Abstract
Introduction
Pegylated interferon alfa in combination with ribavirin has been established as standard therapy for chronic hepatitis C virus (HCV) infection with sustained virologic response rates of 54–63%. The duration of therapy depends on the HCV genotype with currently 48 weeks for genotype 1 and 24 weeks for genotypes 2 and 3.
Results and discussion
The probability of sustained virologic response is very low (<1–2%) in genotype-1-infected patients without a 2-log decline of HCV RNA concentration after 12 weeks of therapy, and treatment can therefore be discontinued early.
Conclusion
Efficient treatment of the multiple side-effects of interferon-based antiviral therapy is essential in order to improve compliance, prevent dose reduction or early discontinuation and therefore enhance the probability of sustained response. Future developments of interferon-based therapy aim at the individualisation of the duration of therapy according to the kinetics of viral reduction. Furthermore, direct antiviral drugs, which are currently under investigation in phase I/II clinical trials, will fundamentally expand the treatment options of HCV infection in the next few years.
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References
Hoofnagle JH, Mullen KD, Jones DB, Rustgi V, Di Bisceglie A, Peters M, Waggoner JG, Park Y, Jones EA (1986) Treatment of chronic non-A, non-B hepatitis with recombinant human alpha interferon. A preliminary report. N Engl J Med 315:1575–1578
McHutchison JG, Gordon SC, Schiff ER, Shiffman ML, Lee WM, Rustgi VK, Goodman ZD, Ling MH, Cort S, Albrecht JK (1998) Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. Hepatitis Interventional Therapy Group. N Engl J Med 339:1485–1492
Poynard T, Marcellin P, Lee SS, Niederau C, Minuk GS, Ideo G, Bain V, Heathcote J, Zeuzem S, Trepo C, Albrecht J (1998) 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. International Hepatitis Interventional Therapy Group (IHIT). Lancet 352:1426–1432
Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, Goodman ZD, Koury K, Ling M, Albrecht JK (2001) Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 358:958–965
Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Gonzales FL, Häussinger D, Diago M, Carosi G, Dhumeaux D, Craxi A, Lin A, Hoffmann J, Yu J (2002) Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 347:975–982
Hadziyannis SJ, Sette H Jr, Morgan TR, Balan V, Diago M, Marcellin P, Ramadori G, Bodenheimer HC Jr, Bernstein D, Rizzetto M, Zeuzem S, Pockros PJ, Lin A, Ackrill AM (2004) Peginterferon-alfa2a and ribavirin combination therapy in chronic hepatitis C. A randomized study of treatment duration and ribavirin dose. Ann Intern Med 140:346–355
Lehmann M, Meyer MF, Monazahian M, Tillmann HL, Manns MP, Wedemeyer H (2004) High rate of spontaneous clearance of acute hepatitis C virus genotype 3 infection. J Med Virol 73:387–391
Gerlach JT, Diepolder HM, Zachoval R, Gruener NH, Jung MC, Ulsenheimer A, Schraut WW, Schirren CA, Waechtler M, Backmund M, Pape GR (2003) Acute hepatitis C: high rate of both spontaneous and treatment-induced viral clearance. Gastroenterology 125:80–88
Jaeckel E, Cornberg M, Wedemeyer H, Santantonio T, Mayer J, Zankel M, Pastore G, Dietrich M, Trautwein C, Manns MP (2001) Treatment of acute hepatitis C with interferon-alfa-2b. N Engl J Med 345:1452–1457
Wiegand J, Boecher W, Buggisch P, Zeuzem S, Gelbmann CM, Cornberg M, Jäckel E, Wedemeyer H, Manns MP (2003) 24 weeks of monotherapy with pegylated interferon alfa-2b in patients with acute hepatitis C. Hepatology 38(Suppl 1):277A
Santantonio T, Fasano M, Sinisi E, Guastadisegni A, Casalino C, Mazzola M, Francavilla R, Pastore G (2005) Efficacy of a 24-week course of PEG-interferon alpha-2b monotherapy in patients with acute hepatitis C after failure of spontaneous clearance. Hepatology 42:329–333
Alberti A, Boccato S, Vario A, Benvegnu L (2002) Therapy of acute hepatitis C. Hepatology 36:S195–S200
Hofer H, Watkins-Riedel T, Janata O, Penner E, Holzmann H, Steindl-Munda P, Gangl A, Ferenci P (2003) Spontaneous viral clearance in patients with acute hepatitis C can be predicted by repeated measurements of serum viral load. Hepatology 37:60–64
Veldt BJ, Saracco G, Boyer N, Camma C, Bellobuono A, Hopf U, Castillo I, Weiland O, Nevens F, Hansen BE, Schalm SW (2004) Long term clinical outcome of chronic hepatitis C patients with sustained virological response to interferon monotherapy. Gut 53:1504–1508
Zeuzem S, Heathcote EJ, Shiffman ML, Wright TL, Bain VG, Sherman M, Feinman SV, Fried MW, Rasenack J, Sarrazin C, Jensen DM, Lin A, Hoffman JH, Sedarati F (2003) Twelve weeks of follow-up is sufficient for the determination of sustained virologic response in patients treated with interferon alpha for chronic hepatitis C. J Hepatol 39:106–111
Poynard T, McHutchison J, Manns M, Trepo C, Lindsay K, Goodman Z, Ling MH, Albrecht J (2002) Impact of pegylated interferon alfa-2b and ribavirin on liver fibrosis in patients with chronic hepatitis C. Gastroenterology 122:1303–1313
Zeuzem S (2004) Standard treatment of acute and chronic hepatitis C. Z Gastroenterol 42:714–719
Fleig WE, Krummenerl P, Lesske J, Dienes HP, Zeuzem S, Schmiegel WH, Häussinger D, Burdelski M, Manns MP (2004) Diagnosis, progression and therapy of hepatitis C virus infection as well as viral infection in children and adolescents—results of an evidenced based consensus conference of the German Society for Alimentary Metabolic Disorders and in cooperation with the Hepatitis Competence Network. Z Gastroenterol 42:703–704
Fleig WE, Krummener P, Lesske J (2004) Criteria for the definition of acute and chronic hepatitis C. Z Gastroenterol 42:707–713
National Institutes of Health (2002) National Institutes of Health consensus development conference statement: management of hepatitis C: 2002 (June 10–12, 2002). Gastroenterology 123:2082–2099
National Institutes of Health (2002) National Institutes of Health consensus development conference statement: management of hepatitis C: 2002 (June 10–12, 2002). Hepatology 36:S3–S20
Zeuzem S, Diago M, Gane E, Reddy R, Pockros P, Prati D, Shiffman M, Farci P, Gitlin N, O'Brien C, Lamour F, Lardelli P, for the PEGASYS Study NR16071 Investigator Group (2004) Peginterferon alfa-2a (40 kilodaltons) and ribavirin in patients with chronic hepatitis C and normal aminotransferase levels. Gastroenterology 127:1724–1732
Reddy KR (2004) Development and pharmacokinetics and pharmacodynamics of pegylated interferon alfa-2a (40 kD). Semin Liver Dis 24(Suppl 2):33–38
Zeuzem S, Welsch C, Herrmann E (2003) Pharmacokinetics of peginterferons. Semin Liver Dis 23(Suppl 1):23–28
