title: S-adenosyl-methionine and betaine improve early virological response in chronic hepatitis C patients with previous nonresponse.
abstract: OBJECTIVE
  Treatment of chronic hepatitis C (CHC) with pegylated interferon α (pegIFNα) and ribavirin results in a sustained response in approximately half of patients. Viral interference with IFNα signal transduction through the Jak-STAT pathway might be an important factor underlying treatment failure. S-adenosyl-L-methionine (SAMe) and betaine potentiate IFNα signaling in cultured cells that express hepatitis C virus (HCV) proteins, and enhance the inhibitory effect of IFNα on HCV replicons. We have performed a clinical study with the aim to evaluate efficacy and safety of the addition of SAMe and betaine to treatment of CHC with pegIFNα/ribavirin.
  
  
  METHODS
  In this open-label pilot study, 29 patients with CHC who failed previous therapy with (peg)IFNα/ribavirin were treated with SAMe, betaine, pegIFNα2b and ribavirin. Treatment duration was 6 or 12 months, depending on genotype, and the protocol comprised a stopping rule at week 12 if early virological response (EVR) was not achieved. Virological and biochemical response and safety were assessed throughout the treatment.
  
  
  RESULTS
  29 patients were enrolled and treated according to the study protocol. 79% of the patients were infected with genotype 1, 72% had advanced fibrosis, 76% had previously received pegIFNα/ribavirin, and only 14% achieved EVR to the previous treatment. When treated with the study medications, 17 patients (59%) showed an EVR, only 3 (10%) however achieved a sustained virological response (SVR). SAMe and betaine were found to be safe when used with pegIFNα/ribavirin.
  
  
  CONCLUSIONS
  The addition of SAMe and betaine to pegIFNα/ribavirin improves early virological response in CHC.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00310336.
authors.affiliation: Hepatology Laboratory, Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Filipowicz
authors.forename: Christine
authors.initials: C
authors.lastname: Bernsmeier
authors.forename: Luigi
authors.initials: L
authors.lastname: Terracciano
authors.forename: Francois H T
authors.initials: FH
authors.lastname: Duong
authors.forename: Markus H
authors.initials: MH
authors.lastname: Heim
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use; D018771:Arthralgia / Q000139:chemically induced; D001622:Betaine / Q000009:adverse effects / Q000627:therapeutic use*; D003967:Diarrhea / Q000139:chemically induced; D004359:Drug Therapy, Combination; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005765:Gastrointestinal Agents / Q000009:adverse effects / Q000627:therapeutic use; D006261:Headache / Q000139:chemically induced; D016174:Hepacivirus / Q000187:drug effects*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000627:therapeutic use; D011446:Prospective Studies; D011994:Recombinant Proteins; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use; D012436:S-Adenosylmethionine / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D005765:Gastrointestinal Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D001622:Betaine; D011092:Polyethylene Glycols; D012254:Ribavirin; D012436:S-Adenosylmethionine; C100416:peginterferon alfa-2a