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Rapid intrahepatic and peripheral blood HCV RNA decline and HCV-specific immune response increase during IFN-free DAA therapy in HCV treatment-naïve patients [exp2]

ABSTRACT: Rapid intrahepatic and peripheral blood HCV RNA decline and HCV-specific immune response increase during IFN-free DAA therapy in HCV treatment-naïve patients [exp2]

PROVIDER: PRJNA451113 | ENA |

REPOSITORIES: ENA

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Rapid intrahepatic and peripheral blood HCV RNA decline and HCV-specific immune response increase during IFN-free DAA therapy in HCV treatment-naïve patients

Project description:Rapid intrahepatic and peripheral blood HCV RNA decline and HCV-specific immune response increase during IFN-free DAA therapy in HCV treatment-naïve patients

| PRJNA451109 | ENA

Rapid intrahepatic and peripheral blood HCV RNA decline and HCV-specific immune response increase during IFN-free DAA therapy in HCV treatment-naïve patients [exp1]

Project description:Rapid intrahepatic and peripheral blood HCV RNA decline and HCV-specific immune response increase during IFN-free DAA therapy in HCV treatment-naïve patients [exp1]

| PRJNA451112 | ENA

Rapid intrahepatic and peripheral blood HCV RNA decline and HCV-specific immune response increase during IFN-free DAA therapy in HCV treatment-naïve patients [exp2]

Project description:Over 12 weeks of treatment with a combination of sofosbuvir, simeprevir and daclatasvir, PBMCs from 9 chronically HCV infected patients were profiled longitudinally (baseline, day 2, week 1, end of treatment (EOT) and post-treatment follow-up week 24)

2021-04-20 | GSE113420 | GEO

Endogenous Intrahepatic Interferons and Association with IFN-free HCV Treatment Outcome

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

Endogenous Intrahepatic Interferons and Association with IFN-free HCV Treatment Outcome

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 (IFNα)-based to IFNα-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.

2014-08-15 | GSE51699 | GEO

Rapid reversal of innate immune dysregulation in blood of patients and liver of humanized mice with HCV following DAA therapy

Project description:Analysis of transcriptional changes in the peripheral blood of patients prior to and following DAA treatment of HCV infection

2017-10-05 | GSE104597 | GEO

Single-cell transcriptomic analyses of T cells in chronic HCV-infected patients dominated by DAA-induced interferon signaling changes

Project description:Chronic infection with HCV is manifested by dysregulation of innate immune responses and impaired T cell function at multiple levels. These changes may impact susceptibility to other infections, responsiveness to antiviral therapies, vaccine responsiveness, and development of complications such as hepatocellular carcinoma. Highly effective direct-acting antiviral (DAA) therapy has revolutionized the management of chronic HCV, with expected cure rates exceeding 95%. DAA treatment represents a unique opportunity to investigate to what extent elimination of viral replication and chronic antigen stimulation can restore immunologic phenotype. In this study we interrogated the global transcriptional profile of isolated peripheral blood T cells before, during and after IFN-free DAA therapy using single cell mRNA sequencing. Our results demonstrate that T cells mapped at single-cell resolution have dramatic transcriptomic changes early after initiation of DAA and many of these changes are sustained after completion of DAA therapy. Specifically, we see a significant reduction in transcripts associated with innate immune activation and interferon signaling such as ISG15, ISG20, IFIT3, OAS and MX1 in many different T cell subsets. Furthermore, we find an early upregulation of a gene involved in suppression of immune activation, DUSP1, in circulating T cells. Conclusion: This study provides the first in-depth transcriptomic analysis at the single-cell level of patients undergoing DAA therapy, demonstrating that IFN-free antiviral therapy in chronic HCV infection induces hitherto unrecognized shifts in innate immune and interferon signaling within T cell populations early, during, and long-term after treatment. The present study provides a rich data source to explore the effects of DAA treatment on bulk T cells.

2021-07-19 | GSE178756 | GEO

Rapid intrahepatic and peripheral blood HCV RNA decline and HCV-specific immune response increase during IFN-free DAA therapy in HCV treatment-naïve patients [exp1]

Project description:Over 12 weeks of treatment with a combination of sofosbuvir, simeprevir and daclatasvir, FNABs from 9 chronically HCV infected patients were profiled longitudinally (baseline, day 2, week 1, end of treatment (EOT) and post-treatment follow-up week 24)

2021-04-20 | GSE113419 | GEO

Memory-like HCV-specific CD8+ T cells retain a chronic scar after cure of chronic HCV infection

Project description:Investigation of phenotypical changes between exhausted HCV-specific CD8+ T cells during chronic infection and after DAA-mediated cure investigation of heterogeneity withhin the HCV-specific CD8+ T cell population

2020-09-08 | GSE150305 | GEO

Memory-like HCV-specific CD8+ T cells retain a molecular scar after cure of chronic HCV infection

2020-09-07 | GSE150345 | GEO