Berg T, Sarrazin C, Herrmann E, Hinrichsen H, Gerlach T, Zachoval R, Wiedenmann B, Hopf U, Zeuzem S (2003) Prediction of treatment outcome in patients with chronic hepatitis C: significance of baseline parameters and viral dynamics during therapy. Hepatology 37:600–609
Bonny C, Roche C, Fontaine H, Poynard T, Hezode C, Larrey D, Marcellin P, Bourliere M, Bronowicki JP, Merle P, Zarski JP, Nicolas C, Randl K, Bommelaer G, Abergel A (2005) Efficacy of interferon (standard or pegylated) plus ribavirin in naive patients with hepatitis C virus genotype 5. A French National Study. J Hepatol 42(Suppl 2):200A
Diago M, Hassanein T, Rodes J, Ackrill AM, Sedarati F (2004) Optimized virologic response in hepatitis C virus genotype 4 with peginterferon-alpha2a and ribavirin. Ann Intern Med 140:72–73
Hasan F, Asker H, Al-Khaldi J, Siddique I, Al-Ajmi M, Owaid S, Varghese R, Al-Nakib B (2004) Peginterferon alfa-2b plus ribavirin for the treatment of chronic hepatitis C genotype 4. Am J Gastroenterol 99:1733–1737
Derbala M, Amer A, Bener A, Lopez AC, Omar M, Rl Ghannam M (2005) Pegylated interferon-alpha 2b-ribavirin combination in Egyptian patients with genotype 4 chronic hepatitis. J Viral Hepat 12:380–385
Zeuzem S, Hultcrantz R, Bourliere M, Goeser T, Marcellin P, Sanchez-Tapias J, Sarrazin C, Harvey J, Brass C, Albrecht J (2004) Peginterferon alfa-2b plus ribavirin for treatment of chronic hepatitis C in previously untreated patients infected with HCV genotypes 2 or 3. J Hepatol 40:993–999
Shiffman ML, Di Bisceglie AM, Lindsay KL, Morishima C, Wright EC, Everson GT, Lok AS, Morgan TR, Bonkovsky HL, Lee WM, Dienstag JL, Ghany MG, Goodman ZD, Everhart JE (2004) Peginterferon alfa-2a and ribavirin in patients with chronic hepatitis C who have failed prior treatment. Gastroenterology 126:1015–1023
Davis GL, Esteban-Mur R, Rustgi V, Hoefs J, Gordon SC, Trepo C, Shiffman ML, Zeuzem S, Craxi A, Ling MH, Albrecht J (1998) Interferon alfa-2b alone or in combination with ribavirin for the treatment of relapse of chronic hepatitis C. International Hepatitis Interventional Therapy Group. N Engl J Med 339:1493–1499
Poynard T, Shiff E, Terg R, Goncales F, Diago M, Reichen J, Moreno R, Bedossa P, Burroughs M, Albrecht J (2005) 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). J Hepatol 42(Suppl 2):40A
Poynard T, Schiff E, Terg R, Udaondo B, McHutchison J, Hopf U, Goncales F Jr, Flamm S, Heathcote J, Reichen J, Tanno H, Moreno R, Bedossa P, Harvey J, Albrecht J (2004) High early viral response (EVR) with PEG-Intron/Rebetol (PR) weight based dosing (WBD) in previous interferon/ribavirin HCV treatment failures; early results of the EPIC-3 trial. Hepatology 40(Suppl 1):238A
Berg T, Kronenberger B, Hinrichsen H, Gerlach T, Buggisch P, Herrmann E, Spengler U, Goeser T, Nasser S, Wursthorn K, Pape GR, Hopf U, Zeuzem S (2003) Triple therapy with amantadine in treatment-naive patients with chronic hepatitis C: a placebo-controlled trial. Hepatology 37:1359–1367
Gish RG, Arora S, Nelson D, Fried M, Reddy KR, Xu Y, Peterson J, Murphy B (2004) End-of-treatment (EOT) response in therapy-naive patients treated for chronic hepatitis C with viramidine in combination with pegylated interferon alfa-2a. Hepatology 40(Suppl 1):388A
