Journal article
S-Adenosyl Methionine Improves Early Viral Responses and Interferon-Stimulated Gene Induction in Hepatitis C Nonresponders
Gastroenterology (New York, N.Y. 1943), Vol.140(3), pp.830-U219
03/01/2011
DOI: 10.1053/j.gastro.2010.09.010
PMCID: PMC3021477
PMID: 20854821
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 log(10) 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.
Details
- Title: Subtitle
- S-Adenosyl Methionine Improves Early Viral Responses and Interferon-Stimulated Gene Induction in Hepatitis C Nonresponders
- Creators
- Jordan J. Feld - National Institute of Diabetes and Digestive and Kidney DiseasesApurva A. Modi - National Institute of Diabetes and Digestive and Kidney DiseasesRamy El-Diwany - NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USAYaron Rotman - National Institutes of HealthEmmanuel Thomas - National Institute of Diabetes and Digestive and Kidney DiseasesGolo Ahlenstiel - National Institute of Diabetes and Digestive and Kidney DiseasesRachel Titerence - National Institute of Diabetes and Digestive and Kidney DiseasesChristopher Koh - National Institute of Diabetes and Digestive and Kidney DiseasesVera Cherepanov - Toronto Western HospitalTheo Heller - National Institute of Diabetes and Digestive and Kidney DiseasesMarc G. Ghany - National Institute of Diabetes and Digestive and Kidney DiseasesYoon Park - National Institute of Diabetes and Digestive and Kidney DiseasesJay H. Hoofnagle - National Institutes of HealthT. Jake Liang - National Institute of Diabetes and Digestive and Kidney Diseases
- Resource Type
- Journal article
- Publication Details
- Gastroenterology (New York, N.Y. 1943), Vol.140(3), pp.830-U219
- DOI
- 10.1053/j.gastro.2010.09.010
- PMID
- 20854821
- PMCID
- PMC3021477
- NLM abbreviation
- Gastroenterology
- ISSN
- 0016-5085
- eISSN
- 1528-0012
- Publisher
- Elsevier
- Number of pages
- 13
- Grant note
- National Institute of Diabetes and Digestive and Kidney Diseases; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) ZIADK054514 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK)
- Language
- English
- Date published
- 03/01/2011
- Academic Unit
- Surgery
- Record Identifier
- 9984966744302771
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