Clin Mol Hepatol.  2018 Mar;24(1):61-76. 10.3350/cmh.2017.0030.

Serum matrix metalloproteinase-1 level represents disease activity as opposed to fibrosis in patients with histologically proven nonalcoholic steatohepatitis

• Ando W
• Yokomori H
• Tsutsui N
• Yamanouchi E
• Suzuki Y
• Oda M
• Inagaki Y
• Otori K
• Okazaki I

• KMID: 2429084
• DOI: http://doi.org/10.3350/cmh.2017.0030

Abstract

BACKGROUND/AIMS
Nonalcoholic steatohepatitis (NASH) is prevalent in both economically developed and developing countries. Twenty percent of NASH progresses to cirrhosis with/without hepatocellular carcinoma, and there is an urgent need to find biomarkers for early diagnosis and monitoring progression of the disease. Using immunohistochemical and immunoelectron microscopic examination we previously reported that expression of matrix metalloproteinase-1 (MMP-1) increased in monocytes, Kupffer cells and hepatic stellate cells in early stage NASH. The present study investigated whether serum MMP-1 levels reflect disease activity and pharmaceutical effects in NASH patients.
METHODS
We measured the serum levels of MMPs, tissue inhibitors of metalloproteinases (TIMPs), and several cytokines/chemokines in patients with histologically proven early and advanced stages of NASH and compared them with those in healthy controls.
RESULTS
Serum MMP-1 levels in stage 1 fibrosis, but not in the more advanced fibrosis stages, were significantly higher than in healthy controls (P=0.019). There was no correlation between serum MMP-1 level and fibrosis stage. Serum MMP- 1 levels in NASH patients represented disease activity estimated by serum aminotransferase values during the follow-up period. In contrast, MMP-2, MMP-9 and TIMPs did not change with disease activity. Consistent with the finding that MMP-1 is expressed predominantly in monocytes and Kupffer cells, serum levels of monocyte chemotactic protein-1 and granulocyte-colony stimulating factor were significantly increased in NASH with stage 1 fibrosis.
CONCLUSIONS
These results suggest that serum MMP-1 levels represent disease activity and may serve as a potential biomarker for monitoring the progression of NASH.

Keyword

Nonalcoholic steatohepatitis; Matrix metalloprotease 1; Cytokines; Liver cirrhosis

MeSH Terms

Biomarkers
Carcinoma, Hepatocellular
Chemokine CCL2
Cytokines
Developing Countries
Early Diagnosis
Fibrosis*
Follow-Up Studies
Hepatic Stellate Cells
Humans
Kupffer Cells
Liver Cirrhosis
Matrix Metalloproteinase 1*
Matrix Metalloproteinases
Metalloproteases
Monocytes
Non-alcoholic Fatty Liver Disease*
Biomarkers
Chemokine CCL2
Cytokines
Matrix Metalloproteinase 1
Matrix Metalloproteinases
Metalloproteases