Pharmacological exposure to ribavirin: A key player in the complex network of factors implicated in virological response and anaemia in hepatitis C treatment

Digestive and Liver Disease

Volumn 43, Issue 11, 2011, Pages 850-855

  Loustaud Ratti, Véronique ^a   Carrier, Paul ^a   Rousseau, Annick ^b   Maynard, Marianne ^c   Babany, Gérard ^d   Alain, Sophie ^e   Trépo, Christian ^c   de Ledinghen, Victor ^f   Bourlière, Marc ^g   Pol, Stanislas ^h   di Martino, Vincent ⁱ   Zarski, Jean Pierre ^j   Pinta, Alexandrina ^d   Sautereau, Denis ^a   Marquet, Pierre ^b  

^a LIMOGES UNIVERSITY HOSPITAL   (France)

^b Univ Limoges   (France)

^c CROIX ROUSSE HOSPITAL   (France)

^d Laboratoires Roche   (France)

^e UNIVERSITY OF LIMOGES   (France)

^f BORDEAUX UNIVERSITY HOSPITAL   (France)

^g HÔPITAL SAINT JOSEPH   (France)

^h CHU Jean Minjoz ^*  (France)

ⁱ UNIVERSITY HOSPITAL JEAN MINJOZ   (France)

^j HÔPITAL MICHALLON   (France)

more..

Author keywords

Chronic hepatitis C; Direct acting agents; IL28B polymorphisms; ITPAse polymorphisms; Pharmacodynamics; Pharmacokinetics; Ribavirin

Indexed keywords

ALPHA INTERFERON; BOCEPREVIR; ERYTHROPOIETIN; GAMMA INTERFERON INDUCIBLE PROTEIN 10; HEMOGLOBIN; INORGANIC PYROPHOSPHATASE; INOSINE TRIPHOSPHATE PYROPHOSPHATASE; INTERLEUKIN 28B; PEGINTERFERON; PEGINTERFERON ALPHA; PEGINTERFERON ALPHA2A; PEGINTERFERON ALPHA2B; RIBAVIRIN; TELAPREVIR; UNCLASSIFIED DRUG;

ANEMIA; ANTIVIRAL ACTIVITY; ANTIVIRAL THERAPY; AREA UNDER THE CURVE; BONE MARROW TOXICITY; CLINICAL TRIAL (TOPIC); COMBINATION CHEMOTHERAPY; DNA POLYMORPHISM; DRUG BLOOD LEVEL; DRUG ERYTHROCYTE LEVEL; DRUG HALF LIFE; DRUG MEGADOSE; DRUG MONITORING; DRUG POTENTIATION; DRUG SAFETY; GENOTYPE; HEMOLYTIC ANEMIA; HEPATITIS C; HEPATITIS C VIRUS; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; MAXIMUM PLASMA CONCENTRATION; MIXED INFECTION; OPTIMAL DRUG DOSE; PRIORITY JOURNAL; REVIEW; SIDE EFFECT; SINGLE NUCLEOTIDE POLYMORPHISM; TREATMENT RESPONSE; VIRUS LOAD;

ANEMIA; ANTIVIRAL AGENTS; DRUG THERAPY, COMBINATION; HEPACIVIRUS; HEPATITIS C; HUMANS; INTERFERON-ALPHA; INTERLEUKINS; POLYETHYLENE GLYCOLS; PYROPHOSPHATASES; RECOMBINANT PROTEINS; RIBAVIRIN; VIRAL LOAD;

EID: 80052943095     PISSN: 15908658     EISSN: 18783562     Source Type: Journal    
DOI: 10.1016/j.dld.2011.04.002     Document Type: Review

References (67)

