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El-Kassas M, Othman HA, Elbadry M, Alswat K, Yilmaz Y. Risk Stratification of Patients with Metabolic Dysfunction-associated Steatotic Liver Disease: Steatohepatitis, Fibrosis, and Hepatocellular Carcinoma. J Clin Exp Hepatol 2025; 15:102415. [DOI: 10.1016/j.jceh.2024.102415] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/03/2025] Open
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Allen AM, Younossi ZM, Diehl AM, Charlton MR, Lazarus JV. Envisioning how to advance the MASH field. Nat Rev Gastroenterol Hepatol 2024; 21:726-738. [PMID: 38834817 DOI: 10.1038/s41575-024-00938-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/02/2024] [Indexed: 06/06/2024]
Abstract
Since 1980, the cumulative effort of scientists and health-care stakeholders has advanced the prerequisites to address metabolic dysfunction-associated steatotic liver disease (MASLD), a prevalent chronic non-communicable liver disease. This effort has led to, among others, the approval of the first drug specific for metabolic dysfunction-associated steatohepatitis (MASH; formerly known as nonalcoholic steatohepatitis). Despite substantial progress, MASLD is still a leading cause of advanced chronic liver disease, including primary liver cancer. This Perspective contextualizes the nomenclature change from nonalcoholic fatty liver disease to MASLD and proposes important considerations to accelerate further progress in the field, optimize patient-centric multidisciplinary care pathways, advance pharmacological, behavioural and diagnostic research, and address health disparities. Key regulatory and other steps necessary to optimize the approval and access to upcoming additional pharmacological therapeutic agents for MASH are also outlined. We conclude by calling for increased education and awareness, enhanced health system preparedness, and concerted action by policy-makers to further the public health and policy agenda to achieve at least parity with other non-communicable diseases and to aid in growing the community of practice to reduce the human and economic burden and end the public health threat of MASLD and MASH by 2030.
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Affiliation(s)
- Alina M Allen
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, USA
| | - Zobair M Younossi
- Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, VA, USA
- The Global NASH Council, Washington DC, USA
| | | | - Michael R Charlton
- Center for Liver Diseases, Department of Medicine, The University of Chicago, Chicago, IL, USA
| | - Jeffrey V Lazarus
- The Global NASH Council, Washington DC, USA.
- CUNY Graduate School of Public Health and Health Policy (CUNY SPH), New York, NY, USA.
- Barcelona Institute for Global Health (ISGlobal), Hospital Clínic, University of Barcelona, Barcelona, Spain.
- Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain.
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Bauer DJM, Nixdorf L, Dominik N, Schwarz M, Hofer BS, Hartl L, Semmler G, Jachs M, Simbrunner B, Jedamzik J, Mozayani B, Gensthaler L, Felsenreich DM, Trauner M, Langer FB, Mandorfer M, Prager G, Reiberger T. The deep abdominal ultrasound transducer (DAX) increases the success rate and diagnostic accuracy of shear wave elastography for liver fibrosis assessment in patients with obesity-A prospective biopsy-controlled study. Aliment Pharmacol Ther 2024; 60:70-82. [PMID: 38693718 DOI: 10.1111/apt.18019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Revised: 12/10/2023] [Accepted: 04/13/2024] [Indexed: 05/03/2024]
Abstract
BACKGROUND Obesity impacts the diagnostic accuracy of shear wave elastography (SWE). A deep abdominal ultrasound transducer (DAX) capable of point (pSWE) and two-dimensional (2D)-SWE has recently been introduced to address this issue. METHODS We performed a prospective study in a cohort of mostly patients with obesity undergoing liver biopsy with a high prevalence of metabolic dysfunction-associate steatotic liver disease (MASLD). Liver stiffness measurement (LSM) was measured using vibration-controlled transient elastography (VCTE), as well as pSWE and 2D SWE on the standard (5C1) and the DAX transducers. RESULTS We included 129 patients with paired LSM and liver biopsy: median age 44.0 years, 82 (63.6%) women, median BMI: 43.2 kg/m2. Histologic fibrosis stages: F0: N = 55 (42.6%), F1: N = 14 (10.9%), F2: N = 50 (38.8%), F3: N = 2 (1.6%), F4: N = 8 (6.2%). VCTE-LSM failed (N = 13) or were unreliable (IQR/median ≤30% in ≥7.1 kPa, N = 14) in 20.9% of patients. The Pearson correlation of reliable VCTE-LSM with both pSWE and 2D SWE was strong (all >0.78). The diagnostic accuracy for all LSM techniques was poor for significant fibrosis (≥F2, AUC: 0.54-0.63); however, it was good to excellent for advanced fibrosis (≥F3, AUC: 0.87-0.99) and cirrhosis (F4, AUC: 0.86-1.00). In intention-to-diagnose analysis, pSWE on DAX was significantly superior to VCTE-LSM. CONCLUSIONS pSWE- and 2D-SWE enable the non-invasive identification of advanced fibrosis and cirrhosis in patients with obese MASLD. The use of the DAX transducer for acoustic radiation force imaging (ARFI)-LSM avoids technical failures in an obese population and subsequently offers advantages over VCTE-LSM for the evaluation of fibrosis in an obese MASLD population at risk for fibrosis.
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Affiliation(s)
- David J M Bauer
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna HIV & Liver Study Group, Medical University of Vienna, Vienna, Austria
- Department of Internal Medicine IV, Klinik Ottakring, Vienna, Austria
| | - Larissa Nixdorf
- Division of General Surgery and Metabolic- and Bariatric Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria
| | - Nina Dominik
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna HIV & Liver Study Group, Medical University of Vienna, Vienna, Austria
| | - Michael Schwarz
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna HIV & Liver Study Group, Medical University of Vienna, Vienna, Austria
| | - Benedikt S Hofer
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna HIV & Liver Study Group, Medical University of Vienna, Vienna, Austria
| | - Lukas Hartl
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna HIV & Liver Study Group, Medical University of Vienna, Vienna, Austria
| | - Georg Semmler
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna HIV & Liver Study Group, Medical University of Vienna, Vienna, Austria
| | - Mathias Jachs
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna HIV & Liver Study Group, Medical University of Vienna, Vienna, Austria
| | - Benedikt Simbrunner
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna HIV & Liver Study Group, Medical University of Vienna, Vienna, Austria
| | - Julia Jedamzik
- Division of General Surgery and Metabolic- and Bariatric Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria
| | - Behrang Mozayani
- Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria
| | - Lisa Gensthaler
- Division of General Surgery and Metabolic- and Bariatric Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria
| | - Daniel Moritz Felsenreich
- Division of General Surgery and Metabolic- and Bariatric Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria
| | - Michael Trauner
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Felix Benedikt Langer
- Division of General Surgery and Metabolic- and Bariatric Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria
| | - Mattias Mandorfer
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna HIV & Liver Study Group, Medical University of Vienna, Vienna, Austria
| | - Gerhard Prager
- Division of General Surgery and Metabolic- and Bariatric Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria
| | - Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna HIV & Liver Study Group, Medical University of Vienna, Vienna, Austria
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Fischer AM, Lechea N, Coxson HO. This Is What Metabolic Dysfunction-Associated Steatotic Liver Disease Looks Like: Potential of a Multiparametric MRI Protocol. Semin Liver Dis 2024; 44:226-238. [PMID: 38806158 DOI: 10.1055/a-2334-8525] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/30/2024]
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent condition with a broad spectrum defined by liver biopsy. This gold standard method evaluates three features: steatosis, activity (ballooning and lobular inflammation), and fibrosis, attributing them to certain grades or stages using a semiquantitative scoring system. However, liver biopsy is subject to numerous restrictions, creating an unmet need for a reliable and reproducible method for MASLD assessment, grading, and staging. Noninvasive imaging modalities, such as magnetic resonance imaging (MRI), offer the potential to assess quantitative liver parameters. This review aims to provide an overview of the available MRI techniques for the three criteria evaluated individually by liver histology. Here, we discuss the possibility of combining multiple MRI parameters to replace liver biopsy with a holistic, multiparametric MRI protocol. In conclusion, the development and implementation of such an approach could significantly improve the diagnosis and management of MASLD, reducing the need for invasive procedures and paving the way for more personalized treatment strategies.
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Affiliation(s)
- Anja M Fischer
- Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany
| | - Nazim Lechea
- Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany
| | - Harvey O Coxson
- Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany
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Ratziu V, Hompesch M, Petitjean M, Serdjebi C, Iyer JS, Parwani AV, Tai D, Bugianesi E, Cusi K, Friedman SL, Lawitz E, Romero-Gómez M, Schuppan D, Loomba R, Paradis V, Behling C, Sanyal AJ. Artificial intelligence-assisted digital pathology for non-alcoholic steatohepatitis: current status and future directions. J Hepatol 2024; 80:335-351. [PMID: 37879461 DOI: 10.1016/j.jhep.2023.10.015] [Citation(s) in RCA: 26] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Revised: 08/28/2023] [Accepted: 10/09/2023] [Indexed: 10/27/2023]
Abstract
The worldwide prevalence of non-alcoholic steatohepatitis (NASH) is increasing, causing a significant medical burden, but no approved therapeutics are currently available. NASH drug development requires histological analysis of liver biopsies by expert pathologists for trial enrolment and efficacy assessment, which can be hindered by multiple issues including sample heterogeneity, inter-reader and intra-reader variability, and ordinal scoring systems. Consequently, there is a high unmet need for accurate, reproducible, quantitative, and automated methods to assist pathologists with histological analysis to improve the precision around treatment and efficacy assessment. Digital pathology (DP) workflows in combination with artificial intelligence (AI) have been established in other areas of medicine and are being actively investigated in NASH to assist pathologists in the evaluation and scoring of NASH histology. DP/AI models can be used to automatically detect, localise, quantify, and score histological parameters and have the potential to reduce the impact of scoring variability in NASH clinical trials. This narrative review provides an overview of DP/AI tools in development for NASH, highlights key regulatory considerations, and discusses how these advances may impact the future of NASH clinical management and drug development. This should be a high priority in the NASH field, particularly to improve the development of safe and effective therapeutics.
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Affiliation(s)
- Vlad Ratziu
- Sorbonne Université, ICAN Institute for Cardiometabolism and Nutrition, Hospital Pitié-Salpêtrière, INSERM UMRS 1138 CRC, Paris, France.
| | | | | | | | | | - Anil V Parwani
- Department of Pathology, The Ohio State University, Columbus, OH, USA
| | | | | | - Kenneth Cusi
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL, USA
| | - Scott L Friedman
- Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Eric Lawitz
- Texas Liver Institute, University of Texas Health San Antonio, San Antonio, TX, USA
| | - Manuel Romero-Gómez
- Hospital Universitario Virgen del Rocío, CiberEHD, Insituto de Biomedicina de Sevilla (HUVR/CSIC/US), Universidad de Sevilla, Seville, Spain
| | - Detlef Schuppan
- Institute of Translational Immunology and Department of Medicine, University Medical Center, Mainz, Germany; Department of Hepatology and Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Rohit Loomba
- NAFLD Research Center, University of California at San Diego, San Diego, CA, USA
| | - Valérie Paradis
- Université Paris Cité, Service d'Anatomie Pathologique, Hôpital Beaujon, Paris, France
| | | | - Arun J Sanyal
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University, Richmond, VA, USA
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Sweeney JR, Arenas DJ, Fortuna D, Tondon R, Furth EE. Virtual biopsies: Proof of concept for a novel quantitative approach to liver biopsy adequacy and pathology education. Am J Clin Pathol 2024; 161:24-34. [PMID: 37598345 DOI: 10.1093/ajcp/aqad104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2023] [Accepted: 07/25/2023] [Indexed: 08/22/2023] Open
Abstract
OBJECTIVES To quantitatively measure liver biopsy adequacy requirements and the effect of a teaching intervention that uses a virtual biopsy platform. METHODS A library of virtual liver biopsies was created using digital whole-slide, trichrome-stained tissue sections from liver resection material and QuPath image analysis software. Blinded participants staged fibrosis on the virtual biopsies before and after a teaching intervention. RESULTS This platform both modeled adequacy requirements for cirrhosis diagnosis on biopsy material and measured the effect of a teaching intervention on participant performance. Using this platform, diagnostic accuracy for cirrhosis could be modeled according to the function y = λ(1 ‒ e‒x/γ). The platform demonstrated that the relationship between biopsy size and diagnostic accuracy was statistically significant and that biopsies smaller than 6 mm long and 0.8 mm wide were insufficient to diagnosis cirrhosis. The platform also measured improvement in fibrosis staging accuracy among participants following a teaching intervention. CONCLUSIONS These results provide proof of concept for a virtual biopsy method by which outstanding questions in anatomic pathology can be addressed quantitatively using open source software. Future work is needed to validate these findings in clinical practice.
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Affiliation(s)
- Jacob R Sweeney
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, US
- Department of Pathology, Cleveland Clinic, Cleveland, Ohio, US
| | - Daniel J Arenas
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, US
| | - Danielle Fortuna
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, US
| | - Rashmi Tondon
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, US
| | - Emma E Furth
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, US
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Tiniakos DG, Anstee QM, Brunt EM, Burt AD. Fatty Liver Disease. MACSWEEN'S PATHOLOGY OF THE LIVER 2024:330-401. [DOI: 10.1016/b978-0-7020-8228-3.00005-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Torkzaban M, Wessner CE, Halegoua-DeMarzio D, Rodgers SK, Lyshchik A, Nam K. Diagnostic Performance Comparison Between Ultrasound Attenuation Measurements From Right and Left Hepatic Lobes for Steatosis Detection in Non-alcoholic Fatty Liver Disease. Acad Radiol 2023; 30:1838-1845. [PMID: 36586759 PMCID: PMC10307925 DOI: 10.1016/j.acra.2022.12.025] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Revised: 11/21/2022] [Accepted: 12/16/2022] [Indexed: 12/30/2022]
Abstract
RATIONALE AND OBJECTIVES Non-alcoholic fatty liver disease (NAFLD) is currently diagnosed by liver biopsy or MRI proton density fat fraction (MRI-PDFF) from left hepatic lobe (LTHL) and/or right hepatic lobe (RTHL). The objective of this study was to compare the diagnostic value of ultrasound attenuation coefficients (ACs) from RTHL and LTHL in detecting hepatic steatosis using biopsy or MRI-PDFF as a reference standard. MATERIALS AND METHODS Sixty-six patients with suspected NAFLD were imaged with an Aplio i800 ultrasound scanner (Canon Medical Systems, Tustin, CA). Five AC measurements from RTHL and LTHL were averaged separately and together to be compared with the reference standard. RESULTS Forty-seven patients (71%) were diagnosed with NAFLD. Mean ACs were significantly higher in fatty livers than non-fatty livers (RTHL: 0.73 ± 0.10 vs. 0.63 ± 0.07 dB/cm/MHZ; p < 0.0001, LTHL: 0.78 ± 0.11 vs. 0.63 ± 0.06 dB/cm/MHz; p < 0.0001, RTHL & LTHL: 0.76 ± 0.09 vs. 0.63 ± 0.05 dB/cm/MHz; p < 0.0001). Biopsy steatosis grades (n =31) were better correlated with the mean ACs of RTHL & LTHL (r = 0.72) compared to LTHL (r = 0.67) or RTHL (r = 0.61). Correlation between MRI-PDFF (n = 35) and mean ACs was better for LTHL (r = 0.69) compared to the RTHL & LTHL (r = 0.66) or RTHL (r = 0.45). Higher diagnostic accuracy was shown for the mean ACs of RTHL & LTHL (AUC 0.89, specificity 94%, sensitivity 78%) compared to LTHL (AUC 0.89, specificity 88%, sensitivity 82%) or RTHL (AUC 0.81, specificity 89%, sensitivity 68%). CONCLUSION Ultrasound ACs from RTHL and LTHL showed comparable diagnostic values in detection of hepatic steatosis with the highest diagnostic accuracy when they were averaged together.
