Demographic and clinical characteristics.

Demographic and clinical characteristics.</p

WFA⁺ -M2BP can discriminate fibrotic NASH & cirrhosis from NAFL & early NASH.

The area under the ROC curve (AUC) of WFA+ -M2BP, APRI and FIB-4 were [0.866 (0.801, 0.931)], [0.792 (0.716, 0.868)] and [0.770 (0.687, 0.852)], respectively.</p

WFA⁺ -M2BP is increased in fibrotic NASH and NASH cirrhosis–Adjusted analysis.

Patients with fibrotic NASH and NASH cirrhosis were found to have significantly higher WFA+ -M2BP levels than healthy controls, NAFL and early NASH (p+ -M2BP levels than fibrotic NASH (p0.20).</p

Minimal dataset.

(XLSX)</p

Correlation between WFA⁺ -M2BP level and other severity measures.

Correlation between WFA+ -M2BP level and other severity measures.</p

<b>Supplemental Material - EDP-514 in healthy subjects and nucleos(t)ide reverse transcriptase inhibitor-suppressed patients with chronic hepatitis B</b>

Supplementary Material for EDP-514 in healthy subjects and nucleos(t)ide reverse transcriptase inhibitor-suppressed patients with chronic hepatitis B by Jordan J Feld, Eric Lawitz, Tuan Nguyen, Jacob Lalezari, Tarek Hassanein, Paul Martin, Steven-Huy Han, Douglas Dieterich, Jeanne-Marie Giard, Guy De La Rosa, Alaa Ahmad, Ed Luo, Annie L Conery, and Nathalie Adda in Antiviral Therapy.</p

A Randomized, Double-Blind, Placebo-Controlled Assessment of BMS-936558, a Fully Human Monoclonal Antibody to Programmed Death-1 (PD-1), in Patients with Chronic Hepatitis C Virus Infection

<div><p></p><p>Expression of the programmed death 1 (PD-1) receptor and its ligands are implicated in the T cell exhaustion phenotype which contributes to the persistence of several chronic viral infections, including human hepatitis C virus (HCV). The antiviral potential of BMS-936558 (MDX-1106) – a fully human anti-PD-1 monoclonal immunoglobulin-G4 that blocks ligand binding – was explored in a proof-of-concept, placebo-controlled single-ascending-dose study in patients (N = 54) with chronic HCV infection. Interferon-alfa treatment-experienced patients (n = 42) were randomized 5∶1 to receive a single infusion of BMS-936558 (0.03, 0.1, 0.3, 1.0, 3.0 mg/kg [n = 5 each] or 10 mg/kg [n = 10]) or of placebo (n = 7). An additional 12 HCV treatment-naïve patients were randomized to receive 10 mg/kg BMS-936558 (n = 10) or placebo (n = 2). Patients were followed for 85 days post-dose. Five patients who received BMS-936558 (0.1 [n = 1] or 10 mg/kg) and one placebo patient achieved the primary study endpoint of a reduction in HCV RNA ≥0.5 log₁₀ IU/mL on at least 2 consecutive visits; 3 (10 mg/kg) achieved a >4 log₁₀ reduction. Two patients (10 mg/kg) achieved HCV RNA below the lower limit of quantitation (25 IU/mL), one of whom (a prior null-responder) remained RNA-undetectable 1 year post-study. Transient reductions in CD4⁺, CD8⁺ and CD19⁺ cells, including both naïve and memory CD4⁺ and CD8⁺ subsets, were observed at Day 2 without evidence of immune deficit. No clinically relevant changes in immunoglobulin subsets or treatment-related trends in circulating cytokines were noted. BMS-936558 exhibited dose-related exposure increases, with a half-life of 20–24 days. BMS-936558 was mostly well tolerated. One patient (10 mg/kg) experienced an asymptomatic grade 4 ALT elevation coincident with the onset of a 4-log viral load reduction. Six patients exhibited immune-related adverse events of mild-to-moderate intensity, including two cases of hyperthyroidism consistent with autoimmune thyroiditis. Further investigation of PD-1 pathway blockade in chronic viral disease is warranted.</p><p>Trial Registration</p><p>ClinicalTrials.gov NCT00703469 <a href="http://www.clinicaltrials.gov/ct2/show/NCT00703469" target="_blank">NCT00703469</a></p></div