Liver gene expression profiles of interferon therapy in chronic hepatitis B Patients
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA277749 | ENA |
REPOSITORIES: ENA
Similar Datasets
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.
2017-02-09 | GSE66699 | GEO
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.
2017-02-09 | GSE66698 | GEO
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.
2017-02-09 | E-GEOD-66698 | biostudies-arrayexpress
Project description:To find novel circulating markers associated with prognosis of interferon therapy,We performed microarray analysis of plasma samples in 94 chronic hepatitis B patients
2011-09-20 | GSE29911 | GEO
Project description:Immune-mediated liver damage is the driver of disease progression in patients with chronic Hepatitis B virus (HBV) infection. Liver damage is an antigen-independent process caused by bystander activation of CD8 T cells and NK cells. How bystander lymphocyte activation is initiated in chronic hepatitis B (CHB) patients remains unclear. Periods of liver damage, called hepatic flares, occur unpredictably, making early events difficult to capture. To address this obstacle, we longitudinally sampled the liver of CHB patients stopping antiviral therapy and analyzed immune composition and activation using flow cytometry and single-cell RNA sequencing (scRNA-seq). At 4 weeks after stopping therapy, HBV replication rebounded but no liver damage was detectable. There were no changes in cell frequencies at viral rebound. ScRNA-seq revealed upregulation of IFN stimulated genes (ISGs) and pro-inflammatory cytokine MIF at viral rebound in patients that go on to develop hepatic flares 6 – 18 w after stopping therapy. The type I IFN signature was only detectable within the liver and neither IFN-α/β or ISG induction could be detected in the peripheral blood. In vitro experiments confirmed the type I IFN-dependent ISG profile whereas MIF was induced primarily by IL-12. MIF exposure further amplified inflammatory cytokine production by myeloid cells. Our data show that innate immune activation is detectable in the liver before clinically significant liver damage is evident. The combination of type I IFN and enhanced cytokine production upon MIF exposure represent the earliest immunological triggers of lymphocyte bystander activation observed in hepatic flares associated with chronic HBV infection.
2024-01-14 | GSE252863 | GEO
Project description:To find novel circulating markers associated with prognosis of interferon therapy,We performed microarray analysis of plasma samples in 94 chronic hepatitis B patients Ninety four HBV patients, who underwent PEG-IFN or conventional interferon treatment were enrolled. Their plasma samples before treatment were collected and subject to miRNA array analysis. miRNA profiles from 13 formalin fixed formaldehyde embedded liver biopsy samples were also analyzed to evaluate the correlation between liver and plasma.
2011-09-19 | E-GEOD-29911 | biostudies-arrayexpress
Project description:Liver-restricted Type I Interferon Signature Precedes Liver Damage in Chronic Hepatitis B Patients Stopping Antiviral Therapy
| PRJNA1062847 | ENA
Project description:Background: Hepatitis E Virus (HEV) is a new causative agent of chronic hepatitis in solid organ transplant recipients in Europe. Factors associated with the occurrence and persistence of chronic HEV infection remain largely unknown but chronic evolution seems to be the consequence of hostM-bM-^@M-^Ys immunological factors rather than of viral factors. Method: In a prospective case-control study, we have determined in whole blood of chronically HEV-infected kidney-transplant recipients the host response using microarray technology. Results: Chronically HEV-infected kidney-transplant recipients exhibited a specific transcriptional program, in which interferon effectors were prominent. The intensity of expression of each signatureM-bM-^@M-^Ys gene was significantly lower in patients who were subsequently cleared of HEV than in patients who were not. Furthermore, in patients who were cleared of HEV, a higher expression of these genes was associated with a longer delay until HEV clearance. Conclusions: The specific transcriptional program determined in chronically HEV-infected kidney-transplant recipients suggests an activation of type I interferon response. Intensity of interferon-stimulated genes expression could be useful to forecast the outcome of infection. High expression of interferon-stimulated genes could signify a dysregulation in the interferon response that might favour the persistence of the HEV infection. TrialM-bM-^@M-^Ys registration number: NCT01090232; RegistryM-bM-^@M-^Ys URL: http://clinicaltrials.gov/ct2/show/study/NCT01090232?term=kidney+transplant+recipients&cntry1=EU%3AFR&rank=2 Total RNA was extracted from whole-blood sample or monocytes of kidney-transplant patients with or without chronic hepatitis E (CHE) infection. Control patients were matched up with CHE patients for age, sex, time since kidney transplant and immunosuppressive treatment.
