Dataset Information

Meta-analysis: influence of host and viral factors in patients with chronic hepatitis C genotype 4 treated with pegylated interferon and ribavirin.

ABSTRACT: The burden of hepatitis C virus genotype 4 (HCV-4) is high in Africa and East Mediterranean countries. Previous reports estimate sustained virologic response (SVR) rates in HCV-4 to be ?20-70%. However, many of these studies are limited by different study designs and small sample sizes. Our aim was to evaluate treatment outcome and host/viral factors on SVR in HCV-4 patients treated with pegylated interferon and ribavirin (PEG IFN+RBV) in a systematic and quantitative manner. A comprehensive literature search in MEDLINE and EMBASE for 'genotype 4' was conducted in November 2013. Abstracts from American Association for the Study of Liver Diseases, Asian Pacific Study of the Liver, Digestive Disease Week, and European Association for the Study of the Liver in 2012/2013 were reviewed. Inclusion criteria were original studies with at least 25 treatment-naive HCV-4 patients treated with PEG IFN+RBV. Exclusion criteria were coinfection with HIV, hepatitis B virus, or other genotypes. Effect sizes were calculated using random-effects models. Heterogeneity was determined by Cochrane Q-test (P<0.05) and I statistic (>50%). We included 51 studies (11?102 HCV-4 patients) in the primary analysis. Pooled SVR was 53% [95% confidence interval (CI): 50-55%] (Q-statistic=269.20, P<0.05; I=81.43). On subgroup analyses, SVR was significantly associated with lower viral load, odds ratio (OR) 3.05 (CI: 1.80-5.17, P<0.001); mild fibrosis, OR 3.17 (CI: 2.19-4.59, P<0.001); and favorable IL28B polymorphisms, rs12979860 CC versus CT/TT, OR 4.70 (CI: 2.87-7.69, P<0.001), and rs8099917 TT versus GT/GG, OR 5.21 (CI: 2.31-11.73, P<0.001). HCV-4 patients treated with PEG IFN+RBV may expect SVR rates of ?50%. Lower viral load, mild fibrosis, and favorable IL28B (rs12979860 CC and rs8099917 TT) are positively associated with SVR.

SUBMITTER: Yee BE

PROVIDER: S-EPMC4180769 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Meta-analysis: influence of host and viral factors in patients with chronic hepatitis C genotype 4 treated with pegylated interferon and ribavirin.

Yee Brittany E BE Nguyen Nghia H NH Zhang Bing B Vutien Philip P Wong Carrie R CR Lutchman Glen A GA Nguyen Mindie H MH

European journal of gastroenterology & hepatology 20141101 11

The burden of hepatitis C virus genotype 4 (HCV-4) is high in Africa and East Mediterranean countries. Previous reports estimate sustained virologic response (SVR) rates in HCV-4 to be ∼20-70%. However, many of these studies are limited by different study designs and small sample sizes. Our aim was to evaluate treatment outcome and host/viral factors on SVR in HCV-4 patients treated with pegylated interferon and ribavirin (PEG IFN+RBV) in a systematic and quantitative manner. A comprehensive lit ...[more]

PMID: 25171028

Similar Datasets

Project description:BackgroundRecent studies of CH-C patients have demonstrated a strong association between IL28B CC genotype and sustained virologic response (SVR) after PEG-IFN/RBV treatment. We aimed to assess whether IL28B alleles rs12979860 genotype influences gene expression in response to PEG-IFN/RBV in CH-C patients.MethodsClinical data and gene expression data were available for 56 patients treated with PEG-IFN/RBV. Whole blood was used to determine IL28B genotypes. Differential expression of 153 human genes was assessed for each treatment time point (Days: 0, 1, 7, 28, 56) and was correlated with IL28B genotype (IL28B C/C or non-C/C) over the course of the PEG-IFN/RBV treatment. Genes with statistically significant changes in their expression at each time point were used as an input for pathway analysis using KEGG Pathway Painter (KPP). Pathways were ranked based on number of gene involved separately per each study cohort.ResultsThe most striking difference between the response patterns of patients with IL28B C/C and T* genotypes during treatment, across all pathways, is a sustained pattern of treatment-induced gene expression in patients carrying IL28B C/C. In the case of IL28B T* genotype, pre-activation of genes, the lack of sustained pattern of gene expression or a combination of both were observed. This observation could potentially provide an explanation for the lower rate of SVR observed in these patients. Additionally, when the lists of IL28B genotype-specific genes which were differentially expressed in patients without SVR were compared at their baseline, IRF2 and SOCS1 genes were down-regulated regardless of patients' IL28B genotype. Furthermore, our data suggest that CH-C patients who do not have the SOCS1 gene silenced have a better chance of achieving SVR. Our observations suggest that the action of SOCS1 is independent of IL28B genotype.ConclusionsIL28B CC genotype patients with CH-C show a sustained treatment-induced gene expression profile which is not seen in non-CC genotype patients. Silencing of SOCS1 is a negative and independent predictor of SVR. These data may provide some mechanistic explanation for higher rate of SVR in IL28B CC patients who are treated with PEG-IFN/RBV.

Project description:Patients receiving therapy for chronic hepatitis C virus (HCV) infection frequently experience cytopenias and weight loss. We retrospectively assessed the pharmacodynamic effects of pegylated interferon (PEG-IFN) alfa-2a and ribavirin by evaluating the relationship between changes in hematologic parameters, body weight, and virologic response. Patients with HCV genotypes 1, 4, 5, or 6 receiving 24 or 48 weeks of PEG-IFN alfa-2a and ribavirin therapy were pooled from four phase 3/4 trials. Maximum decreases in hemoglobin level, neutrophil count, platelet count, and weight during therapy were assessed according to virologic response category (sustained virologic response [SVR], relapse, breakthrough, and nonresponder) and race/ethnicity. Of 1,778 patients analyzed, more than half were male, non-Hispanic Caucasian, and infected with HCV genotype 1; had a baseline HCV RNA >800,000; and had alanine aminotransferase levels ?3 × the upper limit of normal. Virologic responders (SVR, relapse, and breakthrough) experienced greater maximum decreases from baseline in hemoglobin level, neutrophil count, platelet count, and weight compared with nonresponders; however, no clear trend was observed between SVR, relapse, and breakthrough. After adjusting for drug exposure and treatment duration, only decreases in neutrophil count remained associated with virologic response. Significantly greater declines in neutrophil (P < 0.0001) and platelet (P < 0.005) count were observed at weeks 4, 12, and 24 of therapy in virologic responders compared with nonresponders. This difference between responders and nonresponders was also observed among racial/ethnic groups, although statistical significance was not consistent across all groups.This post hoc analysis of HCV patients treated with PEG-IFN alfa-2a and ribavirin shows that maximum decreases from baseline in hematologic parameters and weight loss were associated with virologic response. However, after adjusting for drug exposure and accounting for duration of therapy, only neutropenia was independently associated with virologic response.

Dataset Information

Meta-analysis: influence of host and viral factors in patients with chronic hepatitis C genotype 4 treated with pegylated interferon and ribavirin.

Publications

Meta-analysis: influence of host and viral factors in patients with chronic hepatitis C genotype 4 treated with pegylated interferon and ribavirin.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets