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      Can gadoxetic acid–enhanced magnetic resonance imaging be used to avoid liver biopsy in patients with nonalcoholic fatty liver disease?

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          Abstract

          BACKGROUND

          Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver disease worldwide. The diagnosis of nonalcoholic steatohepatitis (NASH), the most severe form of NAFLD, is crucial and has prognostic and therapeutic implications. However, currently this diagnosis is based on liver biopsy and has several limitations.

          AIM

          To evaluate the performance of gadoxetic acid–enhanced magnetic resonance imaging (GA-MRI) in differentiating isolated steatosis from NASH in patients with NAFLD.

          METHODS

          In this prospective study, 56 patients with NAFLD (18 with isolated steatosis and 38 with NASH) underwent GA-MRI. The contrast enhancement index (CEI) was calculated as the rate of increase of the liver-to-muscle signal intensity ratio from before and 20 min after intravenous GA administration. Between-group differences in mean CEI were examined using Student's t test. The area under the receiver operator characteristic curve and the diagnostic performance of gadoxetic acid–enhanced magnetic resonance imaging were evaluated.

          RESULTS

          The mean CEI for all subjects was 1.82 ± 0.19. The mean CEI was significantly lower in patients with NASH than in those with isolated steatosis ( P = 0.008). Two CEI cut-off points were used: < 1.66 (94% specificity) to characterize NASH and > 2.00 (89% sensitivity) to characterize isolated steatosis. CEI values between 1.66 and 2.00 indicated liver biopsy, and the procedure could be avoided in 40% of patients with NAFLD.

          CONCLUSION

          GA-MRI is an effective noninvasive method that may be useful for the differentiation of NASH from isolated steatosis, and could help to avoid liver biopsy in patients with NAFLD.

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          Most cited references20

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          Histopathology of nonalcoholic fatty liver disease.

          Histological analysis of liver biopsies remains a standard against which other methods of assessment for the presence and amount of hepatic injury due to nonalcoholic fatty liver disease (NAFLD) are measured. Histological evaluation remains the sole method of distinguishing steatosis from advanced forms of NAFLD, i.e. nonalcoholic steatohepatitis (NASH) and fibrosis. Included in the lesions of NAFLD are steatosis, lobular and portal inflammation, hepatocyte injury in the forms of ballooning and apoptosis, and fibrosis. However, patterns of these lesions are as distinguishing as the lesions themselves. Liver injury in adults and children due to NAFLD may have different histological patterns. In this review, the rationale for liver biopsy, as well as the histopathological lesions, the microscopically observable patterns of injury, and the differential diagnoses of NAFLD and NASH are discussed.
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            Early detection of nonalcoholic steatohepatitis in patients with nonalcoholic fatty liver disease by using MR elastography.

            To investigate the diagnostic accuracy (area under the receiver operating characteristic curve [AUROC]) of magnetic resonance (MR) elastography for the early detection of nonalcoholic steatohepatitis (NASH) among patients with nonalcoholic fatty liver disease (NAFLD). An institutional review board-approved and HIPAA-compliant retrospective study was conducted in 58 NAFLD patients. Informed consent was waived by the review board. Hepatic stiffness, relative fat fraction, inflammation grade, and fibrosis stage were assessed from MR elastography, in-phase and out-of-phase gradient-echo imaging, and liver biopsy histopathologic review, respectively. Pairwise t testing, receiver operating characteristic analysis, and partial correlation analysis were performed. The mean hepatic stiffness for patients with simple steatosis (2.51 kPa) was less (P = .028) than that for patients with inflammation but no fibrosis (3.24 kPa). The mean hepatic stiffness for patients with inflammation but no fibrosis was less (P = .030) than that for patients with hepatic fibrosis (4.16 kPa). Liver stiffness had high accuracy (AUROC = 0.93) for discriminating patients with NASH from those with simple steatosis, with a sensitivity of 94% and a specificity 73% by using a threshold of 2.74 kPa. In patients with NAFLD, hepatic stiffness measurements with MR elastography can help identify individuals with steatohepatitis, even before the onset of fibrosis; NAFLD patients with inflammation but no fibrosis have greater liver stiffness than those with simple steatosis and lower mean stiffness than those with fibrosis. RSNA, 2011
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              Radiomics Analysis of Gadoxetic Acid-enhanced MRI for Staging Liver Fibrosis.