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Affiliation(s)
- Mehnoosh Torkzaban
- Department of Radiology, Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Corinne E Wessner
- Department of Radiology, Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Dina Halegoua-DeMarzio
- Department of Medicine, Division of Gastroenterology & Hepatology, Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Shuchi K Rodgers
- Department of Radiology, Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Andrej Lyshchik
- Department of Radiology, Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Kibo Nam
- Department of Radiology, Thomas Jefferson University, Philadelphia, Pennsylvania.
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Goodman ZD. Role of Liver Biopsy in Clinical Trials and Clinical Management of Nonalcoholic Fatty Liver Disease. Clin Liver Dis 2023; 27:353-362. [PMID: 37024212 DOI: 10.1016/j.cld.2023.01.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/08/2023]
Abstract
Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis constitute a spectrum of histologic lesions characterized by varying degrees of hepatocellular injury and fat accumulation with inflammation and scarring. Fibrosis associated with this disease may progress to cirrhosis and its complications. As there are no approved therapies, clinical trials to assess potential forms of drug therapy are conducted to assess drugs for efficacy and safety before submission to regulatory review. Liver biopsies are performed and evaluated to confirm the diagnosis of nonalcoholic steatohepatitis and to assess fibrosis stage for inclusion in trials.
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Affiliation(s)
- Zachary D Goodman
- Center of Liver Diseases, Inova Fairfax Hospital, 3300 Gallows Road, Falls Church, VA 22042, USA.
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Mert-Biberoğlu F, Erdem NZ, Özdenkaya Y, Özdemir EM, Saka B. Effects of Whey Protein, Omega-3 Fatty Acid and Roux-En-Y Gastric Bypass on Body Weight, Biochemical Parameters and Organ Functions in an Obese Rat Model: Experimental Research. Obes Surg 2023; 33:1553-1563. [PMID: 36971930 DOI: 10.1007/s11695-023-06560-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Revised: 03/17/2023] [Accepted: 03/21/2023] [Indexed: 03/29/2023]
Abstract
PURPOSE Extreme obesity (EO) is one of the biggest public health problems in the world and has grown considerably over the years. The aim of the study is to examine the effect of Roux-en-Y gastric bypass (RYGB), whey protein (WP), and omega-3 polyunsaturated fatty acid (PUFA) supplementation applied to EO rats on weight loss, histopathological changes in internal organs and biochemical alterations. MATERIALS AND METHODS Wistar albino female rats (n = 28) were used in the study and randomly divided into four groups. All rats were made obese by adding high fructose corn syrup (HFCS) to their drinking water. After the EO, WP and omega-3 PUFA supplementation was given and RYGB process was applied. At the end of the study, glucose, total cholesterol, HDL, VLDL, AST, ALT and uric acid changes and liver, kidney and pancreatic tissues were evaluated histopathologically. RESULTS WP and omega-3 PUFA supplementation decreased body weight (p > 0.05). Omega-3 PUFA and RYGB caused a decrease in total cholesterol (p < 0.05), WP decreased HDL (p < 0.05), WP and omega-3 PUFA caused an increase in ALT (p < 0.05). WP has been shown to have greater curative effects in rat liver and kidney tissues. It has been determined that RYGB causes necrosis in the liver and HFCS causes inflammation in the kidney. CONCLUSION In the study; the positive effects of WP, omega-3 PUFA and bariatric surgery on obesity and dyslipidemia have been demonstrated. With this result, it was determined that WP, omega-3 PUFA supplementation and bariatric surgery were not superior to each other.
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Nam K, Torkzaban M, Halegoua-DeMarzio D, Wessner CE, Lyshchik A. Improving diagnostic accuracy of ultrasound texture features in detecting and quantifying hepatic steatosis using various beamforming sound speeds. Phys Med Biol 2023; 68:10.1088/1361-6560/acb635. [PMID: 36696691 PMCID: PMC10009771 DOI: 10.1088/1361-6560/acb635] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Accepted: 01/25/2023] [Indexed: 01/26/2023]
Abstract
Objective.While ultrasound image texture has been utilized to detect and quantify hepatic steatosis, the texture features extracted using a single (conventionally 1540 m s-1) beamforming speed of sound (SoS) failed to achieve reliable diagnostic performance. This study aimed to investigate if the texture features extracted using various beamforming SoSs can improve the accuracy of hepatic steatosis detection and quantification.Approach.Patients with suspected non-alcoholic fatty liver disease underwent liver biopsy or MRI proton density fat fraction (PDFF) as part of standard of care, were prospectively enrolled. The radio-frequency data from subjects' right and left liver lobes were collected using 6 beamforming SoSs: 1300, 1350, 1400, 1450, 1500 and 1540 m s-1and analyzed offline. The texture features, i.e. Contrast, Correlation, Energy and Homogeneity from gray-level co-occurrence matrix of normalized envelope were obtained from a region of interest in the liver parenchyma.Main results.Forty-three subjects (67.2%) were diagnosed with steatosis while 21 had no steatosis. Homogeneity showed the area under the curve (AUC) of 0.75-0.82 and 0.58-0.81 for left and right lobes, respectively with varying beamforming SoSs. The combined Homogeneity value over 1300-1540 m s-1from left and right lobes showed the AUC of 0.90 and 0.81, respectively. Furthermore, the combined Homogeneity values from left and right lobes over 1300-1540 m s-1improved the AUC to 0.94. The correlation between texture features and steatosis severity was improved by using the images from various beamforming SoSs. The combined Contrast values over 1300-1540 m s-1from left and right lobes demonstrated the highest correlation (r= 0.90) with the MRI PDFF while the combined Homogeneity values over 1300-1540 m s-1from left and right lobes showed the highest correlation with the biopsy grades (r= -0.81).Significance.The diagnostic accuracy of ultrasound texture features in detecting and quantifying hepatic steatosis was improved by combining its values extracted using various beamforming SoSs.
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Affiliation(s)
- Kibo Nam
- Department of Radiology, Thomas Jefferson University, Philadelphia, PA 19107, USA
| | - Mehnoosh Torkzaban
- Department of Radiology, Thomas Jefferson University, Philadelphia, PA 19107, USA
| | - Dina Halegoua-DeMarzio
- Department of Medicine, Division of Gastroenterology & Hepatology, Thomas Jefferson University, Philadelphia, PA 19107, USA
| | - Corinne E. Wessner
- Department of Radiology, Thomas Jefferson University, Philadelphia, PA 19107, USA
| | - Andrej Lyshchik
- Department of Radiology, Thomas Jefferson University, Philadelphia, PA 19107, USA
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Retrospective comparison of liver chemical shift-encoded PDFF sampling strategies in children and adolescents. ABDOMINAL RADIOLOGY (NEW YORK) 2022; 47:3478-3484. [PMID: 35864263 DOI: 10.1007/s00261-022-03615-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 07/01/2022] [Accepted: 07/05/2022] [Indexed: 01/18/2023]
Abstract
INTRODUCTION Multiple region-of-interest (ROI) sampling strategies have been described for liver fat quantification by MRI PDFF. While adult studies have shown that sampling strategies including as few as four ROIs provide a reasonable tradeoff between laboriousness and quantitative performance, there is a paucity of similar data for pediatric patients. PURPOSE To assess agreement between different ROI sampling strategies for liver MRI PDFF analysis in children and adolescents. MATERIALS AND METHODS This retrospective, internal review board-approved study included clinical MRI PDFF acquisitions for 50 children and adolescents. Four different ROI sampling paradigms reported in the literature were reproduced to measure mean liver PDFF. An 18-ROI (2 in each Couinaud segment) paradigm was considered the reference standard. Spearman correlation, intraclass correlation coefficients (ICCs), and Bland-Altman analyses were used to quantify agreement. RESULTS Mean age for the 50 participants was 14 ± 2.5 years (range 8-17 years). Based on the 18-ROI paradigm, mean PDFF was significantly higher for the right lobe (24.0 ± 13.7% right, 22.0 ± 13.1% left; p = 0.001). PDFF values for each individual Couinaud segment were highly correlated with the reference standard (ρ = 0.977 to 0.993, p < 0.0001). PDFF values derived from all sampling paradigms, including strategies using large free-hand ROIs, were strongly correlated with the reference standard (ρ = 0.995 to 0.998, p < 0.0001) with excellent agreement (ICC range 0.995 to 0.998). CONCLUSION Liver PDFF sampling paradigms using large ROIs showed strong correlation, excellent agreement, and nonsignificant mean differences from a reference standard paradigm sampling every Couinaud segment in children. Paradigms that exclusively sample the right lobe may overestimate liver PDFF.
