September 25, 2010

Gastroenterology. 2010 Sep 17. [Epub ahead of print]

Feld JJ, Modi AA, El-Diwany R, Rotman Y, Thomas E, Koh C, Cherepanov V, Heller T, Ghany MG, Park Y, Hoofnagle JH, Liang TJ.

Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK), National Institutes of Health (NIH), Bethesda, MD; Toronto Western Hospital Liver Center, University Health Network, University of Toronto, Toronto, Canada.

Abstract

BACKGROUND & AIMS: Fewer than half of patients infected with Hepatitis C virus (HCV) achieve sustained viral clearance after peginterferon and ribavirin therapy. S-adenosyl methionine (SAMe) increases interferon signaling in cell culture. We assessed the effect of SAMe on the kinetics of the early anti-viral response and interferon signaling in patients that did not respond to previous therapy (nonresponders) and investigated its mechanisms.

METHODS: Nonresponders with HCV genotype-1 were given 2 weeks of peginterferon alfa-2a and ribavirin (Course A, baseline/control). After a 1-month period, 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 before and after administration of SAMe. However, the slope increased for the second-phase decrease in HCV between courses A and B (Course A=0.11±0.04 log(10)IU/mL/week, Course B=0.27±0.06; P=0.009); 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 after Course B. In cultured cells, SAMe increased induction of ISGs, compared with only peginterferon and ribavirin, and the antiviral effects of interferon by increasing STAT1 methylation, which might promote binding of STAT1 to DNA.

CONCLUSIONS: The addition of SAMe to peginterferon and ribavirin improves the kinetics of the early anti-viral response and induces ISGs in patients with HCV genotype 1 that do not respond to interferon therapy. SAMe might be used with peginterferon-based therapies in patients with chronic HCV infections.

PMID: 20854821 [PubMed - as supplied by publisher]

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