Serum cholesterol and statin use predict virological response to peginterferon and ribavirin therapy

Authors


  • Potential conflict of interest: Dr. McHutchison received grants and is a consultant for Abbott Laboratories, Biolex Therapeutics, GlaxoSmithKline, GlobeImmune, Hoffmann-La Roche, Human Genome Sciences, lntarcia Therapeutics, Merck, Novartis, Pfizer, Pharmassest, Schering-Plough, Gilead, and Vertex. He received grants from Idera Pharmaceutical, Medtronic, Osiris Therapeutics, Three Rivers Pharmaceuticals, ViroChem Pharma. He also a consultant for Anadys, Alnylam, Epiphany Biosciences, ItheRx, National Genetics, One Pharmaceuticals, Santaris, Takeda, and United Therapeutics. Dr. Rossaro is a consultant for, is on the speakers' bureau of, received grants from, and holds intellectual property rights for Genentech, Novartis, and Merck. He is a consultant for, is on the speakers' bureau of, and holds intellectual property rights for Three Rivers. Dr. Harrison is on the speakers' bureau of Bristol-Myers Squibb. Dr. Hu is on the speakers' bureau of, and received grants from, Merck and Genentech. He also received grants from Vertex. Dr. Koury owns stock in Merck. Dr. Noviello owns stock in and is a consultant for Merck. Dr. Sulkowski advises and received grants from Merck, Roche, and Genentech.

  • The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or reflecting the view of the US Department of the Army or the US Department of Defense.

Abstract

Elevated low-density lipoprotein (LDL) levels and statin use have been associated with higher sustained virological response (SVR) rates in patients receiving chronic hepatitis C therapy. However, these relationships have not been well characterized in randomized controlled trials. Furthermore, little is known about the relationship between high-density lipoprotein (HDL) and virological response. To determine whether baseline LDL or HDL levels and statin use affect SVR rates, we retrospectively evaluated the IDEAL (Individualized Dosing Efficacy Versus Flat Dosing to Assess Optimal Pegylated Interferon Therapy) trial, in which 3070 treatment-naive, hepatitis C virus (HCV) genotype 1–infected patients were treated for up to 48 weeks in one of the following arms: (1) peginterferon (PEG-IFN) alfa-2b at 1.5 μg/kg/week with ribavirin (RBV) at 800 to 1400 mg/day, (2) PEG-IFN alfa-2b at 1.0 μg/kg/week with RBV at 800 to 1400 mg/day, or (3) PEG-IFN alfa-2a at 180 μg/week with RBV at 1000 to 1200 mg/day. Virological responses were assessed by pretreatment statin use and baseline elevated LDL levels (≥130 mg/dL) or low HDL levels (<40 mg/dL for men and <50 mg/dL for women). In 1464 patients with baseline elevated LDL levels or low HDL levels, the SVR rate was significantly higher than that in patients with normal levels (44.9% versus 34.0%, P < 0.001). In 66 patients receiving a statin pretreatment, the SVR rate was higher than the rate of those not receiving it (53.0% versus 39.3%, P = 0.02). In a multivariate logistic regression analysis using the stepwise selection method with baseline characteristics, a high LDL level [odds ratio (OR) = 1.6, 95% confidence interval (CI) = 1.4-1.8, P < 0.001], a low HDL level (OR = 0.5, 95% CI = 0.3-0.8, P = 0.004), and statin use (OR = 2.0, 95% CI = 1.1-3.7, P = 0.02) were independently associated with SVR. Conclusion: Baseline elevated LDL levels or low HDL levels and preemptive statin usage were associated with higher SVR rates. Prospective studies may be considered to explore the biological impact of these factors on HCV RNA replication and treatment response. (HEPATOLOGY 2010;)

Ancillary