Expression and significance of T-cell immunoglobulin and mucin domain-containing molecule 3 in peripheral blood CD3+CD56+ natural killer T cells in patients with hepatitis B virus-related acute-on-chronic liver failure

Objective To investigate the expression of T-cell immunoglobulin and mucin domain-containing molecule 3 ( TIM-3) in natural killer T ( NKT) cells and its association with liver injury and prognosis in patients with hepatitis B virus-related acute-on-chronic liver failure ( HBV-ACLF) . Methods Peripheral blood mononuclear cells were isolated from 43 patients with HBV-ACLF and 28 patients with chronic hepatitis B ( CHB) who were treated in Beijing YouAn Hospital, Capital Medical University, from September 2016 to June 2018, and flow cytometry was used to measure the number of peripheral blood CD3+CD56+NKT cells and the expression of TIM-3.The t-test was used for comparison of normally distributed continuous data between two groups. The Kruskal-Wallis H test was used for comparision of non-normally distributed continuous data between multiple groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between groups, and the Pearson correlation coefficient was used to investigate correlation. Results Compared with the CHB group, the HBV-ACLF group had significantly higher alanine aminotransferase ( ALT) , aspartate aminotransferase ( AST) , total bilirubin ( TBil) , creatinine, international normalized ratio ( INR) , HBV DNA, TBil/ALT ratio, and Model for End-Stage Liver Disease ( MELD) score, as well as significantly lower albumin and prothrombin time activity ( PTA) ( all P < 0. 05) . Compared with the CHB group, the HBV-ACLF grouphad a significantly higher number of CD3+CD56+NKT cells ( 19. 13% ± 13. 82% vs 26. 75% ± 11. 84%, t = 2. 401, P = 0. 019) and significantly higher expression of TIM-3 in CD3+CD56+NKT cells [5. 53% ( 2. 95%-10. 2%) vs 1. 59% ( 0. 91%-2. 7%) , Z =-5. 260, P < 0. 001]. The expression of TIM-3 in CD3+CD56+NKT cells was positively correlated with ALT ( r = 0. 637, P < 0. 000 1) , AST ( r = 0. 414, P = 0. 006) , INR ( r = 0. 335, P = 0. 031) , and MELD score ( r = 0. 355, P = 0. 021) and was negatively correlated with PTA% ( r =-0. 313, P = 0. 043) . Among the 43 patients with HBV-ACLF, 12 had early-stage HBV-ACLF, 21 had middle-stage HBV-ACLF, and 10 had advanced HBV-ACLF, and there was no significant difference in the number of CD3+CD56+NKT cells between the three groups ( all P > 0. 05) , but with a tendency of increase; the patients with middle-stage or advanced HBV-ACLF had significantly higher expression of TIM-3 in CD3+CD56+NKT cells than those with early-stage HBV-ACLF [6. 5% ( 3. 16%-11. 45%) /8. 56% ( 4%-10. 93%) vs 2. 58% ( 1. 92%-6. 02%) , Z =-2. 284, -2. 641, both P < 0. 05]. Among the 43 patients with HBV-ACLF, the28-day survival group had significantly lower expression of TIM-3 in CD3+CD56+NKT cells than the 28-day liver transplantation/death group [2. 98% ( 1. 94%-6. 88%) vs 8. 56% ( 4. 27%-11. 43%) , Z =-2. 831, P = 0. 005]. Conclusion There is an increase in the expression of TIM-3 in peripheral blood CD3+CD56+NKT cells in patients with HBV-ACLF, which is associated with the degree of liver injury and prognosis.