Expert opinion on the treatment of patients with chronic hepatitis C

Abstract

Summary. The current preferred treatment for patients with hepatitis C virus (HCV) is combination therapy consisting of pegylated interferon alfa and ribavirin (RBV) for 24–48 weeks. Although this approach appears to be highly effective for patients with HCV genotypes 2 or 3, who have a sustained virological response (SVR) of approximately 80%, the treatment algorithm is less effective for patients with HCV genotype 1, as these patients have SVR rates of just 40–50%. In order to improve treatment outcomes, this article explores potential approaches for the optimization of treatment for patients with HCV genotype 1: considering shorter treatment periods for patients with a rapid virological response (RVR), increasing treatment periods for slow responders, and increasing RBV dose are all suggestions. Results from clinical trials suggest that approximately 20% of the HCV genotype 1‐infected population are slow responders, and around 15% of all HCV genotype‐1 infected patients could benefit from a shorter treatment duration without compromising the SVR rate. Interest has also focused on whether treatment duration could be individualized in some patients with genotype 2 and 3 infection. Here all the findings from recent studies are translated into practical advice, to help practitioners make evidence‐based treatment decisions in everyday clinical practice. Although there are areas where currently available data do not provide conclusive evidence to suggest amending treatment approaches, there is clearly potential for individualized treatment in all aspects of hepatitis treatment in the future.

Shown for reading. Its publisher allows quoting it, not republishing it.

References 83

1. 1.

   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(13):975-982.

   Not in our library10.1056/nejmoa020047

2. 2.

   Manns MP, McHutchison JG, Gordon SC, 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(9286):958-965.

   Not in our library10.1016/s0140-6736(01)06102-5

3. 3.

   Hadziyannis SJ, Sette 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(5):346-355.

   Not in our library10.7326/0003-4819-140-5-200403020-00010

4. 4.

   Consensus Development Panel. National institutes of health consensus development conference statement. Hepatology. 2002;36(Suppl. 1):53-70.

   Not in our library

5. 5.

   Strader DB, Wright T, Thomas DL, Seeff LB. American Association for the Study of Liver Diseases. Diagnosis, management, and treatment of hepatitis C. Hepatology. 2004;39(4):1147-1171.

   Not in our library10.1002/hep.20119

6. 6.

   Farrell GC. New hepatitis C guidelines for the Asia-Pacific region: APASL consensus statements on the diagnosis, management and treatment of hepatitis C virus infection. J Gastroenterol Hepatol. 2007;22(5):607-610.

   Not in our library10.1111/j.1440-1746.2007.04969.x

7. 7.

   This reference’s wording can’t be shown under the paper’s licence.

   Not in our library

8. 8.

   This reference’s wording can’t be shown under the paper’s licence.

   Not in our library

9. 9.

   Shiffman ML, Suter F, Bacon BR, et al. Peginterferon alfa-2a and ribavirin for 16 or 24 weeks in HCV genotype 2 or 3. N Engl J Med. 2007;357(2):124-134.

   Not in our library10.1056/nejmoa066403

10. 10.

    Snoeck E, Wade JR, Duff F, Lamb M, Jorga K. Predicting sustained virological response and anaemia in chronic hepatitis C patients treated with peginterferon alfa-2a (40KD) plus ribavirin. Br J Clin Pharmacol. 2006;62(6):699-709.

    Not in our library10.1111/j.1365-2125.2006.02741.x

11. 11.

    Willems B, Hadziyannis SJ, Morgan TR, et al. Should treatment with peginterferon plus ribavirin be intensified in patients with HCV genotype 2/3 without a rapid virological response? J Hepatol. 2007;46(Suppl 1):S6.

    Not in our library

12. 12.

    Zeuzem S. Standard treatment of acute and chronic hepatitis C. Z Gastroenterol. 2004;42(8):714-719.

    Not in our library10.1055/s-2004-813444

13. 13.

    Yee HS, Currie SL, Darling JM, Wright TL. Management and treatment of hepatitis C viral infection: recommendations from the Department of Veterans Affairs Hepatitis C Resource Center program and the National Hepatitis C Program office. Am J Gastroenterol. 2006;101(10):2360-2378.

    Not in our library10.1111/j.1572-0241.2006.00754.x

14. 14.

    Shiffman ML, Ferreira-Gonzalez A, Reddy KR, et al. Comparison of three commercially available assays for HCV RNA using the international unit standard: implications for management of patients with chronic hepatitis C virus infection in clinical practice. Am J Gastroenterol. 2003;98:1159-1166.

    Not in our library10.1111/j.1572-0241.2003.07449.x

15. 15.

    Sarrazin C, Shiffman ML, Hadziyannis SJ, et al. What is the impact of higher sensitivity assay on response-guided therapy in hepatitis C virus (HCV)? Comparative analysis between TAQMAN and AMPLICOR tests from two large randomised international trials of Pegasys plus Copegus. Hepatology. 2007;46(4 Suppl 1):813A.

    Not in our library

16. 16.

    Sarrazin C, Gärtner BC, Sizmann D, et al. Comparison of conventional PCR with real-time PCR and branched DNA-based assays for hepatitis C virus RNA quantification and clinical significance for genotypes 1 to 5. J Clin Microbiol. 2006;44(3):729-737.

    Not in our library10.1128/jcm.44.3.729-737.2006

17. 17.

    Chevaliez S, Bouvier-Alias M, Brillet R, Pawlotsky JM. Overestimation and underestimation of hepatitis C virus RNA levels in a widely used real-time polymerase chain reaction-based method. Hepatology. 2007;46(1):22-31.

    Not in our library10.1002/hep.21656

18. 18.

    Michelin BD, Muller Z, Stelzl E, Marth E, Kessler HH. Evaluation of the Abbott RealTime HCV assay for quantitative detection of hepatitis C virus RNA. J Clin Virol. 2007;38(2):96-100.

    Not in our library10.1016/j.jcv.2006.11.007

19. 19.

    Halfon PG, Penaranda M, Bourliere H, et al. Assessment of early virological response to antiviral therapy by comparing four assays for HCV RNA quantitation using the international unit standard: implications for clinical management of patients with chronic hepatitis C virus infection. J Med Virol. 2006;78:208-215.

    Not in our library10.1002/jmv.20529

20. 20.

    Chevaliez S, Pawlotsky JM. Hepatitis C virus serologic and virologic tests and clinical diagnosis of HCV-related liver disease. Int J Med Sci. 2006;3(2):35-40.

    Not in our library10.7150/ijms.3.35

21. 21.

    Davis GL, Wong JB, McHutchison JG, Manns MP, Harvey J, Albrecht J. Early virologic response to treatment with peginterferon alfa-2b plus ribavirin in patients with chronic hepatitis C. Hepatology. 2003;38(3):645-652.

    Not in our library10.1053/jhep.2003.50364

22. 22.

    Ferenci P, Fried MW, Shiffman ML, et al. Predicting sustained virological responses in chronic hepatitis C patients treated with peginterferon alfa-2a (40 KD)/ribavirin. J Hepatol. 2005;43(3):425-433.

    Not in our library10.1016/j.jhep.2005.04.009

23. 23.

    Russo MW, Fried MW. Guidelines for stopping therapy in chronic hepatitis C. Curr Gastroenterol Rep. 2004;6(1):17-21.

    Not in our library10.1007/s11894-004-0021-6

24. 24.

    Berg T, Sarrazin C, Herrmann E, et al. Prediction of treatment outcome in patients with chronic hepatitis C: significance of baseline parameters and viral dynamics during therapy. Hepatology. 2003;37(3):600-609.

    Not in our library10.1053/jhep.2003.50106

25. 25.

    Afdhal N, Freilich B, Levine R, et al. Colchicine versus Peg-Intron Long Term (COPILOT) trial: Interim analysis of clinical outcomes at year 2. Hepatology. 2004;40:238A.

    Not in our library

26. 26.

    Afdhal NH, Levine R, Brown R, Freillich B, O’Brien M, Brass C. Colehicine versus peg-interferon alfa 2b long term therapy: results of the 4 year COPILOT trial. J Hepatol. 2008;48(Suppl. 2):S4.

    Not in our library

27. 27.

    Poynard T, Schiff E, Terg R, et al. Sustained virologic response (SVR) in the EPIC(3) trial: week twelve virology predicts SVR in previous interferon/ribavirin treatment failures receiving Pegintron/Rebetol (PR) weight based dosing (WBD). J Hepatol. 2005;42(Suppl 2):40-41.

    Not in our library

28. 28.

    Di Bisceglie A, Shiffman ML, Everson GT, et al. Prolonged antiviral therapy with peginterferon to prevent complications of advanced liver disease associated with hepatitis C: results of the hepatitis C antiviral long-term treatment against cirrhosis (HALT-C) trial. Hepatology. 2007;46(Suppl. 1):290A.

    Not in our library

29. 29.

    Shiffman ML, Morishima C, Lindsay KL, et al. Suppression of serum HCV RNS levels during maintenance peginterferon (PEGIFN) alfa-2a therapy and clinical outcomes in the HALT-C trial. J Hepatol. 2008;48(Suppl. 2).

    Not in our library

30. 30.

    Zeuzem S, Buti M, Ferenci P, et al. Efficacy of 24 weeks treatment with peginterferon alfa-2b plus ribavirin in patients with chronic hepatitis C infected with genotype 1 and low pretreatment viremia. J Hepatol. 2006;44(1):97-103.

    Not in our library10.1016/j.jhep.2005.10.003

31. 31.

    Jensen DM, Morgan TR, Marcellin P, et al. Early identification of HCV genotype 1 patients responding to 24 weeks peginterferon alpha-2a (40 kd)/ribavirin therapy. Hepatology. 2006;43(5):954-960.

    Not in our library10.1002/hep.21159

32. 32.

    Zeuzem S, Diago M, Gane E, et al. Peginterferon alfa-2a (40 kilodaltons) and ribavirin in patients with chronic hepatitis C and normal aminotransferase levels. Gastroenterology. 2004;127(6):1724-1732.

    Not in our library10.1053/j.gastro.2004.09.050

33. 33.

    Poynard T, Marcellin P, Lee SS, et al. Randomised trial of interferon alpha2b plus ribavirin for 48 weeks or for 24 weeks versus interferon alpha2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus. Lancet. 1998;352(9138):1426-1432.

    Not in our library10.1016/s0140-6736(98)07124-4

34. 34.

    McHutchison JG, Gordon SC, Schiff ER, et al. Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. N Engl J Med. 1998;339(21):1485-1492.

    Not in our library10.1056/nejm199811193392101

35. 35.

    Pawlotsky JM, Bouvier-Alias M, Hezode C, et al. Standardization of hepatitis C virus RNA quantification. Hepatology. 2000;32(3):654-659.

    Not in our library10.1053/jhep.2000.16603

36. 36.

    Berg T, von Wagner M, Hinrichsen H, et al. Definition of a pre-treatment viral load cutoff for an optimized prediction of treatment outcome in patients with genotype 1 infection receiving either 48 or 72 weeks of peginterferon alfa-2a plus ribavirin. Hepatololgy. 2006;44(Suppl 1):321A.

    Not in our library

37. 37.

    Zeuzem S, Fried MW, Reddy KR, et al. Improving the clinical relevance of pretreatment viral load as a predictor of sustained virological response (SVR) in patients infected with hepatitis C genotype 1 treated with peginterferon alfa-2a (40kd) (PEGASYS®) plus ribavirin (COPEGUS). Hepatology. 2006;44(Suppl 1):267A.

    Not in our library

38. 38.

    Zehnter E, Mauss S, John C, et al. Better prediction of SVR in patients with HCV genotype 1 (G1) with peginterferon alfa-2a (PEGASYS) plus ribavirin: improving differentiation between low (LVL) and high baseline viral load (HVL). Hepatology. 2006;44(4 Suppl 1):328A.

    Not in our library

39. 39.

    Martinot-Peignoux M, Ripault MP, Maylin S, et al. Optimal pre-treatment viral load cut-off to predict treatment outcome in patients with chronic hepatitis C treated with peginterferon alfa-2b plus ribavirin. J Hepatol. 2007;46(Suppl 1):S234.

    Not in our library

40. 40.

    Ghalib RH, Levine C, Steephen A, Mubarak A, Weinstein J. Factors impacting SVR in HCV genotype 1 patients with EVR and week 24 negativity. Hepatology. 2007;46(Suppl 1):391A.

    Not in our library

41. 41.

