Circulating TREM2 as a noninvasive diagnostic biomarker for NASH in patients with elevated liver stiffness.

Autor:	Indira Chandran V; Department of Molecular Medicine , University of Southern Denmark , Odense , Denmark., Wernberg CW; Liver Research Group , Department of Gastroenterology and Hepatology , University Hospital of South Denmark , Esbjerg , Denmark.; Centre for Liver Research , Department of Gastroenterology and Hepatology , Odense University Hospital , Odense , Denmark., Lauridsen MM; Liver Research Group , Department of Gastroenterology and Hepatology , University Hospital of South Denmark , Esbjerg , Denmark., Skytthe MK; Department of Molecular Medicine , University of Southern Denmark , Odense , Denmark., Bendixen SM; Department of Biochemistry and Molecular Biology , University of Southern Denmark , Odense , Denmark., Larsen FT; Department of Biochemistry and Molecular Biology , University of Southern Denmark , Odense , Denmark., Hansen CD; Centre for Liver Research , Department of Gastroenterology and Hepatology , Odense University Hospital , Odense , Denmark., Grønkjær LL; Liver Research Group , Department of Gastroenterology and Hepatology , University Hospital of South Denmark , Esbjerg , Denmark., Siersbæk MS; Department of Biochemistry and Molecular Biology , University of Southern Denmark , Odense , Denmark., Caterino TD; Department of Pathology , Odense University Hospital , Odense , Denmark., Detlefsen S; Department of Pathology , Odense University Hospital , Odense , Denmark., Møller HJ; Department of Clinical Biochemistry , Aarhus University Hospital , Aarhus , Denmark.; Department of Clinical Medicine , Aarhus University , Aarhus , Denmark., Grøntved L; Department of Biochemistry and Molecular Biology , University of Southern Denmark , Odense , Denmark., Ravnskjaer K; Department of Biochemistry and Molecular Biology , University of Southern Denmark , Odense , Denmark., Moestrup SK; Department of Molecular Medicine , University of Southern Denmark , Odense , Denmark., Thiele MS; Centre for Liver Research , Department of Gastroenterology and Hepatology , Odense University Hospital , Odense , Denmark., Krag A; Centre for Liver Research , Department of Gastroenterology and Hepatology , Odense University Hospital , Odense , Denmark., Graversen JH; Department of Molecular Medicine , University of Southern Denmark , Odense , Denmark.
Jazyk:	angličtina
Zdroj:	Hepatology (Baltimore, Md.) [Hepatology] 2023 Feb 01; Vol. 77 (2), pp. 558-572. Date of Electronic Publication: 2022 Jul 14.
DOI:	10.1002/hep.32620
Abstrakt:	Background and Aims: Reliable noninvasive biomarkers are an unmet clinical need for the diagnosis of NASH. This study investigates the diagnostic accuracy of the circulating triggering receptor expressed on myeloid cells 2 (plasma TREM2) as a biomarker for NASH in patients with NAFLD and elevated liver stiffness. Approach and Results: We collected cross-sectional, clinical data including liver biopsies from a derivation ( n = 48) and a validation cohort ( n = 170) of patients with elevated liver stiffness measurement (LSM ≥ 8.0 kPa). Patients with NAFLD activity scores (NAS) ≥4 were defined as having NASH. Plasma TREM2 levels were significantly elevated in patients with NASH of the derivation cohort, with an area under the receiver operating characteristics curve (AUROC) of 0.92 (95% confidence interval [CI], 0.84-0.99). In the validation cohort, plasma TREM2 level increased approximately two-fold in patients with NASH, and a strong diagnostic accuracy was confirmed (AUROC, 0.83; 95% CI, 0.77-0.89; p  < 0.0001). Plasma TREM2 levels were associated with the individual histologic features of NAS: steatosis, lobular inflammation, and ballooning ( p  < 0.0001), but only weakly with fibrosis stages. Dual cutoffs for rule-in and rule-out were explored: a plasma TREM2 level of ≤38 ng/ml was found to be an optimal NASH rule-out cutoff (sensitivity 90%; specificity 52%), whereas a plasma TREM2 level of ≥65 ng/ml was an optimal NASH rule-in cutoff (specificity 89%; sensitivity 54%). Conclusions: Plasma TREM2 is a plausible individual biomarker that can rule-in or rule-out the presence of NASH with high accuracy and thus has the potential to reduce the need for liver biopsies and to identify patients who are eligible for clinical trials in NASH. (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of American Association for the Study of Liver Diseases.)
Databáze:	MEDLINE
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