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

Stephen A. Harrison, Lorenzo Rossaro, Ke Qin Hu, Keyur Patel, Hans Tillmann, Sandeep Dhaliwal, Dawn M. Torres, Kenneth Koury, Venkata S. Goteti, Stephanie Noviello, Clifford A. Brass, Janice K. Albrecht, John G. McHutchison, Mark S. Sulkowski

Research output: Contribution to journalArticle

108 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)864-874
Number of pages11
JournalHepatology
Volume52
Issue number3
DOIs
StatePublished - Sep 2010

Fingerprint

Hydroxymethylglutaryl-CoA Reductase Inhibitors
Ribavirin
LDL Lipoproteins
Cholesterol
HDL Lipoproteins
Serum
Therapeutics
Odds Ratio
Confidence Intervals
Hepacivirus
Biological Factors
Chronic Hepatitis C
Virus Replication
Interferons
Randomized Controlled Trials
Logistic Models
Genotype
Regression Analysis
Prospective Studies
RNA

ASJC Scopus subject areas

  • Hepatology
  • Medicine(all)

Cite this

Harrison, S. A., Rossaro, L., Hu, K. Q., Patel, K., Tillmann, H., Dhaliwal, S., ... Sulkowski, M. S. (2010). Serum cholesterol and statin use predict virological response to peginterferon and ribavirin therapy. Hepatology, 52(3), 864-874. https://doi.org/10.1002/hep.23787

Serum cholesterol and statin use predict virological response to peginterferon and ribavirin therapy. / Harrison, Stephen A.; Rossaro, Lorenzo; Hu, Ke Qin; Patel, Keyur; Tillmann, Hans; Dhaliwal, Sandeep; Torres, Dawn M.; Koury, Kenneth; Goteti, Venkata S.; Noviello, Stephanie; Brass, Clifford A.; Albrecht, Janice K.; McHutchison, John G.; Sulkowski, Mark S.

In: Hepatology, Vol. 52, No. 3, 09.2010, p. 864-874.

Research output: Contribution to journalArticle

Harrison, SA, Rossaro, L, Hu, KQ, Patel, K, Tillmann, H, Dhaliwal, S, Torres, DM, Koury, K, Goteti, VS, Noviello, S, Brass, CA, Albrecht, JK, McHutchison, JG & Sulkowski, MS 2010, 'Serum cholesterol and statin use predict virological response to peginterferon and ribavirin therapy', Hepatology, vol. 52, no. 3, pp. 864-874. https://doi.org/10.1002/hep.23787
Harrison, Stephen A. ; Rossaro, Lorenzo ; Hu, Ke Qin ; Patel, Keyur ; Tillmann, Hans ; Dhaliwal, Sandeep ; Torres, Dawn M. ; Koury, Kenneth ; Goteti, Venkata S. ; Noviello, Stephanie ; Brass, Clifford A. ; Albrecht, Janice K. ; McHutchison, John G. ; Sulkowski, Mark S. / Serum cholesterol and statin use predict virological response to peginterferon and ribavirin therapy. In: Hepatology. 2010 ; Vol. 52, No. 3. pp. 864-874.
@article{fe4925f530ae45d0836d58a80f09c652,
title = "Serum cholesterol and statin use predict virological response to peginterferon and ribavirin therapy",
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.",
author = "Harrison, {Stephen A.} and Lorenzo Rossaro and Hu, {Ke Qin} and Keyur Patel and Hans Tillmann and Sandeep Dhaliwal and Torres, {Dawn M.} and Kenneth Koury and Goteti, {Venkata S.} and Stephanie Noviello and Brass, {Clifford A.} and Albrecht, {Janice K.} and McHutchison, {John G.} and Sulkowski, {Mark S.}",
year = "2010",
month = "9",
doi = "10.1002/hep.23787",
language = "English (US)",
volume = "52",
pages = "864--874",
journal = "Hepatology",
issn = "0270-9139",
publisher = "John Wiley and Sons Ltd",
number = "3",

}

TY - JOUR

T1 - Serum cholesterol and statin use predict virological response to peginterferon and ribavirin therapy

AU - Harrison, Stephen A.

AU - Rossaro, Lorenzo

AU - Hu, Ke Qin

AU - Patel, Keyur

AU - Tillmann, Hans

AU - Dhaliwal, Sandeep

AU - Torres, Dawn M.

AU - Koury, Kenneth

AU - Goteti, Venkata S.

AU - Noviello, Stephanie

AU - Brass, Clifford A.

AU - Albrecht, Janice K.

AU - McHutchison, John G.

AU - Sulkowski, Mark S.

PY - 2010/9

Y1 - 2010/9

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=77956646681&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77956646681&partnerID=8YFLogxK

U2 - 10.1002/hep.23787

DO - 10.1002/hep.23787

M3 - Article

VL - 52

SP - 864

EP - 874

JO - Hepatology

JF - Hepatology

SN - 0270-9139

IS - 3

ER -