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Roeb E, Canbay A, Bantel H, Bojunga J, de Laffolie J, Demir M, Denzer UW, Geier A, Hofmann WP, Hudert C, Karlas T, Krawczyk M, Longerich T, Luedde T, Roden M, Schattenberg J, Sterneck M, Tannapfel A, Lorenz P, Tacke F. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:1346-1421. [PMID: 36100202 DOI: 10.1055/a-1880-2283] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- E Roeb
- Gastroenterologie, Medizinische Klinik II, Universitätsklinikum Gießen und Marburg, Gießen, Deutschland
| | - A Canbay
- Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Deutschland
| | - H Bantel
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover (MHH), Hannover, Deutschland
| | - J Bojunga
- Medizinische Klinik I Gastroent., Hepat., Pneum., Endokrin., Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - J de Laffolie
- Allgemeinpädiatrie und Neonatologie, Zentrum für Kinderheilkunde und Jugendmedizin, Universitätsklinikum Gießen und Marburg, Gießen, Deutschland
| | - M Demir
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum und Campus Charité Mitte, Berlin, Deutschland
| | - U W Denzer
- Klinik für Gastroenterologie und Endokrinologie, Universitätsklinikum Gießen und Marburg, Marburg, Deutschland
| | - A Geier
- Medizinische Klinik und Poliklinik II, Schwerpunkt Hepatologie, Universitätsklinikum Würzburg, Würzburg, Deutschland
| | - W P Hofmann
- Gastroenterologie am Bayerischen Platz - Medizinisches Versorgungszentrum, Berlin, Deutschland
| | - C Hudert
- Klinik für Pädiatrie m. S. Gastroenterologie, Nephrologie und Stoffwechselmedizin, Charité Campus Virchow-Klinikum - Universitätsmedizin Berlin, Berlin, Deutschland
| | - T Karlas
- Klinik und Poliklinik für Onkologie, Gastroenterologie, Hepatologie, Pneumologie und Infektiologie, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - M Krawczyk
- Klinik für Innere Medizin II, Gastroent., Hepat., Endokrin., Diabet., Ern.med., Universitätsklinikum des Saarlandes, Homburg, Deutschland
| | - T Longerich
- Pathologisches Institut, Universitätsklinikum Heidelberg, Heidelberg, Deutschland
| | - T Luedde
- Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Düsseldorf, Düsseldorf, Deutschland
| | - M Roden
- Klinik für Endokrinologie und Diabetologie, Universitätsklinikum Düsseldorf, Düsseldorf, Deutschland
| | - J Schattenberg
- I. Medizinische Klinik und Poliklinik, Universitätsmedizin Mainz, Mainz, Deutschland
| | - M Sterneck
- Klinik für Hepatobiliäre Chirurgie und Transplantationschirurgie, Universitätsklinikum Hamburg, Hamburg, Deutschland
| | - A Tannapfel
- Institut für Pathologie, Ruhr-Universität Bochum, Bochum, Deutschland
| | - P Lorenz
- Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS), Berlin, Deutschland
| | - F Tacke
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum und Campus Charité Mitte, Berlin, Deutschland
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Authors, Collaborators:. Updated S2k Clinical Practice Guideline on Non-alcoholic Fatty Liver Disease (NAFLD) issued by the German Society of Gastroenterology, Digestive and Metabolic Diseases (DGVS) - April 2022 - AWMF Registration No.: 021-025. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:e733-e801. [PMID: 36100201 DOI: 10.1055/a-1880-2388] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
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15
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CT-based visual grading system for assessment of hepatic steatosis: diagnostic performance and interobserver agreement. Hepatol Int 2022; 16:1075-1084. [PMID: 35789473 DOI: 10.1007/s12072-022-10373-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Accepted: 05/30/2022] [Indexed: 11/04/2022]
Abstract
BACKGROUND Hepatic steatosis (HS) can be comprehensively assessed by visually comparing the hepatic and vessel attenuation on unenhanced computed tomography (CT). We aimed to evaluate the reliability and reproducibility of a CT-based visual grading system (VGS) for comprehensive assessment of HS. METHODS In this retrospective study, a four-point VGS based on the visual comparison of liver and hepatic vessels was validated by six reviewers with diverse clinical experience using the unenhanced CT images of 717 potential liver donors. The diagnostic performance of VGS and quantitative indices (difference and ratio of the hepatic and splenic attenuation) to diagnose HS were evaluated using multi-reader multi-case receiver operating characteristics (ROC) analysis (reference: pathology). The interobserver agreement was assessed using Fleiss κ statistics. RESULTS Using the VGS, all six reviewers showed areas under the ROC curves (AUROCs) higher than 0.9 for diagnosing total steatosis (TS) ≥ 30%, macrovesicular steatosis (MaS) ≥ 30%, and MaS ≥ 10%. No difference was noted between the AUROCs of the VGS and quantitative indices (p ≥ 0.1). The reviewers showed substantial agreement (Fleiss κ, 0.61). Most discrepancies occurred between the two lowest grades of VGS (81.5%; 233/283), in which most subjects (97.0%; 226/233) had a MaS < 10%. The average-reader sensitivity and specificity of the VGS were 0.80 and 0.94 to detect TS ≥ 30% and 0.93 and 0.81 to detect MaS ≥ 10%. CONCLUSION VGS was reliable and reproducible in assessing HS. It may be useful as a non-invasive and simple tool for comprehensive HS assessment.
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Zeng K, Jiang Z, Yang J, Chen K, Lu Q. Role of endoscopic ultrasound-guided liver biopsy: a meta-analysis. Scand J Gastroenterol 2022; 57:545-557. [PMID: 35049405 DOI: 10.1080/00365521.2021.2025420] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2021] [Revised: 12/23/2021] [Accepted: 12/30/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND Endoscopic ultrasound-guided liver biopsy (EUS-LB) is an evolving technique. In this meta-analysis, we aimed to evaluate the value of EUS-LB for parenchymal and focal liver lesions. Besides, we aimed to assess the influences of needle-related factors on the performance of EUS-LB. Additionally, we aimed to assess the influence of various criteria on specimen adequacy. METHODS We searched the PubMed, Embase, Cochrane Library databases up to 10 October 2021. The primary outcome was diagnostic yield, specimen adequacy, qualified specimens evaluated by rapid on-site evaluation (ROSE). The secondary outcome was adverse events. Subgroup analyses were based on needle type, needle size, fine-needle biopsy (FNB) needle type. A sensitivity analysis was conducted on specimen adequacy based on two definition criteria. RESULTS In total, 33 studies were included. Pooled rates of diagnostic yield, specimen adequacy, qualified specimen by ROSE, adverse events were 95%, 84%, 93%, 3%. Subgroup analyses showed that Acquire needles generated higher diagnostic yield than SharkCore needles (99% vs. 88%, p = .047). Additionally, FNB needles demonstrated a higher rate of adverse events than FNA needles (6% vs. 1%, p = .028). Sensitivity analysis on specimen adequacy based on various criteria demonstrated that the specimen adequacy rate defined by the AASLD criterion was lower than that of the commonly-used criterion (37% vs. 84%, p = .001). CONCLUSION EUS-LB is effective and safe for liver biopsy. Acquire needles provide better specimens than SharkCore needles. FNB needles may increase the risk of adverse events compared with FNA needles. The AASLD criterion is harder to achieve than the commonly-used criterion.