2013-01-29 | E-GEOD-36539 | biostudies-arrayexpress
Project description:This dataset is part of the paper: Pegylated interferon-α regulates hepatic gene expression by transient activation of the Jak-STAT pathway; Dill MT et al; Journal of Clinical Investigation; in review Pegylated interferon-α (pegIFN-α) has replaced un-modified recombinant IFN-α for the treatment of chronic viral hepatitis because of its superior anti-viral efficacy that is generally attributed to improved pharmacokinetic properties. However, the pharmacodynamic effects of pegIFN-α in the liver have not been studied. We analyzed pegIFN-α induced signaling and gene regulation in paired liver biopsies obtained before treatment and during the first week after injection of pegIFN-α in 18 patients. Despite sustained high serum concentrations of pegIFN-α over the entire one-week dosing interval, IFN-α signaling through the Jak-STAT pathway occurs only during the first day. PegIFN-α induces hundreds of genes that can be classified into 4 clusters based on different temporal expression profiles. In all clusters, gene transcription is mainly driven by IFN stimulated gene factor 3 (ISGF3). IFN induced secondary transcription factors do not cause additional waves of gene expression. We could not confirm a role of un-phosphorylated STAT1 in prolonging IFN-α induced gene transcription. Collectively, our results reveal that the major effects of pegIFN-α in the liver are caused by an early and transient activation of ISGF3. Prolonging the serum half-life of IFN-α does not necessarily improve its pharmacodynamic properties. Paired liver biopsy samples were collected before and during the first week of pegylated interferon alpha treatment of 21 chronic hepatitis C patients. Total: 21 patients and 42 samples. This dataset is part of the TransQST collection.
2014-01-30 | E-GEOD-48445 | biostudies-arrayexpress
Project description:Hepatitis C virus (HCV) infection is a major cause of chronic liver disease worldwide. The current standard therapy for chronic hepatitis C (CHC) consists of a combination of pegylated IFN alpha (pegIFN-alpha) and ribavirin. It achieves a sustained viral clearance in only 50–60% of patients. To learn more about molecular mechanisms underlying treatment failure, we investigated IFN-induced signaling in paired liver biopsies collected from CHC patients before and after administration of pegIFN-alpha. In patients with a rapid virological response to treatment, pegIFN-alpha induced a strong up-regulation of IFN-stimulated genes (ISGs). As shown previously, nonresponders had high expression levels of ISGs before therapy. Analysis of posttreatment biopsies of these patients revealed that pegIFN-alpha did not induce expression of ISGs above the pretreatment levels. In accordance with ISG expression data, phosphorylation, DNA binding, and nuclear localization of STAT1 indicated that the IFN signaling pathway in nonresponsive patients is preactivated and refractory to further stimulation. Some features characteristic of nonresponders were more accentuated in patients infected with HCV genotypes 1 and 4 compared with genotypes 2 and 3, providing a possible explanation for the poor response of the former group to therapy. Taken together with previous findings, our data support the concept that activation of the endogenous IFN system in CHC not only is ineffective in clearing the infection but also may impede the response to therapy, most likely by inducing a refractory state of the IFN signaling pathway. Keywords: Comparison of human patient biopses before and after interferon treatment
2008-04-17 | GSE11190 | GEO