title: Novel plasma biomarkers associated with liver disease severity in adults with nonalcoholic fatty liver disease.
abstract: Despite the high prevalence of nonalcoholic fatty liver disease (NAFLD), therapeutic options and noninvasive markers of disease activity and severity remain limited. We investigated the association between plasma biomarkers and liver histology in order to identify markers of disease activity and severity in patients with biopsy-proven NAFLD. Thirty-two plasma biomarkers chosen a priori as possible discriminators of NAFLD were measured in participants enrolled in the Nonalcoholic Steatohepatitis (NASH) Clinical Research Network. Dichotomized histologic outcomes were evaluated using centrally read biopsies. Biomarkers with statistically significant associations with NAFLD histology were evaluated in multivariable models adjusted for clinical factors. Of 648 participants (74.4% white, 61.7% female, mean age 47.7 years), 58.0% had definite NASH, 55.5% had mild/no fibrosis (stage 0-1), and 44.4% had significant fibrosis (stage 2-4). Increased activated plasminogen activator inhibitor 1 had a strong association with definite NASH compared to not NASH or borderline NASH in multivariable analysis (odds ratio = 1.20, 95% confidence interval 1.08-1.34, P < 0.001). Biomarkers associated with significant fibrosis (versus mild/no fibrosis) in multivariable analysis included higher levels of interleukin-8, monocyte chemoattractant protein-1, resistin, soluble interleukin-1 receptor I, soluble interleukin-2 receptor alpha, and tumor necrosis factor alpha and lower levels of insulin-like growth factor 2.
  
  
  
  Specific plasma biomarkers are significantly associated with disease activity and severity of fibrosis in NAFLD and are potentially valuable tools for noninvasive stratification of patients with NAFLD and identification of targets for therapeutic intervention. (Hepatology 2017;65:65-77).
authors.affiliation: Division of Gastroenterology and, University of California-San Francisco, San Francisco, CA.
authors.forename: Veeral
authors.initials: V
authors.lastname: Ajmera
authors.affiliation: Division of Pediatric Gastroenterology, University of California-San Francisco, San Francisco, CA.
authors.forename: Emily R
authors.initials: ER
authors.lastname: Perito
authors.affiliation: Division of Gastroenterology and, University of California-San Francisco, San Francisco, CA.
authors.forename: Nathan M
authors.initials: NM
authors.lastname: Bass
authors.affiliation: Division of Gastroenterology and, University of California-San Francisco, San Francisco, CA.
authors.forename: Norah A
authors.initials: NA
authors.lastname: Terrault
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
authors.forename: Katherine P
authors.initials: KP
authors.lastname: Yates
authors.affiliation: Division of Pathology, University of California-San Francisco, San Francisco, CA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Gill
authors.affiliation: Division of Gastroenterology, University of California-San Diego, San Diego, CA.
authors.forename: Rohit
authors.initials: R
authors.lastname: Loomba
authors.affiliation: Division of Gastroenterology, Duke University, Durham, NC.
authors.forename: Anna Mae
authors.initials: AM
authors.lastname: Diehl
authors.affiliation: Bluestone Center for Clinical Research, New York University, New York City, NY.
authors.forename: Bradley E
authors.initials: BE
authors.lastname: Aouizerat
mesh_terms: D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008099:Liver / Q000473:pathology*; D008107:Liver Diseases / Q000097:blood / Q000150:complications / Q000473:pathology; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood* / Q000150:complications / Q000473:pathology*; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers