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      Severity of coronary artery disease is associated with non-alcoholic fatty liver dis-ease: A single-blinded prospective mono-center study

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          Abstract

          Background and aims

          Liver steatosis has shown to be associated with coronary artery disease (CAD). The aim of our study was to evaluate the association between the presence and severity of CAD and Non-alcoholic fatty liver disease (NAFLD) assessed by transient elastography (TE) and controlled attenuation parameter (CAP).

          Methods

          576 Patients undergoing coronary angiography were enrolled in this prospective study, receiving at least 10 TE and CAP measurements using the FibroScan® M-probe. Clinically relevant CAD (CAD 3) was defined as stenosis with ≥75% reduction of the luminal diameter. NAFLD was determined by CAP ≥234 dB/m. NAFLD with advanced fibrosiswas determined by TE-values ≥7.9kPa in the presence of NAFLD and absence of congestive or right-sided heart failure. Rates and 95% confidence intervals are shown.

          Results

          505 patients were available for analysis of NAFLD. However, only 392 patients were available for analysis of NAFLD with advanced fibrosis, since 24 patients had to be excluded due to non valid TE-measurements and 89 patients due to congestive or right-sided heart failure or suspected concomitant liver disease, respectively. 70.5% (66.3%-74.4%) of patients had CAD 3, 71.5% (67.3%-75.4%) were diagnosed with NAFLD, and 11.2% (8.3%-14.8%) with NAFLD with advanced fibrosis. Patients with CAD 3 had higher median CAP-values (273±61 vs. 260±66 dB/m; p = 0.038) and higher degrees of steatosis as compared to patients without CAD 3. While NAFLD was significantly more often diagnosed in patients with CAD 3 (75.0% vs. 63.1%, p = 0.0068), no significant difference was found for NAFLD with advanced fibrosis (10.7% vs. 12.5%, p = 0.60).

          Conclusions

          Clinically relevant CAD is frequently associated with the presence of NAFLD, but not NAFLD with advanced fibrosis.

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          Most cited references27

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          Determination of reliability criteria for liver stiffness evaluation by transient elastography.

          Liver stiffness evaluation (LSE) is usually considered as reliable when it fulfills all the following criteria: ≥10 valid measurements, ≥60% success rate, and interquartile range / median ratio (IQR/M) ≤0.30. However, such reliable LSE have never been shown to be more accurate than unreliable LSE. Thus, we aimed to evaluate the relevance of the usual definition for LSE reliability, and to improve reliability by using diagnostic accuracy as a primary outcome in a large population. 1,165 patients with chronic liver disease from 19 French centers were included. All patients had liver biopsy and LSE. 75.7% of LSE were reliable according to the usual definition. However, these reliable LSE were not significantly more accurate than unreliable LSE with, respectively: 85.8% versus 81.5% well-classified patients for the diagnosis of cirrhosis (P = 0.082). In multivariate analyses with different diagnostic targets, LSE median and IQR/M were independent predictors of fibrosis staging, with no significant influence of ≥10 valid measurements or LSE success rate. These two reliability criteria determined three LSE groups: "very reliable" (IQR/M ≤0.10), "reliable" (0.10 0.30 with LSE median 0.30 with LSE median ≥7.1 kPa). The rates of well-classified patients for the diagnosis of cirrhosis were, respectively: 90.4%, 85.8%, and 69.5% (P < 10(-3) ). According to these new reliability criteria, 9.1% of LSE were poorly reliable (versus 24.3% unreliable LSE with the usual definition, P < 10(-3) ), 74.3% were reliable, and 16.6% were very reliable. The usual definition for LSE reliability is not relevant. LSE reliability depends on IQR/M according to liver stiffness median level, defining thus three reliability categories: very reliable, reliable, and poorly reliable LSE. (HEPATOLOGY 2013). Copyright © 2012 American Association for the Study of Liver Diseases.
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            Acute viral hepatitis increases liver stiffness values measured by transient elastography.

            Liver tissue alterations other than fibrosis may have an impact on liver stiffness measurement. In this study we evaluated 18 patients without a previous clinical history of liver disease, consecutively admitted for acute viral hepatitis. In each patient, aminotransferase determination and liver stiffness measurement were performed on the same study day, at 3 different points: (1) peak increase in aminotransferase; (2) aminotransferase 50% or less of the peak; (3) aminotransferase levels
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              Transient elastography: a new surrogate marker of liver fibrosis influenced by major changes of transaminases.

