ABSTRACT

To determine the association between the expression patterns of mat-rix metalloproteinases (MMPs) and extent of fibrosis and inflammation in chro-nic viral hepatitis.

We examined the expression and localization of MMP-2 and MMP-9 and correlated the data with their main inhibitors, tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2), in 67 chronic viral he-patitis patients. Immunohistochemistry was performed for MMPs and TIMPs in liver biopsies of 5 normal controls, 27 patients with chronic hepatitis B, and 40 patients with chronic hepatitis C.

In viral hepatitis, MMP-9 expression in hepatocytes was very small (3%), whereas MMP-2 was expressed in hepatocytes and in some spindle cells in the portal tracts in 43% of the cases. Variable degrees of staining were ob-served in hepatocytes, sinusoidal cells, and spindle cells in the portal tract for TIMP-1 and TIMP-2 (12% and 21%, respectively). Only TIMP-1 expression correlated with the expression of MMP-2 (p=0.01). On the other hand, neither MMP-2 and MMP-9 nor TIMP-1 and TIMP-2 expressions showed any correla-tion with the extent of inflammation and fibrosis.

Our findings sho-wed that alterations in the expression patterns of MMP-2, MMP-9, TIMP-1, and TIMP-2 in the samples of viral hepatitis do not explain the changes in se-rum concentrations and do not mirror the progression of the disease. Thus, it is still unclear whether their circulating levels are liver specific.