Significance of triggering receptor expressed on myeloid cells-2 prognostic evaluation in hepatitis B virus-related acute-on-chronic liver failure

Abstract

Objective: To explore the significance of triggering receptor expressed on myeloid cells-2 (TREM-2) prognostic evaluation so as to provide novel biological markers in clinical practice for patients with hepatitis B virus-related acute-on-chronic liver failure ( HBV-ACLF). Methods: The research subjects of this study were divided into an experimental group and a control group. Fifty HBV-ACLF cases admitted to the Department of Infectious Diseases of the First Affiliated Hospital of Nanchang University from January 1, 2019 to December 31, 2019 were selected as the experimental group. Patients were divided into survival and death groups according to the actual prognosis at discharge (self-discharge and dead patients were considered death groups, and all enrolled patients were hospitalized for more than 28 days). Twenty-five healthy subjects were chosen as the control group. Peripheral venous blood was collected from the experimental group and the control group. Plasma and peripheral blood mononuclear cells (PBMC) were isolated. The concentrations of TREM-2, interleukin (IL)-6, and IL-8 were detected in the plasma. TREM-2 mRNA expression was detected in PBMC. A single blood sample was collected from the control group, whereas five blood samples were dynamically collected from the experimental group on the day of admittance and at 7, 14, 21, and 28 days after treatment commenced. Simultaneously, upon admission, the relevant clinical indicators of HBV-ACLF patients were monitored, including the liver function test: alanine aminotransferase, aspartate aminotransferase, total bilirubin, albumin, coagulation function test: international normalized ratio, prothrombin time, and other indicators. Measurement data were expressed as mean±standard deviation (x±s). Count data were compared and analyzed using the χ(2) test. The intra-group factor mean was compared using a repeated measures ANOVA. The means were analyzed by t-tests between the two groups. Bivariate correlation analysis was used to analyze the correlation between the two variables. The value of TREM-2 as a diagnostic marker was analyzed using the receiver operating characteristic (ROC) curve. Results: The mRNA expression of TREM-2 in the PBMC of HBV-ACLF patients showed a gradually increasing trend at various time points and was significantly higher in the survival group than that of the control group at 28 days (P < 0.01), while the death group showed a gradually weakening trend at various time points and was significantly lower than the control group at 28 days (P < 0.01). (1) The levels of TREM-2 in the plasma of HBV-ACLF patients generally showed a gradually increasing trend at various time points in the survival group. The levels on the day of admission and 7, 14, 21, and 28 days after the initiation of treatment were (1.49±0.85), (1.62±0.58), (1.95±0.69), (2.33±0.71), and (2.00±0.67) ng/ml, respectively. The expression of TREM-2 in the death group showed a gradually weakening trend at various time points. The levels on the day of admission and 7, 14, 21, and 28 days after initiation of treatment were (1.40±0.73), (1.59±0.79), (1.56±0.80), (1.05±0.49), and (0.81±0.21) ng/ml, respectively. The survival group's various detection time points were higher than those of the death group, and the difference was statistically significant. The plasma level of TREM-2 in the healthy control group was (1.25±0.35) ng/ml. (2) The concentrations of IL-6 and IL-8 in the plasma of HBV-ACLF patients showed a gradually decreasing trend at various time points in the survival group. The levels on the day of admission and 7, 14, 21, and 28 days after initiation of treatment were (46.70±26.31), (33.98±20.28), (19.07±10.24), (14.76±7.84), (9.12±7.65) and (108.29±47.07), (93.85±26.53), (79.27±34.63), (56.72 ±18.30), (37.81±13.88) pg/ml, respectively. However, its concentration in the death group fluctuated within a relatively high range. The levels on the day of admission and 7, 14, 21, and 28 days after the initiation of treatment were (41.94±24.19), (36.99±19.78), (34.30±20.62), (34.14±14.52), (36.64±23.61) and (104.65±50.16), (112.98±45.03), (118.43±45.00), (111.67±40.44), (109.55±27.54) pg/ml, respectively. (3) Bivariate correlation analysis results indicated that the plasma TREM-2 content was negatively correlated with the plasma levels of pro-inflammatory cytokines IL-6 and IL-8 (r = -0.224, P = 0.025; r = - 0.223, P = 0.026). ROC curve analysis showed that the mRNA levels of TREM-2 in PBMCs at various time points for prognostic evaluation of HBV-ACLF patients were 1d=0.667, 7d=0.757, 14d=0.979, 21d=0.986, and 28d= 0.993. The areas under the ROC curve of the TREM-2 content in the plasma at various time points were 1d=0.522, 7d=0.571, 14d=0.658, 21d=0.927, and 28d=0.994. Conclusion: TREM-2 mRNA expression in PBMC and TREM-2 content in plasma have a significant relationship to the prognosis of HBV-ACLF patients and may inhibit the liver inflammatory response by regulating the secretion of pro-inflammatory cytokines IL-6 and IL-8. Dynamic monitoring of TREM-2 expression in peripheral blood is favorable for evaluating the prognostic condition of HBV-ACLF patients.