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      Multiparametric magnetic resonance for the non-invasive diagnosis of liver disease

      research-article
      1 , , 1 , 2 , , 1 , 1 , 3 , 4 , 2 , 5 , 1 , 6 , 6 , 3 , 6 , 1 , 2 , 7 , , 1 , * ,
      Journal of Hepatology
      Elsevier
      MR, Magnetic Resonance, BMI, Body Mass Index, NAFLD, Non-Alcoholic Fatty Liver Disease, CPA, Collagen Proportionate Area, CoV, Coefficient of Variance, 1H MRS, Proton Magnetic Resonance Spectroscopy, shMOLLI, shortened Modified Look Locker Inversion, HLC, Hepatic Lipid Content, ROI, Region of interest, ANOVA, Analysis of Variance, AUROC, Area Under the Receiver Operating Characteristic Curve, Magnetic resonance T1 mapping, Proton magnetic resonance spectroscopy, Magnetic resonance T2⁎ mapping, Iron corrected T1, Liver fibrosis, Liver steatosis, Liver haemosiderosis

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          Abstract

          Background & Aims

          With the increasing prevalence of liver disease worldwide, there is an urgent clinical need for reliable methods to diagnose and stage liver pathology. Liver biopsy, the current gold standard, is invasive and limited by sampling and observer dependent variability. In this study, we aimed to assess the diagnostic accuracy of a novel magnetic resonance protocol for liver tissue characterisation.

          Methods

          We conducted a prospective study comparing our magnetic resonance technique against liver biopsy. The individual components of the scanning protocol were T1 mapping, proton spectroscopy and T2 * mapping, which quantified liver fibrosis, steatosis and haemosiderosis, respectively. Unselected adult patients referred for liver biopsy as part of their routine care were recruited. Scans performed prior to liver biopsy were analysed by physicians blinded to the histology results. The associations between magnetic resonance and histology variables were assessed. Receiver-operating characteristic analyses were also carried out.

          Results

          Paired magnetic resonance and biopsy data were obtained in 79 patients. Magnetic resonance measures correlated strongly with histology (r s = 0.68 p <0.0001 for fibrosis; r s = 0.89 p <0.001 for steatosis; r s = −0.69 p <0.0001 for haemosiderosis). The area under the receiver operating characteristic curve was 0.94, 0.93, and 0.94 for the diagnosis of any degree of fibrosis, steatosis and haemosiderosis respectively.

          Conclusion

          The novel scanning method described here provides high diagnostic accuracy for the assessment of liver fibrosis, steatosis and haemosiderosis and could potentially replace liver biopsy for many indications. This is the first demonstration of a non-invasive test to differentiate early stages of fibrosis from normal liver.

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          Most cited references17

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          Histological grading and staging of chronic hepatitis.

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            Elastography for the diagnosis of severity of fibrosis in chronic liver disease: a meta-analysis of diagnostic accuracy.

            Transient elastography is a non-invasive method, for the assessment of hepatic fibrosis, developed as an alternative to liver biopsy. We studied the performance of elastography for diagnosis of fibrosis using meta-analysis. MEDLINE, EMBASE, SCI, Cochrane Library, conference abstracts books, and article references were searched. We included studies using biopsy as a reference standard, with the data necessary to calculate the true and false positive, true and false negative diagnostic results of elastography for a fibrosis stage, and with a 3-month maximum interval between tests. The quality of the studies was rated with the QUADAS tool. We identified 40 eligible studies. Summary sensitivity and specificity was 0.79 (95% CI 0.74-0.82) and 0.78 (95% CI 0.72-0.83) for F2 stage and 0.83 (95% CI 0.79-0.86) and 0.89 (95% CI 0.87-0.91) for cirrhosis. After an elastography result at/over the threshold value for F2 or cirrhosis ("positive" result), the corresponding post-test probability for their presence (if pre-test probability was 50%) was 78%, and 88% respectively, while, if values were below these thresholds ("negative" result), the post-test probability was 21% and 16%, respectively. No optimal stiffness cut-offs for individual fibrosis stages were validated in independent cohorts and cut-offs had a wide range and overlap within and between stages. Elastography theoretically has good sensitivity and specificity for cirrhosis (and less for lesser degrees of fibrosis); however, it should be cautiously applied to everyday clinical practice because there is no validation of the stiffness cut-offs for the various stages. Such validation is required before elastography is considered sufficiently accurate for non-invasive staging of fibrosis. Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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              Performance of ELF serum markers in predicting fibrosis stage in pediatric non-alcoholic fatty liver disease.