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Affiliation(s)
- Keyu Zeng
- Department of Ultrasound, West China Hospital, Sichuan University, Chengdu, China
| | - Zhenpeng Jiang
- Department of Ultrasound, West China Hospital, Sichuan University, Chengdu, China
| | - Jie Yang
- Department of Ultrasound, West China Hospital, Sichuan University, Chengdu, China
| | - Kefei Chen
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, China
| | - Qiang Lu
- Department of Ultrasound, West China Hospital, Sichuan University, Chengdu, China
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Rowe IA, Parker R. The Placebo Response in Randomized Trials in Nonalcoholic Steatohepatitis Simply Explained. Clin Gastroenterol Hepatol 2022; 20:e564-e572. [PMID: 34091047 DOI: 10.1016/j.cgh.2021.05.059] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Revised: 05/13/2021] [Accepted: 05/31/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Liver histology is the primary endpoint in phase III trials in nonalcoholic steatohepatitis (NASH). There is an appreciable response to placebo that confounds endpoint assessment. The aim of this study was to quantify contributors to the placebo response and its impact on liver fibrosis improvement. METHODS Estimates of fibrosis improvement in placebo-treated participants were made using probabilistic simulation. Each simulated trial included 120 participants. Parameters considered in the model included sampling and observer variability, regression to the mean, and net fibrosis progression calibrated to reported trial outcomes. RESULTS In large phase IIb and III trials, 22% of placebo-treated participants with fibrosis stage 2 or 3 NASH at baseline improved by at least 1 fibrosis stage with minimal net disease progression. Estimates of sampling and observer variability in simultaneous biopsy studies highlighted an imbalance where apparent fibrosis improvement was more likely than worsening. Using these estimates and known trial outcomes, net fibrosis progression was estimated at 0.05 stages per year. Simulations of the placebo response rate showed a rate of 22% with 80% of trials falling between 15 and 30%, in keeping with trials reported to date. Additional increases in observer variability further increased the placebo response. CONCLUSIONS The analyses presented simply define the placebo response in liver fibrosis in trials in NASH in terms of sampling and observer variability, regression to the mean, and fibrosis progression. Factors relating to liver biopsy are largely unmodifiable, and the variation in placebo response rates, both simulated and observed, challenges the role of biopsy in trial endpoint assessment.
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Affiliation(s)
- Ian A Rowe
- Leeds Institute for Medical Research, University of Leeds, Leeds, United Kingdom; Leeds Liver Unit, St James's University Hospital, Leeds, United Kingdom.
| | - Richard Parker
- Leeds Liver Unit, St James's University Hospital, Leeds, United Kingdom
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18
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Hong CW, Cui JY, Batakis D, Xu Y, Wolfson T, Gamst AC, Schlein AN, Negrete LM, Middleton MS, Hamilton G, Loomba R, Schwimmer JB, Fowler KJ, Sirlin CB. Repeatability and accuracy of various region-of-interest sampling strategies for hepatic MRI proton density fat fraction quantification. Abdom Radiol (NY) 2021; 46:3105-3116. [PMID: 33609166 DOI: 10.1007/s00261-021-02965-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2020] [Revised: 01/13/2021] [Accepted: 01/16/2021] [Indexed: 12/19/2022]
Abstract
PURPOSE To evaluate repeatability of ROI-sampling strategies for quantifying hepatic proton density fat fraction (PDFF) and to assess error relative to the 9-ROI PDFF. METHODS This was a secondary analysis in subjects with known or suspected nonalcoholic fatty liver disease who underwent MRI for magnitude-based hepatic PDFF quantification. Each subject underwent three exams, each including three acquisitions (nine acquisitions total). An ROI was placed in each hepatic segment on the first acquisition of the first exam and propagated to other acquisitions. PDFF was calculated for each of 511 sampling strategies using every combination of 1, 2, …, all 9 ROIs. Intra- and inter-exam intra-class correlation coefficients (ICCs) and repeatability coefficients (RCs) were estimated for each sampling strategy. Mean absolute error (MAE) was estimated relative to the 9-ROI PDFF. Strategies that sampled both lobes evenly ("balanced") were compared with those that did not ("unbalanced") using two-sample t tests. RESULTS The 29 enrolled subjects (23 male, mean age 24 years) had mean 9-ROI PDFF 11.8% (1.1-36.3%). With more ROIs, ICCs increased, RCs decreased, and MAE decreased. Of the 60 balanced strategies with 4 ROIs, all (100%) achieved inter- and intra-exam ICCs > 0.998, 55 (92%) achieved intra-exam RC < 1%, 50 (83%) achieved inter-exam RC < 1%, and all (100%) achieved MAE < 1%. Balanced sampling strategies had higher ICCs and lower RCs, and lower MAEs than unbalanced strategies in aggregate (p < 0.001 for comparisons between balanced vs. unbalanced strategies). CONCLUSION Repeatability improves and error diminishes with more ROIs. Balanced 4-ROI strategies provide high repeatability and low error.
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Syväri J, Junker D, Patzelt L, Kappo K, Al Sadat L, Erfanian S, Makowski MR, Hauner H, Karampinos DC. Longitudinal changes on liver proton density fat fraction differ between liver segments. Quant Imaging Med Surg 2021; 11:1701-1709. [PMID: 33936958 DOI: 10.21037/qims-20-873] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Background To study the spatial heterogeneity of liver fat fraction changes during a long-term lifestyle intervention study using magnetic resonance imaging (MRI). Methods Thirty-two subjects underwent two MRI-scans in a span of one year. A chemical shift encoding-based water-fat separation method was applied to measure liver proton density fat fraction (PDFF) maps. The PDFF changes in the two liver lobes and the Couinaud segments were compared with the mean liver PDFF change. Results The slope of the relationship between mean liver PDFF changes and PDFF liver lobe changes was higher in the right compared to the left lobe (slopemean PDFF whole liver ~ mean PDFF right lobe =1.08, slopemean PDFF whole liver ~ mean PDFF left lobe =0.93, P<0.001). The highest slope of agreement between PDFF changes in each specific liver segment and mean liver PDFF changes was observed in segment VII (slope =1.12). The lowest slope of agreement between PDFF changes in each specific liver segment and mean liver PDFF changes was observed in segment I (slope =0.77). Conclusions Larger PDFF changes in the right liver lobe were observed compared to PDFF changes in the left liver lobe (LLL) in subjects with both increasing and decreasing mean liver PDFF after one year. The results are in line with the existing literature reporting a heterogeneous spatial distribution of liver fat and highlight the need to spatially resolve liver fat fraction changes in longitudinal studies.
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Affiliation(s)
- Jan Syväri
- Department of Diagnostic and Interventional Radiology, School of Medicine, Technical University of Munich, Munich, Germany
| | - Daniela Junker
- Department of Diagnostic and Interventional Radiology, School of Medicine, Technical University of Munich, Munich, Germany
| | - Lisa Patzelt
- Department of Diagnostic and Interventional Radiology, School of Medicine, Technical University of Munich, Munich, Germany
| | - Katharina Kappo
- Institute for Nutritional Medicine, Else Kroener-Fresenius-Center of Nutritional Medicine, School of Medicine, Technical University of Munich, Munich, Germany
| | - Loubna Al Sadat
- Institute for Nutritional Medicine, Else Kroener-Fresenius-Center of Nutritional Medicine, School of Medicine, Technical University of Munich, Munich, Germany
| | - Sonia Erfanian
- Institute for Nutritional Medicine, Else Kroener-Fresenius-Center of Nutritional Medicine, School of Medicine, Technical University of Munich, Munich, Germany
| | - Marcus R Makowski
- Department of Diagnostic and Interventional Radiology, School of Medicine, Technical University of Munich, Munich, Germany
| | - Hans Hauner
- Institute for Nutritional Medicine, Else Kroener-Fresenius-Center of Nutritional Medicine, School of Medicine, Technical University of Munich, Munich, Germany.,German Center for Diabetes Research, Helmholtz Diabetes Center, Neuherberg, Germany
| | - Dimitrios C Karampinos
- Department of Diagnostic and Interventional Radiology, School of Medicine, Technical University of Munich, Munich, Germany
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Yoon YI, Song GW, Lee SG, Park GC, Hwang S, Kim KH, Ahn CS, Moon DB, Ha TY, Jung DH, Kim KW, Shim JH, Tak EY, Kirchner VA, Pruett TL. Safe use of right lobe living donor livers with moderate steatosis in adult-to-adult living donor liver transplantation: a retrospective study. Transpl Int 2021; 34:872-881. [PMID: 33660330 DOI: 10.1111/tri.13859] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Revised: 02/09/2021] [Accepted: 02/28/2021] [Indexed: 01/22/2023]
Abstract
Hepatic steatosis (HS) beyond a certain degree can jeopardize living donor (LD) safety, particularly in right lobe (RL) donors, making it a major obstacle for donor pool expansion in adult-to-adult living donor liver transplantation (ALDLT). From July 2004 to June 2016, 58 LDs donated their RLs despite having moderate HS (30%-50% steatosis) determined by intraoperative biopsy at a single center. We performed greedy matching to compare the outcomes of the donors and recipients of this group with those of LDs with no HS. The mean left lobe (LL) HS value in the 58 cases was 20.9 ± 12.4%, which was significantly lower than the mean RL HS value (38.8 ± 6.7%, P < 0.001). The mean ratio of the remnant LL to the total liver volume was 37.8 ± 2.2. No differences were observed in the postoperative liver function and donor and recipient morbidity and mortality rates. The liver regeneration rates in recipients and donors at 1 month, 6 months, and 1 year postoperatively did not differ significantly. The patient and graft survival rates of the recipients showed no differences. The use of well-selected RL grafts with moderate steatosis does not impair graft function, recipient outcomes, or donor safety.
