S-adenosyl methionine improves early viral responses and interferon-stimulated gene induction in hepatitis C nonresponders

Jordan J. Feld, Apurva A. Modi, Ramy Eldiwany, Yaron Rotman, Emmanuel Thomas, Golo Ahlenstiel, Rachel Titerence, Christopher Koh, Vera Cherepanov, Theo Heller, Marc G. Ghany, Yoon Park, Jay H. Hoofnagle, T. Jake Liang

Research output: Contribution to journalArticle

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Abstract

Background & Aims Less than half of patients infected with hepatitis C virus (HCV) achieve sustained viral clearance after pegylated interferon (peginterferon) and ribavirin therapy. S-adenosyl methionine (SAMe) improves interferon signaling in cell culture. We assessed the effect of SAMe on the kinetics of the early antiviral response and interferon signaling in nonresponders to previous antiviral therapy and investigated the mechanisms involved. Methods Nonresponders with HCV genotype 1 were given peginterferon alfa-2a and ribavirin for 2 weeks (course A, baseline/control). After 1 month, patients received SAMe (1600 mg daily) for 2 weeks and then peginterferon and ribavirin for 48 weeks (course B; completed by 21 of 24 patients). Viral kinetics and interferon-stimulated gene (ISG) expression in peripheral blood mononuclear cells (PBMCs) were compared between courses. Results The decrease in HCV RNA from 0 to 48 hours (phase 1) was similar with and without SAMe. However, the second phase slope of viral decline was improved with SAMe (course A, 0.11 ± 0.04 log10 IU/mL/wk; course B, 0.27 ± 0.06; P = .009); 11 patients (53%) achieved an early virological response, and 10 (48%) had undetectable HCV RNA by week 24. Induction of ISGs in PBMCs was significantly greater during course B. In cultured cells, SAMe increased induction of ISGs and the antiviral effects of interferon by increasing STAT1 methylation, possibly affecting STAT1-DNA binding. Conclusions The addition of SAMe to peginterferon and ribavirin improves the early viral kinetics and increases ISG induction in nonresponders to previous therapy. SAMe might be a useful adjunct to peginterferon-based therapies in chronic HCV infection.

Original languageEnglish
Pages (from-to)830-839
Number of pages10
JournalGastroenterology
Volume140
Issue number3
DOIs
StatePublished - Mar 1 2011
Externally publishedYes

Fingerprint

Hepatitis C
Methionine
Interferons
Hepacivirus
Ribavirin
Genes
Antiviral Agents
Blood Cells
RNA
Chronic Hepatitis C
Virus Diseases
Therapeutics
Methylation
Cultured Cells
Cell Culture Techniques
Genotype
Gene Expression
DNA

Keywords

  • Interferon Signaling
  • Transcription Factor, Chronic Hepatitis

ASJC Scopus subject areas

  • Gastroenterology

Cite this

S-adenosyl methionine improves early viral responses and interferon-stimulated gene induction in hepatitis C nonresponders. / Feld, Jordan J.; Modi, Apurva A.; Eldiwany, Ramy; Rotman, Yaron; Thomas, Emmanuel; Ahlenstiel, Golo; Titerence, Rachel; Koh, Christopher; Cherepanov, Vera; Heller, Theo; Ghany, Marc G.; Park, Yoon; Hoofnagle, Jay H.; Liang, T. Jake.

In: Gastroenterology, Vol. 140, No. 3, 01.03.2011, p. 830-839.

Research output: Contribution to journalArticle

Feld, JJ, Modi, AA, Eldiwany, R, Rotman, Y, Thomas, E, Ahlenstiel, G, Titerence, R, Koh, C, Cherepanov, V, Heller, T, Ghany, MG, Park, Y, Hoofnagle, JH & Liang, TJ 2011, 'S-adenosyl methionine improves early viral responses and interferon-stimulated gene induction in hepatitis C nonresponders', Gastroenterology, vol. 140, no. 3, pp. 830-839. https://doi.org/10.1053/j.gastro.2010.09.010
Feld, Jordan J. ; Modi, Apurva A. ; Eldiwany, Ramy ; Rotman, Yaron ; Thomas, Emmanuel ; Ahlenstiel, Golo ; Titerence, Rachel ; Koh, Christopher ; Cherepanov, Vera ; Heller, Theo ; Ghany, Marc G. ; Park, Yoon ; Hoofnagle, Jay H. ; Liang, T. Jake. / S-adenosyl methionine improves early viral responses and interferon-stimulated gene induction in hepatitis C nonresponders. In: Gastroenterology. 2011 ; Vol. 140, No. 3. pp. 830-839.
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abstract = "Background & Aims Less than half of patients infected with hepatitis C virus (HCV) achieve sustained viral clearance after pegylated interferon (peginterferon) and ribavirin therapy. S-adenosyl methionine (SAMe) improves interferon signaling in cell culture. We assessed the effect of SAMe on the kinetics of the early antiviral response and interferon signaling in nonresponders to previous antiviral therapy and investigated the mechanisms involved. Methods Nonresponders with HCV genotype 1 were given peginterferon alfa-2a and ribavirin for 2 weeks (course A, baseline/control). After 1 month, patients received SAMe (1600 mg daily) for 2 weeks and then peginterferon and ribavirin for 48 weeks (course B; completed by 21 of 24 patients). Viral kinetics and interferon-stimulated gene (ISG) expression in peripheral blood mononuclear cells (PBMCs) were compared between courses. Results The decrease in HCV RNA from 0 to 48 hours (phase 1) was similar with and without SAMe. However, the second phase slope of viral decline was improved with SAMe (course A, 0.11 ± 0.04 log10 IU/mL/wk; course B, 0.27 ± 0.06; P = .009); 11 patients (53{\%}) achieved an early virological response, and 10 (48{\%}) had undetectable HCV RNA by week 24. Induction of ISGs in PBMCs was significantly greater during course B. In cultured cells, SAMe increased induction of ISGs and the antiviral effects of interferon by increasing STAT1 methylation, possibly affecting STAT1-DNA binding. Conclusions The addition of SAMe to peginterferon and ribavirin improves the early viral kinetics and increases ISG induction in nonresponders to previous therapy. SAMe might be a useful adjunct to peginterferon-based therapies in chronic HCV infection.",
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AU - Feld, Jordan J.

