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Interferon alpha-2b and ribavirin in combination for patients with chronic hepatitis C who failed to respond to, or relapsed after, interferon alpha therapy: a randomized trial

      Abstract

      PURPOSE: To assess the efficacy of interferon alpha-2b and ribavirin in combination in the treatment of patients with chronic hepatitis C who had either failed to respond to therapy with interferon alpha (nonresponders), or who had relapsed after interferon therapy (relapsers).
      SUBJECTS AND METHODS: Four hundred patients with chronic hepatitis C (200 nonresponders and 200 relapsers) were randomly assigned in equal numbers to receive either subcutaneous administration of recombinant interferon alpha-2b (3 million units three times per week) and ribavirin (1,000 to 1,200 mg/daily orally) or interferon alpha-2b alone (6 million units three times per week). Both ribavirin and interferon alpha-2b were given for 24 weeks. The patients were then followed for an additional 24 weeks.
      RESULTS: At the end of the treatment period, normalization of serum alanine aminotransferase levels and absence of hepatitis C virus RNA were seen in 21% of nonresponders and in 39% of relapsers who were treated with interferon alpha-2b and ribavirin, compared with 5% of nonresponders (P = 0.001) and 9% of relapsers treated with interferon alpha-2b alone (P <0.001). At the end of follow-up, 14% of nonresponders and 30% of relapsers treated with the combination therapy had a sustained response, compared with 1% of nonresponders (P = 0.001) and 5% of relapsers treated with interferon alpha alone (P <0.001).
      CONCLUSIONS: A 24-week course of treatment with interferon alpha-2b and ribavirin offers a chance of sustained response, whereas retreatment with interferon alpha-2b alone does not give satisfactory results. The role of long-term therapy in inducing prolonged remission remains to be explored.
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      References

