24 research outputs found

    Impact of sequential NUC therapy on the expression of NK cell receptors and functional capacity of NK cells.

    No full text
    <p>Percent of CD56<sup>bright</sup> NK cells expressing (A) NKG2D (B) NKG2A (C) NKp30, (D) TRAIL, (E) CD107 and (F) IFN╬│ in 9 paired cross-sectional samples pre-treatment, last sampling treatment time-point on PegIFN╬▒ therapy and final sampling time-point on sequential NUC therapy with representative FACS plots at these time-points. Significant changes marked with asterisks, *P<0.05;**P<0.01;***P<0.001, ns = not significant. Clinical data showing (G) changes in ALT (IU/L), HBV DNA and HBsAg (log<sub>10</sub>IU/ml) throughout treatments. Corresponding cumulative summary data indicating dynamic changes in (H) NCRs (NKp30, NKp44 and NKp46), (I) TRAIL, CD107 and IFN╬│ expression throughout treatment, correlating with treatment time-points in (G) (Pre = pre-treatment time-point; 12<sup>I</sup> = last PegIFN╬▒ therapy time-point; 0<sup>N</sup> = Sequential NUC initiation time-point; 3<sup>N</sup>, 6<sup>N</sup>, 9<sup>N</sup> = 3, 6 and 9-month sampling time-points on sequential NUC therapy).</p

    Impact of PegIFN╬▒ and sequential NUC therapy on NK cell numbers, proliferation and activation.

    No full text
    <p>Cumulative longitudinal data demonstrating change in CD56<sup>bright</sup> NK cells over the course of PegIFN╬▒ therapy by (A) percent and absolute cell number (median ┬▒ 95%CI), (n = 18). Change in the number of (B) CD56<sup>bright</sup> NK cells and (C) CD56<sup>dim</sup> NK cells (by percent and absolute number) in 9 paired cross-sectional samples in patients on sequential NUC therapy; showing pre-treatment numbers, last sampling treatment time-point on PegIFN╬▒ therapy and final sampling time-point on sequential NUC therapy. (D) Corresponding overall ALT, HBV DNA and HBsAg levels (mean + SEM) at the aforementioned sampling time-points. Proportion of CD56<sup>bright</sup> NK cells expressing (E) Ki67 and (F) HLA-DR, in 9 paired samples, pre-treatment, on PegIFN╬▒ and sequential NUC therapy, with representative FACS plots at these time-points. Significant changes marked with asterisks, *P<0.05;**P<0.01; ***P<0.001, ns = not significant.</p

    Expression of NK cell migration markers on sequential NUC therapy compared with de novo NUC therapy & PegIFN╬▒ only therapy.

    No full text
    <p>Percentage of CD56<sup>bright</sup> NK cells expressing (A) CD62L and (B) CXCR3 in the cohort of patients treated with sequential NUC therapy (Cohort 1; n = 14, red outline bars), compared with the cohorts of patients treated with nucleos(t)ide analoguesÔÇöde novo NUC therapy (Cohort 2; n = 12, green outline bars), without previous PegIFN╬▒ exposure, and with PegIFN╬▒ alone with no further therapy for 9 months (Cohort 3; n = 10, grey outline bars). Sampling time-point is at viral suppression for patients in cohort 1 and 2. The end of treatment (EoT) PegIFN╬▒ sampling time-point for cohort 1, is shown in the blue outline bars for comparison. Representative FACS plots for each corresponding treatment cohort are shown. Results are expressed as mean ┬▒ SEM. Significant changes marked with asterisks, *P<0.05;**P<0.01; ***P<0.001, ns = not significant.</p

    Comparison of NK cells on sequential NUC therapy with de novo NUC therapy & PegIFN╬▒ only therapy.

    No full text
    <p>Percentage of CD56<sup>bright</sup> NK cells and markers in the cohort of patients treated with sequential NUC therapy (Cohort 1; n = 14, red outline bars), compared with the cohorts of patients treated with nucleos(t)ide analoguesÔÇöde novo NUC therapy (Cohort 2; n = 12, green outline bars), without previous PegIFN╬▒ exposure, and with PegIFN╬▒ alone with no further therapy for 9 months (Cohort 3; n = 10, grey outline bars). Sampling time-point is at viral suppression for patients in cohort 1 and 2. The end of treatment (EoT) PegIFN╬▒ sampling time-point for cohort 1, is shown in the blue outline bars for comparison. Markers shown (A) CD56<sup>bright</sup> NK cells, Ki67, CD69, (B) NKG2A, NKG2D, (C) NKp30, NKp44, NKp46, (D) TRAIL, CD107, IFN╬│. Results are expressed as mean ┬▒ SEM. Significant changes marked with asterisks, *P<0.05;**P<0.01; ***P<0.001, ns = not significant.</p

    Schematic overview of patients studied for immune analysis.

    No full text
    <p>Cohort 1 indicates sequential NUC therapy patients studied; 18 consecutive patients were analysed longitudinally during a 48 week course of PegIFN╬▒ therapy (blue dashed outline), of which 9/18 patients progressed to sequential NUC therapy, following a 6ÔÇô12 week interval gap (grey shaded box), and were sampled longitudinally; *indicates 5 further patients analysed undergoing sequential NUC therapy, sampled at time-point month 0 and 9 only on sequential therapy (total sequential NUC therapy cohort; n = 14) (red dashed outline). Cohort 2; n = 12 patients analysed at a single time-point at viral suppression on de novo NUC therapy (green dashed outline). Cohort 3; n = 10 patients treated with PegIFN╬▒ therapy for 48 weeks that did not undergo any further treatment (grey dashed outline), and sampled at 9 months following cessation of PegIFN╬▒. Arrows under time-points indicate sampling time for immune analysis in each cohort.</p

    Enrollment and patient disposition.

    No full text
    <p><sup>a</sup>Other reasons (more than one reason may apply to a given patient): no final confirmation from the investigator (n = 56); contraindications to therapy (n = 15); HCV RNA-negative at screening/baseline (n = 12); end-stage renal disease (n = 7); major organ transplantation (n = 2); not treated with peginterferon alfa (n = 1) or ribavirin (n = 2); acute hepatitis C (n = 1); co-infection with HIV (n = 115); co-infection with HBV (n = 74); treatment with regimen other than peginterferon alfa-2a/ribavirin or peginterferon alfa-2b/ribavirin (n = 14); treatment-naive and intended treatment duration of 72 weeks (n = 6).</p

    Cox proportional hazards analysis for time to first safety-related dose reductions or discontinuations in patients treated for 24 or 48 weeks with peginterferon alfa-2a or alfa-2b and ribavirin.

    No full text
    <p>(A) All treatment-naive patients (G1ÔÇô6) assigned to 24 or 48 weeks of treatment with peginterferon alfa-2a or alfa-2b/RBV (N = 3181); (B) Subgroup 2: treatment-naive Caucasian, G1 noncirrhotic patients assigned to 48 weeks of treatment with peginterferon alfa-2a/RBV (n = 951).</p
    corecore