Soluble TREM2 is a novel diagnostic and prognostic biomarker of acute-on-chronic liver failure in patients receiving liver transplantation.

Abstract

Background: Acute-on-chronic liver failure (ACLF) is a severe syndrome with high short-term mortality. Triggering receptor expressed on myeloid cells-2 (TREM2) is highly expressed in the livers of patients with ACLF, but the role of its soluble form, soluble TREM2 (sTREM2), in ACLF is not clear.

Methods: We enrolled 96 consecutive patients receiving liver transplantation (LT), including 40 ACLF patients and 56 non-ACLF patients, and collected plasma at pre-LT and day 3, 7 and 14 after LT. We also enrolled 22 healthy controls (HC). The plasma sTREM2 level was detected using the enzyme-linked immunosorbent assay. The expression of TREM2 in the livers was examined using quantitative polymerase chain reaction.

Results: The pre-LT sTREM2 of the ACLF group was significantly higher than that of the non-ACLF group (13.4 ng/mL vs. 2.6 ng/mL, P < 0.001) and the HC group (13.4 ng/mL vs. 0.57 ng/mL, P < 0.001), but sTREM2 did not correlate with the grades of ACLF. The level of sTREM2 was positively correlated with the expression of TREM2 in the livers and had tight correlations with liver function and liver failure-related scores. To diagnose ACLF, sTREM2 showed an area under the receiver operating characteristic curve (AUROC) of 0.863 (P < 0.001). When the cut-off value was 6.5 ng/mL, the sensitivity was 74.3% and the specificity was 93.0%. sTREM2 levels tested at day 7 and 14 after LT were associated with mortality [hazard ratio (HR): 1.187 and 1.078, P < 0.001 and P = 0.043, respectively], and sTREM2 tested at day 3 after LT was a risk factor for early allograft dysfunction (EAD) [odds ratio (OR): 1.060, P = 0.023].

Conclusions: sTREM2 was a good biomarker for liver injury. Pre-LT sTREM2 could be used to diagnose ACLF and persistently high levels of sTREM2 after LT predicted poor survival and incidence of EAD.