Abstract: Objective To explore the clinical value of glutamate dehydrogenase (GLDH) and glutathione reductase (GR) in the diagnosis of drug-induced liver injury (DILI).Methods The clinical data and serum liver function indexes of 111 DILI patients hospitalized in the military liver disease center of Qinhuai Medical Treatment Area of General Hospital of Eastern Theater CommandPLA from January 2021 to March 2022 and 100 healthy people in the physical examination center of the hospital in the same period were retrospectively analyzed. A total of 56 DILI patients were hospitalized for more than 10 days and had at least three liver function tests. The differences between DILI group and healthy group and the diagnostic efficiency of GLDH and GR were analyzed, Correlation with other liver function indexes, the indexes of other liver functions at different activity levels of GR and the changes of liver function indexes in DILI patients during hospitalization were evaluated by stratified comparison.Results GLDH and GR in DILI group [12.1 (6.8, 24.8) U/L, 87 (74, 108.7) U/L] were significantly higher than those in healthy group [3.80 (2.50, 5.68) U/L, 58.15 (51.35, 62.80) U/L] (P<0.001); The correlation coefficients of GLDH with alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) were 0.296, 0.328, 0.308, 0.262 and 0.234 respectively, and the correlation coefficients of GR with ALT, AST, GGT, ALP and LDH were 0.464, 0.612, 0.322, 0.375 and 0.543 respectively. The area under the AUC curve, sensitivity, specificity, and Jordan index of GLDH were 0.861, 72.97%, 89.0% and 0.620 respectively, while those of GR were 0.941, 90.99%, 95.00% and 0.824 respectively. The GR results were stratified according to the interquartile distance and divided into four groups. It was found that there was no statistical significance in liver function indicators from Q1 to Q2 (P>0.05), while the most significant indicators in Q3 and Q4 were AST [165 (97, 256) U/L, 282 (171, 501) U/L], ALT [302 (158, 502) U/L, 545 (234, ,974.75) U/L], LDH [221 (185, 243) U/L, 294 (225.5, 376.25) U/L] and PA [(154 ± 80.23) mg/l, (103.07 ± 86.00) mg/L] (P<0.001) were used to analyze the changes of liver function indexes of 56 hospitalized DILI patients during hospitalization. It was found that GLDH was 20.05 (13.45, 31.3) U/L at admission, and decreased to 8.3 (4.53, 15.38) U/L after (5 ± 2) days of admission, most of them can return to the normal range of 5.5 (2.93, 10.7) U/L after (10 ± 2) days.Conclusion Compared with traditional liver function indexes, GLDH and GR play a great supplementary role in clinical diagnosis and treatment of DILI in terms of diagnostic efficacy, early diagnosis and curative effect observation. They can be used as new serum markers of DILI in clinical popularization.

Key words: Drug induced liver injury, Glutamate dehydrogenase, Glutathione reductase