Gish RG, Nelson D, Arora S, Fried MW, Reddy KR, Xu Y, Murphy B (2005) Virologic response and safety outcomes in therapy-naive patients treated for chronic hepatitis C with viramidine in combination with pegylated interferon alfa-2a. J Hepatol 42(Suppl 2):39A
Kaiser S, Hass H, Gregor M (2004) Successful retreatment of chronic hepatitis C patients with a nonresponse to standard interferon/ribavirin using daily consensus interferon and ribavirin. Hepatology 40(Suppl 1):240A
Afdhal N, Freilich B, Levine R, Black M, Brown R, Monsour H, O'Brien M, Brass C (2004) Colchicine versus PEG-Intron long term (COPILOT) trial: interim analysis of clinical outcomes at year 2. Hepatology 40(Suppl 1):239A
Diago M, Romero-Gomez M, Crespo J, Olveira A, Perez R, Barcena R, Sanchez-Tapias JM, Munoz SJ (2004) Peginterferon alfa-2a (40 kD) and ribavirin in patients infected with HCV genotype 1 who failed to respond to interferon and ribavirin: final results of the Spanish high-dose induction pilot trial. Hepatology 40(Suppl 1):389A
Manns MP, Berg T, Wedemeyer H, Hinrichsen H, Cholewinska G, Zeuzem S, Blum HE, Buerger V, Klade C, Tauber E, Jelovcan S, Buschle M, Frisch J (2004) Immunization with the therapeutic hepatitis C virus (HCV) peptide vaccine IC41 in 66 chronic hepatitis C non-responder patients. Hepatology 40(Suppl 1):251A
Hinrichsen H, Benhamou Y, Wedemeyer H, Reiser M, Sentjens RE, Calleja JL, Forns X, Erhardt A, Cronlein J, Chaves RL, Yong CL, Nehmiz G, Steinmann GG (2004) Short-term antiviral efficacy of BILN 2061, a hepatitis C virus serine protease inhibitor, in hepatitis C genotype 1 patients. Gastroenterology 127:1347–1355
Lamarre D, Anderson PC, Bailey M, Beaulieu P, Bolger G, Bonneau P, Bos M, Cameron DR, Cartier M, Cordingley MG, Faucher AM, Goudreau N, Kawai SH, Kukolj G, Lagace L, LaPlante SR, Narjes H, Poupart MA, Rancourt J, Sentjens RE, St George R, Simoneau B, Steinmann G, Thibeault D, Tsantrizos YS, Weldon SM, Yong CL, Llinas-Brunet M (2003) An NS3 protease inhibitor with antiviral effects in humans infected with hepatitis C virus. Nature 426:186–189
Dalgard O, Bjoro K, Hellum KB, Myrvang B, Ritland S, Skaug K, Raknerud N, Bell H (2004) Treatment with pegylated interferon and ribavirin in HCV infection with genotype 2 or 3 for 14 weeks: a pilot study. Hepatology 40:1260–1265
Mangia A, Minerva N, Ricci GL, Romano M, Carretta V, Persico M, Bacca D, Spirito R, Vinelli F, Annese M, Giangaspero A, Scotto G, Andriulli A (2004) HCV genotype 2 and 3 can be cured by PEG-IFN-alfa 2b and ribavirin for 12 weeks: a randomized controlled study. J Hepatol 40(Suppl 1):34A
von Wagner M, Huber M, Berg T, Hinrichsen H, Rasenack J, Heintges T, Bergk A, Bernsmeier C, Zeuzem S (2005) Randomized multicenter study comparing 16 vs. 24 weeks of combination therapy with peginterferon alfa-2a plus ribavirin in patients chronically infected with HCV genotype 2 or 3. Gastroenterology (in press)
Herrmann E, Zeuzem S, Sarrazin C, Hinrichsen H, Benhamou JP, Wedemeyer H, Reiser M, Sentjens R, Calleja JL, Forns X, Steinmann G, Nehmiz G (2004) Viral kinetics in patients with chronic hepatitis C treated with the serine protease inhibitor BILN 2061. J Hepatol 40(Suppl 1):A
Reiser M, Hinrichsen H, Benhamou JP, Sentjens R, Wedemeyer H, Calleja L, Forns X, Croenlein J, Yong C, Nehmiz G, Steinmann G (2003) Antiviral effect of BILN 2061, a novel HCV serine protease inhibitor, after oral treatment over 2 days in patients with chronic hepatitis C, non genotype 1. Hepatology 38(Suppl 1):221A
