Clinical—Liver, Pancreas, and Biliary TractS-Adenosyl Methionine Improves Early Viral Responses and Interferon-Stimulated Gene Induction in Hepatitis C Nonresponders
Section snippets
Patients
Patients with a documented history of nonresponse to combination treatment with standard interferon or peginterferon and ribavirin were eligible for enrollment. Inclusion criteria included age 18 years or older, documented genotype 1 chronic HCV infection, and a history of at least 3 months of combination antiviral therapy (with interferon or peginterferon plus ribavirin) and failure to achieve an early virological response (EVR), defined as a 2-log10 IU/mL decline in HCV RNA levels by week 12
Results
Twenty-four patients were enrolled (Table 1) between October 2007 and April 2009. Eighteen (75%) had a liver biopsy specimen available, which showed advanced fibrosis (Ishak score ≥3) in 8 (44%) and cirrhosis in 5 (21%). Baseline viral levels ranged from 5.0 to 7.9 log10 IU/mL. Three patients (13%) completed course A only; one patient developed a severe rash attributed to ribavirin, one patient experienced a relapse of benzodiazepine abuse during the initial course, and one patient withdrew
Discussion
Peginterferon and ribavirin are likely to remain the backbone of antiviral treatment for chronic HCV for many years, even once new direct antivirals become available.8, 9 As a result, improving the response to interferon-based therapy remains a major priority. Results from this pilot study show that addition of SAMe to standard therapy improves early viral kinetics, likely by improving interferon signaling.
Previous in vitro data suggested that SAMe may improve interferon signaling and antiviral
Acknowledgments
J.J.F. and A.A.M. contributed equally to this study.
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Cited by (47)
Demethylase JMJD6 as a New Regulator of Interferon Signaling: Effects of HCV and Ethanol Metabolism
2018, Cellular and Molecular Gastroenterology and HepatologyCitation Excerpt :In addition, an ethanol-induced increase in JMJD6 expression in the liver also was confirmed by in vivo feeding of C57Bl/6 and humanized mice. In vitro and in vivo studies have shown that promethylating agents SAM and betaine restore HCV-impaired STAT1 methylation and suppress HCV RNA.4,26,31 However, it is not clear whether these agents also reverse ethanol-metabolism–enhanced JMJD6.
Autoimmune Hepatitis
2017, Liver Pathophysiology: Therapies and AntioxidantsImmunopathogenesis of Autoimmune Liver Damage
2017, Handbook of Systemic Autoimmune DiseasesCitation Excerpt :Its frequent occurrence in severe liver inflammation and its noxious attributes have justified concern that oxidative stress may worsen or sustain inflammatory activity. This concern has driven investigational efforts that have included preliminary clinical trials of anti-oxidants in patients with alcoholic liver disease [96–100], non-alcoholic steatohepatitis [101], and chronic hepatitis C [102,103]. Importantly, meta-analyses have not demonstrated that supplemental antioxidant therapies have been beneficial in preventing cancer, cardiovascular diseases, and death, and such therapies may have had harmful effects, including an increase in all-cause mortality [104–106].
Glucocorticoid-induced S-adenosylmethionine enhances the interferon signaling pathway by restoring STAT1 protein methylation in hepatitis B virus-infected cells
2014, Journal of Biological ChemistryCitation Excerpt :It is thus necessary to further investigate the effect of the GC-induced increase of AdoMet production on the STAT pathway to obtain a more accurate picture. Recent studies have shown that AdoMet can increase the induction of ISGs and the antiviral effects of IFN-α by increasing STAT1 methylation, possibly affecting STAT1-DNA binding (31). Inhibition of STAT1 methylation is involved in the resistance of hepatitis B virus to IFN-α (18).
Conflicts of interest The authors disclose the following: Dr Feld is on the advisory board of Roche Pharmaceuticals and Schering-Plough (Merck) Pharmaceuticals. The remaining authors disclose no conflicts.
Funding Supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases. Pharmavite LLC provided SAMe for the study but had no involvement in study design, data analysis, or manuscript preparation.