              Purpose To develop and validate a radiomics-based model for staging liver fibrosis by using gadoxetic acid-enhanced hepatobiliary phase MRI. Materials and Methods In this retrospective study, 436 patients (mean age, 51 years; age range, 18-86 years; 319 men [mean age, 51 years; age range, 18-86 years]; 117 women [mean age, 50 years; age range, 18-79 years]) with pathologic analysis-proven liver fibrosis who underwent gadoxetic acid-enhanced MRI from June 2015 to December 2016 were randomized in a three-to-one ratio into development (n = 329) and test (n = 107) cohorts, respectively. In the development cohort, a model was developed to calculate radiomics fibrosis index (RFI) by using logistic regression with elastic net regularization to differentiate stage F3-F4 from stage F0-F2. Optimal RFI cutoffs to diagnose clinically significant fibrosis (stage F2-F4), advanced fibrosis (stage F3-F4), and cirrhosis (stage F4) were determined by receiver operating characteristic curve analysis. In the test cohort, the diagnostic performance of RFI was compared with that of normalized liver enhancement, aspartate transaminase-to-platelet ratio index (APRI), and fibrosis-4 index by using the Obuchowski index. Results In the test cohort, RFI (Obuchowski index, 0.86) significantly outperformed normalized liver enhancement (Obuchowski index, 0.77; P < .03), APRI (Obuchowski index, 0.60; P < .001), and fibrosis-4 index (Obuchowski index, 0.62; P < .001) for staging liver fibrosis. By using the cutoffs, RFI had sensitivities and specificities as follows: 81% (95% confidence interval: 71%, 89%) and 78% (95% confidence interval: 63%, 89%) for diagnosing stage F2-F4, respectively; 79% (95% confidence interval: 67%, 88%) and 82% (95% confidence interval: 69%, 91%), respectively, for diagnosing stage F3-F4; and 92% (95% confidence interval: 79%, 98%) and 75% (95% confidence interval: 62%, 83%), respectively, for diagnosing stage F4. Conclusion Radiomics analysis of gadoxetic acid-enhanced hepatobiliary phase images allows for accurate diagnosis of liver fibrosis. © RSNA, 2018 Online supplemental material is available for this article.
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                Author and article information

                Contributors
                Journal
                World J Hepatol
                WJH
                World Journal of Hepatology
                Baishideng Publishing Group Inc
                1948-5182
                27 September 2020
                27 September 2020
                : 12
                : 9
                : 661-671
                Affiliations
                Research Department, D’Or Institute for Research and Education, Rio de Janeiro 22281, Brazil
                Radiology Department, Brazilian National Cancer Institute, Rio de Janeiro 20230-130, Brazil
                Radiology Department, Fleury Group S.A., Rio de Janeiro 20765-000, Brazil. viviane1brandao@ 123456gmail.com
                Research Department, D’Or Institute for Research and Education, Rio de Janeiro 22281, Brazil
                Radiology Department, Hospital Universitário Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro 21941-590, Brazil
                São Carlos Institute of Physics, University of São Paulo, São Carlos 13560-970, Brazil
                Research Department, D’Or Institute for Research and Education, Rio de Janeiro 22281, Brazil
                Radiology Department, Quinta D'Or Hospital, Rio de Janeiro 20941-150, Brazil
                Radiology Department, Centro de Diagnóstico Médico do Maranhão, Maranhão 65074-441, Brazil
                Department of Clinical Medicine, Hospital Universitário Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro 21941-590, Brazil
                Gastroenterology and Hepatology Department, Hospital Federal de Bonsucesso, Rio de Janeiro 21041-030, Brazil
                Department of Pathology and Laboratories, University of the State of Rio de Janeiro, Rio de Janeiro 20551-030, Brazil
                Department of Clinical Medicine, Hospital Universitário Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro 21941-590, Brazil
                Research Department, D’Or Institute for Research and Education, Rio de Janeiro 22281, Brazil
                Internal Medicine Department, Hospital Universitário Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro 21941-590, Brazil
                Gastroenterology Department, Hospital Universitário Pedro Ernesto, University of the State of Rio de Janeiro, Rio de Janeiro 20551-030, Brazil
                Research Department, D’Or Institute for Research and Education, Rio de Janeiro 22281, Brazil
                Radiology Department, Hospital Universitário Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro 21941-590, Brazil
                Author notes

                Author contributions: Amorim VB, Parente DB, Leite NC, Perez RM, and Rodrigues RS drafted the manuscript, was involved with data collection and analysis, and participated in design of the study; Parente DB participated in study design; Paiva FF contributed with imaging protocol, and data analysis; Oliveira Neto JA contributed with imaging protocol; Miranda AA, Moreira CC, and Fernades FF contributed equally to collecting the data; Campos CFF analyzed histopathological data; Perez RM performed statistical analysis; all authors read and approved the final manuscript.

                Supported by D’ Or Institute for Research and Education, No. CAAE-50521015.2.0000.5249.

                Corresponding author: Viviane Brandão Amorim, MD, PhD, Research Scientist, Staff Physician, Research Department, D’Or Institute for Research and Education, No. 30 Rua Diniz Cordeiro, Botafogo, Rio de Janeiro 22281-100, Brazil. viviane1brandao@ 123456gmail.com

                Article
                jWJH.v12.i9.pg661
                10.4254/wjh.v12.i9.661
                7522564
                33033571
                a0e8df2d-fda7-4872-9708-7ec30ce28049
                ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.

                This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.

                History
                : 4 June 2020
                : 29 June 2020
                : 15 August 2020
                Categories
                Prospective Study

                fatty liver,nonalcoholic fatty liver disease,nonalcoholic steatohepatitis,gadoxetic acid

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