TY - JOUR

T1 - TIMP-1 in patients with cirrhosis

T2 - relation to liver dysfunction, portal hypertension, and hemodynamic changes

AU - Busk, Troels M

AU - Bendtsen, Flemming

AU - Nielsen, Hans J

AU - Jensen, Vibeke

AU - Brünner, Nils

AU - Møller, Søren

PY - 2014/9

Y1 - 2014/9

N2 - OBJECTIVE: Cirrhotic portal hypertensive patients often develop hemodynamic complications and the diagnosis is often based on liver biopsy and measurements of the hepatic venous pressure gradient (HVPG). Potential noninvasive biomarkers for the severity of cirrhosis are the matrix metalloproteinase and their specific inhibitors such as tissue inhibitor of metalloproteinases-1 (TIMP-1). The aim of the study was to investigate TIMP-1 levels in cirrhosis in relation to the degree of liver dysfunction, portal hypertension, and hemodynamic changes.MATERIALS AND METHODS: We retrospectively studied 84 patients with cirrhosis and 14 controls without liver disease. All individuals underwent a liver vein catheterization with a hemodynamic assessment. TIMP-1 was determined in arterial and hepatic venous plasma using an MAC-15 TIMP-1 ELISA.RESULTS: Hepatic venous concentrations of TIMP-1 were significantly increased in patients compared to controls: 336 (166) ng/ml versus 145 (100) (median/IQ range) (p < 0.001) with a progressive increase throughout the Child classes (p < 0.001). Circulating TIMP-1 correlated significantly with indocyanine green clearance (r = -0.44, p < 0.0001), Child Turcotte score (r = 0.50, p < 0.0001), HVPG (r = 0.40, p < 0.0001), mean arterial pressure (r = -0.29, p = 0.008), and systemic vascular resistance (r = -0.23, p = 0.03). Receiver operating characteristic curve analysis enabled us to establish cutoff values for TIMP-1 with regard to portal hypertension.CONCLUSIONS: TIMP-1 is significantly increased in patients with cirrhosis and correlates with the severity of the disease, degree of portal hypertension, and vasodilatory state. TIMP-1 is therefore a promising new noninvasive marker to predict hemodynamic-related complications in cirrhosis.

AB - OBJECTIVE: Cirrhotic portal hypertensive patients often develop hemodynamic complications and the diagnosis is often based on liver biopsy and measurements of the hepatic venous pressure gradient (HVPG). Potential noninvasive biomarkers for the severity of cirrhosis are the matrix metalloproteinase and their specific inhibitors such as tissue inhibitor of metalloproteinases-1 (TIMP-1). The aim of the study was to investigate TIMP-1 levels in cirrhosis in relation to the degree of liver dysfunction, portal hypertension, and hemodynamic changes.MATERIALS AND METHODS: We retrospectively studied 84 patients with cirrhosis and 14 controls without liver disease. All individuals underwent a liver vein catheterization with a hemodynamic assessment. TIMP-1 was determined in arterial and hepatic venous plasma using an MAC-15 TIMP-1 ELISA.RESULTS: Hepatic venous concentrations of TIMP-1 were significantly increased in patients compared to controls: 336 (166) ng/ml versus 145 (100) (median/IQ range) (p < 0.001) with a progressive increase throughout the Child classes (p < 0.001). Circulating TIMP-1 correlated significantly with indocyanine green clearance (r = -0.44, p < 0.0001), Child Turcotte score (r = 0.50, p < 0.0001), HVPG (r = 0.40, p < 0.0001), mean arterial pressure (r = -0.29, p = 0.008), and systemic vascular resistance (r = -0.23, p = 0.03). Receiver operating characteristic curve analysis enabled us to establish cutoff values for TIMP-1 with regard to portal hypertension.CONCLUSIONS: TIMP-1 is significantly increased in patients with cirrhosis and correlates with the severity of the disease, degree of portal hypertension, and vasodilatory state. TIMP-1 is therefore a promising new noninvasive marker to predict hemodynamic-related complications in cirrhosis.

U2 - 10.3109/00365521.2014.934910

DO - 10.3109/00365521.2014.934910

M3 - Journal article

C2 - 25048331

VL - 49

SP - 1103

EP - 1110

JO - Scandinavian Journal of Gastroenterology

JF - Scandinavian Journal of Gastroenterology

SN - 0036-5521

IS - 9

ER -