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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

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE113421 | GEO | 2021/04/20

REPOSITORIES: GEO

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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]

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

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

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 [exp2]

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 [exp2]

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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 [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]

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Endogenous intrahepatic IFNs and association with IFN-free HCV treatment outcome.

Project description:BACKGROUND. Hepatitis C virus (HCV) infects approximately 170 million people worldwide and may lead to cirrhosis and hepatocellular carcinoma in chronically infected individuals. Treatment is rapidly evolving from IFN-α-based therapies to IFN-α-free regimens that consist of directly acting antiviral agents (DAAs), which demonstrate improved efficacy and tolerability in clinical trials. Virologic relapse after DAA therapy is a common cause of treatment failure; however, it is not clear why relapse occurs or whether certain individuals are more prone to recurrent viremia. METHODS. We conducted a clinical trial using the DAA sofosbuvir plus ribavirin (SOF/RBV) and performed detailed mRNA expression analysis in liver and peripheral blood from patients who achieved either a sustained virologic response (SVR) or relapsed. RESULTS. On-treatment viral clearance was accompanied by rapid downregulation of IFN-stimulated genes (ISGs) in liver and blood, regardless of treatment outcome. Analysis of paired pretreatment and end of treatment (EOT) liver biopsies from SVR patients showed that viral clearance was accompanied by decreased expression of type II and III IFNs, but unexpectedly increased expression of the type I IFN IFNA2. mRNA expression of ISGs was higher in EOT liver biopsies of patients who achieved SVR than in patients who later relapsed. CONCLUSION. These results suggest that restoration of type I intrahepatic IFN signaling by EOT may facilitate HCV eradication and prevention of relapse upon withdrawal of SOF/RBV. TRIAL REGISTRATION. ClinicalTrials.gov NCT01441180.

| S-EPMC4109554 | biostudies-literature

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 livers of humanized mice with HCV following DAA therapy.

Project description:RESULTS:First, in patients receiving two different combinations of DAAs, we found that DAAs induced not only rapid viral clearance, but also a re-setting of antiviral immune responses in the peripheral blood. Specifically, we see a rapid decline in the expression of genes associated with chronic IFN stimulation (IFIT3, USP18, IFIT1) as well as a rapid decline in genes associated with inflammation (IL1?, CXCL10, CXCL11) in the peripheral blood that precedes the complete removal of virus from the blood. Interestingly, this rapid reversal of innate immune activation was not seen in patients who successfully clear chronic HCV infection using IFN-based therapy. Next, using a novel humanized mouse model (Fah-/-RAG2-/-IL2rgnull-FRG), we assessed the changes that occur in the hepatic tissue following DAA treatment. DAA-mediated rapid HCV clearance resulted in blunting of the expression of proinflammatory responses while functionally restoring the RIG-I/MAVS axis in the liver of humanized mice. CONCLUSIONS:Collectively, our data demonstrate that the rapid viral clearance following treatment with DAAs results in the rebalancing of innate antiviral response in both the peripheral blood and the liver as well as enhanced antiviral signaling within previously infected hepatocytes.

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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