title: Open-label, ascending dose, prospective cohort study evaluating the antiviral efficacy of Rosuvastatin therapy in serum and lipid fractions in patients with chronic hepatitis C.
abstract: HMG CoA reductase inhibition suppresses in vitro HCV replication through depletion of cellular sterol proteins such as geranylgeraniol. Our aims were to prospectively evaluate the changes in serum and lipid fraction HCV RNA with Rosuvastatin in non-responder (NR) patients with CHC. A total of 11 patients with CHC genotype-1 received Rosuvastatin at 20 mg qd (weeks 0-4), 40 mg qd (weeks 5-12), with 4 week follow up. Lipid fractions were separated by a sucrose density gradient ultracentrifugation, HCV RNA determined at wks 0, 2, 4, 8, 12, 16 in serum, and in selected very low- (VLDF) to high-density (HDF) lipid fractions. A reduction in LDL and total cholesterol (TC) was not accompanied by significant decline in HCV RNA. At baseline, there was an inverse correlation between HDL and HCV RNA (ρ = -0.45, P = 0.036). At 20 mg, there was correlation between change (Δ) in TG and Δ HCV RNA (ρ = 0.75, P = 0.007), Δ ALT and Δ TC (ρ = -0.64, P = 0.03) and Δ LDL (ρ = -0.67, P = 0.02). At 40 mg, Δ TG maintained a positive correlation with Δ HCV RNA (ρ = 0.65, P = 0.03). There was a group difference for HCV RNA in relation to lipid fractions (P = 0.04) but not study time intervals (P = 0.17); mean log HCV RNA was greater in VLDF compared to HDF (5.81 ± 0.59 vs 5.06 ± 0.67, P = 0.0002) with no other differences to study time intervals (P = 0.099). Short-term Rosuvastatin monotherapy is not associated with significant changes in serum or lipid fraction HCV RNA in NR patients. HCV co-localizes with the lowest density lipid fractions in serum.
authors.affiliation: Duke Clinical Research Institute and Division of Gastroenterology, Duke University Medical Center, Durham, NC, USA. cvellozzi@cdc.gov
authors.forename: K
authors.initials: K
authors.lastname: Patel
authors.forename: R
authors.initials: R
authors.lastname: Jhaveri
authors.forename: J
authors.initials: J
authors.lastname: George
authors.forename: G
authors.initials: G
authors.lastname: Qiang
authors.forename: C
authors.initials: C
authors.lastname: Kenedi
authors.forename: K
authors.initials: K
authors.lastname: Brown
authors.forename: C
authors.initials: C
authors.lastname: Cates
authors.forename: A
authors.initials: A
authors.lastname: Zekry
authors.forename: H L
authors.initials: HL
authors.lastname: Tillmann
authors.forename: L
authors.initials: L
authors.lastname: Elliott
authors.forename: R
authors.initials: R
authors.lastname: Kilaru
authors.forename: J
authors.initials: J
authors.lastname: Albrecht
authors.forename: A
authors.initials: A
authors.lastname: Conrad
authors.forename: J G
authors.initials: JG
authors.lastname: McHutchison
mesh_terms: D015331:Cohort Studies; D005260:Female; D005464:Fluorobenzenes / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D005500:Follow-Up Studies; D016174:Hepacivirus / Q000187:drug effects* / Q000472:pathogenicity; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000187:drug effects*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011743:Pyrimidines / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood; D000068718:Rosuvastatin Calcium; D013223:Statistics as Topic; D013449:Sulfonamides / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D011743:Pyrimidines; D012367:RNA, Viral; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium; D006903:Hydroxymethylglutaryl CoA Reductases