title: Clinical significance of serum matrix metalloproteinases and tissue inhibitors of metalloproteinases in chronic liver disease.
abstract: 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.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Tokai University School of Medicine, Bohseidai, Isehara, Japan. norihito@is.icc.u-tokai.ac.jp
authors.forename: Norihito
authors.initials: N
authors.lastname: Watanabe
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nishizaki
authors.forename: Sei-ichiro
authors.initials: S
authors.lastname: Kojima
authors.forename: Shinji
authors.initials: S
authors.lastname: Takashimizu
authors.forename: Naruhiko
authors.initials: N
authors.lastname: Nagata
authors.forename: Tatehiro
authors.initials: T
authors.lastname: Kagawa
authors.forename: Koichi
authors.initials: K
authors.lastname: Shiraishi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mine
authors.forename: Shohei
authors.initials: S
authors.lastname: Matsuzaki
mesh_terms: D000328:Adult; D000368:Aged; D002908:Chronic Disease; D024141:Collagen Type IV / Q000097:blood; D018450:Disease Progression; D005260:Female; D005355:Fibrosis / Q000097:blood / Q000473:pathology; D006801:Humans; D007797:Laminin / Q000097:blood; D008107:Liver Diseases / Q000097:blood* / Q000201:enzymology* / Q000473:pathology; D008297:Male; D020782:Matrix Metalloproteinases / Q000097:blood*; D008875:Middle Aged; D011393:Procollagen-Proline Dioxygenase / Q000097:blood; D019714:Tissue Inhibitor of Metalloproteinases / Q000097:blood*
chemical_list: D024141:Collagen Type IV; D007797:Laminin; D019714:Tissue Inhibitor of Metalloproteinases; D011393:Procollagen-Proline Dioxygenase; D020782:Matrix Metalloproteinases