    Sulkowski M, Lawitz E, Shiffman ML, et al. Final results of the IDEAL (individualized dosing efficacy versus flat dosing to assess optimal pegylated interferon therapy) Phase IIIB study. J Hepatol. 2008;48(Suppl. 2):S370-S371.

    Not in our library

42. 42.

    Lindahl K, Stahle L, Bruchfeld A, Schwarcz R. High-dose ribavirin in combination with standard dose peginterfern for treatment of patients with chronic hepatitis C. Hepatology. 2005;41:275-279.

    Not in our library10.1002/hep.20563

43. 43.

    Fried M, Jensen D, Rodriguez-Torres M, et al. Improved sustained virological response (SVR) rates with higher, fixed doses of peginterferon alfa-2a (40KD) (PEGASYS®) plus ribavirin (RBV)(COPEGUS®) in patients with ‘difficult-to-cure’ characteristics. Hepatology. 2006;44(Suppl 1):314A.

    Not in our library

44. 44.

    Shiffman ML, Salvatore J, Hubbard S, et al. Treatment of chronic hepatitis C virus genotype 1 with peginterferon, ribavirin, and epoetin alpha. Hepatology. 2007;46(2):371-379.

    Not in our library10.1002/hep.21712

45. 45.

    Berg T, von Wagner M, Nasser S, et al. Extended treatment duration for hepatitis C virus type 1: comparing 48 versus 72 weeks of peginterferon-alfa-2a plus ribavirin. Gastroenterology. 2006;130(4):1086-1097.

    Not in our library10.1053/j.gastro.2006.02.015

46. 46.

    Sanchez-Tapias JM, Diago M, Escartin P, et al. Peginterferon-alfa2a plus ribavirin for 48 versus 72 weeks in patients with detectable hepatitis C virus RNA at week 4 of treatment. Gastroenterology. 2006;131(2):451-460.

    Not in our library10.1053/j.gastro.2006.05.016

47. 47.

    Pearlman BL, Ehleben C, Saifee S. Treatment extension to 72 weeks of peginterferon and ribavirin in hepatitis C genotype 1-infected slow responders. Hepatology. 2007;46(6):1688-1694.

    Not in our library10.1002/hep.21919

48. 48.

    Sanchez-Tapias JM, Ferenci P, Diago M, Romero-Gomez M, Zeuzem S, Berg T. How can we identify HCV genotype 1 patients who may benefit from an extended treatment duration with peginterferon alfa-2a (40 kd) plus RBV? J Hepatol. 2007;46(Suppl 1):S243.

    Not in our library

49. 49.

    Mangia A, Santoro R, Minerva N, et al. Peginterferon alfa-2b and ribavirin for 12 vs 24 weeks in HCV genotype 2 or 3. N Engl J Med. 2005;352:2609-2617.

    Not in our library10.1056/nejmoa042608

50. 50.

    von Wagner M, Huber M, Berg T, et al. Peginterferon-alpha-2a (40 KD) and ribavirin for 16 or 24 weeks in patients with genotype 2 or 3 chronic hepatitis C. Gastroenterology. 2005;129:522-527.

    Not in our library10.1016/j.gastro.2005.05.008

51. 51.

    Andriulli A, Dalgard O, Bjøro K, Mangia A. Short-term treatment duration for HCV-2 and HCV-3 infected patients. Dig Liver Dis. 2006;38(10):741-748.

    Not in our library10.1016/j.dld.2006.06.006

52. 52.

    Yu ML, Dai CY, Huang JF, et al. A randomised study of peginterferon and ribavirin for 16 versus 24 weeks in patients with genotype 2 chronic hepatitis C. Gut. 2007;56:553-559.

    Not in our library10.1136/gut.2006.102558

53. 53.

    Dalgard O, Bjoro K, Hellum KB, et al. Treatment with pegylated interferon and ribavirin in HCV infection with genotype 2 or 3 for 14 weeks: a pilot study. Hepatology. 2004;40:1260-1265.

    Not in our library10.1002/hep.20467

54. 54.

    Dalgard O, Bjøro K, Ring-Larsen H, et al. Pegylated interferon alfa-2b and ribavirin for 14 versus 24 weeks in patients with hepatitis C virus genotype 2 or 3 and rapid virological response. Hepatology. 2008;47(1):35-42.

