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Cholesterol esterification in plasma as a biomarker for liver function and prediction of mortality

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      Abstract

      BackgroundAdvanced stages of liver cirrhosis lead to a dramatically increased mortality. For valid identification of these patients suitable biomarkers are essential. The most important biomarkers for liver function are bilirubin and prothrombin time expressed as International Normalized Ratio (INR). However, the influence of several anticoagulants on the prothrombin time limits its diagnostic value.Aim of this study was the evaluation of cholesterol esterification (CE) fraction (esterified cholesterol vs. total cholesterol) as an alternative biomarker for liver synthesis and mortality prediction. Under physiological conditions the CE fraction in blood is closely regulated by lecithin-cholesterol acyltransferase (LCAT) which is produced in the liver.MethodsOne hundred forty-two patients with liver disease clinically considered for orthotopic liver transplant for different indications were enrolled in the study. One patient was excluded because of the intake of a direct oral factor Xa inhibitor which has a strong impact on prothrombin time.ResultsResults of CE fraction were in good agreement with INR (R2 = 0.73; p < 0.001). In patients who died or survived within three months mean CE fraction was 56% vs. 74% (p < 0.001) and mean INR was 2.0 vs. 1.3 (p < 0.001), respectively. The predictive value of CE fraction for three-month mortality risk was higher compared to INR (p = 0.04). Results for one-year mortality were comparable.ConclusionsThe cholesterol esterification fraction is a valid biomarker for liver synthesis and allows reliable prediction of mortality. In contrast to INR, it is independent of anticoagulation and other analytical limitations of coagulation tests.Electronic supplementary materialThe online version of this article (doi:10.1186/s12876-017-0614-9) contains supplementary material, which is available to authorized users.

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      A model to predict survival in patients with end-stage liver disease.

      A recent mandate emphasizes severity of liver disease to determine priorities in allocating organs for liver transplantation and necessitates a disease severity index based on generalizable, verifiable, and easily obtained variables. The aim of the study was to examine the generalizability of a model previously created to estimate survival of patients undergoing the transjugular intrahepatic portosystemic shunt (TIPS) procedure in patient groups with a broader range of disease severity and etiology. The Model for End-Stage Liver Disease (MELD) consists of serum bilirubin and creatinine levels, International Normalized Ratio (INR) for prothrombin time, and etiology of liver disease. The model's validity was tested in 4 independent data sets, including (1) patients hospitalized for hepatic decompensation (referred to as "hospitalized" patients), (2) ambulatory patients with noncholestatic cirrhosis, (3) patients with primary biliary cirrhosis (PBC), and (4) unselected patients from the 1980s with cirrhosis (referred to as "historical" patients). In these patients, the model's ability to classify patients according to their risk of death was examined using the concordance (c)-statistic. The MELD scale performed well in predicting death within 3 months with a c-statistic of (1) 0.87 for hospitalized patients, (2) 0.80 for noncholestatic ambulatory patients, (3) 0.87 for PBC patients, and (4) 0.78 for historical cirrhotic patients. Individual complications of portal hypertension had minimal impact on the model's prediction (range of improvement in c-statistic: <.01 for spontaneous bacterial peritonitis and variceal hemorrhage to ascites: 0.01-0.03). The MELD scale is a reliable measure of mortality risk in patients with end-stage liver disease and suitable for use as a disease severity index to determine organ allocation priorities.
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        Enzymatic determination of total serum cholesterol.

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          The model for end-stage liver disease (MELD).

          The Model for End-stage Liver Disease (MELD) was initially created to predict survival in patients with complications of portal hypertension undergoing elective placement of transjugular intrahepatic portosystemic shunts. The MELD which uses only objective variables was validated subsequently as an accurate predictor of survival among different populations of patients with advanced liver disease. The major use of the MELD score has been in allocation of organs for liver transplantation. However, the MELD score has also been shown to predict survival in patients with cirrhosis who have infections, variceal bleeding, as well as in patients with fulminant hepatic failure and alcoholic hepatitis. MELD may be used in selection of patients for surgery other than liver transplantation and in determining optimal treatment for patients with hepatocellular carcinoma who are not candidates for liver transplantation. Despite the many advantages of the MELD score, there are approximately 15%-20% of patients whose survival cannot be accurately predicted by the MELD score. It is possible that the addition of variables that are better determinants of liver and renal function may improve the predictive accuracy of the model. Efforts at further refinement and validation of the MELD score will continue.
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            Author and article information

            Affiliations
            [1 ]ISNI 0000 0000 8517 9062, GRID grid.411339.d, Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, , University Hospital Leipzig, ; Paul-List-Str. 13-15, 04103 Leipzig, Germany
            [2 ]ISNI 0000 0000 8517 9062, GRID grid.411339.d, Department of Visceral, Vascular, Thoracic and Transplant Surgery, , University Hospital Leipzig, ; Leipzig, Germany
            [3 ]ISNI 0000 0000 8517 9062, GRID grid.411339.d, Section of Hepatology, Department of Gastroenterology and Rheumatology, , University Hospital Leipzig, ; Leipzig, Germany
            [4 ]ISNI 0000 0000 8517 9062, GRID grid.411339.d, Institute for Medical Informatics, Statistics and Epidemiology (IMISE), , University Hospital Leipzig, ; Leipzig, Germany
            [5 ]ISNI 0000 0000 8517 9062, GRID grid.411339.d, LIFE – Leipzig Research Center for Civilization Diseases, , University Hospital Leipzig, ; Leipzig, Germany
            Contributors
            +49 341 9722200 , Thorsten.Kaiser@medizin.uni-leipzig.de
            Benedict.Kinny-Koester@medizin.uni-leipzig.de
            michael.bartels@helios-kliniken.de
            Thomas.Berg@medizin.uni-leipzig.de
            markus.scholz@imise.uni-leipzig.de
            Cornelius.Engelmann@medizin.uni-leipzig.de
            Daniel.Seehofer@medizin.uni-leipzig.de
            Susen.Becker@medizin.uni-leipzig.de
            Uta.Ceglarek@medizin.uni-leipzig.de
            Joachim.Thiery@medizin.uni-leipzig.de
            Journal
            BMC Gastroenterol
            BMC Gastroenterol
            BMC Gastroenterology
            BioMed Central (London )
            1471-230X
            20 April 2017
            20 April 2017
            2017
            : 17
            28427335
            5397767
            614
            10.1186/s12876-017-0614-9
            © The Author(s). 2017

            Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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            © The Author(s) 2017

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