              Nonalcoholic fatty liver disease (NAFLD) is the most frequent chronic liver disease in children and adolescents in industrialized countries. It is important to accurately determine the stage of fibrosis in these patients. The enhanced liver fibrosis (ELF) test has been validated for staging liver fibrosis in adult patients with chronic liver diseases, including NAFLD. We investigated the performance of this test in assessing liver fibrosis in children and adolescents with NAFLD, identified by biopsy. The ELF test was performed on a panel of serum samples collected from 112 consecutive subjects that were likely to have NAFLD (64 male, mean age of 13.8+/-3.3). A previously described and validated algorithm was used to analyze the data on hyaluronic acid (HA), amino-terminal propeptide of type III collagen (PIIINP), and tissue inhibitor of metalloproteinase 1 (TIMP-1) levels. In pediatric patients with NAFLD, the ELF test predicted liver fibrosis stage with a high degree of sensitivity and specificity; results were superior to those reported for adults. The area under receiver operating characteristic curves/best possible ELF test cut-off values for the prediction of "any" (>or= stage 1), moderate-perisinusoidal (>or= stage 1b), moderate-portal/periportal (>or= stage 1c), significant (>or= stage 2), or advanced (>or= stage 3) fibrosis were 0.92/9.28, 0.92/9.33, 0.90/9.54, 0.98/10.18 and 0.99/10.51, respectively. The ELF test can be used to accurately assess the level of liver fibrosis in pediatric patients with NAFLD. This information is important for identifying patients with progressive fibrosis that require further histopathological analysis or therapeutic follow-up.
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                Author and article information

                Journal
                J Hepatol
                J. Hepatol
                Journal of Hepatology
                Elsevier
                0168-8278
                1600-0641
                1 January 2014
                January 2014
                : 60
                : 1
                : 69-77
                Affiliations
                [1 ]Oxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, West Wing, Level 6, John Radcliffe Hospital, Oxford, UK
                [2 ]Translational Gastroenterology Unit, University of Oxford, Level 5, John Radcliffe Hospital, Oxford, UK
                [3 ]Medical Sciences Division, University of Oxford, Medical Sciences Office, John Radcliffe Hospital, Oxford, UK
                [4 ]Department of Radiology, Churchill Hospital, Old Road, Oxford, UK
                [5 ]Department of Gastroenterology, Royal Berkshire Hospital, London Road, Reading, UK
                [6 ]Department of Histopathology, John Radcliffe Hospital, Headley Way, Oxford, UK
                [7 ]Oxford NIHR Biomedical Research Centre, Nuffield Department of Medicine, and Peter Medawar Building, University of Oxford, South Parks Rd, Oxford, UK
                Author notes
                [* ]Corresponding author. Address: Oxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK. Tel.: +44 1865 851085. stefan.neubauer@ 123456cardiov.ox.ac.uk
                [†]

                These authors contributed equally to this work.

                [‡]

                These authors share senior authorship.

                Article
                S0168-8278(13)00650-8
                10.1016/j.jhep.2013.09.002
                3865797
                24036007
                7c755261-71b0-4737-bfa5-a1ce54d45721
                © 2014 Elsevier B.V.

                This document may be redistributed and reused, subject to certain conditions.

                History
                : 14 June 2013
                : 23 August 2013
                : 2 September 2013
                Categories
                Research Article

                Gastroenterology & Hepatology
                bmi, body mass index,cov, coefficient of variance,1h mrs, proton magnetic resonance spectroscopy,shmolli, shortened modified look locker inversion,auroc, area under the receiver operating characteristic curve,magnetic resonance t1 mapping,proton magnetic resonance spectroscopy,magnetic resonance t2⁎ mapping,liver fibrosis,iron corrected t1,mr, magnetic resonance,nafld, non-alcoholic fatty liver disease,cpa, collagen proportionate area,hlc, hepatic lipid content,roi, region of interest,anova, analysis of variance,liver steatosis,liver haemosiderosis

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