    Not in our library10.1002/hep.21975

55. 55.

    Zeuzem S, Pawlotsky JM, Lukasiewicz E, et al. International, multicenter, randomized, controlled study comparing dynamically individualized versus standard treatment in patients with chronic hepatitis C. J Hepatol. 2005;43(2):250-257.

    Not in our library10.1016/j.jhep.2005.05.016

56. 56.

    Brown R, Jacobson I, Afdhal N, et al. Risk factors for relapse in genotype 3 high viral load patients with hepatitis C in the WIN-R trial. Hepatology. 2006;44(Suppl 1):609A-610A.

    Not in our library

57. 57.

    Aghemo A, Rumi MG, Soffredini R, et al. Impaired response to interferon-alpha2b plus ribavirin in cirrhotic patients with genotype 3a hepatitis C virus infection. Antivir Ther. 2006;11(6):797-802.

    Not in our library

58. 58.

    Dixit NM, Perelson AS. The metabolism, pharmacokinetics and mechanisms of antiviral activity of ribavirin against hepatitis C virus. Cell Mol Life Sci. 2006;8:832-842.

    Not in our library10.1007/s00018-005-5455-y

59. 59.

    Ferenci P, Brunner H, Laferl H, et al. Further reduction of ribavirin dose in HCV genotype 2/3 patients receiving peginterferon alfa-2a (40 kd) (PEGASYS®) plus ribavirin (COPEGUS®): interim results of a randomised controlled trial. J Hepatol. 2006;44(Suppl 2):S37.

    Not in our library

60. 60.

    Dieterich DT, 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(11):2491-2499.

    Not in our library10.1111/j.1572-0241.2003.08700.x

61. 61.

    Afdhal NH, Dieterich DT, Pockros PJ, et al. Epoetin alfa maintains ribavirin dose in HCV-infected patients: a prospective, double-blind, randomized controlled study. Gastroenterology. 2004;126(5):1302-1311.

    Not in our library10.1053/j.gastro.2004.01.027

62. 62.

    Pockros PJ, Shiffman ML, Schiff ER, et al. Epoetin alfa improves quality of life in anemic HCV-infected patients receiving combination therapy. Hepatology. 2004;40(6):1450-1458.

    Not in our library10.1002/hep.20482

63. 63.

    Lindahl K, Schvarcz R, Bruchfeld A, Stahle L. Evidence that plasma concentration rather than dose per kilogram body weight predicts ribavirin-induced anaemia. J Viral Hepat. 2004;11(1):84-87.

    Not in our library10.1046/j.1365-2893.2003.00475.x

64. 64.

    McHutchison JG, Manns MP, Brown RS, Reddy KR, Shiffman ML, Wong JB. Strategies for managing anemia in hepatitis C patients undergoing antiviral therapy. Am J Gastroenterol. 2007;102(4):880-889.

    Not in our library10.1111/j.1572-0241.2007.01139.x

65. 65.

    Ferenci P, Brunner H, Laferl H, et al. A randomized, prospective trial of ribavirin 400 mg/day versus 800 mg/day in combination with peginterferon alfa-2a in hepatitis C virus genotypes 2 and 3. Hepatology. 2008;47:1816-1823.

    Not in our library10.1002/hep.22262

66. 66.

    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(4):1061-1069.

    Not in our library10.1053/gast.2002.35950

67. 67.

    Shiffman ML, Di Bisceglie AM, Lindsay KL, Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis Trial Group, et al. Peginterferon alfa-2a and ribavirin in patients with chronic hepatitis C who have failed prior treatment. Gastroenterology. 2004;126(4):1015-1023.

    Not in our library10.1053/j.gastro.2004.01.014

68. 68.

    Ferenci P, Brunner H, Nachbaur K, et al. Combination of interferon induction therapy and ribavirin in chronic hepatitis C. Hepatology. 2001;34(5):1006-1011.

    Not in our library10.1053/jhep.2001.28706

69. 69.

    Mulhall BP, Younossi Z. Impact of adherence on the outcome of antiviral therapy for chronic hepatitis C. J Clin Gastroenterol. 2005;39(1 Suppl):S23-S27.

    Not in our library10.1097/01.mcg.0000145538.43865.72

70. 70.