Afdhal N, Godofsky E, Dienstag J, Rustgi V, Schick L, McEniry D, Zhou XJ, Chao G, Fang C, Fielman B, Myers M, Brown N (2004) Final phase I/II trial results for NM283, a new polymerase inhibitor for hepatitis C: antiviral efficacy and tolerance in patients with HCV-1 infection, including previous interferon failures. Hepatology 40(Suppl 1):726A
Poynard T, McHutchison J, Goodman Z, Ling MH, Albrecht J (2000) Is an “a la carte” combination interferon alfa-2b plus ribavirin regimen possible for the first line treatment in patients with chronic hepatitis C? The ALGOVIRC Project Group. Hepatology 31:211–218
Weich V, Herrmann E, Sarrazin C, Hinrichsen H, Buggisch P, Gerlach T, Klinker H, Spengler U, Bergk A, Wiedemann B, Zeuzem S, Berg T (2004) Gamma-Glutamyltranspeptidase (GGT) is the most reliable predictive single parameter for treatment outcome in HCV type 1-infected patients. Hepatology 40:333A
Davis GL, Wong JB, McHutchison JG, Manns MP, Harvey J, Albrecht J (2003) Early virologic response to treatment with peginterferon alfa-2b plus ribavirin in patients with chronic hepatitis C. Hepatology 38:645–652
Sarrazin C, Teuber G, Kokka R, Rabenau H, Zeuzem S (2000) Detection of residual hepatitis C virus RNA by transcription-mediated amplification in patients with complete virologic response according to polymerase chain reaction-based assays. Hepatology 32:818–823
Mihm U, Kronenberger B, Hofmann WP, Zeuzem S, Sarrazin C (2004) Highly sensitive HCV RNA detection assays for decision of treatment (dis)continuation in patients with chronic hepatitis C. J Hepatol 42(4):605–606
Sarrazin C, Gärtner B, Welker M, Traver S, Zeuzem S (2004) Evaluation of a new, highly sensitive, real time PCR based assay for quantification of HCV RNA. J Hepatol 40(Suppl 1):150A
Ross RS, Viazov S, Sarr S, Hoffmann S, Kramer A, Roggendorf M (2002) Quantitation of hepatitis C virus RNA by third generation branched DNA-based signal amplification assay. J Virol Methods 101:159–168
Pawlotsky JM, Bouvier-Alias M, Hezode C, Darthuy F, Remire J, Dhumeaux D (2000) Standardization of hepatitis C virus RNA quantification. Hepatology 32:654–659
McHutchison JG, Manns M, Patel K, Poynard T, Lindsay KL, Trepo C, Dienstag J, Lee WM, Mak C, Garaud JJ, Albrecht JK (2002) Adherence to combination therapy enhances sustained response in genotype-1-infected patients with chronic hepatitis C. Gastroenterology 123:1061–1069
Kraus MR, Schafer A, Al Taie O, Scheurlen M (2005) Prophylactic SSRI during interferon alpha re-therapy in patients with chronic hepatitis C and a history of interferon-induced depression. J Viral Hepat 12:96–100
Schaefer M, Schmidt F, Folwaczny C, Lorenz R, Martin G, Schindlbeck N, Heldwein W, Soyka M, Grunze H, Koenig A, Loeschke K (2003) Adherence and mental side-effects during hepatitis C treatment with interferon alfa and ribavirin in psychiatric risk groups. Hepatology 37:443–451
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Friedrich-Rust, M., Zeuzem, S. & Sarrazin, C. Current therapy for hepatitis C. Int J Colorectal Dis 22, 341–349 (2007). https://doi.org/10.1007/s00384-005-0038-9
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DOI: https://doi.org/10.1007/s00384-005-0038-9