Citation

Sheridan DA, Bridge SH, Crossey MME, Felmlee DJ, Fenwick FI, Thomas HC, Neely RDG, Taylor-Robinson SD, Bassendine MF. Liver Int. 2014; 34(5): 737-747.

Copyright

(Copyright © 2014, John Wiley and Sons)

DOI

10.1111/liv.12316

PMID

unavailable

Abstract

Background & Aims: 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. © 2013 John Wiley & Sons A/S.

Language: en

Keywords

Humans; Adult; Female; Male; Middle Aged; adult; human; female; male; Pilot Projects; pilot study; depression; randomized controlled trial; suicide attempt; disease severity; Drug Therapy, Combination; article; major clinical study; controlled study; cholesterol blood level; triacylglycerol; unclassified drug; Cholesterol; middle aged; gastrointestinal symptom; cholesterol; hydroxymethylglutaryl coenzyme A reductase inhibitor; drug safety; follow up; patient compliance; drug efficacy; drug withdrawal; disease exacerbation; hepatitis C; immunotherapy; drug megadose; blood level; drug effect; Hepatitis C virus; ribavirin; alanine aminotransferase; fluindostatin; blood; low drug dose; liver cirrhosis; high density lipoprotein cholesterol; omega 3 fatty acid; antivirus agent; drug combination; Interferon-α; monotherapy; antiviral activity; virus RNA; virus resistance; genotype; virus load; adjuvant therapy; drug dose increase; outcome assessment; Viral Load; Hepatitis C, Chronic; drug treatment failure; treatment duration; open study; Antiviral Agents; alanine aminotransferase blood level; Alanine Transaminase; Fatty Acids, Omega-3; Hydroxymethylglutaryl-CoA Reductase Inhibitors; recommended drug dose; antiviral therapy; Indoles; indole derivative; peginterferon alpha; factorial design; virus particle; monounsaturated fatty acid; drug effects; apolipoprotein B; Chemokine CXCL10; compensated cirrhosis; CXCL10 protein, human; Fatty Acids, Monounsaturated; Fluvastatin; gamma interferon inducible protein 10; infection resistance; lipoviral particle; Lipoviral particle; non high density lipoprotein cholesterol; non lipoviral particle; omega 3 acid ethyl ester; Polyunsaturated fatty acid (omega-3 fatty acids)