Omega-3 fatty acids and/or fluvastatin in hepatitis C prior non-responders to combination antiviral therapy - a pilot randomised clinical trial.
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.
['Sheridan|David A|DA|', 'Bridge|Simon H|SH|', 'Crossey|Mary M E|MM|', 'Felmlee|Daniel J|DJ|', 'Fenwick|Fiona I|FI|', 'Thomas|Howard C|HC|', 'Neely|R Dermot G|RD|', 'Taylor-Robinson|Simon D|SD|', 'Bassendine|Margaret F|MF|']
D000328:Adult D000410:Alanine Transaminase D000998:Antiviral Agents D054357:Chemokine CXCL10 D004359:Drug Therapy, Combination D005229:Fatty Acids, Monounsaturated D015525:Fatty Acids, Omega-3 D005260:Female D000077340:Fluvastatin D019698:Hepatitis C, Chronic D006801:Humans D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors D007211:Indoles D008297:Male D008875:Middle Aged D010865:Pilot Projects D019562:Viral Load
fluvastatin hepatitis C virus cholesterol lipoviral particle interferon-α polyunsaturated fatty acid (omega-3 fatty acids)