1. Fried M.W., Shiffman M.L., Reddy K.R., et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 2002, 347:975-982.
2. Heathcote J., Zeuzem S. Pegylated interferon monotherapy for chronic hepatitis C. Semin Liver Dis 2004, 24:39-45.
3. Bronowicki J.P., Ouzan D., Asselah T., et al. Effect of ribavirin in genotype 1 patients with hepatitis C responding to pegylated interferon alfa-2a plus ribavirin. Gastroenterology 2006, 131:1040-1048.
4. Hezode C., Forestier N., Dusheiko G., et al. Telaprevir and peginterferon with or without ribavirin for chronic HCV infection. N Engl J Med 2009, 360:1839-1850.
5. Jen J., Laughlin M., Chung C., et al. Ribavirin dosing in chronic hepatitis C: application of population pharmacokinetic-pharmacodynamic models. Clin Pharmacol Ther 2002, 72:349-361.
6. Larrat S., Stanke-Labesque F., Plages A., et al. Ribavirin quantification in combination treatment of chronic hepatitis C. Antimicrob Agents Chemother 2003, 47:124-129.
7. 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, 47:1453-1461.
8. Maynard M., Pradat P., Gagnieu M.C., et al. Prediction of sustained virological response by ribavirin plasma concentration at week 4 of therapy in hepatitis C virus genotype 1 patients. Antivir Ther 2008, 13:607-611.
9. Brillanti S., Garson J., Foli M., et al. A pilot study of combination therapy with ribavirin plus interferon alfa for interferon alfa-resistant chronic hepatitis C. Gastroenterology 1994, 107:812-817.
10. Di Bisceglie A.M., Conjeevaram H.S., Fried M.W., et al. Ribavirin as therapy for chronic hepatitis C. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 1995, 123:897-903.
11. Manns M.P., McHutchison J.G., Gordon S.C., 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, 358:958-965.
12. Bain V.G., Lee S.S., Peltekian K., et al. Clinical trial: exposure to ribavirin predicts EVR and SVR in patients with HCV genotype 1 infection treated with peginterferon alpha-2a plus ribavirin. Aliment Pharmacol Ther 2008, 28:43-50.
13. Yu M.L., Dai C.Y., Huang J.F., et al. Rapid virological response and treatment duration for chronic hepatitis C genotype 1 patients: a randomized trial. Hepatology 2008, 47:1884-1893.
14. Lindahl K., Stahle L., Bruchfeld A., et al. High-dose ribavirin in combination with standard dose peginterferon for treatment of patients with chronic hepatitis C. Hepatology 2005, 41:275-279.
15. Lindhal K., Hörnfeldt E., Carlsson T., et al. Individualized high dose ribavirin in combination with peginterferon to hepatitis C genotype 1 patients with previous non response. Hepatology 2010, 52:710A. [abstr 814].
16. Kwo P.Y., Lawitz E.J., McCone J., et al. Efficacy of boceprevir, an NS3 protease inhibitor, in combination with peginterferon alfa-2b and ribavirin in treatment-naive patients with genotype 1 hepatitis C infection (SPRINT-1): an open-label, randomised, multicentre phase 2 trial. Lancet 2010, 376:705-716.
17. McHutchison J.G., Manns M.P., Muir A.J., et al. Telaprevir for previously treated chronic HCV infection. N Engl J Med 2010, 362:1292-1303.
18. Foster G.R., Hezode C., Bronowicki J.P., et al. Activity of telaprevir alone or in combination with peginterferon alpha 2a and ribavirin in treatment naive genotype 2 and 3 hepatitis C patients: interim results of study C209. J Hepatol 2009, 50:S22. [abstr 50].
19. Benhamou Y., Moussalli J., Ratziu V., et al. Results of a proof of concept study (C210) of telaprevir monotherapy and in combination with peginterferon alpha 2 a and ribavirin in treatment naïve genotype 4 HCV patients. J Hepatol 2009, 50:S6. [abstr 10].
20. Zeuzem S., Buggisch P., Agarwal K., et al. Dual, triple and quadruple combination treatment with a protease inhibitor (GS 9256) and a polymerase inhibitor (GS 9190) alone and in combination with ribavirin or Peginterferon/ribavirin for up to 28 days in treatment naive, genotype 1 HCV subjects. Hepatology 2010, 52:400A. [abstr LB1].
21. Donnerer J., Grahovac M., Stelzl E., et al. Ribavirin levels and haemoglobin decline in early virological responders and non-responders to hepatitis C virus combination therapy. Pharmacology 2006, 76:136-140.
22. Crespo M., Pou L., Esteban J.I., et al. Early monitoring of ribavirin serum concentration is not useful to optimize hepatitis C virus treatment in HIV-coinfected patients. Antivir Ther 2007, 12:1217-1223.
23. Morello J., Soriano V., Barreiro P., et al. Plasma ribavirin trough concentrations at week 4 predict hepatitis C virus (HCV) relapse in HIV-HCV-coinfected patients treated for chronic hepatitis C. Antimicrob Agents Chemother 2010, 54:1647-1649.
