Baseline cholesterol is associated with the response to antiviral therapy in chronic hepatitis C

Economou, Michael; Milionis, Haralampos; Filis, S.; Baltayiannis, Gerasimos; Christou, Leonidas; Elisaf, Moses; Tsianos, Epameinondas V.

doi:10.1111/j.1440-1746.2007.04911.x

Cited by 39 publications

(52 citation statements)

References 34 publications

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“…Despite an association of smoking with SVR and clear effects on serum lipids, we found no significant correlation of lipid parameters with SVR. This is in contrast to the data reported by Economou et al, who found higher serum baseline levels of total cholesterol and LDL cholesterol to be associated with better response towards PEG-IFN, suggesting that smoking might have a positive effect for the treatment response as smoking leads to higher baseline total and LDL cholesterol concentrations [5][6][7][8]28]. Since it is known that statin treatment might improve SVR rates, patients with this medication were excluded from the analysis [10][11][12].…”

Section: Matched Pair Analysis (Mpa)contrasting

confidence: 79%

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Effects of Smoking on Pegylated Interferon alpha 2a and First Generation Protease Inhibitor-based Antiviral Therapy in Naïve Patients Infected with Hepatitis C Virus Genotype 1

Zimmermann

Hueppe²,

Mauss

et al. 2016

JGLD

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Background & Aims: Smoking has multiple effects on factors influencing hepatitis C and antiviral therapy, including lipid metabolism, fibrosis, platelet count and adherence aspects. The aim of this analysis was to determine the impact of smoking on hepatitis C virus antiviral therapy. Methods: Data of two cohorts of an observational multicenter study including therapy-naïve patients infected with genotype 1 hepatitis C virus (HCV) treated with dual antiviral therapy (n=7,796) with pegylated interferon alpha 2a in combination with ribavirin, or triple antiviral therapy (n=1,122) containing telaprevir or boceprevir, were analysed. Results: In the univariate matched pair analysis of dual antiviral therapy patients (n=584), smoking was significantly associated with lower sustained viral response rates (p=0.026, OR 0.69 CI: 0.50 – 0.96). The effect of smoking on sustained viral response remained significant (p=0.028, OR 0.67 CI: 0.47 – 0.96) in the multivariate analysis when adjusting for all other baseline parameters with a significant association in the univariate analysis, i.e. diabetes, fibrosis, body mass index, transaminases and baseline viral load. Under protease inhibitors the influence of smoking on virological response did not arise. Conclusions: Smoking has a negative impact on antiviral therapy in naïve patients infected with HCV genotype 1 independently of age, gender, history of drug use or alcoholic liver disease. The effects of smoking might be overcome by the new antiviral agents.Abbreviations: APRI: AST to platelet ratio index; DAA: direct antiviral agent; DT: dual antiviral therapy; EoTR: end of treatment response; RVR: rapid virological response; EVR: early virological response; HCV: hepatitis C virus; IFN: interferon alpha; MPA: Matched Pair Analysis; NS: non-smokers; PEG-IFN: pegylated interferon alpha 2a; PI: protease inhibitor; RBV: ribavirin; SAE: serious adverse event; SOC: standard of care; S: smokers; SVR: sustained viral response.

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Section: Matched Pair Analysis (Mpa)contrasting

confidence: 79%

“…Hepatitis C virus partially interacts with LDL receptors when entering the cell, suggesting a role for lipids in regulating HCV clearance [8]. Higher serum baseline levels of total cholesterol and LDL cholesterol were reported to be associated with better response towards PEG-IFN [8].…”

Section: Do the Effects Of Smoking On Lipid Metabolism Affect Svr Rates?mentioning

confidence: 99%

Effects of Smoking on Pegylated Interferon alpha 2a and First Generation Protease Inhibitor-based Antiviral Therapy in Naïve Patients Infected with Hepatitis C Virus Genotype 1

Zimmermann

Hueppe²,

Mauss

et al. 2016

JGLD

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“…Indeed, HCV circulates in patient sera in the form of triglyceride-rich particles and consequently, lipoproteins and lipoprotein receptors may play an important role in hepatic virus uptake. 4,5 For reasons of the association of HCV with apoB-and apoE-containing low-density and very low density lipoproteins, the LDL receptor has been proposed as a potential entry factor for HCV. Although the function of LDL-R in…”