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Affiliation(s)
- Young-In Yoon
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Gi-Won Song
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sung-Gyu Lee
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Gil-Chun Park
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Shin Hwang
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ki-Hun Kim
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Chul-Soo Ahn
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Deok-Bog Moon
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Tae-Yong Ha
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Dong-Hwan Jung
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Kyung-Won Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ju-Hyun Shim
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Eun-Young Tak
- Asan Institute for Life Sciences and Asan-Minnesota Institute for Innovating Transplantation, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Varvara A Kirchner
- Division of Transplantation, Department of Surgery, and Asan-Minnesota Institute for Innovating Transplantation, University of Minnesota, Minneapolis, MN, USA
| | - Timothy L Pruett
- Division of Transplantation, Department of Surgery, and Asan-Minnesota Institute for Innovating Transplantation, University of Minnesota, Minneapolis, MN, USA
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Del Chicca F, Richter H, Steger GL, Salesov E, Reusch CE, Kircher PR. Sample strategies for quantification of hepatic fat fraction mean MRI in healthy cats during body weight gain. PLoS One 2020; 15:e0241905. [PMID: 33180808 PMCID: PMC7660519 DOI: 10.1371/journal.pone.0241905] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Accepted: 10/22/2020] [Indexed: 11/26/2022] Open
Abstract
Hepatic fat fraction (HFF) can be non-invasively estimated with magnetic resonance imaging (MRI) multiple echo gradient recalled echo (GRE) sequence. The aim of this study was to test different methods of sampling strategies to quantify the HFF in healthy cats during body weight gain. Twelve healthy adult male cats were examined in a 3 Tesla MRI unit. Sequences included morphological images, and multiple echo GRE sequence. Cats were scanned at the beginning of the study and twice, each 20 weeks apart during body weight gain. HFF was calculated with 5 different methods of sampling on the multiple echo GRE sequence with different number, size and position of regions of interest (ROIs) and by 2 operators. Results indicated that HFF increased with increasing body weight, and the increase was appreciated with all the 5 methods. There was overall excellent agreement (interclass correlation coefficient = 0.820 (95% confidence interval:0.775–0.856)) between the 2 operators. HFF in the left lateral hepatic lobe was lower than in the other analyzed lobes. HFF measured on large free-hand drawn ROIs was higher than HFF measured with smaller ROIs size. This study proves that different sampling methods for quantification of HFF on multiple echo GRE sequence have overall excellent repeatability and ability to appreciate increased HFF.
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Affiliation(s)
- Francesca Del Chicca
- Clinic for Diagnostic Imaging, Department of Diagnostics and Clinical Services, Vetsuisse-Faculty Zurich, Zurich, Switzerland
- * E-mail:
| | - Henning Richter
- Clinic for Diagnostic Imaging, Department of Diagnostics and Clinical Services, Vetsuisse-Faculty Zurich, Zurich, Switzerland
| | - Gian-Luca Steger
- Clinic for Diagnostic Imaging, Department of Diagnostics and Clinical Services, Vetsuisse-Faculty Zurich, Zurich, Switzerland
| | - Elena Salesov
- Clinic of Small Animal Internal Medicine, Vetsuisse-Faculty Zurich, Zurich, Switzerland
| | - Claudia E. Reusch
- Clinic of Small Animal Internal Medicine, Vetsuisse-Faculty Zurich, Zurich, Switzerland
| | - Patrick R. Kircher
- Clinic for Diagnostic Imaging, Department of Diagnostics and Clinical Services, Vetsuisse-Faculty Zurich, Zurich, Switzerland
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Giuffrè M, Giuricin M, Bonazza D, Rosso N, Giraudi PJ, Masutti F, Palmucci S, Basile A, Zanconati F, de Manzini N, Tiribelli C, Palmisano S, Crocè LS. Optimization of Point-Shear Wave Elastography by Skin-to-Liver Distance to Assess Liver Fibrosis in Patients Undergoing Bariatric Surgery. Diagnostics (Basel) 2020; 10:795. [PMID: 33036418 PMCID: PMC7601552 DOI: 10.3390/diagnostics10100795] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2020] [Revised: 10/01/2020] [Accepted: 10/03/2020] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Obesity is a primary limiting factor in liver stiffness measurement (LSM). The impact of obesity has always been evaluated in terms of body mass index (BMI), without studying the effects of skin-to-liver distance (SLD) on LSM. We studied the impact of SLD on LSM in a cohort of obese patients undergoing bariatric surgery and intra-operatory liver biopsy. MATERIALS AND METHODS 299 patients underwent LSM by point-shear wave elastography (ElastPQ protocol), with two different ultrasound machines. SLD was measured as the distance between the skin and the liver capsule, perpendicular to where the region of interest (ROI) was positioned. We used the following arbitrary cut-offs: <5.7 kPa, F0-1; 5.7-7.99 kPa, F2; ≥8 kPa, F3-4. RESULTS We developed two logistic regression models using elastography-histology agreement (EHA) as the dependent variable and SLD as the independent variable. The model based on the second machine showed strongly more performant discriminative and calibration metrics (AIC 38.5, BIC 44.2, Nagelkerke Pseudo-R2 0.894, AUROC 0.90). The SLD cut-off value of 34.5 mm allowed a correct EHA with a sensitivity of 100%, a specificity of 93%, negative predictive value of 100%, positive predictive value of 87%, an accuracy of 96%, and positive likelihood ratio of 3.56. CONCLUSION The impact of SLD is machine-dependent and should be taken into consideration when interpreting LSM. We believe that our findings may serve as a reference point for appropriate fibrosis stratification by liver elastography in obese patients.
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Affiliation(s)
- Mauro Giuffrè
- Department of Medical, Surgical and Health Sciences, University of Trieste, 34149 Trieste, Italy; (D.B.); (F.Z.); (N.d.M.); (S.P.); (L.S.C.)
- Italian Liver Foundation, 34149 Trieste, Italy; (N.R.); (P.J.G.); (C.T.)
| | - Michela Giuricin
- General Surgery Clinic, Azienda Sanitaria Universitaria Giuliano-Isontina, 34149 Trieste, Italy;
| | - Deborah Bonazza
- Department of Medical, Surgical and Health Sciences, University of Trieste, 34149 Trieste, Italy; (D.B.); (F.Z.); (N.d.M.); (S.P.); (L.S.C.)
