Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA210196 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Gene expression profiling of liver biopsies from 21 chronic hepatitis C patients undergoing antiviral therapy
2020-04-16 | E-GEOD-48445 | ExpressionAtlas
Project description:Hepatitis C virus (HCV) chronically infects 170 million people worldwide and is a leading cause of liver-related mortality due to hepatocellular carcinoma and cirrhosis1. Standard-of-care treatment is shifting from interferon-alpha (IFNM-NM-1)-based to IFNM-NM-1-free directly acting antiviral (DAA) regimens, which demonstrate improved efficacy and tolerability in clinical trials2,3. Virologic relapse after completion of DAA therapy is a common cause of treatment failure, although mechanisms are unclear2,3. We conducted a clinical trial using the DAA sofosbuvir with ribavirin (SOF/RBV)4, and report here detailed mRNA expression analysis of pre- and end-of-treatment (EOT) liver biopsies and blood samples. On-treatment viral clearance was accompanied by rapid down-regulation of interferon-stimulated genes (ISGs) in liver and blood. Analysis of paired liver biopsies from patients who achieved a sustained virologic response (SVR) revealed that viral clearance was accompanied by decreased expression of ISGs, IFNG, and IFNLs, but increased expression of IFNA2. Patients who achieved SVR had higher expression of a hepatic type-I interferon gene signature in unpaired EOT liver biopsies than patients who later relapsed. Together, these results support a model whereby restoration of type-I intrahepatic interferon signaling at the EOT is associated with sustained hepatic HCV suppression and prevention of relapse upon withdrawal of SOF/RBV. Sustained Virologic Response for Chronic Hepatitis C Patients Treated with Sofosbuvir and Ribavirin
2014-08-15 | E-GEOD-51699 | biostudies-arrayexpress
Project description:Chronic liver disease is becoming a leading cause of illness and mortality in people living with human immunodeficiency virus (HIV) (PLWH) undergoing suppressive anti-retroviral therapy. Its main etiology has been reported to be coinfection with hepatitis B (HBV) and C (HCV) viruses. Accumulating evidence indicate chronic liver inflammation and fibrosis can potentially lead to the development of hepatocellular carcinoma (HCC). Therefore, monitoring of the disease progression in PLWH is required. The present study aimed to explore the plasma protein profiles of patients with HIV infection and those coinfected with HBV and HCV using shotgun proteomics.
2024-06-29 | PXD053504 | JPOST Repository
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.
2014-12-19 | E-GEOD-54747 | biostudies-arrayexpress
Project description:Background & Aims: Chronic HBV patients with concomitant metabolic dysfunction-associated steatohepatitis (MASH) have been shown to develop more advanced fibrosis faster with more severe liver disease as compared to patients with chronic HBV alone. However, our understanding of the underlying mechanisms is limited. Here we study how MASH co-morbidity impact immune activity in the liver of patients with chronic HBV infection. Methods: Bulk RNA sequencing was performed on liver biopsies from patients with only MASH (n=10), only HBeAg-negative chronic HBV (ENEG; n=11), combined MASH/ENEG (n=9) and healthy controls (n=9). Biopsies with no or minimal fibrosis (≤F2) were selected to avoid confounding effects of fibrosis. We compared whole transcriptome data from patients with MASH/ENEG to those with ENEG alone to determine the impact of MASH co-morbidity on chronic hepatitis B. Results: There is a high degree of overlap of liver gene expression profiles in patients with only ENEG versus those with only MASH compared to healthy controls, suggesting a largely shared mechanism of liver dysfunction and immune activity for these distinct conditions. In patients with ENEG, MASH co-morbidity significantly reduced interferon pathway activity (NES=2.03, p.adj=0.0251), the expression of ISGs (e.g., IFIT2, IFI27, IFITM1, IFI6), and macrophage gene signatures (e.g., MARCO, CD163, CD5L, CD63), when compared to patients with ENEG alone. Conclusions: Transcriptomic profiling of the liver suggests that MASH negatively impacts ISGs expression in the liver of patients with ENEG, which may affect antiviral immune pathways, viral replication and inflammatory responses resulting in an increased risk of advanced fibrosis in patients with chronic hepatitis B. Our study provides valuable insights for guiding future research aimed at developing effective, tailored strategies for managing patients with both conditions.
2024-10-31 | GSE274114 | GEO
Project description:Although treatment of chronic hepatitis C virus (HCV) infection with direct acting antivirals (DAAs) results in high rates of cure, liver fibrosis does not resolve immediately after HCV eradication. Resolution of fibrosis occurs in some, but not all patients, after HCV cure, and hepatic decompensation and hepatocellular carcinoma can still occur in patients with pre-existing cirrhosis. We hypothesized that evaluation of the host liver proteome in the context of HCV treatment would provide insight into how inflammatory and fibrinogenic pathways change upon HCV eradication. We evaluated the whole liver proteome and phosphoproteome using paired liver biopsies from 8 HCV-infected patients collected before or immediately after treatment with DAAs in clinical trials. We identify interferon stimulated proteins as the predominant pathways that decrease with HCV treatment, which is consistent with previous analyses of the liver transcriptome during DAA therapy. While there was no change in the proteome of pathways associated with liver fibrosis, we identified a decrease in the phosphoproteome signature for ERK1/ERK2 as a result of HCV treatment. Conclusion: There is a reduction in the endogenous interferon-mediated antiviral response and alterations in the phosphoproteome that may precede resolution of fibrosis in the liver immediately after treatment of HCV with DAAs.
2023-03-11 | PXD024846 | Pride
Project description:Despite advances in antiviral therapy, molecular drivers of Hepatitis C Virus (HCV)-related liver disease remain poorly characterised. Chronic infection with HCV genotypes (1 and 3) differ in presentation of liver steatosis and virological response to therapies, both to interferon and direct acting antivirals. Using whole transcriptome microarrays, we analysed gene expression profiles of liver tissue obtained from individuals infected with either HCV G1 or G3 in progressive and advanced liver disease and identified key altered cellular pathways.
2019-06-01 | E-MTAB-7751 | biostudies-arrayexpress
Project description:Chronic hepatitis C virus infection (HCV) causes liver inflammation and fibrosis, leading to development of severe liver disease, such as cirrhosis or hepatocellular carcinoma (HCC). Approval of direct acting antiviral (DAA) drug combinations has revolutionized chronic HCV therapy, with virus eradication in >98% of the treated patients. The efficacy of these treatments is such that it is formally possible for cured patients to carry formerly infected cells that display irreversible transcriptional alterations directly caused by chronic HCV Infection. Combining differential transcriptomes from two different persistent infection models, we observed a major reversion of infection-related transcripts after complete infection elimination. However, a small number of transcripts were abnormally expressed in formerly infected cells. Comparison of the results obtained in proliferating and growth-arrested cell culture models suggest that permanent transcriptional alterations may be established by several mechanisms. Interestingly, some of these alterations were also observed in the liver biopsies of virologically cured patients. Overall, our data suggest a direct and permanent impact of persistent HCV infection on the host cell transcriptome even after virus elimination, possibly contributing to development of HCC.
2024-07-11 | GSE267834 | GEO
Project description:The objective of this study is to identify immunological mechanisms that contribute to normalization of liver inflammation in chronic hepatitis B (CHB) patients starting the antiviral nucleoside analogue, Tenofovir alafenamide (TAF).
2022-12-01 | GSE216314 | GEO
Project description:Liver-restricted Type I Interferon Signature Precedes Liver Damage in Chronic Hepatitis B Patients Stopping Antiviral Therapy
| PRJNA1062847 | ENA