Matrix metalloproteinases and their inhibitors as markers of inflammation and fibrosis in chronic liver disease (Review).

Chronic liver disease (CLD) is a cause of morbidity and mortality worldwide, due to haemodynamic and metabolic complications of liver cirrhosis. During CLD the extracellular matrix undergoes a process of remodelling, leading to new collagen formation and deposition. Tissue remodelling is regulated by fine molecular mechanisms, involving proteases, inhibitors and growth factors. The major role in matrix degradation is played by matrix metalloproteinases (MMPs), a class of zinc and calcium-dependent enzymes, and their tissue inhibitors (TIMPs). Along with the progress in diagnostic techniques, leading to more precise and less invasive methods, the concept of monitoring has gained importance for the clinical management of CLD. At the present state of our knowledge, liver biopsy still represents an essential procedure for staging liver disease. However, despite its importance, liver biopsy presents some limitations: the risk of a disease underestimation is the most significant one, as hepatic lesions are often irregularly located within the liver. Parallel to the limitations of liver biopsy, clinical needs for an early identification of progressive fibrosis require additional non-invasive techniques to be developed. In this review we discuss the major problems concerning this important clinical necessity. Moreover, we focus on the role of MMPs and TIMPs in the pathogenesis of CLD, as well as their possible use as non-invasive serum markers for inflammation and fibrosis in this pathology.