- Department of Pathology, Azienda Sanitaria Universitaria Giuliano-Isontina, Cattinara Hospital, 34149 Trieste, Italy
| | - Natalia Rosso
- Italian Liver Foundation, 34149 Trieste, Italy; (N.R.); (P.J.G.); (C.T.)
| | - Pablo José Giraudi
- Italian Liver Foundation, 34149 Trieste, Italy; (N.R.); (P.J.G.); (C.T.)
| | - Flora Masutti
- Liver Clinic, Azienda Sanitaria Universitaria Giuliano-Isontina, Cattinara Hospital, 34149 Trieste, Italy;
| | - Stefano Palmucci
- Department of Medical Surgical Sciences and Advanced Technologies G.F. Ingrassia University of Catania, 95124 Catania, Italy; (S.P.); (A.B.)
| | - Antonio Basile
- Department of Medical Surgical Sciences and Advanced Technologies G.F. Ingrassia University of Catania, 95124 Catania, Italy; (S.P.); (A.B.)
| | - Fabrizio Zanconati
- Department of Medical, Surgical and Health Sciences, University of Trieste, 34149 Trieste, Italy; (D.B.); (F.Z.); (N.d.M.); (S.P.); (L.S.C.)
- Department of Pathology, Azienda Sanitaria Universitaria Giuliano-Isontina, Cattinara Hospital, 34149 Trieste, Italy
| | - Nicolò de Manzini
- Department of Medical, Surgical and Health Sciences, University of Trieste, 34149 Trieste, Italy; (D.B.); (F.Z.); (N.d.M.); (S.P.); (L.S.C.)
- General Surgery Clinic, Azienda Sanitaria Universitaria Giuliano-Isontina, 34149 Trieste, Italy;
| | - Claudio Tiribelli
- Italian Liver Foundation, 34149 Trieste, Italy; (N.R.); (P.J.G.); (C.T.)
| | - Silvia Palmisano
- Department of Medical, Surgical and Health Sciences, University of Trieste, 34149 Trieste, Italy; (D.B.); (F.Z.); (N.d.M.); (S.P.); (L.S.C.)
- General Surgery Clinic, Azienda Sanitaria Universitaria Giuliano-Isontina, 34149 Trieste, Italy;
| | - Lory Saveria Crocè
- Department of Medical, Surgical and Health Sciences, University of Trieste, 34149 Trieste, Italy; (D.B.); (F.Z.); (N.d.M.); (S.P.); (L.S.C.)
- Italian Liver Foundation, 34149 Trieste, Italy; (N.R.); (P.J.G.); (C.T.)
- Liver Clinic, Azienda Sanitaria Universitaria Giuliano-Isontina, Cattinara Hospital, 34149 Trieste, Italy;
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Sousa-Filho PHF, Jimenez LS, Callejas GH, Concon MM, Braga JGR, Marques RA, Chaim FDM, Gestic MA, Utrini MP, Ramos AC, Chaim EA, Cazzo E. Bilobar Hepatic Histological Variability in Obese Individuals Undergoing Bariatric Surgery: an Analysis of Paired Wedge Biopsies. Obes Surg 2020; 30:5125-5128. [PMID: 32949000 DOI: 10.1007/s11695-020-04991-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Revised: 09/11/2020] [Accepted: 09/15/2020] [Indexed: 01/29/2023]
Affiliation(s)
- Pedro H F Sousa-Filho
- Department of Surgery, Faculty of Medical Sciences, State University of Campinas (UNICAMP), R. Alexander Fleming, s/n; Cidade Universitaria Zeferino Vaz, Campinas, SP, CEP 13085-000, Brazil
| | - Laísa S Jimenez
- Department of Surgery, Faculty of Medical Sciences, State University of Campinas (UNICAMP), R. Alexander Fleming, s/n; Cidade Universitaria Zeferino Vaz, Campinas, SP, CEP 13085-000, Brazil
| | - Guilherme H Callejas
- Department of Surgery, Faculty of Medical Sciences, State University of Campinas (UNICAMP), R. Alexander Fleming, s/n; Cidade Universitaria Zeferino Vaz, Campinas, SP, CEP 13085-000, Brazil
| | - Matheus M Concon
- Department of Surgery, Faculty of Medical Sciences, State University of Campinas (UNICAMP), R. Alexander Fleming, s/n; Cidade Universitaria Zeferino Vaz, Campinas, SP, CEP 13085-000, Brazil
| | - João G R Braga
- Department of Surgery, Faculty of Medical Sciences, State University of Campinas (UNICAMP), R. Alexander Fleming, s/n; Cidade Universitaria Zeferino Vaz, Campinas, SP, CEP 13085-000, Brazil
| | - Rodolfo A Marques
- Department of Surgery, Faculty of Medical Sciences, State University of Campinas (UNICAMP), R. Alexander Fleming, s/n; Cidade Universitaria Zeferino Vaz, Campinas, SP, CEP 13085-000, Brazil
| | - Felipe D M Chaim
- Department of Surgery, Faculty of Medical Sciences, State University of Campinas (UNICAMP), R. Alexander Fleming, s/n; Cidade Universitaria Zeferino Vaz, Campinas, SP, CEP 13085-000, Brazil
| | - Martinho A Gestic
- Department of Surgery, Faculty of Medical Sciences, State University of Campinas (UNICAMP), R. Alexander Fleming, s/n; Cidade Universitaria Zeferino Vaz, Campinas, SP, CEP 13085-000, Brazil
| | - Murillo P Utrini
- Department of Surgery, Faculty of Medical Sciences, State University of Campinas (UNICAMP), R. Alexander Fleming, s/n; Cidade Universitaria Zeferino Vaz, Campinas, SP, CEP 13085-000, Brazil
| | - Almino C Ramos
- Department of Surgery, Faculty of Medical Sciences, State University of Campinas (UNICAMP), R. Alexander Fleming, s/n; Cidade Universitaria Zeferino Vaz, Campinas, SP, CEP 13085-000, Brazil
| | - Elinton A Chaim
- Department of Surgery, Faculty of Medical Sciences, State University of Campinas (UNICAMP), R. Alexander Fleming, s/n; Cidade Universitaria Zeferino Vaz, Campinas, SP, CEP 13085-000, Brazil
| | - Everton Cazzo
- Department of Surgery, Faculty of Medical Sciences, State University of Campinas (UNICAMP), R. Alexander Fleming, s/n; Cidade Universitaria Zeferino Vaz, Campinas, SP, CEP 13085-000, Brazil.
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24
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Park HJ, Kim KW, Kwon JH, Lee J, Park T, Kwon HJ, Song GW, Lee SG. Lifestyle Modification Leads to Spatially Variable Reduction in Hepatic Steatosis in Potential Living Liver Donors. Liver Transpl 2020; 26:487-497. [PMID: 32061052 DOI: 10.1002/lt.25733] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2019] [Accepted: 01/09/2020] [Indexed: 02/07/2023]
Abstract
The spatial variability of hepatic fat reduction in potential living liver donors with hepatic steatosis (HS) who undergo lifestyle modification has not been investigated. Here, we aimed to examine the intrasegmental and intersegmental variability of changes in liver attenuation on computed tomography (CT) in potential living liver donors with HS after diet modification and exercise. A total of 87 living liver donor candidates (30.5 ± 7.0 years; 74 males) with biopsy-proven macrovesicular fat (MaF) ≥10% were included. All underwent diet modification and exercise to improve HS, baseline and follow-up unenhanced CT scans, and liver biopsies. Attenuation and its variability (mean and standard deviation, respectively, in Hounsfield units) in segmental, lobar, superficial, deep, and whole areas of the liver were measured across 32 different regions of interest on both baseline and follow-up CT. At baseline, the right lobe and superficial areas of liver showed significantly lower and more variable attenuation than left lobe and deep areas. Greater variability was noted in patients with more severe HS. Mean interval changes in liver attenuation and variability before and after diet modification and exercise were 13.7 (range, -10.6 to 46.2) and 4.7 (1.6-10.6), respectively. The mean interval change in liver attenuation was significantly higher in the right lobe than in the left (14.7 versus 12.7; P < 0.001), and in superficial areas than in deep areas (14.0 versus 13.4; P = 0.02). Greater variability and larger interval changes in liver attenuation were noted in those who responded (≥20% decrease in MaF) to diet modification and exercise than in those who did not. In conclusion, potential living liver donors with HS show significant intrasegmental and intersegmental variability in hepatic fat reduction on CT before and after diet modification and exercise.