24. Arase Y., Ikeda K., Tsubota A., et al. Significance of serum ribavirin concentration in combination therapy of interferon and ribavirin for chronic hepatitis C. Intervirology 2005, 48:138-144.
25. Nicot F., Legrand-Abravanel F., Lafont T., et al. Serum concentrations of ribavirin and pegylated interferon and viral responses in patients infected with HIV and HCV. J Med Virol 2008, 80:1523-1529.
26. Pedersen C., Alsiö A., Lagging M., et al. Ribavirin plasma concentration is a predictor of sustained virological response in patients treated for chronic hepatitis C virus genotype 2/3 infection. J Viral Hepat 2011, 18:245-251.
27. Baiocchi L., De Leonardis F., Delle Monache M., et al. Plasma/erythrocyte ribavirin ×100 ratio as an indicator of sustained virological response in HCV genotype 1 patients with early virological response. Antivir Ther 2010, 15:633-639.
28. Sherman K.E., Flamm S.L., Afdahl N.H., et al. Telprevir in combination with peginterferon alfa 2A and ribavirin for 24 or 48 weeks in treatment-naïve genotype 1 HCV patients who achieved an extended rapid virological response: final results of phase 3 illuminate study. Hepatology 2010, 52:400A. [abstr LB2].
29. Jacobson I.M., Mc Hutchinson J.G., Dusheiko G.M., et al. Telaprevir in combination with peginterferon and ribavirin in genotype 1 HCV treatment-naive patients: final results of phase III advance study. Hepatology 2010, 52:427A. [abstr 211].
30. Poordad F., Mc Cone J., Bacon B.R., et al. Boceprevir combined with peginterferon/ribavirin for treatment-naive patients with hepatitis C virus genotype 1: SPRINT 2 final results. Hepatology 2010, 52:402A. [abstr LB4].
31. Kieffer T.L., Sarrazin C., Miller J.S., et al. Telaprevir and pegylated interferon-alpha-2a inhibit wild-type and resistant genotype 1 hepatitis C virus replication in patients. Hepatology 2007, 46:640-648.
32. Sarrazin C., Kieffer T.L., Bartels D., et al. Dynamic hepatitis C virus genotypic and phenotypic changes in patients treated with the protease inhibitor telaprevir. Gastroenterology 2007, 132:1767-1777.
33. Ge D., Fellay J., Thompson A.J., et al. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 2009, 461:399-401.
34. Suppiah V., Moldovan M., Ahlenstiel G., et al. IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy. Nat Genet 2009, 41:1100-1104.
35. Tanaka Y., Nishida N., Sugiyama M., et al. Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C. Nat Genet 2009, 41:1105-1109.
36. McCarthy J.J., Li J.H., Thompson A., et al. Replicated association between an IL28B gene variant and a sustained response to pegylated interferon and ribavirin. Gastroenterology 2006, 138:2307-2314.
37. Rauch A., Kutalik Z., Descombes P., et al. Genetic variation in IL28B is associated with chronic hepatitis C and treatment failure: a genome-wide association study. Gastroenterology 2010, 138:1338-1345.
38. Asselah T., Essioux L., Marcellin P., et al. Differential association of a chromosome 19 single nucleotide (SNP RS12979860) to outcome (early virologic response/sustained virologic response) in naïve versus retreated HCV patients treated with IFN-based therapies. Hepatology 2010, 52:773A. [abstr 939].
39. Mangia A., Thompson A.J., Santoro R., et al. An IL28B polymorphism determines treatment response of hepatitis C virus genotype 2 or 3 patients who do not achieve a rapid virologic response. Gastroenterology 2010, 139:821-827.
40. Sarrazin C., Susser S., Doehring A., et al. Importance of IL28B gene polymorphisms in hepatitis C virus genotype 2 and 3 infected patients. J Hepatol 2011, 54:415-421.
41. Thompson A.J., Muir A.J., Sulkowski M.S., et al. Hepatitis C trials that combine investigational agents with pegylated interferon alfa should be stratified by IL28B genotype. Hepatology 2010, 52:708A. [abstr 810].
42. Casrouge A., Decalf J., Ahloulay M., Lababidi C., et al. Evidence for an antagonist form of the chemokine CXCL10 in patients chronically infected with HCV. J Clin Invest 2011, 121:308-317.
43. Darling J.M., Aerssens J., Fanning G., et al. Quantitation of pretreatment serum interferon-γ-inducible protein-10 improves the predictive value of an IL28B gene polymorphism for hepatitis C treatment response. Hepatology 2011, 53:14-22.
44. De 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.
45. Gaeta G.B., Precone D.F., Felaco F.M., 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, 16:1633-1639.
