Assay validation and clinical performance of chronic inflammatory and chemokine biomarkers of NASH fibrosis.

Nonalcoholic steatohepatitis (NASH) is a chronic liver disease that can lead to cirrhosis, liver transplant, and even hepatocellular carcinoma. While liver biopsy remains the reference standard for disease diagnosis, analytical and clinical development of non-invasive soluble biomarkers of NASH are of great importance to advance the field. To this end, we performed analytical and clinical validation on a series of pro-inflammatory cytokines and chemokines implicated hepatic inflammation; IL-6, CRP, TNFα, MCP-1, MIP-1ß, eotaxin, VCAM-1. Biomarker assays were validated for accuracy and precision. Clinical performance was evaluated in a random sample of 52 patients with biopsy-proven NAFLD/NASH. Patients were categorized into three groups according to their fibrosis stage; advanced (F3-F4), mild (F1-2) and no (F0) fibrosis. Serum IL-6 was increased in patients with advanced fibrosis (2.71 pg/mL; 1.26 pg/mL; 1.39 pg/mL p<0.01) compared to patients with mild or no fibrosis respectively. While, there was no significant difference noted in CRP, TNFα, MCP-1, MIP-1ß, eotaxin among the three groups, VCAM-1 levels were increased by 55% (p<0.01) and 40% (p<0.05) in the advanced cohort compared to the mild and no fibrosis groups respectively. VCAM-1 also displayed good clinical performance as a biomarker of advanced fibrosis with an area under the receiver operating curve of 0.87. The VCAM-1 assay demonstrated robust accuracy and precision, and VCAM-1 outperformed IL-6, CRP, TNFα, and the chemokines MCP-1, MIP-1ß, and eotaxin as a biomarker of advanced fibrosis in NASH. Addition of biomarkers such as IL-6 and VCAM-1 to panels may yield increased sensitivity and specificity for staging of NASH.

Evaluation of HbA1c screening during outreach events for prediabetes subject recruitment for clinical research.

BACKGROUND: There are a number of obstacles which may impede the recruitment of underserved populations in clinical research studies; some of these factors include mistrust of medical research, socioeconomic constraints, cultural factors, and language barriers. For chronic metabolic disease indications, these barriers may also include lack of disease awareness. Recently, national organizations such as the American Diabetes Association (ADA) and Centers for Disease Control and Prevention (CDC) have highlighted the need for prediabetes recognition. Therefore the aim of the study was twofold: to raise prediabetes awareness in an under-represented Hispanic community and to engage prediabetes participants in clinical research. METHODS: Hemoglobin A1c (HbA1c) screening was performed at major outreach events catered to the Hispanic community. All participants signed an ethics review board approved waiver which collected basic demographic information and the HbA1c test was performed with a hand-held monitor and finger-stick blood sample. Participants were given their HbA1c results at the event as well as information on prediabetes and upcoming clinic studies. After the event, participants were contacted by a study participant recruiter to assess interest in participating in clinical research. RESULTS: The majority of participants screened fell within a prediabetes HbA1c range. Mean HbA1c was similar among men and women, yet higher in individuals aged 45-65 years compared to adults aged < 45 years (p < 0.05). For recruitment purposes, the highest number of leads came from participants attending a faith-based community event. In all, 17% of individuals contacted expressed interest in participating in clinical research and created a profile within our database to be eligible for future studies. CONCLUSIONS: Providing no-cost HbA1c screening is an excellent recruitment tool for clinical research as well as an opportunity to raise prediabetes awareness in a traditionally underserved population.