              Liver stiffness was measured by transient elastography (FibroScan) in 228 consecutive patients with chronic viral hepatitis, with (115) or without cirrhosis (113), to study its correlations with serum transaminases [alanine aminotransferase (ALT)], fibrosis stage and surrogate noninvasive markers of fibrosis (APRI, FORNS, FibroTest and hyaluronic acid). The dynamic profiles of serum transaminases and liver stiffness were compared by multiple testing in 31 patients during a 6-month follow-up. We identified 8.3 and 14 kPa as the fibrosis >/=F2 and cirrhosis cut-offs, respectively: their sensitivities were 85.2%/78.3%; specificities 90.7%/98.2%; positive predictive values 93.9%/97.8%; negative predictive values 78.8%/81.6%; diagnostic accuracies 87.3%/88.2%. FibroScan performed better than the other surrogate markers of fibrosis (P < 0.001). Other than fibrosis, other factors independently associated with liver stiffness were ALT for all patients and chronic hepatitis patients (P < 0.001), and 12-month persistently normal ALT (biochemical remission, P < 0.001) in cirrhotics. In patients with biochemical remission either spontaneous or after antiviral therapy (48 of 228, 21%), liver stiffness was lower than in patients with identical fibrosis stage, but elevated ALT (P < 0.001). The liver stiffness dynamic profiles paralleled those of ALT, increasing 1.3- to 3-fold during ALT flares in 10 patients with hepatitis exacerbations. Liver stiffness remained unchanged in 21 with stable biochemical activity (P = 0.001). In conclusion, transient elastography is a new liver parameter that behaves as a reliable surrogate marker of fibrosis in chronic viral hepatitis patients, provided that its relationship with major changes of biochemical activity is taken into account.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: InvestigationRole: Writing – original draft
                Role: Formal analysisRole: MethodologyRole: Writing – original draft
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: ResourcesRole: Writing – review & editing
                Role: Formal analysisRole: MethodologyRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: MethodologyRole: SoftwareRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: InvestigationRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: Project administrationRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                26 October 2017
                2017
                : 12
                : 10
                : e0186720
                Affiliations
                [1 ] Department of Internal Medicine 1, Hospital of the Goethe University, Frankfurt, Germany
                [2 ] Department of Internal Medicine 3, Hospital of the Goethe University, Frankfurt, Germany
                [3 ] Department of Medicine, Institute of Biostatistics and Mathematical Modelling, Goethe University Frankfurt, Frankfurt, Germany
                [4 ] German Center for Cardiovascular Research, DZHK, partner site Frankfurt Rhine-Main, Berlin, Germany
                Medizinische Fakultat der RWTH Aachen, GERMANY
                Author notes

                Competing Interests: The authors declare the following interest: the authors are affiliated with the commercial company, Echosens, only in so far as this company provided material support for this study. There are no patents, products in development, or marketed products to declare. This does not alter the authors’ adherence to all PLOS ONE policies on sharing data and materials.

                Author information
                http://orcid.org/0000-0003-0937-3076
                Article
                PONE-D-17-24088
                10.1371/journal.pone.0186720
                5658076
                29073252
                b66b11b1-5352-4946-8ca8-5341ba46d8bb
                © 2017 Friedrich-Rust et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 25 June 2017
                : 8 October 2017
                Page count
                Figures: 4, Tables: 4, Pages: 14
                Funding
                The commercial company, Echosens, provided material support by lending the FibroScan® M-probe used in this study to the authors ( http://www.echosens.us/). The funders did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Vascular Medicine
                Coronary Heart Disease
                Medicine and Health Sciences
                Cardiology
                Coronary Heart Disease
                Biology and Life Sciences
                Developmental Biology
                Fibrosis
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Anatomical Pathology
                Cytopathology
                Steatosis
                Medicine and Health Sciences
                Gastroenterology and Hepatology
                Liver Diseases
                Fatty Liver
                Medicine and Health Sciences
                Gastroenterology and Hepatology
                Liver Diseases
                Liver Fibrosis
                Medicine and Health Sciences
                Cardiovascular Medicine
                Cardiovascular Imaging
                Angiography
                Medicine and Health Sciences
                Diagnostic Medicine
                Diagnostic Radiology
                Cardiovascular Imaging
                Angiography
                Research and Analysis Methods
                Imaging Techniques
                Diagnostic Radiology
                Cardiovascular Imaging
                Angiography
                Medicine and Health Sciences
                Radiology and Imaging
                Diagnostic Radiology
                Cardiovascular Imaging
                Angiography
                Medicine and Health Sciences
                Metabolic Disorders
                Medicine and Health Sciences
                Diagnostic Medicine
                Diagnostic Radiology
                Ultrasound Imaging
                Research and Analysis Methods
                Imaging Techniques
                Diagnostic Radiology
                Ultrasound Imaging
                Medicine and Health Sciences
                Radiology and Imaging
                Diagnostic Radiology
                Ultrasound Imaging
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

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