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      Non-Invasive Assessment of Hepatic Steatosis in Patients with NAFLD Using Controlled Attenuation Parameter and 1H-MR Spectroscopy

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          Abstract

          Introduction

          Non-invasive assessment of steatosis and fibrosis is of growing relevance in non-alcoholic fatty liver disease (NAFLD). 1H-Magnetic resonance spectroscopy ( 1H-MRS) and the ultrasound-based controlled attenuation parameter (CAP) correlate with biopsy proven steatosis, but have not been correlated with each other so far. We therefore performed a head-to-head comparison between both methods.

          Methods

          Fifty patients with biopsy-proven NAFLD and 15 healthy volunteers were evaluated with 1H-MRS and transient elastography (TE) including CAP. Steatosis was defined according to the percentage of affected hepatocytes: S1 5-33%, S2 34–66%, S3 ≥67%.

          Results

          Steatosis grade in patients with NAFLD was S1 36%, S2 40% and S3 24%. CAP and 1H-MRS significantly correlated with histopathology and showed comparable accuracy for the detection of hepatic steatosis: areas under the receiver-operating characteristics curves were 0.93 vs. 0.88 for steatosis ≥S1 and 0.94 vs. 0.88 for ≥S2, respectively. Boot-strapping analysis revealed a CAP cut-off of 300 dB/m for detection of S2-3 steatosis, while retaining the lower cut-off of 215 dB/m for the definition of healthy individuals. Direct comparison between CAP and 1H-MRS revealed only modest correlation (total cohort: r = 0.63 [0.44, 0.76]; NAFLD cases: r = 0.56 [0.32, 0.74]). For detection of F2–4 fibrosis TE had sensitivity and specificity of 100% and 98.1% at a cut-off value of 8.85 kPa.

          Conclusion

          Our data suggest a comparable diagnostic value of CAP and 1H-MRS for hepatic steatosis quantification. Combined with the simultaneous TE fibrosis assessment, CAP represents an efficient method for non-invasive characterization of NAFLD. Limited correlation between CAP and 1H-MRS may be explained by different technical aspects, anthropometry, and presence of advanced liver fibrosis.

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          Most cited references35

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          Receiver-operating characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine.

          The clinical performance of a laboratory test can be described in terms of diagnostic accuracy, or the ability to correctly classify subjects into clinically relevant subgroups. Diagnostic accuracy refers to the quality of the information provided by the classification device and should be distinguished from the usefulness, or actual practical value, of the information. Receiver-operating characteristic (ROC) plots provide a pure index of accuracy by demonstrating the limits of a test's ability to discriminate between alternative states of health over the complete spectrum of operating conditions. Furthermore, ROC plots occupy a central or unifying position in the process of assessing and using diagnostic tools. Once the plot is generated, a user can readily go on to many other activities such as performing quantitative ROC analysis and comparisons of tests, using likelihood ratio to revise the probability of disease in individual subjects, selecting decision thresholds, using logistic-regression analysis, using discriminant-function analysis, or incorporating the tool into a clinical strategy by using decision analysis.
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            Impact of current treatments on liver disease, glucose metabolism and cardiovascular risk in non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of randomised trials.

            Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum ranging from simple steatosis to non-alcoholic steatohepatitis (NASH): NAFLD causes an increased risk of cardiovascular disease, diabetes and liver-related complications (the latter confined to NASH). The effect of proposed treatments on liver disease, glucose metabolism and cardiovascular risk in NAFLD is unknown. We reviewed the evidence for the management of liver disease and cardio-metabolic risk in NAFLD. Publications through November 2011 were systematically reviewed by two authors. Outcomes evaluated though standard methods were: histological/radiological/biochemical features of NAFLD, variables of glucose metabolism and cardiovascular risk factors. Seventy-eight randomised trials were included (38 in NASH, 40 in NAFLD): 41% assessed post-treatment histology, 71% assessed glucose metabolism and 88% assessed cardiovascular risk factors. Lifestyle intervention, thiazolidinediones, metformin and antioxidants were most extensively evaluated. Lifestyle-induced weight loss was safe and improved cardio-metabolic risk profile; a weight loss ≥7% improved histological disease activity, but was achieved by <50% patients. Statins and polyunsaturated fatty acids improved steatosis, but their effects on liver histology are unknown. Thiazolidinediones improved histological disease activity, glucose, lipid and inflammatory variables and delayed fibrosis progression. Pioglitazone also improved blood pressure. Weight gain (up to 4.8%) was common. Antioxidants yielded mixed histological results: vitamin E improved histological disease activity when administered for 2 years, but increased insulin resistance and plasma triacylglycerols. Weight loss is safe, and improves liver histology and cardio-metabolic profile. For patients not responding to lifestyle intervention, pioglitazone improves histological disease activity, slows fibrosis progression and extensively ameliorates cardio-metabolic endpoints. Further randomised controlled trials (RCTs) of adequate size and duration will assess long-term safety and efficacy of proposed treatments on clinical outcomes.
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              Non-invasive assessment and quantification of liver steatosis by ultrasound, computed tomography and magnetic resonance.