AU - Modi, Apurva A.

AU - Eldiwany, Ramy

AU - Rotman, Yaron

AU - Thomas, Emmanuel

AU - Ahlenstiel, Golo

AU - Titerence, Rachel

AU - Koh, Christopher

AU - Cherepanov, Vera

AU - Heller, Theo

AU - Ghany, Marc G.

AU - Park, Yoon

AU - Hoofnagle, Jay H.

AU - Liang, T. Jake

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N2 - Background & Aims Less than half of patients infected with hepatitis C virus (HCV) achieve sustained viral clearance after pegylated interferon (peginterferon) and ribavirin therapy. S-adenosyl methionine (SAMe) improves interferon signaling in cell culture. We assessed the effect of SAMe on the kinetics of the early antiviral response and interferon signaling in nonresponders to previous antiviral therapy and investigated the mechanisms involved. Methods Nonresponders with HCV genotype 1 were given peginterferon alfa-2a and ribavirin for 2 weeks (course A, baseline/control). After 1 month, patients received SAMe (1600 mg daily) for 2 weeks and then peginterferon and ribavirin for 48 weeks (course B; completed by 21 of 24 patients). Viral kinetics and interferon-stimulated gene (ISG) expression in peripheral blood mononuclear cells (PBMCs) were compared between courses. Results The decrease in HCV RNA from 0 to 48 hours (phase 1) was similar with and without SAMe. However, the second phase slope of viral decline was improved with SAMe (course A, 0.11 ± 0.04 log10 IU/mL/wk; course B, 0.27 ± 0.06; P = .009); 11 patients (53%) achieved an early virological response, and 10 (48%) had undetectable HCV RNA by week 24. Induction of ISGs in PBMCs was significantly greater during course B. In cultured cells, SAMe increased induction of ISGs and the antiviral effects of interferon by increasing STAT1 methylation, possibly affecting STAT1-DNA binding. Conclusions The addition of SAMe to peginterferon and ribavirin improves the early viral kinetics and increases ISG induction in nonresponders to previous therapy. SAMe might be a useful adjunct to peginterferon-based therapies in chronic HCV infection.

AB - Background & Aims Less than half of patients infected with hepatitis C virus (HCV) achieve sustained viral clearance after pegylated interferon (peginterferon) and ribavirin therapy. S-adenosyl methionine (SAMe) improves interferon signaling in cell culture. We assessed the effect of SAMe on the kinetics of the early antiviral response and interferon signaling in nonresponders to previous antiviral therapy and investigated the mechanisms involved. Methods Nonresponders with HCV genotype 1 were given peginterferon alfa-2a and ribavirin for 2 weeks (course A, baseline/control). After 1 month, patients received SAMe (1600 mg daily) for 2 weeks and then peginterferon and ribavirin for 48 weeks (course B; completed by 21 of 24 patients). Viral kinetics and interferon-stimulated gene (ISG) expression in peripheral blood mononuclear cells (PBMCs) were compared between courses. Results The decrease in HCV RNA from 0 to 48 hours (phase 1) was similar with and without SAMe. However, the second phase slope of viral decline was improved with SAMe (course A, 0.11 ± 0.04 log10 IU/mL/wk; course B, 0.27 ± 0.06; P = .009); 11 patients (53%) achieved an early virological response, and 10 (48%) had undetectable HCV RNA by week 24. Induction of ISGs in PBMCs was significantly greater during course B. In cultured cells, SAMe increased induction of ISGs and the antiviral effects of interferon by increasing STAT1 methylation, possibly affecting STAT1-DNA binding. Conclusions The addition of SAMe to peginterferon and ribavirin improves the early viral kinetics and increases ISG induction in nonresponders to previous therapy. SAMe might be a useful adjunct to peginterferon-based therapies in chronic HCV infection.

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