Abstract:

Objective: To analyze levels of matrix metalloproteinases (MMP) and the correlation between the levels and anti-tuberculosis drug-induced liver injury (ATB-DILI). Methods: A retrospective research was conducted in 98 pulmonary tuberculosis patients with ATB-DILI treated in the Third People’s Hospital of Kunming from June 2019 to June 2020 (case group), and 30 outpatients with physical examination in the same period were selected as the control group. A total of 6 ml fasting venous blood was collected from the subjects in the morning. The concentrations of MMP-1, MMP-2, MMP-7, MMP-9, MMP-13 and MMP-14 were detected by double antibody sandwich method. According to the clinical classification of ATB-DILI, the subjects of the case group were divided into hepatocyte injury type (group A), cholestasis type (group B), hepatic vascular injury type (group C), and mixed type (group D); according to the severity of ATB-DILI, they were divided into grade 0 (no liver injury), grade 1 (mild liver injury), grade 2 (moderate liver injury), grade 3 (severe liver injury), grade 4 (acute liver failure), and grade 5 (lethal). The MMP levels of different clinical classification groups and the control group were compared, and the correlation between MMP levels and ATB-DILI severity classification was analyzed. Results: According to ATB-DILI clinical classification, there were 51 cases in group A, 12 cases in group B, 15 cases in group C, and 20 cases in group D. According to the ATB-DILI severity classification, there were 33 cases in grade 1, 27 cases in grade 2, 22 cases in grade 3, 14 cases in grade 4, and 2 cases in grade 5. In groups A, B, C, D and control group, concentrations of MMP-1 were (89.1±11.2) ng/ml, (32.3±6.3) ng/ml, (47.5±9.1) ng/ml, (55.2±11.1) ng/ml, and (27.5±8.2) ng/ml, respectively; MMP-2 concentrations were (8.21±2.1) ng/ml, (6.2±2.3) ng/ml, (15.5±1.8) ng/ml, (7.2±1.6) ng/ml, and (3.2±1.3) ng/ml, respectively; MMP-9 concentrations were 36.1 (25.9, 47.3) ng/ml, 11.3 (5.1, 20.6) ng/ml, 14.1 (6.1, 21.3) ng/ml, 15.3 (3.8, 28.1) ng/ml, and 6.4 (2.8, 8.6) ng/ml, respectively; MMP-14 concentrations were 5.2 (2.8, 7.5) ng/ml, 6.0 (3.6, 8.9) ng/ml, 11.2 (5.2, 17.4) ng/ml, 4.0 (1.8, 6.2) ng/ml, 2.8 (1.4, 4.3) ng/ml. The concentrations of MMP-1 and MMP-9 in group A were significantly increased, and the concentrations of MMP-2 and MMP-14 in group C were also significantly increased, both the differences were statistically significant (F=7.983, P=0.031; H=9.979, P=0.041; F=9.381, P=0.010; H=10.555, P=0.032). MMP-9 concentrations in patients with ATB-DILI severity 1, 2, 3, 4, and 5 were 16.2(13.2, 19.3) ng/ml, 21.5(18.4, 23.6) ng/ml, 24.3(20.6, 27.1) ng/ml, 30.3(25.1, 35.3) ng/ml, 38.5(33.9, 43.1) ng/ml respectively, which was positively correlated with the severity classification (r=0.882, P=0.000). Conclusion: The concentrations of MMP-1, MMP-2, MMP-9 and MMP-14 in patients with different clinical types of ATB-DILI increased to different degrees. MMP-9 concentrations are positively correlated with ATB-DILI severity. MMP level may be an influencing factor for the occurrence of ATB-DILI.

Key words: Matrix metalloproteinases, Drug-induced liver injury, Antitubercular agents, Regression analysis