Project description:With 350 million carriers worldwide who may suffer from serious sequelae, including hepatocellular carcinoma, chronic hepatitis B virus (CHB) infection remains an important health issue. Current antiviral therapies hardly eradicate the virus. Therefore, there are still imperative need to develop new therapeutic strategies and predictors for treatment response to cure the disease and avoid futile treatment. By taking the advantage of having the paired liver biopsy samples of IFNalpha responders before/after treatment and pretreatment samples from responders and non-responders, we could characterize the intrahepatic expression profiles associated with necroinflammatory activity and the profiles/signature potentially predictive of response to IFNalpha therapy for CHB in this study. RNA was extracted from pairedliver tissues for gene expression analysis. The gene expression profiles of seven paired liver biopsy samples of IFNalpha responders before/after treatment and other 3 pre- treatment samples were obtained by Affymatrix U133plus2 microarray. We also pooled samples of 11 responders and 11 non-responders to perform affymatrix EXON ST 1.0 array. This dataset is part of the TransQST collection.
Project description:As hepatitis B virus is widely spread, WHO recommend vaccination from infancy to reduce acute infection and chronic carriers. However current subunit vaccines are not 100% efficacious and leaves 5-10% persistent non-responders unprotected. To handle large inter-individual variability in immune response after the first Engerix-B vaccination, we employed whole blood early gene expression signatures at day 3 and 7. Immune related pathways are differential expressed in the responders group mostly at day 3 and at day 7 in the non-responders. A notable difference between both groups are significant differential expressed genes at day 0, before vaccination, showing the inter-individual variation. The granulin precursor (GRN) was significant downregulated in responders while upregulated in non-responders. Further absolute granulocytes numbers were significant higher in non-responders. So there is a certain diversity in basic innate immune system.
Project description:In this study we aimed to identify a baseline intrahepatic transcriptional signature associated with response in chronic hepatitis B patients treated with peginterferon-alfa-2a (peg-IFN) and adefovir. Liver gene expression values of patients with combined response (responders; n=9) and non-response (n=6) were compared for 21,462 annotated gene transcripts. We identified 182 genes which differed on average more than 1.5-fold, of which 53 were relatively upregulated in non-responders and 129 in responders. 15 liver biopsies of chronic hepatitis B patients were selected for RNA extraction and hybridization on Affymetrix microarrays. Expression values in 9 biopsies of patients with a combined response to therapy were compared with 6 biopsies of non-responders. Differentially expressed genes between responders and non-responders were determined using filtering on minimal average expression, fold change (1.5 fold) and p-values from 2-sided t-tests (0 permutations) in GenePattern. This dataset is part of the TransQST collection.
Project description:In this study we aimed to identify a baseline intrahepatic transcriptional signature associated with response in chronic hepatitis B patients treated with peginterferon-alfa-2a (peg-IFN) and adefovir. Liver gene expression values of patients with combined response (responders; n=9) and non-response (n=6) were compared for 21,462 annotated gene transcripts. We identified 182 genes which differed on average more than 1.5-fold, of which 53 were relatively upregulated in non-responders and 129 in responders.
Project description:With 350 million carriers worldwide who may suffer from serious sequelae, including hepatocellular carcinoma, chronic hepatitis B virus (CHB) infection remains an important health issue. Current antiviral therapies hardly eradicate the virus. Therefore, there are still imperative need to develop new therapeutic strategies and predictors for treatment response to cure the disease and avoid futile treatment. By taking the advantage of having the paired liver biopsy samples of IFNalpha responders before/after treatment and pretreatment samples from responders and non-responders, we could characterize the intrahepatic expression profiles associated with necroinflammatory activity and the profiles/signature potentially predictive of response to IFNalpha therapy for CHB in this study.
Project description:With 350 million carriers worldwide who may suffer from serious sequelae, including hepatocellular carcinoma, chronic hepatitis B virus (CHB) infection remains an important health issue. Current antiviral therapies hardly eradicate the virus. Therefore, there are still imperative need to develop new therapeutic strategies and predictors for treatment response to cure the disease and avoid futile treatment. By taking the advantage of having the paired liver biopsy samples of IFNalpha responders before/after treatment and pretreatment samples from responders and non-responders, we could characterize the intrahepatic expression profiles associated with necroinflammatory activity and the profiles/signature potentially predictive of response to IFNalpha therapy for CHB in this study.
Project description:We present an approach for quantification of differential mRNA expression by targeted resequencing of cDNA using single-molecule molecular inversion probes (cDNA-smMIPs), which enable highly multiplexed resequencing of cDNA target regions of ~100 nt and counting of individual molecules. We show that accurate estimates of differential expression can be obtained from molecule counts for hundreds of smMIPs per reaction and that smMIPs are also suitable for quantification of relative gene expression and allele-specific expression. cDNA-smMIPs are a cost-effective tool for hypothesis-driven expression analysis in large numbers of genes (10 to 500) and samples (hundreds to thousands).
Project description:Background/Aims: Ribavirin improves treatment response to pegylated-interferon (PEG-IFN) in chronic hepatitis C but the mechanism remains controversial. We studied correlates of response and mechanism of action of ribavirin in treatment of hepatitis C. Methods: 70 treatment-naïve patients were randomized to 4 weeks of ribavirin (1000-1200 mg/d) or none, followed by PEG-IFN alfa-2a and ribavirin at standard doses and durations. Patients were randomized to undergo a liver biopsy either 24 hours before, or 6 hours after starting PEG-IFN. Hepatic gene expression was assessed by microarray and interferon-stimulated gene (ISG) expression quantified by the nCounter platform. Temporal changes in ISG expression were assessed by qPCR in peripheral-blood mononuclear cells (PBMC) and by serum levels of IP-10. Results: After four weeks of ribavirin monotherapy, HCV levels decreased by 0.5±0.5 log10 (p=0.009 vs. controls) and ALT by 33% (p<0.001). Ribavirin pretreatment, while modestly augmenting the induction of ISGs by PEG-IFN, did not modify the virological response to subsequent PEG-IFN and ribavirin treatment. However, biochemical, but not virological response to ribavirin monotherapy predicted response to subsequent combination treatment (rapid virological response, 71% in biochemical responders vs. 22% non-responders, p=0.01; early virological response, 100% vs. 68%, p=0.03, sustained virological response 83% vs. 41%, p=0.053). Ribavirin monotherapy lowered serum IP-10 levels but had no effect on ISG expression in PBMC. Conclusion: Ribavirin is a weak antiviral but its clinical effect in combination with PEG-IFN seems to be mediated by a separate, indirect mechanism, which may act to reset the interferon responsiveness in HCV-infected liver. Ribavirin pretreatment does not alter the clinical outcome of subsequent combination therapy. Analysis of liver biopsy samples from 52 patients under 4 different treatment conditions.
Project description:Study goal is to disclose features of gene expressio profile of non-cancerous liver-infiltrating lymphocytes of type C hepatitis patients with hepatocellular carcinomas and tumor-infiltrating lymphocytes of type C hepatitis patients with hepatocellular carcinomas. Keywords: gene expression profile, non-cancerous liver-infiltrating lymphocytes, tumor-infiltrating lymphocytes, type C hepatitis, hepatocellular carcinoma
Project description:Whole-genome resequencing of eight transcription factor mutants and one wild-type, in order to verify the T-DNA insertion site and its uniqueness.