Summary of adverse events for patients without severe renal impairment^a.

Summary of adverse events for patients without severe renal impairmenta.</p

Baseline demographics and clinical characteristics.

Baseline demographics and clinical characteristics.</p

Summary of post-baseline laboratory abnormalities.

Summary of post-baseline laboratory abnormalities.</p

Safety and efficacy of glecaprevir/pibrentasvir for the treatment of chronic hepatitis C in patients aged 65 years or older - Fig 1

Sustained virologic response at post-treatment week 12 by A) hepatitis C virus genotype; B) fibrosis stage; C) glecaprevir/pibrentasvir treatment duration; and D) glecaprevir/pibrentasvir treatment compliancea (ITT analyses). aCompliant was defined as 80%–120% of expected glecaprevir/pibrentasvir intake. F, fibrosis stage; GT, genotype; ITT, intention-to-treat; SVR12, sustained virologic response at post-treatment week 12; VF, virologic failure.</p

Concomitant medications.

Concomitant medications.</p

Summary of adverse events for patients with severe renal impairment^a.

Summary of adverse events for patients with severe renal impairmenta.</p

Association of change in HBsAg and functional capacity of NK cells.

(A) Change in HBsAg titre (log10IU/ml) from initiation of NUC to viral suppression in the sequential NUC therapy cohort (Cohort 1) compared with de novo NUC therapy (Cohort 2). (B) Findings in (A) confirmed in a larger cohort of patients; sequential NUC therapy [n = 28; Baseline (BL): ALT 92 IU/L, HBV DNA 6.65 logIU/ml HBsAg 3.86 logIU/ml], de-novo NUC therapy (n = 30; BL: ALT 70, HBV DNA 5.79 log IU/ml, HBsAg 3.75 logIU/ml); (p = ns for all BL clinical parameters between the cohorts). Results are expressed as mean ± SEM. Change in (C) HBsAg titre (log10IU/ml) from initiation of sequential NUC to viral suppression (9-months of sequential NUC therapy in all patients) in the cohort of sequential therapy treated patients (unshaded = HBsAg responder; shaded red = HBsAg non-responder), (Patient number corresponding with number in Table 1 and S1 Table). Change in percentage of (D) CD107+, (E) IFNγ+ and (F) TRAIL+ CD56bright NK cells from initiation of sequential NUC to viral suppression in each patient in the sequential therapy cohort with corresponding summary data for HBsAg responders (unshaded) vs. non-responders (shaded red) for each marker. Significant changes between the groups are marked with asterisks *P<0.05;**P<0.01;***P<0.001, ns = not significant.</p

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

<p>Percent of CD56^bright NK cells expressing (A) NKG2D (B) NKG2A (C) NKp30, (D) TRAIL, (E) CD107 and (F) IFNγ in 9 paired cross-sectional samples pre-treatment, last sampling treatment time-point on PegIFNα 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 (log₁₀IU/ml) throughout treatments. Corresponding cumulative summary data indicating dynamic changes in (H) NCRs (NKp30, NKp44 and NKp46), (I) TRAIL, CD107 and IFNγ expression throughout treatment, correlating with treatment time-points in (G) (Pre = pre-treatment time-point; 12^I = last PegIFNα therapy time-point; 0^N = Sequential NUC initiation time-point; 3^N, 6^N, 9^N = 3, 6 and 9-month sampling time-points on sequential NUC therapy).</p

Baseline characteristics & clinical features of patients (Cohort 1).

<p>Baseline characteristics & clinical features of patients (Cohort 1).</p

Impact of PegIFNα and sequential NUC therapy on NK cell numbers, proliferation and activation.

<p>Cumulative longitudinal data demonstrating change in CD56^bright NK cells over the course of PegIFNα therapy by (A) percent and absolute cell number (median ± 95%CI), (n = 18). Change in the number of (B) CD56^bright NK cells and (C) CD56^dim 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 PegIFNα 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^bright NK cells expressing (E) Ki67 and (F) HLA-DR, in 9 paired samples, pre-treatment, on PegIFNα 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