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

BACKGROUND & AIMS: Reliable non-invasive 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 & 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 NASH patients of the derivation cohort, with an area under the receiver operating characteristics curve (AUROC) of 0.92 (95% CI: 0.84-0.99). In the validation cohort, plasma TREM2 level increased ~2-fold in NASH patients 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 cut-offs 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 cut-off (sensitivity 90%, specificity 52%), whereas a plasma TREM2 level of ≥65 ng/ml was an optimal NASH rule-in cut-off (specificity 89% and sensitivity 54%).

CONCLUSION: 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.