Tissue Inhibitors of Metalloproteinase-1 and 2 and Obesity Related Non-Alcoholic Fatty Liver Disease: Is There a Relationship?

Abstract

Background/Aims: Non-alcoholic fatty liver disease is a spectrum of clinical conditions, including simple steatosis and non-alcoholic steatohepatitis (NASH). The aim of the study is to evaluate the tissue inhibitors of metalloproteinase-1 and 2 (TIMPs) as noninvasive predictors of NASH. Methods: Three groups were included in the study. Obese patients (n = 30) with normal liver enzymes were included in group I and obese patients (n = 30) with elevated liver enzymes with liver biopsy-based diagnosis of NASH were included in group II. Age-matched subjects (n = 30) formed the control as group III. The lipid profile, liver enzyme levels and levels of TIMPs were compared among all the patients and subjects. Results: Comparison of groups I and II showed significantly elevated levels of TIMP-1 and TIMP-2 in group II as compared to group I (p < 0.05). Similarly, comparison between groups II and III showed significantly increased levels of TIMP-1 and TIMP-2 in group II as compared to group III (p < 0.05). TIMP-1 (sensitivity 96.7%, specificity 100%) and TIMP-2 (sensitivity 93.3%, specificity 100%) showed high accuracy in NASH diagnosis. Conclusion: TIMP-1 and TIMP-2 may be considered noninvasive markers for the diagnosis of NASH.

The GLP-1 Analogs Liraglutide and Semaglutide Reduce Atherosclerosis in ApoE−/− and LDLr−/− Mice by a Mechanism That Includes Inflammatory Pathways

“…Of particular translational relevance to human treatment, semaglutide partially prevented the WD-induced expression of TIMP-1 and the S100 calcium-binding proteins A8 and A9 (S100A8 and S100A9) at all dose levels. Serum TIMP-1 levels have been used to detect fibrosis (45), whereas S100A8/-A9 are biomarkers for cirrhosis in chronic hepatitis C infection and various other diseases (46). Similar to findings in the vascular bed, we did not identify GLP-1R expression in the liver (data not shown), concordant with previous reports 38, 39, 47.…”

Dietary fat stimulates development of NAFLD more potently than dietary fructose in Sprague–Dawley rats

“…Accordingly, serum and hepatic levels of proinflammatory cytokines such as tumor-necrosis factor alpha (TNF-α) and monocyte-chemoattractant protein-1 (MCP-1) have been found to be increased in patients with both simple hepatic steatosis and NASH [ 6 – 9 ]. Also, the glycoproteins haptoglobin and tissue-inhibitor of metalloproteinase 1 (TIMP-1) have been shown to be elevated in plasma of patients with more advanced stages of NAFLD and have therefore recently been suggested as useful clinical plasma biomarkers, indicative of hepatocyte ballooning and liver fibrosis, respectively [ 10 , 11 ].…”

A New Endemic of Concomitant Nonalcoholic Fatty Liver Disease and Chronic Hepatitis B

“…Several specific fibrosis markers and panels are also available. These include hyaluronic acid (HA) [ 70 ], N-terminal propeptide of procollagen type III (PIIINP) [ 71 ], Pro-C3 [ 72 ], tissue metalloproteinases 1 (TIMP1) [ 73 , 74 ], laminin [ 75 ], enhanced liver fibrosis (ELF) [ 76 ], FibroTest [ 77 ], and FibroMeter NAFLD [ 78 , 79 ]. Most of the biomarkers have a high negative predictive value of > 90% in ruling out fibrosis.…”