Objective: We have attempted to determine serum levels of type IV collagen (IV-C), laminin (LM), prolylhydroxylase (PH), metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) in chronic liver disease to elucidate the clinical significance of MMPs and TIMPs in the process of hepatic fibrosis.
Methods: Serum samples were collected from 60 patients with chronic liver disease caused by hepatitis B or C. Serum levels of IV-C, LM, PH, MMP-1, 2 and 3, and TIMP-1 and 2 were measured by a one-step sandwich enzyme immunoassay using monoclonal antibodies. The values were correlated with Histology Activity Index (HAI) scores of liver biopsy specimens.
Results: LM and IV-C levels markedly increased in parallel with the progression of the chronic liver disease. The MMP-2 and MMP-3 levels tended to increase in chronic active hepatitis (CAH), and significantly elevated in liver cirrhosis (LC). There was a positive correlation between the IV-C and MMP-2 levels, and the ratio of IV-C to MMP-2 levels was significantly elevated in LC. Both TIMP-1 and TIMP-2 levels were markedly increased in LC. The HAI scores were positively correlated with the serum IV-C and MMP-2 levels.
Conclusions: Serum IV-C and MMP-2 levels may be useful diagnostic markers for hepatic fibrosis, since they increased in parallel with the progression of chronic liver disease. In addition, the imbalances between IV-C, LM, and TIMP-1 and 2 as fibrogenic factors and MMP-2 and 3 as fibrolytic factors may lead to fibrosis in chronic viral liver disease, especially in cirrhosis.