ADAMTSL2 protein and a soluble biomarker signature identify at-risk non-alcoholic steatohepatitis and fibrosis in adults with NAFLD

• DOI: 10.1016/j.jhep.2021.09.026
• Publication Date: 2021-10-01T05:56:17Z
• Authors: Kathleen E. Corey; Rebecca Pitts; Michelle Lai; Joseph Loureiro; Ricard Masia; Stephanie A. Osga...; Jenna L. Gustafson; Matthew M. Hutter; Denise W. Gee; Ozanan R. Meireles; Elan R. Witkowski; Shola M. Richards; Jaison Jacob; Nancy Finkel; Debby Ngo; Thomas J. Wang; Robert E. Gerszten; Chinweike Ukomadu; Lori L. Jennings
• Keywords: Steatohepatitis

•Aptamer-based profiling platform used to find proteins that non-invasively identify significant fibrosis in 316 adults with NAFLD.•An 8-protein panel can distinguish NAFL/NASH stage 0-1 from 2-4 an AUROC of 0.87-0.89.•The ADAMTSL2 protein alone 0.83-0.86.•Both the and showed superior performance NAFLD score fibrosis-4 score. Background & AimsIdentifying non-alcoholic fatty liver disease (NAFLD) is essential predict liver-related outcomes guide treatment decisions. A protein-based signature could serve as a valuable, non-invasive diagnostic tool. This study sought circulating associated NAFLD.MethodsWe aptamer-based proteomics measure 4,783 2 cohorts (Cohort B). Targeted, quantitative assays coupling pull down mass spectrometry (SPMS) validated results bariatric cohort C D, respectively). Generalized linear modeling-logistic regression assessed ability candidate classify fibrosis.ResultsFrom multiplex profiling, 16 differed significantly by (n = 62) B 98). Quantitative robust SPMS were developed for 8 Cohorts 71) D 84). The disintegrin metalloproteinase thrombospondin motifs like (ADAMTSL2) accurately distinguished (NAFL)/non-alcoholic steatohepatitis (NASH) (F0-1) at-risk NASH 2-4, AUROCs 0.83 0.86 respectively, (F2-3), 0.80 respectively. An F0-1 (AUROCs 0.90 0.87 Cohort respectively) F2-3 0.89 had score.ConclusionThe soluble biomarker are highly fibrosis; they exhibited compared standard care scores.Lay SummaryNon-alcoholic one most common causes worldwide. Diagnosing identifying (scarring liver) currently requires biopsy. Our identified novel found blood which may without need Identifying NAFLD. We fibrosis. From scores.