Section: Acknowledgementmentioning

confidence: 99%

“…[2][3][4][5][6] The direct relationship between HCV entry into cells is a multi-step and slow process. It is believed that the initial capture of HCV particles by glycosaminoglycans and ⁄ or lipoprotein receptors is followed by coordinated interactions with the scavenger receptor class B type I (SR-BI), a major receptor of high-density lipoprotein (HDL), the CD81 tetraspanin, and the tight junction protein Claudin-1, ultimately leading to uptake and cellular penetration of HCV via low-pH endosomes.…”

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confidence: 99%

Towards predicting the therapeutic response in patients with hepatitis C

Féray

2009

Aliment Pharmacol Ther

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The study by Angelico et al., recently published in Alimentary Pharmacology & Therapeutics 1 confirms the strong positive correlation between the level of HDL cholesterol at baseline and the virological response to the combined therapy using interferon-alfa and ribavirin. [2][3][4][5][6] The direct relationship between HCV entry into cells is a multi-step and slow process. It is believed that the initial capture of HCV particles by glycosaminoglycans and ⁄ or lipoprotein receptors is followed by coordinated interactions with the scavenger receptor class B type I (SR-BI), a major receptor of high-density lipoprotein (HDL), the CD81 tetraspanin, and the tight junction protein Claudin-1, ultimately leading to uptake and cellular penetration of HCV via low-pH endosomes. Competitive inhibition of HCV binding to SR-BI by HDL has been shown in vitro and is a better candidate than LDL receptor. If similar inhibition occurs in vivo, an elevated concentration of HDL may reduce the efficiency of infecting hepatocytes with HCV by competitively inhibiting HCV viral SR-BI receptor binding. This effect could be important during the initiation of therapy.Another possible explanation could be indirect relationships between factors regulating the cholesterol levels and the therapeutic response. The more obvious is that the level of plasma cholesterol depends on the severity of liver disease, which is a major determinant for therapeutic response. 7 In the study

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“…2 Recent evidence from small retrospective studies suggests that elevated low-density lipoprotein (LDL) levels may be associated with higher SVR rates in patients infected with HCV genotype 1. [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] In vitro data suggest that lipid-lowering agents (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors or statins) may inhibit viral replication. However, cell culture models of HCV infection have demonstrated that anti-HCV activity is not the same for all statins: fluvastatin, atorvastatin, simvastatin, and lovastatin inhibit viral replication to variable extents, whereas pravastatin and rosuvastatin have little to no anti-HCV activity.…”

mentioning

confidence: 99%

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

et al. 2010

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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 lg/kg/week with ribavirin (RBV) at 800 to 1400 mg/day, (2) PEG-IFN alfa2b at 1.0 lg/kg/week with RBV at 800 to 1400 mg/day, or (3) PEG-IFN alfa-2a at 180 lg/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 5 0.02). In a multivariate logistic regression analysis using the stepwise selection method with baseline characteristics, a high LDL level [odds ratio (OR) 5 1.6, 95% confidence interval (CI) 5 1.4-1.8, P < 0.001], a low HDL level (OR 5 0.5, 95% CI 5 0.3-0.8, P 5 0.004), and statin use (OR 5 2.0, 95% CI 5 1.1-3.7, P 5 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;52:864-874)

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Baseline cholesterol is associated with the response to antiviral therapy in chronic hepatitis C

Abstract: Baseline serum total cholesterol levels and BMI could be helpful in discriminating responders to antiviral therapy among patients with HCV infection.

Cited by 39 publications

References 34 publications

Effects of Smoking on Pegylated Interferon alpha 2a and First Generation Protease Inhibitor-based Antiviral Therapy in Naïve Patients Infected with Hepatitis C Virus Genotype 1

Effects of Smoking on Pegylated Interferon alpha 2a and First Generation Protease Inhibitor-based Antiviral Therapy in Naïve Patients Infected with Hepatitis C Virus Genotype 1

Towards predicting the therapeutic response in patients with hepatitis C

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

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