        • Davis G
        • Balart L
        • Schiff E
        • et al.
        Treatment of chronic hepatitis C with recombinant interferon alpha. A multicenter randomized, controlled trial.
        NEJM. 1989; 321: 1501-1506
        • Di Bisceglie A
        • Martin P
        • Kassianides C
        • et al.
        Recombinant interferon alpha therapy for chronic hepatitis C. A randomized, double-blind, placebo-controlled trial.
        NEJM. 1989; 321: 1506-1510
        • Schvarcz R
        • Weiland O
        • Wejstàl R
        • et al.
        A randomized controlled open study of interferon alpha-2b treatment of chronic non-A, non-B post-transfusion hepatitis. No correlation of outcome to presence of hepatitis C virus antibodies.
        Scand J Infect Dis. 1989; 21: 617-625
        • Tine F
        • Magrin S
        • Craxi A
        • Pagliaro L
        Interferon for non-A, non-B chronic hepatitis. A meta-analysis of randomized clinical trials.
        J Hepatol. 1991; 13: 192-199
        • Reichard O
        • Andersson J
        • Schvarcz R
        • Weiland O
        Ribavirin treatment for chronic hepatitis C.
        Lancet. 1991; 337: 1056-1061
        • Di Bisceglie A
        • Shindo M
        • Fong T
        • et al.
        A pilot study of ribavirin therapy for chronic hepatitis C.
        Hepatology. 1992; 16: 649-654
        • Camps J
        • Garcia N
        • Riezu-Boj J
        • et al.
        Ribavirin in the treatment of chronic hepatitis C unresponsive to alpha interferon.
        J Hepatol. 1993; 19: 408-412
        • Reichard O
        • Yun Z
        • Sonneborg A
        • Weiland O
        Hepatitis C viral RNA titers in serum prior to, during and after oral treatment with ribavirin for chronic hepatitis C.
        J Med Virol. 1993; 41: 99-102
        • Brillant S
        • Garson J
        • Foli M
        • et al.
        A pilot study of combination therapy with ribavirin plus interferon alpha for interferon alpha-resistant chronic hepatitis C.
        Gastroenterology. 1994; 107: 812-817
        • Brillanti S
        • Miglioli M
        • Barbara L
        Combination antiviral therapy with ribavirin and interferon alpha in interferon alpha relapsers and non-responders.
        J Hepatol. 1995; 23: 13-16
        • Schvarcz R
        • Yun Z.B
        • Sonneborg A
        • Weiland O
        Combined treatment with interferon alpha-2b and ribavirin for chronic hepatitis C in patients with a previous non response or non-sustained response to interferon alone.
        J Med Virol. 1995; 46: 43-47
        • Reichard O
        • Norkrans G
        • Fryden A
        • et al.
        Randomized, double-blind, placebo-controlled trial of interferon α-2b with and without ribavirin for chronic hepatitis C.
        Lancet. 1998; 351: 83-87
        • McHutchinson J.G
        • Gordon S.C
        • Schiff E.R
        • et al.
        Interferon alpha-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C.
        NEJM. 1998; 339: 1485-1492
        • Davis G.L
        • Esteban-Mur R
        • Rustgi V
        • et al.
        Interferon alpha-2b alone or in combination with ribavirin for the treatment of relapse of chronic hepatitis C.
        NEJM. 1998; 339: 1493-1499
        • Okamoto H
        • Okada S
        • Sugiyama Y
        • et al.
        The 5′ terminal sequence of the hepatitis C virus genome.
        Jpn J Exp Med. 1990; 60: 167-177
        • Shindo M
        • Di Bisceglie A.M
        • Cheung L
        • et al.
        Decrease in hepatitis C virus RNA during alpha-interferon therapy for chronic hepatitis C.
        Ann Intern Med. 1990; 115: 700-704
        • Chomczynski P
        • Sacchi N
        Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.
        Anal Biochem. 1987; 162: 156-159
        • Okamoto H
        • Sugiyama Y
        • Okada S
        • et al.
        Typing hepatitis C virus by polymerase chain reaction with type-specific primers.
        J Gen Virol. 1992; 73: 673-679
        • Okamoto H
        • Tokita H
        • Sakamoto M
        • et al.
        Characterization of the genomic sequence of the type V (or 3a) hepatitis C virus isolates and PCR primers for specific detection.
        J Gen Virol. 1994; 75: 629-635
        • Knodell R.G
        • Ishak K.G
        • Black W.C
        • et al.
        Formulation and application of numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis.
        Hepatology. 1981; 1: 431-435
      1. Armitage P, Berry G. Statistical Methods in Medical Research, 3rd ed. Oxford, England: Blackwell Scientific, 1994.

        • Sarracco G
        • Rosina F
        • Abate M
        • et al.
        Long-term follow-up of patients with chronic hepatitis C treated with different doses of interferon alpha-2b.
        Hepatology. 1993; 18: 1300-1305
        • Davis G.L
        • Lau J.Y
        • Lim H.L
        Therapy for chronic hepatitis C.
        Gastroenterol Clin North Am. 1994; 23: 603-613
        • Patterson J.L
        • Fernandez-Larsson R
        Molecular mechanisms of action of ribavirin.
        Rev Infect Dis. 1990; 12: 1139-1146
        • Hayden F.C
        • Schlepushkin A.N
        • Pushkarskaya N.L
        Combined interferon α-2, rimantadine hydrochloride and ribavirin inhibition of influenza virus replication in vitro.
        Antimicrob Agents Chemother. 1984; 25: 53-57
      2. Maertens G, Stuyver L. Genotypes and genetic variation of hepatitis C virus. In: Harrison TJ, Zuckerman AJ, eds. The Molecular Medicine of Viral Hepatitis. New York: John Wiley & Sons Ltd. 1997:226–227.

        • Scotto G
        • Fazio V
        • Tantimonaco G
        Pilot study of short course of ribavirin and alpha interferon in the treatment of chronic active hepatitis C not responding to alpha interferon alone.
        Ital J Gastroenterol. 1996; 28: 505-511
        • Schalm S.W
        • Brouwer J.T
        • Chemello L
        • et al.
        Interferon-ribavirin combination therapy for chronic hepatitis C.
        Dig Dis Sci. 1996; 41: 131S-134S