title: Omega-3 fatty acids and/or fluvastatin in hepatitis C prior non-responders to combination antiviral therapy - a pilot randomised clinical trial.
abstract: OBJECTIVE
  Hepatitis C virus (HCV) utilises cholesterol and lipoprotein metabolism for replication and infectivity. Statins and omega-3 (n-3) polyunsaturated fatty acids (PUFA) have been shown to have antiviral properties in vitro. This open label pilot study evaluated the efficacy of fluvastatin (Lescol(®) 40-80 mg) and n-3 PUFA (Omacor(®) 1 g and 2-4 g) on HCV-RNA and lipoviral particles (LVP) in difficult to treat prior non-responders.
  
  
  METHODS
  Patients (n = 60) were randomly allocated in a factorial design to: no active drug; low-dose n-3 PUFA; high-dose n-3 PUFA; fluvastatin; low-dose n-3 PUFA + fluvastatin; or high-dose n-3 PUFA + fluvastatin. 50/60 completed study drugs for 12 weeks and followed up to week 24. Comparison was made between fluvastatin (n = 24) vs no fluvastatin (n = 26) and n-3 PUFA high-dose (n = 17) vs low-dose (n = 17) vs none (n = 16). The primary outcomes were change in total HCV-RNA, LVP and ALT at week 12 compared with baseline. Secondary outcome was change in interferon-gamma-inducible protein-10 (IP10) as a measure of interferon activation.
  
  
  RESULTS
  35% had compensated cirrhosis and 45% were prior null responders. There was no significant change in total HCV RNA, LVP, non-LVP or LVP ratio in patients receiving fluvastatin or n-3 PUFAs. ALT was not significantly different in those treated with fluvastatin or n-3 PUFAs. 12 weeks of low-dose n-3 PUFA decreased median IP10 concentration by -39 pg/ml (-111, 7.0 pg/ml Q1-Q3).
  
  
  CONCLUSIONS
  Fluvastatin and n-3 PUFAs have no effect on plasma HCV-RNA or LVP. The effect of low-dose n-3 PUFA on IP10 warrants further prospective evaluation as a supplemental therapy to enhance interferon sensitivity.
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: David A
authors.initials: DA
authors.lastname: Sheridan
authors.forename: Simon H
authors.initials: SH
authors.lastname: Bridge
authors.forename: Mary M E
authors.initials: MM
authors.lastname: Crossey
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Felmlee
authors.forename: Fiona I
authors.initials: FI
authors.lastname: Fenwick
authors.forename: Howard C
authors.initials: HC
authors.lastname: Thomas
authors.forename: R Dermot G
authors.initials: RD
authors.lastname: Neely
authors.forename: Simon D
authors.initials: SD
authors.lastname: Taylor-Robinson
authors.forename: Margaret F
authors.initials: MF
authors.lastname: Bassendine
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D054357:Chemokine CXCL10 / Q000097:blood; D004359:Drug Therapy, Combination; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology / Q000627:therapeutic use*; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D000077340:Fluvastatin; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D019562:Viral Load / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D005229:Fatty Acids, Monounsaturated; D015525:Fatty Acids, Omega-3; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D000077340:Fluvastatin; D000410:Alanine Transaminase
keywords: cholesterol; fluvastatin; hepatitis C virus; interferon-α; lipoviral particle; polyunsaturated fatty acid (omega-3 fatty acids)