Trial reportHepatology (Baltimore, Md.)2012
Early changes in interferon signaling define natural killer cell response and refractoriness to interferon-based therapy of hepatitis C patients.
Trial report in Hepatology (Baltimore, Md.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
60 citing papers in PubMed, 110 citations in OpenAlex.
- Ribavirin improves the IFN-γ response of natural killer cells to IFN-based therapy of hepatitis C virus infection.Hepatology (Baltimore, Md.) · 2014Trial
- Long-term effect on natural killer cells by interferon-α therapy on the outcomes of HCV infection.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2014Trial
- PEG-IFN alpha but not ribavirin alters NK cell phenotype and function in patients with chronic hepatitis C.PloS one · 2014Trial
- HCV immunodominant peptide mapping reveals unique HLA-A*02-restricted signatures: insights for CD8Immunogenetics · 2025Article
- Hepatitis and periodontal health: an emerging oral-liver axis.Therapeutic advances in chronic disease · 2025Review
- Role of immune cell interactions in alcohol-associated liver diseases.Liver research (Beijing, China) · 2024Review
- RNA Sequencing Analysis of Patients with Chronic Hepatitis B Treated Using PEGylated Interferon.International journal of general medicine · 2024Article
- The Role of JAK/STAT Pathway in Fibrotic Diseases: Molecular and Cellular Mechanisms.Biomolecules · 2023Review
- Changes of natural killer cells' phenotype in patients with chronic hepatitis B in intermittent interferon therapy.Frontiers in immunology · 2023Article
- Article
- Periodontitis, chronic liver diseases, and the emerging oral-gut-liver axis.Periodontology 2000 · 2022Review
- Clearance of pegylated interferon by Kupffer cells limits NK cell activation and therapy response of patients with HBV infection.Science translational medicine · 2021Article
- Direct-acting antiviral treatment downregulates immune checkpoint inhibitor expression in patients with chronic hepatitis C.Clinical and experimental medicine · 2020Article
- Immunomodulation of the Natural Killer Cell Phenotype and Response during HCV Infection.Journal of clinical medicine · 2020Review
- Insights From Antiviral Therapy Into Immune Responses to Hepatitis B and C Virus Infection.Gastroenterology · 2019Review
- Type I Interferon Receptor on NK Cells Negatively Regulates Interferon-γ Production.Frontiers in immunology · 2019Article
- Baseline Intrahepatic and Peripheral Innate Immunity are Associated with Hepatitis C Virus Clearance During Direct-Acting Antiviral Therapy.Hepatology (Baltimore, Md.) · 2018Article
- Natural Killer Cell Dysfunction in Hepatocellular Carcinoma: Pathogenesis and Clinical Implications.International journal of molecular sciences · 2018Review
- Recovery of natural killer cells is mainly in post-treatment period in chronic hepatitis C patients treated with sofosbuvir plus ledipasvir.World journal of gastroenterology · 2018Article
- Aberrant cell signalling in PBMCs upon IFN-α stimulation in primary Sjögren's syndrome patients associates with type I interferon signature.European journal of immunology · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
unlabelledNatural killer (NK) cells exhibit a polarized phenotype with increased cytotoxicity and decreased interferon gamma (IFN-γ) production in chronic hepatitis C virus (HCV) infection. Here, we asked whether this is caused by type I interferon (IFN)-induced expression and phosphorylation levels of signal transducer and activator of transcription (STAT) molecules in NK cells and whether it affects the response and refractoriness of NK cells to IFN-α-based therapy of HCV. STAT1 levels in NK cells were significantly higher in patients with chronic HCV infection than in uninfected controls. STAT1 levels and induction of phosphorylated STAT1 (pSTAT1) increased further during IFN-α-based therapy with preferential STAT1 over STAT4 phosphorylation. Induction of pSTAT1 correlated with increased NK cytotoxicity (tumor necrosis factor-apoptosis-inducing ligand [TRAIL] expression and degranulation) and decreased IFN-γ production. NK cells from patients with a greater than 2 log(10) first-phase HCV RNA decline to IFN-α-based therapy (>99% IFN effectiveness) displayed strong pSTAT1 induction in vivo and were refractory to further stimulation in vitro. In contrast, NK cells from patients with a less than 2 log(10) first-phase HCV RNA decline exhibited lower pSTAT1 induction in vivo (P = 0.024), but retained greater IFN-α responsiveness in vitro (P = 0.024). NK cells of all patients became refractory to in vivo and in vitro stimulation by IFN-α during the second-phase virological response.
conclusionThese data show that IFN-α-induced modulation of STAT1/4 phosphorylation underlies the polarization of NK cells toward increased cytotoxicity and decreased IFN-γ production in HCV infection, and that NK cell responsiveness and refractoriness correlate to the antiviral effectiveness of IFN-α-based therapy.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.