Final results of a double-blind, placebo-controlled trial of the antifibrotic efficacy of interferon-γ1b in chronic hepatitis C patients with advanced fibrosis or cirrhosis

Paul J. Pockros, Lennox J Jeffers, Nezam Afdhal, Zachary D. Goodman, David Nelson, Robert G. Gish, K. Rajender Reddy, Robert Reindollar, Maribel Rodriguez-Torres, Sarah Sullivan, Lawrence M. Blatt, Sima Faris-Young

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Abstract

Interferon-γ1b (IFN-γ1b) is a pleiotropic cytokine that displays antifibrotic, antiviral, and antiproliferative activity. A total of 502 patients with compensated liver disease and an Ishak fibrosis score of 4-6 were randomized in a double-blind, placebo-controlled study, and 488 of these patients received subcutaneous injections of IFN-γ1b 100 μg (group 1, n = 169), IFN-γ1b 200 μg (group 2, n = 157), or placebo (group 3, n = 162) 3 times a week for 48 weeks. Most patients (83.6%) had cirrhosis at baseline (Ishak score = 5 or 6). Posttreatment liver biopsies were assessed in a blinded fashion for a reduction of 1 or more Ishak points (primary endpoint). Four hundred twenty patients with pretreatment and posttreatment liver biopsies were evaluable and showed no improvement in Ishak score between the 3 treatment groups (12.1%, 12.4%, and 16% of patients in groups 1, 2, and 3, respectively; P > 0.05). Analysis of IFN-γ-inducible biomarkers revealed that interferon-inducible T cell-alpha chemoattractant (ITAC), an IFN-γ-inducible CXCR3 chemokine was an independent predictor of stable or improving Ishak score. IFN-γ1b was well tolerated. There were similar numbers of deaths in all 3 arms (5, 5, and 4, respectively), and most were related to complications of cirrhosis. Conclusion: IFN-γ1b therapy was not able to reverse fibrosis in patients with advanced liver disease for 1 year. Subgroups of patients with elevated ITAC levels and perhaps less advanced disease may be considered for future studies with IFN-γ1b.

Original languageEnglish
Pages (from-to)569-578
Number of pages10
JournalHepatology
Volume45
Issue number3
DOIs
StatePublished - Mar 1 2007

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Chronic Hepatitis C
Interferons
Fibrosis
Placebos
Chemotactic Factors
Liver Diseases
T-Lymphocytes
Biopsy
Liver
Subcutaneous Injections
Chemokines
Antiviral Agents
Biomarkers
Cytokines
Therapeutics

ASJC Scopus subject areas

  • Hepatology

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Final results of a double-blind, placebo-controlled trial of the antifibrotic efficacy of interferon-γ1b in chronic hepatitis C patients with advanced fibrosis or cirrhosis. / Pockros, Paul J.; Jeffers, Lennox J; Afdhal, Nezam; Goodman, Zachary D.; Nelson, David; Gish, Robert G.; Reddy, K. Rajender; Reindollar, Robert; Rodriguez-Torres, Maribel; Sullivan, Sarah; Blatt, Lawrence M.; Faris-Young, Sima.

In: Hepatology, Vol. 45, No. 3, 01.03.2007, p. 569-578.

Research output: Contribution to journalArticle

Pockros, PJ, Jeffers, LJ, Afdhal, N, Goodman, ZD, Nelson, D, Gish, RG, Reddy, KR, Reindollar, R, Rodriguez-Torres, M, Sullivan, S, Blatt, LM & Faris-Young, S 2007, 'Final results of a double-blind, placebo-controlled trial of the antifibrotic efficacy of interferon-γ1b in chronic hepatitis C patients with advanced fibrosis or cirrhosis', Hepatology, vol. 45, no. 3, pp. 569-578. https://doi.org/10.1002/hep.21561
Pockros, Paul J. ; Jeffers, Lennox J ; Afdhal, Nezam ; Goodman, Zachary D. ; Nelson, David ; Gish, Robert G. ; Reddy, K. Rajender ; Reindollar, Robert ; Rodriguez-Torres, Maribel ; Sullivan, Sarah ; Blatt, Lawrence M. ; Faris-Young, Sima. / Final results of a double-blind, placebo-controlled trial of the antifibrotic efficacy of interferon-γ1b in chronic hepatitis C patients with advanced fibrosis or cirrhosis. In: Hepatology. 2007 ; Vol. 45, No. 3. pp. 569-578.
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abstract = "Interferon-γ1b (IFN-γ1b) is a pleiotropic cytokine that displays antifibrotic, antiviral, and antiproliferative activity. A total of 502 patients with compensated liver disease and an Ishak fibrosis score of 4-6 were randomized in a double-blind, placebo-controlled study, and 488 of these patients received subcutaneous injections of IFN-γ1b 100 μg (group 1, n = 169), IFN-γ1b 200 μg (group 2, n = 157), or placebo (group 3, n = 162) 3 times a week for 48 weeks. Most patients (83.6{\%}) had cirrhosis at baseline (Ishak score = 5 or 6). Posttreatment liver biopsies were assessed in a blinded fashion for a reduction of 1 or more Ishak points (primary endpoint). Four hundred twenty patients with pretreatment and posttreatment liver biopsies were evaluable and showed no improvement in Ishak score between the 3 treatment groups (12.1{\%}, 12.4{\%}, and 16{\%} of patients in groups 1, 2, and 3, respectively; P > 0.05). Analysis of IFN-γ-inducible biomarkers revealed that interferon-inducible T cell-alpha chemoattractant (ITAC), an IFN-γ-inducible CXCR3 chemokine was an independent predictor of stable or improving Ishak score. IFN-γ1b was well tolerated. There were similar numbers of deaths in all 3 arms (5, 5, and 4, respectively), and most were related to complications of cirrhosis. Conclusion: IFN-γ1b therapy was not able to reverse fibrosis in patients with advanced liver disease for 1 year. Subgroups of patients with elevated ITAC levels and perhaps less advanced disease may be considered for future studies with IFN-γ1b.",
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AU - Pockros, Paul J.