    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(1):124-129.

    Not in our library10.1016/j.cgh.2006.10.008

71. 71.

    Parise E, Cheinquer H, Crespo D, et al. Peginterferon alfa-2a (40 KD) (PEGASYS) plus ribavirin (COPEGUS) in retreatment of chronic hepatitis C patients, nonresponders and relapsers to previous conventional interferon plus ribavirin therapy. Braz J Infect Dis. 2006;10(1):11.

    Not in our library10.1590/s1413-86702006000100003

72. 72.

    Sherman M, Yoshida EM, Deschenes M, et al. Peginterferon alfa-2a (40 KD) plus ribavirin in chronic hepatitis C patients who failed previous interferon therapy. Gut. 2006;55(11):1631-1638.

    Not in our library10.1136/gut.2005.083113

73. 73.

    Mathew A, Peiffer LP, Rhoades K, McGarrity T. Sustained viral response to pegylated interferon alpha-2b and ribavirin in chronic hepatitis C refractory to prior treatment. Dig Dis Sci. 2006;51(11):1956-1961.

    Not in our library10.1007/s10620-006-9192-3

74. 74.

    Basso M, Torre F, Blanchi S, Delfino A, Picciotto A. Long-term virological follow-up of patients with chronic hepatitis C who obtained a sustained virological response after treatment with pegylated interferon and ribavirin. J Hepatol. 2007;46(Suppl 1):S201.

    Not in our library

75. 75.

    Sagir A, Heintges T, Akyazi Z, Oette M, Erhardt A, Häussinger D. Relapse to prior therapy is the most important factor for the retreatment response in patients with chronic hepatitis C virus infection. Liver Int. 2007;27(7):954-959.

    Not in our library10.1111/j.1478-3231.2007.01508.x

76. 76.

    Moucari R, Ripault MP, Oulès V, et al. High predictive value of early viral kinetics in retreatment with peginterferon and ribavirin of chronic hepatitis C patients non-responders to standard combination therapy. J Hepatol. 2007;46(4):596-604.

    Not in our library10.1016/j.jhep.2006.10.016

77. 77.

    Poynard T, Schiff E, Terg R, Moreno-Otero R, Flamm S, et al. Platelet count predicts sustained viral response (SVR) in the re-treatment of previous interferon/ribavirin non-responders (NR): Results from the EPIC3 program. J Hepatol. 2008;48(Suppl 2):822A.

    Not in our library

78. 78.

    Cecil BD, Lavelle M. Sustained viral response improves survival in patients with either compensated or decompensated hepatitis C. J Hepatol. 2005;42(Suppl 2):A21.

    Not in our library

79. 79.

    Cammà C, Giunta M, Chemello L, et al. Chronic hepatitis C: interferon retreatment of relapsers. A meta-analysis of individual patient data. Hepatology. 1999;30(3):801-807.

    Not in our library10.1002/hep.510300329

80. 80.

    Cummings KJ, Lee SM, West ES, et al. Interferon and ribavirin vs interferon alone in the re-treatment of chronic hepatitis C previously nonresponsive to interferon: A meta-analysis of randomized trials. J Am Med Assoc. 2001;285(2):193-139.

    Not in our library10.1001/jama.285.2.193

81. 81.

    Poynard T, Schiff E, Terg R, et al. HCV RNA negativity after 12 weeks of therapy is the best predictor of sustained virological response (SVR) in the re-treatment of previous interferon alfa/ribavirin non-responders (NR): results from the EPIC3 program. Hepatology. 2006;44:606A.

    Not in our library

82. 82.

    Jensen DM, Freilich B, Andreones P, et al. Pegylated interferon alfa-2a (40 KD) plus ribavirin (RBV) in prior non-responders to pegylated interferon alfa-2b (12 KD)/RBV: final efficacy and safety outcomes of the REPEAT study. Hepatology. 2007;46(4 Suppl):80A.

    Not in our library

83. 83.

    Kaiser S, Lutze B, Sauter B, et al. Long-term low dose treatment with pegylated interferon alpha 2b leads to a significant reduction in fibrosis and inflammatory score in chronic hepatitis C nonresponder patients with fibrosis or cirrhosis. Hepatology. 2007;46(4 Suppl):820A.

    Not in our library

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