Abstract
Ten patients with interferon-nonresponsive chronic hepatitis C were treated with high-dose interferon-α2b (IFN-α2b; 20 MU/day for two days, then 3 MU/day for 24 weeks, followed by 3 MU three times weekly for 24 more weeks) plus ribavirin (1000–1200 mg/day). End-of-treatment virologic responses occurred in 50% of cases and sustained virologic responses in 37.5%. Hepatitis C virus RNA decreased significantly (2.15 logs; P < 0.0001) after the two 20-MU interferon doses but rebounded when the interferon dose was lowered to 3 MU/day. Thereafter, hepatitis C virus RNA showed a progressive, significant decrease, most notably at week 10 (3.3 logs; P = 0.001). Patients with a sustained response exhibited a more pronounced hepatitis C virus RNA decrease, especially from weeks 3 to 8 (P = 0.036). Two patients discontinued therapy because of adverse events, and one patient required a ribavirin dose reduction. Retreatment with an initial high-dose IFN-α2b plus ribavirin significantly reduces viral load in genotype 1-infected, interferon-nonresponsive patients.
Similar content being viewed by others
REFERENCES
McHutchison JG, Gordon SC, Schiff ER, Shiffmen MT, Lee W, Rustgi VK, Goodman ZD, Ling M-H, Cort S, Albrecht JK, Hepatitis Interventional Therapy Group: Interferon alpha-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. N Engl J Med 339:1485–1492, 1998
Poynard T, Marcellin P, Lee SS, Niederau C, Minuk GS, Ideo G, Bain V, Heathcote J, Zeuzem S, Trepo C, Albrecht JK for the International Hepatitis Interventional Therapy Group Randomised trial of interferon alfa2b plus ribavirin for 48 weeks or for 24 weeks versus interferon alfa b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C. Lancet 352:1426–1432, 1998
Lam NP, Neumann AU, Gretch DR, Wiley TE, Perelson AS, Layden TJ: Dose-dependent acute clearance of hepatitis C genotype 1 virus with interferon alfa. Hepatology 26:226–231, 1997
Zeuzem S, Lee JH, Franke A, Franke A, Ruster B, Prúmmer O, Herrmann G, Roth WK: Quantification of the initial decline of serum Hepatitis C virus RNA and response to interferon alfa. Hepatology 27:1149–1156, 1998
Bekkering FC, Brouwer JT, Leroux-Roels G, Van Vlierberghe H, Elewaut A, Schalm SW: Ultrarapid hepatitis C virus clearance by daily high-dose interferon in non-responders to standard therapy. J Hepatol 28:960–964, 1998
Martell M, Gomez J, Esteban JI, Sauleda S, Quer J, Cabot B, Esteban R, Guardia J: High-throughout real-time reverse transcription-PCR quatitation of hepatitis C virus RNA. J Clin Microbiol 37:327–332, 1999
Reichard O, Schvarcz R, Weiland O: Therapy of hepatitis C: Alfa interferon and ribavirin. Hepatology 26(suppl):108–111, 1997
Davis GL, Esteban-Mur R, Rustgi V, Hoefs J, Gordon SC, Trepo C, Shiffman ML, Zeuzem S, Craxi A, Ling M-H, Albrecht J, International Hepatitis Interventional Therapy Group: Interferon alfa-2b alone or in combination with ribavirin for the treatment of relapse of chronic hepatitis C. N Engl J Med 339:1493–1499, 1998
Di Marco V, Almasio P, Vaccaro A, Ferraro D, Parisi P, Cataldo MG, Di Stefano R, Craxi A: Combined treatment of relapse of chronic hepatitis C with high-dose α2b interferon plus ribavirin for 6 or 12 months. J Hepatol 33:456–462, 2000
Brillanti S, Garson J, Foli M, Whitby K, Deaville R, Masci C, Miglioli M, Barbara L: A pilot study of combination therapy with ribavirin plus interferon for interferon-resistant chronic hepatitis C. Gastroenterology 107:812–817, 1994
Schvarcz R, Yun ZB, Sonnerborg A, Weiland O: Combination treatment with interferon -2b and ribavirin for chronic hepatitis C in patients with a previous non-response or nonsustained response to interferon alone. J Med Virol 46:43–47, 1995
Brouwer J, Nevens F, Michielsen P: What options are left when hepatitis C does not respond to interferon? Placebo-controlled Benelux multicentre retreatment trial on ribavirin monotherapy versus combination with interferon. J Hepatol 21:17A, 1994
Pol S: Ribavirin-interferon vs interferon (alfa 2b-IFN) alone in non-responders to alfa-2b IFN in chronic hepatitis C. Hepatology 24:356A, 1996
Buti M, Olive G, Stalgis C, Esteban R, Guardia J: Quantification of serum hepatitis C virus RNA with daily or standard interferon doses plus ribavirin in nonresponder patients with chronic hepatitis C. Dig Dis Sci 45:1–5, 2000
EASL International Consensus Conference of Hepatitis C: Consensus statement. J Hepatol 30:956–961, 1999
Bellobuono A, Mondazzi L, Tempini S, Chiodo F, MaglianoE, Furiano L, Ideù G: Early addition of ribavirin to interferon in chronic hepatitis c not responsive to interferon monotherapy. J Hepatol 33:463–468, 2000
Castro FJ, Esteban JI, Sauleda S, Viladomiu L, Dragon EA, Esteban R, Guardia J: Utility of early testing for HCV viremia as predictive factor of sustained response during interferon or interferon plus ribavirin treatment.J Hepatol 32:843–849, 2000
Poynard T, McHutchison J, Goodman Z, Ling MH, Albrecht J for the ALGOVIRC Project Group: Is “A la carte” combination interferon alfa-2b plus ribavirin regimen possible for the first line treatment in patients with chronic hepatitis C? Hepatology 31:211–218, 2000
Min AD, Joners JL, Lebovics E, Jacobson IM, Klion FM, Goldman IS, Espositos S, Geders JM, Tobias U, Brodenheimer UC: Interferon alfa2b and ribavirin in patients with resistant chronic hepatitis B. Hepatology 30:192A, 1999
Iacono OL, Castro A, Diago M, Cors R, Borque MJ, Garcia Buey L, Garcia-Nonzon C, Pedreire J, Moreno-Otero R: Interferon alpha plus ribavirin for chronic hepatitis C genotype 1b non-responders patients to interferon alone. Hepatology 30:266A, 1999
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Buti, M., Morral, S., Sanchez, F. et al. High-Dose Interferon-α2b Plus Ribavirin for Retreatment of Interferon-Nonresponsive Patients Infected with Genotype 1 Hepatitis C Virus. Dig Dis Sci 46, 2396–2400 (2001). https://doi.org/10.1023/A:1012355332052
Issue Date:
DOI: https://doi.org/10.1023/A:1012355332052