Our aim was to assess sustained virologic response (SVR)-associated early gene expression in patients with HCV receiving pegylated interferon-alpha2a (PEG-IFN-alpha2a) or PEG-IFN-alpha2b and ribavirin with the duration based on genotypes.
These findings suggest that IFN-α can inhibit HCV replication through a STAT2-dependent but STAT1-independent pathway, whereas IFN-λ induces ISG expression and inhibits HCV replication exclusively through a STAT1- and STAT2-dependent pathway.
To characterize the response of HCV-infected patients to treatment with IFNα, the expression of an IFN-response gene signature comprised of IFN-stimulated genes and genes that play an important role in the innate immune response was examined in liver biopsies from HCV-infected patients enrolled in a clinical trial.
Currently, the combination of RNAi (LV-shIRES) with IFN-α has been proposed to prevent therapeutic resistance, and to promote enhanced antiviral activity against HCV.
At biochemical and virological long-term follow-up performed in 26 sustained virological responders 3.5-8.8 years (mean +/- SD, 5.4+/-1.6 years) after the end of IFN therapy, 22 patients (85%) had normal serum ALT levels, and 24 patients (92%) were HCV RNA negative in serum.
Thirty-eight patients with chronic HCV hepatitis were investigated for the serum levels of the previously mentioned cytokines in a randomized opened controlled trial (22 patients treated with pegylated IFN and 16 patients treated with standard IFN).
Sessions included: IFN-λ Biology, Therapy and Genetic Variation; IFN-λ and Hepatitis C Virus Infection; IFN-λ in Other Infections; and IFN-λ-Hepatic Fibrosis and Cancer.
Thus, the causative role, played by HCV in SMZL development, is once again reinforced, whereby the antiviral, rather than the anti-proliferative activity of IFN is indirectly proven.
When the effect of the inhibition on the cells infected with hepatitis C virus (HCV) was examined, the significant decrease of IFN stimulated gene expression and the enhancement of initial HCV replication were observed, suggesting that the steady-state production of IFN-α plays a role in amplification of antiviral responses to control the spread of RNA viral infection in human hepatocytes.
Levels of IL-29 and IFN-? serum were significantly higher in SVR at ETR and 6 months later compared to those of the relapsed patients, but there was no difference between the two groups regarding the presence or absence of plus-/minus HCV strand in PBMCs.
To investigate the intra-hepatic activation of the IFN system in patients affected by chronic HCV-infection in comparison with that observed in a non-infectious liver disease such as non-alcoholic steatohepatitis, we measured the liver steady state mRNA levels of interferon-alpha, interferon-beta and interferon-gamma as well as of IFN-related genes (IFNAR-1, STAT1alpha, PKR, 2-5 AS, IRF-1, ICE and IL-18).
We showed that IFN-λ4, produced at low level only in T/T cells induced expression of IL28B and IL-29 and prevented IFN-α antiviral activity in HCV cell culture.
Therefore, the current study was aimed to prospectively utilize the baseline IL-8 levels in the HCV infected serum and predicts its role in sustained virological response (SVR) to IFN-α+ribavirin therapy, in chronic HCV patients in Pakistan.
Interestingly, co-infection resulted in down regulation of several IFN genes and significant up regulation of TGF-β genes leading to an overall enhancement of HCV replication.
In this study, we show that miR-208b and miR-499a-5p also dampen type I IFN signaling in HCV-infected hepatocytes by directly down-regulating expression of the type I IFN receptor chain, IFNAR1.
Weekly PEG-IFN-lambda with or without daily RBV for 4 weeks is well tolerated with minimal adverse events and hematologic effects and is associated with clear antiviral activity across a broad range of doses in patients with chronic HCV.
Importantly, the expression of CD100 on NK cells from HCV patients was inversely associated with the HCV-RNA levels in the early phase of IFN-α therapy, and the IFN-α upregulated CD100 led to an enhanced NK killing activity through ligations with its receptors plexin-B1/B2 on target cells.
To clarify the effects of hepatitis C virus nonstructural protein 5A (NS5A) on antiviral activity of IFN, in particular on PKR kinase activity, in mammalian cells, we established inducible NS5A-expressing cell lines derived from human osteosarcoma (Saos-2).
The occurrence of elevated ALT levels in HCV-RNA-negative patients during PEG-IFN and ribavirin therapy is a fairly frequent and unpredictable phenomenon.
The high level of degranulation activity observed before treatment was associated with a high HCV RNA decline at the early stage of peg-IFN-α/ribavirin treatment in patients with favorable genotypes.
We investigated the expression of hepatic IFN receptor alpha/beta (IFNAR2c) mRNA and its association with the effectiveness of IFN plus ribavirin (RBV) therapy and with the clinical features in patients with HCV genotype 1b (HCV-1b) infection.