1–3), Candidate of Medical Sciences; N. Tikhonova (4) 1 -I.M. Sechenov First Moscow State Medical University 2 -Department of Health-Promotion Technologies, Research Center, I.M. Sechenov First Moscow State Medical University 3 -City Clinical Hospital Twenty Four, Moscow Healthcare Department 4 -M.V. Lomonosov Moscow State University

Current triple antiviral therapy for chronic hepatitis C, by using the first wave, first-generation hepatitis C virus protease inhibitor boceprevir, results in the higher incidence of anemia, including severe one, than dual therapy with pegylated interferon and ribavirin; moreover, the hemoglobin reduction is more marked and occurs earlier. The paper deals with the present views of the pathogenesis of anemia; its risk factors; today’s optimal approaches to its prediction, prevention, and management of patients with chronic hepatitis C who receive triple antiviral therapy using boceprevir.
Keywords: 
chronic hepatitis C
antiviral therapy
first wave
first-generation protease inhibitor
boceprevir
anemia
erythropoietin
ribavirin dose reduction

It appears your Web browser is not configured to display PDF files. Download adobe Acrobat или click here to download the PDF file.

References: 
  1. Ghany M., Nelson D., Strader D. et al. Genotype 1 HCV treatment guidelines // Hepatology. – 2011; 54: 1433–44.
  2. Poordad F., McCone J., Bacon B. et al. Boceprevir for untreated chronic HCV genotype 1 infection // N. Engl. J. Med. – 2011; 364: 1195–206.
  3. Bacon B., Gordon S., Lawitz E. et al. Boceprevir for previously treated chronic HCV genotype 1 infection // N. Engl. J. Med. – 2011; 364: 1207–17.
  4. Rebetol®. Instruktsija po meditsinskomu primeneniju.
  5. Sulkowski M., Shiffman M., Afdhal N. et al. Treatment-Related Anemia Is Associated With Higher SVR Rates Among Persons Treated With Peginterferon. Ribavirin: Results From the IDEAL Study / AASLD, 2008.
  6. Romero-Gomez M., Berenguer M., Molina E. et al. Management of anemia induced by triple therapy in patients with chronic hepatitis C: Challenges, opportunities and recommendations // J. Hepatol. – 2013; 59 (6): 1323–30.
  7. Ramachandran P., Fraser A., Agarwal K. 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 (6): 647–62.
  8. Teixeira R., Nascimento Yde A., Crespo D. Safety aspects of protease inhibitors for chronic hepatitis C: adverse events and drug-to-drug interactions // Braz. J. Infect. Dis. – 201; 17 (2): 194–204.
  9. McHutchison J., Lawitz E., Shiffman M. et al. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection // N. Engl. J. Med. – 2009; 36: 580–9.
  10. Adiwijaya B., Kieffer T., Adda N. et al.: Quantification the effect of adherence to clinical outcomes in telaprevir-based regimens. HepDART, 2011, Poster 53.
  11. Sulkowski M., Reddy K., Pedicone L. et al. ITPA Deficiency is Associated with Lower Rates of Anemia and EPO use in Patients Treated with Boceprevir (BOC) plus Peginterferon/Ribavirin (PR) / AASLD, 2011.
  12. Sulkowski M., Poordad F., Manns M. et al. Anemia During Treatment With Peginterferon Alfa-2b/Ribavirin With or Without Boceprevir is Associated With Higher SVR Rates: Analysis of Previously Untreated and Previous Treatment-Failure Patients / EASL, 2011.
  13. Poordad F., Lawitz E., Reddy K. et al. Timing and Magnitude of Ribavirin Dose Reduction do not impact SVR with Boceprevir + Peginterferon. Ribavirin in the Anemia Management Study in HCV G1 Patients / AASLD, 2012.
  14. Poordad F., Lawitz E., Reddy K. et al. A randomized trial comparing ribavirin dose reduction versus erythropoietin for anemia management in previously untreated patients with chronic hepatitis S receiving boceprevir plus peginterferon/ribavirin / EASL, 2012.
  15. Poordad F., Lawitz E., Reddy K. et al. Effects of ribavirin dose reduction vs erythropoietin for boceprevir-related anemia in patients with chronic hepatitis C virus genotype 1 infection a randomized trial // Gastroenterology. – 2013; 145 (5): 1035–44.
  16. Hezode C., Dorival C., Zoulim F. et al. Safety of telaprevir or boceprevir in combination with peginterferon alfa/ribavirin, in cirrhotic non responders: first results of the French early access program (ANRS CO20-CUPIC) / EASL, 2012.
  17. Franceschi L., Fattovich G., Turrini F. et al. Hemolytic anemia induced by ribavirin therapy in patients with chronic hepatitis C virus infection: role of membrane oxidative damage // Hepatology. – 2000; 31: 997–1004.