46. Sulkowski M.S., Shiffman M.L., Afdhal N.H., Hepatitis C, et al. Virus treatment-related anemia is associated with higher sustained virologic response rate. Gastroenterology 2010, 139:1602-1611.
47. Van Vlerken L.G., Van Soest H., Janssen M.P., et al. Suboptimal endogenous erythropoietin response in chronic hepatitis C patients during ribavirin and PEG interferon treatment. Eur J Gastroenterol Hepatol 2010, 22:1308-1315.
48. Fellay J., Thompson A.J., Ge D., et al. ITPA gene variants protect against anaemia in patients treated for chronic hepatitis C. Nature 2010, 464:405-408.
49. Thompson A.J., 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, 139:1181-1189.
50. Brochot E., Castelain S., Duverlie G., et al. Ribavirin monitoring in chronic hepatitis C therapy: anaemia versus efficacy. Antivir Ther 2010, 15:687-695.
51. Peck-Radosavljevic M., Wichlas M., Homoncik-Kraml M., et al. Rapid suppression of hematopoiesis by standard or pegylated interferon-alpha. Gastroenterology 2002, 123:141-151.
52. Balan V., Schwartz D., Wu G.Y., et al. HCV Natural History Study Group Erythropoietic response to anemia in chronic hepatitis C patients receiving combination pegylated interferon/ribavirin. Am J Gastroenterol 2005, 100:299-307.
53. Mac Nicholas R., Norris S. Review article: optimizing SVR and management of the haematological side effects of peginterferon/ribavirin antiviral therapy for HCV-the role of epoetin. G-CSF and novel agents. Aliment Pharmacol Ther 2010, 31:929-937.
54. Dieterich D.T., Wasserman R., Bräu N., et al. Once-weekly epoetin alfa improves anemia and facilitates maintenance of ribavirin dosing in hepatitis C virus-infected patients receiving ribavirin plus interferon alfa. Am J Gastroenterol 2003, 98:2491-2499.
55. Afdhal N.H., Dieterich D.T., Pockros P.J., et al. Epoetin alfa maintains ribavirin dose in HCV-infected patients: a prospective, double-blind, randomized controlled study. Gastroenterology 2004, 126:1302-1311.
56. Stravitz R.T., Chung H., Sterling R.K., et al. Antibody-mediated pure red cell aplasia due to epoetin alfa during antiviral therapy of chronic hepatitis C. Am J Gastroenterol 2005, 100:1415-1419.
57. Schecter J.M., Mears J.G., Alobeid B., et al. Anti-erythropoietin antibody-mediated pure red cell aplasia in a living donor liver transplant recipient treated for hepatitis C virus. Liver Transpl 2007, 13:1589-1592.
58. Costiniuk C.T., Camacho F., Cooper C.L. Erythropoiesis-stimulating agent use for anemia induced by interferon-ribavirin treatment in patients with hepatitis C virus infection is not associated with increased rates of cardiovascular disease, thrombosis, malignancy, or death. Clin Infect Dis 2008, 47:198-202.
59. Shiffman M.L., Salvatore J., Hubbard S., et al. Treatment of chronic hepatitis C virus genotype 1 with peginterferon, ribavirin, and epoetin alpha. Hepatology 2007, 46:371-379.
60. Lebray P., Nalpas B., Vallet-Pichard A., et al. The impact of haematopoietic growth factors on the management and efficacy of antiviral treatment in patients with hepatitis C virus. Antivir Ther 2005, 10:769-776.
61. Younossi Z.M., Nader F.H., Bai C., et al. A phase II dose finding study of darbepoetin alpha and filgrastim for the management of anaemia and neutropenia in chronic hepatitis C treatment. J Viral Hepat 2008, 15:370-378.
62. Jen J.F., Glue P., Gupta S., et al. Population pharmacokinetic and pharmacodynamic analysis of ribavirin in patients with chronic hepatitis C. Ther Drug Monit 2000, 22:555-565.
63. Morello J., Cuenca L., Soriano V., et al. Influence of a single nucleotide polymorphism at the main ribavirin transporter gene on the rapid virological response to pegylated interferon-ribavirin therapy in patients with chronic hepatitis C virus infection. J Infect Dis 2010, 202:1185-1191.
64. McHutchison J.G., Everson G.T., Gordon S.C., et al. Telaprevir with peginterferon and ribavirin for chronic HCV genotype 1 infection. N Engl J Med 2009, 360:1827-1838.
65. 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, 53:415-421.
66. Aguilar Marucco D., Gonzalez de Requena D., Bonora S., et al. The use of trough ribavirin concentration to predict sustained virological response and haematological toxicity in HIV/HCV-co-infected patients treated with ribavirin and pegylated interferon. J Antimicrob Chemother 2008, 6:919-924.
67. Breilh D., Djabarouti S., Trimoulet P., et al. Ribavirin plasma concentration predicts sustained virological response to peginterferon Alfa 2a plus ribavirin in previously treated HCV-HIV-coinfected patients. J Acquir Immune Defic Syndr 2009, 52:428-430.