Predictive factors of early and sustained responses to peginterferon plus ribavirin combination therapy in Japanese patients infected with hepatitis C virus genotype 1b: Amino acid substitutions in the core region and low-density lipoprotein cholesterol levels

Akuta, Norio; Suzuki, Fumitaka; Kawamura, Yusuke; Yatsuji, Hiromi; Sezaki, Hitomi; Suzuki, Yoshiyuki; Hosaka, Tetsuya; Kobayashi, Masahiro; Kobayashi, Mariko; Arase, Yasuji; Ikeda, Kenji; Kumada, Hiromitsu

doi:10.1016/j.jhep.2006.09.019

Cited by 257 publications

(326 citation statements)

References 43 publications

Supporting

Mentioning

296

Contrasting

Order By: Relevance

“…Smaller previous studies have suggested that this might be the case for LDL, 3,4 but this is the largest trial to date to corroborate these findings and the first published study to our knowledge to show a relationship between HDL and SVR. In a small retrospective study, Gopal et al 4 found that, among patients with EVR, EOT response, and SVR, the LDL and total cholesterol levels were higher, and this was independent of age.…”

Section: Discussionsupporting

confidence: 67%

“…In a small retrospective study, Gopal et al 4 found that, among patients with EVR, EOT response, and SVR, the LDL and total cholesterol levels were higher, and this was independent of age. 4 Subsequently, Akuta et al 3 found that an LDL level ! 86 mg/dL was an independent predictor in a multivariate logistic regression analysis of EVR and SVR in 114 Japanese adults with HCV genotype 1 who were treated with PEG-IFN and RBV for 48 weeks.…”

Section: Discussionmentioning

confidence: 99%

“…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%

See 2 more Smart Citations

Serum Cholesterol and Statin Use Predict Virological Response to Peginterferon and Ribavirin Therapy†,‡

et al. 2010

View full text Add to dashboard Cite

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)

show abstract

Section: Discussionsupporting

confidence: 67%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Serum Cholesterol and Statin Use Predict Virological Response to Peginterferon and Ribavirin Therapy†,‡

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Several viral factors may predict the outcome of Peg-IFNα-2a/RBV combination therapy; for instance, 40 amino acids in the non-structural 5A (NS5A) region (9,10), and amino acid substitutions in the core region have been reported as predictors of hepatitis C therapy outcome (11,12).…”

Section: Introductionmentioning

confidence: 99%

Genetic Variation in Interleukin-28B and Response to Peg-IFNα-2a/RBV Combination Therapy in Patients with Hepatitis C Virus Infection

Bokharaei‐Salim

Salehi‐Vaziri

Sadeghi

et al. 2016

Jundishapur J Microbiol

View full text Add to dashboard Cite

Background: The hepatitis C virus (HCV) infection is one of the major causes of progressive liver diseases worldwide. Despite the new treatments for HCV infection, antiviral therapy with a combination of pegylated interferon-α 2a plus ribavirin (Peg-IFNα-2a/RBV) is still used in developing countries. Objectives: The aim of the current study was to determine the relationship between rs12979860 polymorphism in the interleukin 28B gene (IL28B) and response to Peg-IFNα-2a/RBV combination therapy in Azerbaijani patients with chronic HCV infection. Methods: A total of 72 Azerbaijani patients with established chronic HCV-1b took part in this cross-sectional study between January 2010 and September 2015. Genomic DNA was extracted from peripheral blood mononuclear cells (PBMCs) of the patients and the rs12979860 single nucleotide polymorphism was diagnosed by polymerase chain reaction-restriction fragment length polymorphism assay (PCR-RFLP).

show abstract

“…In particular, there are more males than females in the group having more than two mutations in the ISDR of HCV NS5A. This is important because some reports show that sex could be associated with a sustained virological response, although this conclusion is still subject to controversy [20]. It has been described that sex may impact Th1/Th2 cytokine production in response to certain infections and treatment.…”

mentioning

confidence: 99%

The long way toward understanding host and viral determinants of therapeutic success in HCV infection

2012

View full text Add to dashboard Cite

Predictive factors of early and sustained responses to peginterferon plus ribavirin combination therapy in Japanese patients infected with hepatitis C virus genotype 1b: Amino acid substitutions in the core region and low-density lipoprotein cholesterol levels

Cited by 257 publications

References 43 publications

Serum Cholesterol and Statin Use Predict Virological Response to Peginterferon and Ribavirin Therapy†,‡

Serum Cholesterol and Statin Use Predict Virological Response to Peginterferon and Ribavirin Therapy†,‡

Genetic Variation in Interleukin-28B and Response to Peg-IFNα-2a/RBV Combination Therapy in Patients with Hepatitis C Virus Infection

The long way toward understanding host and viral determinants of therapeutic success in HCV infection

Contact Info

Product

Resources

About