  18. Hezode C. Boceprevir and telaprevir for the treatment of chronic hepatitis C: safety management in clinical practice // Liver Int. – 2012; 32 (Suppl. 1): 32–8.
  19. Peck-Radosavljevic M., Wichlas M., Homoncik-Kraml M. et al. Rapid suppression of hematopoiesis by standard or pegylated interferon-alpha // Gastroenterology. – 2002; 123: 141–51.
  20. Sulkowski M., Poordad F., Manns M. et al. Anemia during treatment with peginterferon alfa-2b/ribavirin with or without boceprevir is associated with higher SVR rates: analysis of previously untreated and previous-treatment-failure patients // J. Hepatol. – 2011; 54 (Suppl. 1): 195–6.
  21. Hezode C., Fontaine H., Dorival C. et al. Triple therapy in treatment-experienced patients with HCV-cirrhosis in a multicentre cohort of the French Early Access Programme (ANRS CO20-CUPIC) – NCT01514890 // J. Hepatol. – 2013; 59 (3): 434–41.
  22. Butt A., McGinnis K., Skanderson M. et al. Hepatitis C treatment completion rates in routine clinical care // Liver Int. – 2010; 30: 240–50.
  23. EASL Clinical Practice Guidelines: management of hepatitis C virus infection // J. Hepatol. – 2011; 55 (2): 245–64.
  24. Sulkowski M., Poordad F., Manns M. 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 (3): 974–84.
  25. Fellay J., Thompson A., Ge D. et al. ITPA gene variants protect against anaemia in patients treated for chronic hepatitis C // Nature. – 2010; 464 (7287): 405–8.
  26. Naggie S., Rallon N., Benito J. et al. Variants in the ITPA gene protect against ribavirin-induced hemolytic anemia in HIV/HCV-coinfected patients with all HCV genotypes // J. Infect. Dis. – 2012; 205: 376–83.
  27. Nishimura T., Osaki R., Shioya M. et al. Polymorphism of the inosine triphosphate pyrophosphatase gene predicts ribavirin-induced anemia in chronic hepatitis C patients // Mol. Med. Report. – 2012; 5: 517–20.
  28. Thompson A., Fellay J., Patel K. et al. Variants in the ITPA gene protect against ribavirin-induced hemolytic anemia and decrease the need for ribavirin dose reduction // Gastroenterology. – 2010; 139 (4): 1181–9.
  29. Rau M., Stickel F., Russmann S. et al. Impact of genetic SLC28 transporter and ITPA variants on ribavirin serum level, hemoglobin drop and therapeutic response in patients with HCV infection // J. Hepatol. – 2013; 58 (4): 669–75.
  30. Aghemo A., Degasperi E., Colombo M. Directly acting antivirals for the treatment of chronic hepatitis C: unresolved topics from registration trials // Dig. Liver Dis. – 2013; 45 (1): 1–7.
  31. Ochi H., Maekawa T., Abe H. et al. ITPA polymorphism affects ribavirin-induced anemia and outcomes of therapy – a genome-wide study of Japanese HCV virus patients // Gastroenterology. – 2010; 139 (4): 1190–7.
  32. Suzuki F., Suzuki Y., Akuta N. et al. Influence of ITPA polymorphisms on decreases of hemoglobin during treatment with pegylated interferon, ribavirin, and telaprevir // Hepatology. – 2011; 53 (2): 415–21.
  33. Sulkowski M., Shiffman M., Afdhal N. et al. Hepatitis C virus treatment-related anemia is associated with higher sustained virologic response rate // Gastroenterology. – 2010; 139 (5): 1602–11.
  34. McHutchison J. The role of genetic markers in hepatitis C virus therapy: a major step for individualized care // Liver Int. – 2011; 31 (Suppl. 1): 29–35.
  35. McHutchison J., Lawitz E., Shiffman M. et al. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection // N. Engl. J. Med. – 2009; 36: 580–9.
  36. Reddy K., Shiffman M., Morgan T. 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 (1): 124–9.
  37. Shiffman M., Ghany M., Morgan T. et al. Impact of reducing peginterferon alfa-2a and ribavirin dose during retreatment in patients with chronic hepatitis C // Gastroenterology. – 2007; 132: 103–12.
  38. Reddy K., Nelson D., Zeuzem S. Ribavirin: current role in the optimal clinical management of chronic hepatitis C // J. Hepatol. – 2009; 50 (2): 402–11.
  39. Hezode C., Forestier N., Dusheiko G. et al. Telaprevir and peg-interferon with or without ribavirin for chronic HCV infection // N. Engl. J. Med. – 2009; 360: 1827–38.
  40. Kwo P., Lawitz E., McCone J. et al. Efficacy of boceprevir, an NS3 protease inhibitor, in combination with peginterferon alfa-2b and ribavirin in treatmentnapve patients with genotype 1 hepatitis C infection (SPRINT-1): an open-label, randomized, multicenter phase 2 trial // Lancet. – 2010; 376: 705–16.