Cardiac and proinflammatory markers predict prognosis in cirrhosis

Abstract

Inflammation and cardiac dysfunction plays an important role in the development of complications leading to increased mortality in patients with cirrhosis. Novel cardiac markers such as prohormone of ANP (proANP), copeptin and high-sensitivity troponin T (hs-TnT) and proinflammatory markers including soluble urokinase-type plasminogen activator receptor (suPAR) and high-sensitive C-reactive protein (hs-CRP) are related to these complications. We aimed to investigate if cardiac and proinflammatory markers are related to severity of liver disease, cardiac and haemodynamic changes, and long-term survival. One hundred and ninety-three stable cirrhotic patients (Child class: A=46; B=97; C=50) had a full haemodynamic investigation performed with measurement of splanchnic and systemic haemodynamics and measurement of circulating levels of proBNP, proANP, copeptin, hs-TnT, LBP, IL 6, IL 8, IP 10, VEGF, hs-CRP and suPAR. Soluble urokinase-type plasminogen activator receptor soluble urokinase-type plasminogen activator receptor, hs-CRP, and hs-TnT were significantly different throughout the Child classes (P<0.01; P<0.01; P<0.02). All markers except copeptin correlated with indicators of disease severity in cirrhosis; ProANP and suPAR correlated with hepatic venous pressure gradient (r=0.24 and r=0.34; P<0.001) and systemic vascular resistance (r=-0.24 and r=-0.33; P<0.001). Cardiac (proANP, hs-TnT; P<0.01) and proinflammatory (hs-CRP, suPAR; P<0.05) markers were associated with mortality in a univariate Cox analysis, however, the strongest predictors of mortality in a multivariate Cox analysis were hs-TnT, ascites and hepatic venous pressure gradient (reg.coeff.: 0.34, P<0.001; 0.16, P<0.001; 0.06, P=0.04). Markers of cardiac dysfunction and inflammation are significantly associated with disease severity, degree of portal hypertension and survival in cirrhosis. In particular, hs-TnT and suPAR seem to contain prognostic information.