Dataset Information

Roles of ITPA and IL28B genotypes in chronic hepatitis C patients treated with peginterferon plus ribavirin.

ABSTRACT: It has been reported that inosine triphosphatase (ITPA) gene variants protect against ribavirin-induced anemia in patients treated for chronic hepatitis C. IL28B variants also influence the treatment response of peginterferon plus ribavirin treatment in these patients. In the present study, we examined how ITPA and IL28B genotypes have clinical impacts on treatment-induced hematotoxicities and treatment response in HCV-infected patients treated with peginterferon plus ribavirin. ITPA genotypes (rs1127354 and rs6051702) and IL28B genotype (rs8099917) were determined by TaqMan SNP assay. We compared clinical background, treatment course and treatment response in terms of these genotypes. Only IL28B rs8099917 major type could predict sustained virological response. ITPA rs1127354 major type leads to significantly greater ribavirin-induced anemia than ITPA rs1127354 minor type between days 0 and 84. We noticed that IL28B rs8099917 minor genotype was associated with higher reduction of neutrophils and platelets. ITPA rs1127354 is useful for the prediction of ribavirin-induced anemia in the early phase after the commencement of peginterferon plus ribavirin treatment and IL28B rs8099917 is useful for the prediction of sustained virological response. Use of the combination of these two genotypes could lead to safe and effective treatment of chronic hepatitis C patients.

SUBMITTER: Miyamura T

PROVIDER: S-EPMC3446761 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Roles of ITPA and IL28B genotypes in chronic hepatitis C patients treated with peginterferon plus ribavirin.

Miyamura Tatsuo T Kanda Tatsuo T Nakamoto Shingo S Wu Shuang S Jiang Xia X Arai Makoto M Fujiwara Keiichi K Imazeki Fumio F Yokosuka Osamu O

Viruses 20120814 8

It has been reported that inosine triphosphatase (ITPA) gene variants protect against ribavirin-induced anemia in patients treated for chronic hepatitis C. IL28B variants also influence the treatment response of peginterferon plus ribavirin treatment in these patients. In the present study, we examined how ITPA and IL28B genotypes have clinical impacts on treatment-induced hematotoxicities and treatment response in HCV-infected patients treated with peginterferon plus ribavirin. ITPA genotypes ( ...[more]

PMID: 23012624

Similar Datasets

Project description:AIM:To evaluate addition of boceprevir to peginterferon/ribavirin (PR) in Russian patients with chronic hepatitis C virus (HCV). METHODS:Treatment-naive (TN) and treatment-experienced (TE) patients (who had failed prior treatment with PR for ? 12 wk) with chronic HCV genotype 1 infection were enrolled in this placebo-controlled, double-blind study. All patients initially received PR for 4 wk. Patients randomized to control treatment then received PR for an additional 44 wk. TN patients randomized to triple therapy received boceprevir (800 mg three times daily) plus PR for 24 wk and then further therapy according to treatment week 8 (TW8) HCV RNA levels. TE patients received boceprevir plus PR for 32 wk and then further therapy according to TW8 HCV RNA levels. Treatment was discontinued for TN patients with detectable HCV RNA at TW24 and TE patients with detectable HCV RNA at TW12 because of futility. The primary efficacy end point was sustained virologic response (SVR) defined as undetectable HCV RNA 24 wk after completing all study therapy. RESULTS:SVR was 74.8% in the boceprevir plus PR arm compared with 46.2% in the control arm, with a stratification-adjusted treatment difference of 29.2% (95%CI: 16.4-41.5; P < 0.0001). Rates of SVR were higher in the boceprevir arm in both TN and TE patient groups (TN 78.4% vs 56.3%; TE 69.4% vs 30.0%). Within TE patients, the rates of SVR were higher with boceprevir plus PR compared with PR, regardless of treatment failure type (null responder, partial responder, and relapser). Most patients receiving boceprevir plus PR in both TN (86%) and TE (71%) populations were eligible for reduced treatment duration. Anemia was increased in patients receiving boceprevir plus PR vs PR alone (47.2% vs 24.4%); there was a corresponding increase in ribavirin dose reduction and erythropoietin use. Among patients receiving boceprevir plus PR, SVR rates were similar in patients with anemia (< 10 g/dL) and those without anemia (71.2% vs 77.4%). CONCLUSION:Regulatory approval has been obtained for boceprevir plus PR in Russian patients with HCV genotype 1 infection based on the results of this study.

Project description:BackgroundMany studies have been published on the association between single nucleotide polymorphisms (SNP) near the IL28B gene and response to the combined treatments of pegylated-interferon (PegIFN) and ribavirin (RBV) in chronic HCV-infected patients, but without identical conclusions. The aim of this study was to assess impact of the IL28B polymorphisms on the effect of HCV standard treatment using meta-analysis based method.MethodsAssociation studies between polymorphisms of rs12979860 or rs8099917 and response to PegIFN/RBV treatment in chronic HCV patients were retrieved from PubMed. Data of qualified studies on sustained virological response (SVR) in different genotypes were extracted and analyzed using meta-analysis method in Stata 10 software.ResultsThirty-four papers, containing 46 independent studies, were included in the analysis. In the HCV G1/4 patients without treatment history, individuals carrying rs12979860 CC genotype were more likely to achieve SVR (OR 3.97, 95%CI 3.29-4.80) compared to those carrying CT/TT genotypes. Similar results were observed in the HCV G1/4 patients with unsuccessful or unknown treatment history (OR 3.76, 95%CI 2.67-5.28) or in the patients co-infected with human immunodeficiency virus (OR 5.20, 95%CI 3.04-8.90). However, associations could not be observed in HCV G2/3 patients. For rs8099917, similar results were obtained for genotype TT compared to genotypes TG/GG, indicating that TT genotype was significantly associated with better treatment response in patients infected with genotype 1 or 4 HCV, but not genotype 2 or 3 HCV.ConclusionPolymorphisms of rs12979860 and rs8099917 near IL28B only associate with the treatment response to PegIFN/RBV in patients infected with HCV genotype 1 or 4 but not with genotype 2 or 3, irrespective of the previous treatment history or HIV co-infected status. Therefore, identification of IL28B genotypes is necessary only in patients infected with relatively difficult-to-treat genotype 1 or 4 HCV.

Project description:BackgroundRandomized clinical trials (RCTs) of interventions for the hepatitis C virus have historically used sustained virological response (SVR) at 24 weeks after treatment (SVR24) as the key effect measure. However, recent RCTs investigating the efficacy of new direct acting agents (DAAs) have used SVR at 12 weeks after treatment (SVR12). While there is evidence to suggest SVR24 and SVR12 are similar in patients receiving new DAAs, this is unlikely to be true for patients receiving backbone peginterferon-ribavirin control treatment. Establishing the difference between SVR12 and SVR24 for patients receiving peginterferon-ribavirin treatment is therefore necessary to avoid biased interpretations of the benefits of newer DAAs.MethodsWe searched the MEDLINE®, Embase™, and Cochrane CENTRAL for RCTs with a peginterferon-ribavirin arm that used SVR24 and/or SVR12. As no RCTs reported on both, we pooled SVR12 and SVR24 proportions using conventional meta-analysis. Proportions were pooled separately for peginterferon alpha-2a and alpha-2b. Further, a Bayesian meta-regression model was employed to estimate the difference between SVR12 and SVR24.ResultsThirty-five RCTs including a peginterferon arm were identified. Twenty-four trials included a peginterferon alpha-2a plus ribavirin arms, of which 20 reported SVR24 and five reported SVR12. Seventeen trials included a peginterferon alpha-2b plus ribavirin arm, of which 16 reported SVR24 and one reported SVR12. Using Bayesian meta-regression, the pooled SVR12 was 6% higher than SVR24 with peginterferon alpha-2a (53% versus 47%) and 5% higher with peginterferon alpha-2b (45% versus 40%) and 95% credible intervals (CrIs) were only marginally overlapping. The meta-regression also demonstrated a marginally significant relative risk of 1.13 (95% CrI 0.99-1.26) of SVR12 versus SVR24. The conventional pairwise meta-analyses were consistent with these findings.ConclusionConsidering the relatively large difference observed between SVR12 and SVR24, it seems reasonable to insist that future clinical trials report both to allow for complete transparency and clarity in their interpretation.

Project description:This study investigates differences in depression and anxiety between patients with chronic hepatitis C who are treated with peginterferon alpha-2a (PegIFN-?-2a) plus ribavirin and those who are treated with peginterferon alpha-2b (PegIFN-?-2b) plus ribavirin.In this 24 week, non-randomized, observational, prospective study, 55 patients with chronic hepatitis C were treated with PegIFN-?-2a plus ribavirin (Group 1), and 26 patients were treated with PegIFN-?-2b plus ribavirin (Group 2). All patients underwent assessment using the Hospital Anxiety and Depression Scale (HADS) at the baseline and at weeks 4, 12 and 24. Patients with depression scores (HADS-D)???8 and anxiety scores (HADS-A)???8 were defined as having depression and anxiety, respectively. The factors that were associated with depression and anxiety during the 24 week antiviral treatment were determined.During the 24 week antiviral treatment, the proportion of patients with depression significantly increased over time in both groups (Group 1: p?=?0.048; Group 2: p?=?0.044). The proportion of patients with anxiety did not significantly change during the follow-up period in either group. Incidences of depression or anxiety did not differ significantly between Group 1 and Group 2. A history of alcohol use disorder was an independent predictor of depression at week 12 (p?<?0.001) and week 24 (p?<?0.001), and a poor virological response to treatment was associated with depression at week 24 (p?=?0.029). Patients who had more physical comorbidities were more likely to suffer from anxiety at week 12 (p?=?0.038).This study did not identify significant differences in depression or anxiety between in patients with chronic hepatitis C who underwent a 24 week antiviral treatment regimen with PegIFN-?-2a plus ribavirin and those who underwent a regiment with PegIFN-?-2b plus ribavirin. Future research with larger samples and a randomized, controlled design are required to verify the findings in this study.This clinical study has been registered at ClinicalTrials.gov. (Trial registration: NCT02943330 ).

Dataset Information

Roles of ITPA and IL28B genotypes in chronic hepatitis C patients treated with peginterferon plus ribavirin.

Publications

Roles of ITPA and IL28B genotypes in chronic hepatitis C patients treated with peginterferon plus ribavirin.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets