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Treatment of nonresponders to standard hepatitis C therapy

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Abstract

Over 40% of patients with chronic hepatitis C fail to achieve sustained virologic response to treatment with pegylated interferon and ribavirin. They represent a growing population of patients with chronic hepatitis C. Those more likely to be nonresponders include patients with genotype 1 (especially with high viral load), advanced fibrosis, or HIV coinfection, as well as African Americans. Prior treatment history must be carefully reviewed and the pattern of nonresponse ascertained to formulate appropriate management strategies. Modi.-able factors associated with poor response should be identified prior to retreatment and addressed to improve the efficacy of retreatment. Patients with mild inflammation and mild fibrosis are at low risk of progression to cirrhosis and may reasonably be offered observation with periodic follow-up. The treatment of naïve patients needs to be optimized in order to minimize the growth of the population of “difficult to treat” nonresponders with chronic hepatitis C.

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References and Recommended Reading

  1. 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 randomized trial. Lancet 2001, 358:958–965.

    Article  PubMed  CAS  Google Scholar 

  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, 347:975–982.

    Article  PubMed  CAS  Google Scholar 

  3. Hadziyannis SJ, Sette H Jr, Morgan TR, et al.: Peginterferon- α2a and ribavirin combination therapy in chronic hepatitis C. A randomized study of treatment duration and ribavirin dose. Ann Intern Med 2004, 140:346–355.

    PubMed  CAS  Google Scholar 

  4. Blatt LM, Mutchnick MG, Tong MJ, et al.: Assessment of hepatitis C virus RNA and genotype from 6807 patients with chronic hepatitis C in the United States. J Viral Hepat 2000, 7:196–202.

    Article  PubMed  CAS  Google Scholar 

  5. Muir AJ, Bornstein JD, Killenberg PG: Peginterferon alfa-2b and ribavirin for the treatment of chronic hepatitis C in blacks and non-Hispanic whites. N Engl J Med 2004, 350:2265–2271. A controlled trial that demonstrated that African Americans have a significantly lower rate of sustained virologic response than non- Hispanic white patients.

    Article  PubMed  CAS  Google Scholar 

  6. Jeffers LJ, Cassidy W, Howell CD, et al.: Peginterferon alfa- 2a (40kd) and ribavirin for black American patients with chronic HCV genotype 1. Hepatology 2004, 39:1702–1708.

    Article  PubMed  CAS  Google Scholar 

  7. Torriani FJ, Rodriguez-Torres M, Rockstroh JK, et al.: Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection in HIV-infected patients. N Engl J Med 2004, 351:438–450.

    Article  PubMed  CAS  Google Scholar 

  8. Carrat F, Bani-Sadr F, Pol S, et al.: Pegylated interferon alfa-2b vs standard interferon alfa-2b, plus ribavirin, for chronic hepatitis C in HIV-infected patients: a randomized controlled trial. JAMA 2004, 292:2839–2848.

    Article  PubMed  CAS  Google Scholar 

  9. Shiffman ML, Di Bisceglie AM, Lindsay KL, et al.: Peginterferon alfa-2a and ribavirin in patients with chronic hepatitis C who have failed prior treatment. Gastroenterology 2004, 126:1015–1023. A prospective controlled trial that demonstrated that selected nonresponders to prior interferon-based therapy can achieve sustained virologic response following retreatment with peginterferon alfa-2a and ribavirin; it also showed the importance of the optimal dose of ribavirin in the first 20 weeks of therapy.

    Article  PubMed  CAS  Google Scholar 

  10. Jacobson IM, Gonzalez SA, Ahmed F, et al.: A randomized trial of pegylated interferon α-2b plus ribavirin in the treatment of chronic hepatitis C. Am J Gastroenterol 2005, 100:2453–2462. A randomized trial showing combination therapy with peginterferon alfa-2b plus ribavirin to be more effective in relapsers after combination standard interferon plus ribavirin than in nonresponders to interferon-based therapy.

    Article  PubMed  CAS  Google Scholar 

  11. Krawitt EL, Ashikaga T, Gordon SR, et al.: Peginterferon alfa-2b and ribavirin for treatment-refractory chronic hepatitis C. J Hepatol 2005, 43:243–249.

    Article  PubMed  CAS  Google Scholar 

  12. Gross J, Johnson S, Kwo P, et al.: Double-dose peginterferon alfa-2B with weight-based ribavirin improves response for interferon/ribavirin non-responders with hepatitis C: final results of “RENEW” [abstract]. Hepatology 2005, 42suppl 1:)219A.

    Google Scholar 

  13. Poynard T, Schiff E, Terg R, et al.: Sustained virologic response (SVR) in the EPIC3 trial: Week twelve virology predicts SVR in previous interferon/ribavirin treatment failures receiving PEG-INTRON/Rebetol (PR) weight based dosing (WBD) [abstract]. J Hepatol 2005, 42(suppl 2):A96.

    Google Scholar 

  14. 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, 123:1061–1069.

    Article  PubMed  CAS  Google Scholar 

  15. Strader D, Wright T, Thomas DL, et al.: AASLD practice guideline: diagnosis, management, and treatment of hepatitis C. Hepatology 2004, 39:1147–1171.

    Article  PubMed  Google Scholar 

  16. Shiffman ML: Management of interferon therapy nonresponders. Clin Liver Dis 2001, 5:1025–1043.

    Article  PubMed  CAS  Google Scholar 

  17. Sethi A, Shiffman ML: Approach to the management of patients with chronic hepatitis C who failed to achieve sustained virologic response. Clin Liver Dis 2005, 9:453–471.

    Article  PubMed  Google Scholar 

  18. Davis GL, Wong JB, McHutchison JG, et al.: Early virologic response to treatment with peginterferon alfa-2b plus ribavirin in patients with chronic hepatitis C. Hepatology 2003, 38:645–652. Important subanalysis data from the pivotal trial demonstrating that patients who fail to achieve early virologic response will not clear virus even with an additional 9 months of therapy.

    Article  PubMed  CAS  Google Scholar 

  19. Sanchez-Tapias JM, Diago M, Escartin P, et al.: Longer treatment duration with peginterferon alfa-2a (40KD) (Pegasys ®) and ribavirin (Copegus®) in naïve patients with chronic hepatitis C and detectable HCV RNA by week 4 of therapy: final results of the randomized, multicenter TERAVIC-4 study [abstract]. Hepatology 2004, 40(suppl 1):218A.

    Google Scholar 

  20. 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, 130:1086–1097.

    Article  PubMed  CAS  Google Scholar 

  21. Shiffman ML, Fromm H, Mills P, et al.: Enhanced efficacy of pegylated (40 kDa) interferon alfa-2a (Pegasys) compared with interferon alfa-2a (Roferon-A) for chronic hepatitis C in blacks [abstract]. Hepatology 2000, 32(suppl):348A.

    Article  Google Scholar 

  22. Lindsay KL, McHutchison JG, Ling MH, et al.: Response to PEG-IFN alfa-2b (PEG-Intron) in blacks and Hispanics with HCV is higher than with standard IFN alfa-2b (IFN) [abstract]. Hepatology 2000, 32(suppl):347A.

    Google Scholar 

  23. Peters MG, Terrault NA: Alcohol use and hepatitis C. Hepatology 2002, 36(suppl 1):S220-S225.

    Article  PubMed  Google Scholar 

  24. Bressler BL, Guindi M, Tomlinson G, et al.: High body mass index is an independent risk factor for nonresponse to antiviral treatment in chronic hepatitis C. Hepatology 2003, 38:639–644. Retrospective study identifying obesity (BMI > 30 kg/m2) as an independent negative predictor of response to hepatitis C treatment.

    Article  PubMed  CAS  Google Scholar 

  25. Iyoda K, Kato M, Izumi Y, et al.: Retreatment for non-responders in initial interferon therapy suppresses carcinogenesis and improves long-term survival of chronic hepatitis C patients [abstract]. Hepatology 2005, 42(suppl1):654A.

    Google Scholar 

  26. Cheng SJ, Bonis PAL, Lau J, et al.: Interferon and ribavirin for patients with chronic hepatitis C who did not respond to previous interferon therapy: a meta-analysis of controlled and uncontrolled trials. Hepatology 2001, 33:231–240.

    Article  PubMed  CAS  Google Scholar 

  27. 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 metaanalysis of randomized trials. JAMA 2001, 285:193–199.

    Article  PubMed  CAS  Google Scholar 

  28. Lawitz EJ, Cantu NS, Becker S, et al.: Pegylated interferon alfa-2b (PEG-IFN) and ribavirin for hepatitis C patients who were nonresponders to previous therapy [abstract]. Gastroenterology 2003, 124:A783.

    Article  Google Scholar 

  29. Jacobson I, Brown R, McCone J, et al.: Weight-based ribavirin dosing improves virologic response in HCV-infected genotype 1 African-Americans (AA) compared to flat dose ribavirin with peginterferon alfa-2b combination therapy [abstract]. Hepatology 2004, 40(suppl 1):217A.

    Google Scholar 

  30. Jacobson IM, Brown RS, Freilich B, et al.: Weight-based ribavirin dosing (WBD) increases sustained viral response (SVR) in patients with chronic hepatitis C (CHC): final results of the WIN-R study, a US community based trial [abstract]. Hepatology 2005, 42(suppl 1):749A.

