Abstract: Objective The pathogenesis of drug-induced liver injury (DILI) is not yet fully understood. Clinical diagnosis relies on the scores of RUCAM scale. In particular, it is often confused with the diagnosis of autoimmune hepatitis (AIH) in clinical practice. Therefore, the search for early warning signs of DILI is of great significance for clinical diagnosis of DILI. Based on our previous work, this study further explored the expression of ILC3 cells in drug-induced liver injury. Methods 30 patients with DILI, 10 patients with AIH and 10 patients with healthy control (HC) were included in the diagnosis and treatment guidelines for drug-induced liver injury in 2015. Peripheral blood was collected and clinical demographic information was described. Peripheral blood mononuclear cells (PBMC) of patients and healthy subjects were isolated by Ficoll density gradient centrifugation. After antibody staining, flow cytometry was used to count the frequency of lin-CD127⁺NKP46⁺ILC3 in each group, and analyze the correlation between DILI and AIH. Results (1) The mean cell frequency percentages of NKp46⁺ILC3 in PBMC in DILI group and AIH group were 0.011%±0.002% and 0.019%±0.004%, which were significantly lower than those in HC healthy group (0.041%±0.003%, P<0.001). (2) The mean cell frequency percentage of NKp46⁺ILC3 in PBMC of DILI group was significantly lower than that of AIH group, with statistically significant difference (P<0.01). (3) The frequency percentage of NKp46⁺ILC3 in DILI group increased gradually with the improvement of the disease, while the frequency percentage of NKp46⁺ILC3 cells in AIH group showed no significant change during the same period of treatment. (4) The frequency percentage of ILCs in DILI and AIH group was 0.060%±0.006% and 0.074±0.009, which were significantly lower than those in healthy group (0.162±0.015) (P<0.001). However, there was no significant difference of ILCs between DILI and AIH group (P=0.03). (5) The mean cell frequency percentage of NKp46⁺ILC3 in DILI patients was not correlated with the liver function level of aspartate aminotransferase (AST), glutamate aminotransferase (ALT) and total bilirubin (TBil). Conclusion The frequency of ILC3 cells in the peripheral blood of DILI patients was significantly decreased, which was significantly lower than that of AIH group and healthy control group. The cell frequency was related to the progression of disease, but was irrelevant to transaminase, total bilirubin and other biochemical markers.

Key words: Type 3 innate lymphocytes, Drug-induced liver injury, Autoimmune hepatitis