A Noninvasive Predictors of Significant Histological Activity in Chronic Liver Diseases: The Role of Matrix Metalloproteinases

Aim of investigation. To study the prognostic significance of clinical and laboratory markers of liver pathology, including components of the matrix metalloproteinase (MMP) system, to identify moderate/significant activity in chronic liver diseases (CLD). Materials and methods. 76 patients with CLD of viral or alcoholic etiology aged from 18 to 64 years were examined. Minimal (histological activity index — HAI 1-3 points), minor (HAI 4-8 points), moderate (HAI 9-12 points) and significant morphological activity (HAI more than 12 points) were detected in 19 (25.0 %), 34 (44.7 %), 14 (18.4 %) and 9 (11.9 %) of cases, respectively. Enzyme immunoassay was used to determine the blood levels of MMP-1, MMP-9, tissue inhibitor of matrix metalloproteinases-1 (TIMP-1), and the of TIMP-1/MMP-1, TIMP-1/MMP-9 was calculated. Results. According to multivariate logistic regression data, moderate/significant histological activity of CLD was associated with γ-glutamyltranspeptidase (GGT) (odds ratio (OR) 1.016; 95 % confidence interval (CI) (1.006-1.024), p=0.001), international normalized ratio (INR) (OR 1.079; 95 % CI (1.028-1.132), p=0.002), and TIMP-1/MMP- 9 ratio (OR 0.554; 95 % CI (0.380-0.809), p=0.002). The combination of these parameters had sensitivity of 82.6 %, specificity of 92.5 % and accuracy of 89.5 % in detecting HAI of 9 or more points. Conclusion. The increased values of GGT and INR, as well as a reduced ratio of TIMP-1/MMP-9, are independent risk factors for moderate/significant histological activity in CLD, due to their participation in the processes of hepatic inflammation.