              Hepatic steatosis is the most prevalent liver disorder in the developed world. It is closely associated with features of metabolic syndrome, especially insulin resistance and obesity. The two most common conditions associated with fatty liver are alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD). Liver biopsy is considered the gold standard for the assessment of liver fat, but there is a need for less invasive diagnostic techniques. New imaging modalities are emerging, which could provide more detailed information about hepatic tissue or even replace biopsy. In the present review, available imaging modalities (ultrasound, computed tomography, magnetic resonance imaging and proton magnetic resonance spectroscopy) are presented which are employed to detect or even quantify the fat content of the liver. The advantages and disadvantages of the above-mentioned imaging modalities are discussed. Although none of these techniques is able to differentiate between microvesicular and macrovesicular steatosis and to reveal all features visible using histology, the proposed diagnostic modalities offer a wide range of additional information such as anatomical and morphological information non-invasively. In particular, magnetic resonance imaging and proton magnetic resonance spectroscopy are able to quantify the hepatic fat content hence avoiding exposure to radiation. Except for proton magnetic resonance spectroscopy, all modalities offer additional information about regional fat distribution within the liver. MR elastography, which can estimate the amount of fibrosis, also appears promising in the differentiation between simple steatosis and steatohepatitis.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2014
                17 March 2014
                : 9
                : 3
                : e91987
                Affiliations
                [1 ]IFB AdiposityDiseases, Leipzig University Medical Center, Leipzig, Germany
                [2 ]Department of Medicine, Neurology and Dermatology, Division of Gastroenterology and Rheumatology, University Hospital Leipzig, Leipzig, Germany
                [3 ]Clinical Trial Center, University of Leipzig, Leipzig, Germany
                [4 ]Department of Diagnostics and Interventional Radiology, University Hospital Leipzig, Leipzig, Germany
                [5 ]Department of Medicine, Neurology and Dermatology, Division of Gastroenterology and Rheumatology, Section of Hepatology, University Hospital Leipzig, Leipzig, Germany
                [6 ]Institute of Pathology, University Hospital Leipzig, Leipzig, Germany
                [7 ]Clinic for Gastroenterology and Hepatology, Klinikum St. Georg, Leipzig, Germany
                Lady Davis Institute for Medical Research/McGill University, Canada
                Author notes

                Competing Interests: The authors have read the journal's policy and have the following conflicts: TK received travel grants from Echosens/France. All other authors have declared that no competing interests exist. The authors confirm that this does not alter their adherence to all PLOS ONE policies on sharing data and materials.

                Conceived and designed the experiments: T. Karlas NG HT CW HB T. Kahn JM TB MT VK JW. Performed the experiments: T. Karlas NG SB CW NL AS HB MT VK JW. Analyzed the data: T. Karlas DP NG SB CW MW IS NL AS HB T. Kahn JM TB MT VK JW. Contributed reagents/materials/analysis tools: T. Karlas DP NG SB HT CW MW IS NL AS HB T. Kahn JM TB MT VK JW. Wrote the paper: T. Karlas DP NG SB HT CW HB JM TB MT VK JW. Figure preparation: DP. Study Logistics: HT. Reference Pathology: CW. Revision of manuscript: MW IS NL AS T. Kahn.

                Article
                PONE-D-13-50919
                10.1371/journal.pone.0091987
                3956815
                24637477
                911dde7a-91c7-4820-b57a-c9711245ec8b
                Copyright @ 2014

                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
                : 3 December 2013
                : 16 February 2014
                Page count
                Pages: 11
                Funding
                This work was supported by the Federal Ministry of Education and Research (BMBF), Germany, FKZ: 01EO1001 (Project No. K7-40). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Diagnostic Medicine
                Diagnostic Radiology
                Magnetic Resonance Imaging
                Gastroenterology and Hepatology
                Liver Diseases
                Cirrhosis
                Nonalcoholic Steatohepatitis
                Radiology and Imaging
                Physical Sciences
                Chemistry
                Applied Chemistry
                Chemical Properties
                Physical Chemistry
                Physics
                Condensed Matter Physics
                Magnetism
                Nuclear Magnetic Resonance

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                Uncategorized

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