AU - Jeffers, Lennox J

AU - Afdhal, Nezam

AU - Goodman, Zachary D.

AU - Nelson, David

AU - Gish, Robert G.

AU - Reddy, K. Rajender

AU - Reindollar, Robert

AU - Rodriguez-Torres, Maribel

AU - Sullivan, Sarah

AU - Blatt, Lawrence M.

AU - Faris-Young, Sima

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N2 - Interferon-γ1b (IFN-γ1b) is a pleiotropic cytokine that displays antifibrotic, antiviral, and antiproliferative activity. A total of 502 patients with compensated liver disease and an Ishak fibrosis score of 4-6 were randomized in a double-blind, placebo-controlled study, and 488 of these patients received subcutaneous injections of IFN-γ1b 100 μg (group 1, n = 169), IFN-γ1b 200 μg (group 2, n = 157), or placebo (group 3, n = 162) 3 times a week for 48 weeks. Most patients (83.6%) had cirrhosis at baseline (Ishak score = 5 or 6). Posttreatment liver biopsies were assessed in a blinded fashion for a reduction of 1 or more Ishak points (primary endpoint). Four hundred twenty patients with pretreatment and posttreatment liver biopsies were evaluable and showed no improvement in Ishak score between the 3 treatment groups (12.1%, 12.4%, and 16% of patients in groups 1, 2, and 3, respectively; P > 0.05). Analysis of IFN-γ-inducible biomarkers revealed that interferon-inducible T cell-alpha chemoattractant (ITAC), an IFN-γ-inducible CXCR3 chemokine was an independent predictor of stable or improving Ishak score. IFN-γ1b was well tolerated. There were similar numbers of deaths in all 3 arms (5, 5, and 4, respectively), and most were related to complications of cirrhosis. Conclusion: IFN-γ1b therapy was not able to reverse fibrosis in patients with advanced liver disease for 1 year. Subgroups of patients with elevated ITAC levels and perhaps less advanced disease may be considered for future studies with IFN-γ1b.

AB - Interferon-γ1b (IFN-γ1b) is a pleiotropic cytokine that displays antifibrotic, antiviral, and antiproliferative activity. A total of 502 patients with compensated liver disease and an Ishak fibrosis score of 4-6 were randomized in a double-blind, placebo-controlled study, and 488 of these patients received subcutaneous injections of IFN-γ1b 100 μg (group 1, n = 169), IFN-γ1b 200 μg (group 2, n = 157), or placebo (group 3, n = 162) 3 times a week for 48 weeks. Most patients (83.6%) had cirrhosis at baseline (Ishak score = 5 or 6). Posttreatment liver biopsies were assessed in a blinded fashion for a reduction of 1 or more Ishak points (primary endpoint). Four hundred twenty patients with pretreatment and posttreatment liver biopsies were evaluable and showed no improvement in Ishak score between the 3 treatment groups (12.1%, 12.4%, and 16% of patients in groups 1, 2, and 3, respectively; P > 0.05). Analysis of IFN-γ-inducible biomarkers revealed that interferon-inducible T cell-alpha chemoattractant (ITAC), an IFN-γ-inducible CXCR3 chemokine was an independent predictor of stable or improving Ishak score. IFN-γ1b was well tolerated. There were similar numbers of deaths in all 3 arms (5, 5, and 4, respectively), and most were related to complications of cirrhosis. Conclusion: IFN-γ1b therapy was not able to reverse fibrosis in patients with advanced liver disease for 1 year. Subgroups of patients with elevated ITAC levels and perhaps less advanced disease may be considered for future studies with IFN-γ1b.

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