    Google Scholar 

  31. Curry MP, Afdhal NH: Use of growth factors with antiviral therapy for chronic hepatitis C. Clin Liver Dis 2005, 9:439–451.

    Article  PubMed  Google Scholar 

  32. Rustgi VK, Esposito S, Freilich B, et al.: Interim analysis of the safety and efficacy of peginterferon alfa-2a plus ribavirin in chronic hepatitis C patients unable to tolerate or nonresponsive to treatment with peginterferon alfa-2b plus ribavirin [abstract]. Hepatology 2005, 42(suppl 1):692A.

    Google Scholar 

  33. Marcellin P, Jensen D: Retreatment with Pegasys® in patients not responding to prior peginterferon alfa-2b/ribavirin (RBV) combination therapy—efficacy analysis of the 12-week induction period of the REPEAT study. Hepatology 2005, 42(suppl 1):749A.

    Google Scholar 

  34. White C, Wentworth C, Mallet P, et al.: The TARGET trial: final results using 3.0 mcg/kg pegylated interferon alfa-2b (PEG; PEG-Intron®) plus ribavirin (RBV; Rebetol®) for chronic hepatitis C patients with were non-responders (NR) and relapsers (R) to previous therapy [abstract]. Hepatology 2005, 42(suppl 1):651A.

    Google Scholar 

  35. Cornberg M, Hadem J, Herrmann E, et al.: Treatment with daily consensus interferon (CIFN) plus ribavirin in nonresponder patients with chronic hepatitis C: a randomized open-label pilot study. J Hepatol 2006, 44:291–301. First published trial evaluating treatment with daily consensus interferon plus ribavirin in prior nonresponders to interferon or interferon-plus-ribavirin therapy.

    Article  PubMed  CAS  Google Scholar 

  36. Kaiser S, Hass H, Gregor M: Successful retreatment of peginterferon nonresponder patients with chronic hepatitis C with high dose consensus interferon induction therapy [abstract]. Gastroenterology 2004, 126(suppl 2). Abstract 125.

    Google Scholar 

  37. Leevy C II, Chalmers C, Blatt LM: Comparison of African American and non African American patient end of treatment response for PEG-IFN alfa2 plus weight-based ribavirin nonresponders retreated with IFN alfacon-1 plus weight-based ribavirin [abstract]. Hepatology 2004; 40(suppl 1):240A.

    Google Scholar 

  38. Chen K, Seraphin P, Murphy L, et al.: Consensus interferon and ribavirin in patients with chronic hepatitis C who were nonresponders to prior therapy with either interferon alfa and ribavirin or pegylated interferon and ribavirin [abstract]. Hepatology 2005, 42(suppl 1):670A.

    Google Scholar 

  39. Dollinger MM, Dridi Y, Lesske J, et al.: Efficacy of daily consensus interferon and ribavirin compared to peg-interferon α-2B and ribavirin in non-responders with chronic hepatitis C [abstract]. Hepatology 2005, 42(suppl 1):691A.

    Google Scholar 

  40. Yano M, Kumada H, Kage M, et al.: The long-term pathological evaluation of chronic hepatitis C. Hepatology 1996, 23:1334–1340.

    Article  PubMed  CAS  Google Scholar 

  41. Hezode C, Roudot-Thoraval F, Nguyen S, et al.: Daily cannabis smoking as a risk factor for progression of fibrosis in chronic hepatitis C. Hepatology 2005, 42:63–71.

    Article  PubMed  CAS  Google Scholar 

  42. Vento S, Garofano T, Renzini C, et al.: Fulminant hepatitis associated with hepatitis A virus superinfection in patients with chronic hepatitis C. N Engl J Med 1998; 338:286–290.

    Article  PubMed  CAS  Google Scholar 

  43. Shiffman ML, Hofman CM, Contos MJ, et al.: A randomized, controlled trial of maintenance interferon therapy for patients with chronic hepatitis C virus and persistent viremia. Gastroenterology 1999, 117:1164–1172.

    Article  PubMed  CAS  Google Scholar 

  44. Afdhal N, Freilich B, Levine R, et al.: Colchicine versus PEG-INTRON long term (COPILOT) trial: interim analysis of clinical outcomes at year 2 [abstract]. Hepatology 2004, 40(suppl_1):239A.

    Google Scholar 

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Correspondence to Ira M. Jacobson MD.

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Gambarin-Gelwan, M., Jacobson, I.M. Treatment of nonresponders to standard hepatitis C therapy. Curr hepatitis rep 5, 108–113 (2006). https://doi.org/10.1007/s11901-006-0013-0

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