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Plasma Levels of Matrix Metalloproteinase-2 (MMP-2) and Tissue Inhibitors of Metalloproteinases-1 and -2 (TIMP-1 and TIMP-2) as Noninvasive Markers of Liver Disease in Chronic Hepatitis C Comparison Using ROC Analysis

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Abstract

As chronic liver disease progresses, animbalance occurs between synthesis and breakdown ofextracellular matrix (ECM). Matrix metalloproteinases(MMPs) are involved in degrading ECM while tissueinhibitors of metalloproteinases (TIMPs) prevent theirfibrolytic action. We determined if plasma levels ofMMP-2, TIMP-1 and TIMP-2 are related to liver histologyin patients with chronic hepatitis C. Plasma MMP-2, TIMP-1 and TIMP-2 levels were measured in 43patients with chronic hepatitis C. Plasma levels ofMMP-2, TIMP-1 and TIMP-2 and serum ALT were correlatedwith liver biopsy score and specificity and sensitivity of the assays in detecting advanced liverdisease were calculated from ROC analysis. Plasma TIMP-1was significantly correlated with histological activityindex (r = 0.45), portal inflammation (r = 0.48), periportal necrosis (r = 0.34) and focalnecrosis (r = 0.38). Plasma TIMP-2 was significantlycorrelated with fibrosis (r = 0.43) and confluentnecrosis (r = 0.41). Using ROC analysis both TIMP-1 andTIMP-2 had significant diagnostic ability in detectingadvanced liver disease (Area under the curve 0.73 forboth, p 0.015 and 0.036 respectively). A normal plasmaTIMP-1 excluded advanced liver disease. NeiThe r plasma MMP-2 or serum ALT were related tofibrosis or to histological activity index. Withincreased severity of liver disease in chronic hepatitisC The re is increased plasma levels of TIMPs-1 and-2.Plasma TIMP-1 and TIMP-2 aResensitive and to a lesserextent specific in detecting advanced liver disease inchronic hepatitis C and could be used in preference toserum ALT.

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Authors
  1. Kevin Michael Walsh
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  2. Peter Timms
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  3. Stewart Campbell
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  4. Ronald Norman
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  5. Maciver Macsween
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  6. Allan John Morris
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Walsh, K.M., Timms, P., Campbell, S. et al. Plasma Levels of Matrix Metalloproteinase-2 (MMP-2) and Tissue Inhibitors of Metalloproteinases-1 and -2 (TIMP-1 and TIMP-2) as Noninvasive Markers of Liver Disease in Chronic Hepatitis C Comparison Using ROC Analysis. Dig Dis Sci 44, 624–630 (1999). https://doi.org/10.1023/A:1026630129025

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  • DOI: https://doi.org/10.1023/A:1026630129025

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