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Affiliation(s)
- Hyo Jung Park
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Kyoung Won Kim
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Jae Hyun Kwon
- Division of Liver Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Jeongjin Lee
- School of Computer Science and Engineering, Soongsil University, Seoul, Korea
| | - Taeyong Park
- School of Computer Science and Engineering, Soongsil University, Seoul, Korea
| | - Heon-Ju Kwon
- Department of Radiology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Gi-Won Song
- Division of Liver Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Sung-Gyu Lee
- Division of Liver Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
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25
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Evaluation of the histological variability of core and wedge biopsies in nonalcoholic fatty liver disease in bariatric surgical patients. Surg Endosc 2020; 35:1210-1218. [PMID: 32170564 DOI: 10.1007/s00464-020-07490-y] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2019] [Accepted: 03/02/2020] [Indexed: 10/24/2022]
Abstract
BACKGROUND Liver biopsy remains the gold standard for characterizing and evaluating treatment response in nonalcoholic fatty liver disease (NAFLD). Liver heterogeneity and sampling variability can affect the reliability of results. This study aimed to compare histological variability of intraoperative wedge and core liver biopsies from different lobes in bariatric patients, to better inform surgeons on biopsy method and guide interpretation of results. METHODS We prospectively recruited bariatric surgical patients. Intraoperative core biopsies were taken from the left and right lobe, with a wedge biopsy taken from the left. All biopsies were graded by a specialist liver pathologist, blinded to clinical details and biopsy site. Concordance of histological findings between sites was evaluated. RESULTS There were 91 participants (72.2% female), mean age 46.8 ± 12.0 years, body mass index 45.9 ± 9.4 kg/m2. There was no significant pattern for up- or down-grading disease dependent on biopsy technique. Moderate to strong agreement was seen in the presence of NAFLD and nonalcoholic steatohepatitis (NASH, κ = 0.609-0.865, p < 0.001) between biopsy sites. Individual components (steatosis, inflammation, ballooning) showed weaker agreement (κ = 0.386-0.656, p < 0.01). Fibrosis showed particularly poor agreement (κ = 0.223-0.496, p < 0.01). Detection of pathology improved with a combination of biopsy techniques, compared to a single biopsy method. CONCLUSION Overall diagnosis of NAFLD or NASH shows good agreement between biopsy sites, but individual components, particularly fibrosis stage, vary significantly. Clinicians should consider biopsies from varied sites, to better assess liver disease severity. These data have important implications in fibrosis assessment of NAFLD and are relevant in the interpretation of histological efficacy of investigational pharmacotherapies. TRIAL REGISTRATION ACTRN12615000875505 (Australian Clinical Trials Register).
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FABP4 and MMP9 levels identified as predictive factors for poor prognosis in patients with nonalcoholic fatty liver using data mining approaches and gene expression analysis. Sci Rep 2019; 9:19785. [PMID: 31874999 PMCID: PMC6930227 DOI: 10.1038/s41598-019-56235-y] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2019] [Accepted: 12/07/2019] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty liver (NAFLD) may progress to nonalcoholic steatohepatitis (NASH) and ultimately to cirrhosis and hepatocellular carcinoma (HCC). Prognostic markers for these conditions are poorly defined. The aim of this study was to identify predictive gene markers for the transition from NAFL to NASH and then to poorer conditions. Gene expression omnibus datasets associated with a prediction analysis algorithm were used to create a matrix composed of control subject (n = 52), healthy obese (n = 51), obese with NAFL (n = 42) and NASH patients (n = 37) and 19,085 genes in order to identify specific genes predictive of the transition from steatosis to NASH and from NASH to cirrhosis and HCC and thus patients at high risk of complications. A validation cohort was used to validate these results. We identified two genes, fatty acid binding protein-4 (FABP4) and matrix metalloproteinase-9 (MMP9), which respectively allowed distinguishing patients at risk of progression from NAFL to NASH and from NASH to cirrhosis and HCC. Thus, NAFL patients expressing high hepatic levels of FABP4 and NASH patients expressing high hepatic levels of MMP9 are likely to experience disease progression. Therefore, using FABP4 and MMP9 as blood markers could help to predict poor outcomes and/or progression of NAFL during clinical trial follow-up.
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27
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Jensen VS, Tveden-Nyborg P, Zacho-Rasmussen C, Quaade ML, Ipsen DH, Hvid H, Fledelius C, Wulff EM, Lykkesfeldt J. Variation in diagnostic NAFLD/NASH read-outs in paired liver samples from rodent models. J Pharmacol Toxicol Methods 2019; 101:106651. [PMID: 31733366 DOI: 10.1016/j.vascn.2019.106651] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2019] [Revised: 08/26/2019] [Accepted: 11/05/2019] [Indexed: 02/06/2023]
Abstract
INTRODUCTION In animal models of non-alcoholic fatty liver disease (NAFLD), assessment of disease severity and treatment effects of drugs rely on histopathological scoring of liver biopsies. However, little is known about the sampling variation in liver samples from animal models of NAFLD, even though several histopathological hallmarks of the disease are known to be affected by sampling variation in patients. The aim of this study was to assess the sampling variation in multiple paired liver biopsies from three commonly used diet-induced rodent models of NAFLD. METHODS Eight male C57BL/6 mice, 8 male Sprague Dawley rats and 16 female Hartley guinea pigs were fed a NAFLD-inducing high-fat diet for 16 weeks (mice and rats), 20 or 24 weeks (guinea pigs). After the initial diet period, liver sections were sampled and subsequently assessed by histopathological scoring and biochemical analyses. RESULTS Fibrosis was heterogeneously distributed throughout the liver in mice, manifesting as both intra- and interlobular statistically significant differences. Hepatic triglyceride content showed interlobular differences in mice, and both intra- and interlobular differences in guinea pigs (24-week time point) all of which were statistically significant. Also, hepatic cholesterol content was subject to significant intra-lobular sampling variation in mice, and hepatic glycogen content differed significantly between lobes in mice and guinea pigs. DISCUSSION Dependent on animal model, both histopathological and biochemical end-points differed between sampling sites in the liver. Based on these findings, we recommend that sample site location is highly standardized and properly reported in order to minimize potential sampling variation and to optimize reproducibility and meaningful comparisons of preclinical studies of NAFLD.
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Affiliation(s)
- Victoria S Jensen
- Section of Experimental Animal Models, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Ridebanevej 9, DK-1870 Frederiksberg, Denmark; Global Research, Novo Nordisk A/S, Novo Nordisk Park 1, DK-2760 Maaloev, Denmark.
| | - Pernille Tveden-Nyborg
- Section of Experimental Animal Models, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Ridebanevej 9, DK-1870 Frederiksberg, Denmark.
| | - Christina Zacho-Rasmussen
- Section of Experimental Animal Models, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Ridebanevej 9, DK-1870 Frederiksberg, Denmark.
| | - Michelle L Quaade
- Section of Experimental Animal Models, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Ridebanevej 9, DK-1870 Frederiksberg, Denmark.
| | - David H Ipsen
- Section of Experimental Animal Models, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Ridebanevej 9, DK-1870 Frederiksberg, Denmark.
| | - Henning Hvid
- Global Research, Novo Nordisk A/S, Novo Nordisk Park 1, DK-2760 Maaloev, Denmark.
| | - Christian Fledelius
- Global Research, Novo Nordisk A/S, Novo Nordisk Park 1, DK-2760 Maaloev, Denmark.
| | - Erik M Wulff
- Global Research, Novo Nordisk A/S, Novo Nordisk Park 1, DK-2760 Maaloev, Denmark.
| | - Jens Lykkesfeldt
- Section of Experimental Animal Models, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Ridebanevej 9, DK-1870 Frederiksberg, Denmark.
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Zheng JL, Peng LB, Zhu QL, Zhang XL, Hu W. Waterborne zinc induced lobe-dependent effect on oxidative stress and energy metabolism in hepatopancreas of Larimichthys crocea. AQUATIC TOXICOLOGY (AMSTERDAM, NETHERLANDS) 2019; 215:105270. [PMID: 31401473 DOI: 10.1016/j.aquatox.2019.105270] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/10/2019] [Revised: 08/02/2019] [Accepted: 08/04/2019] [Indexed: 06/10/2023]
Abstract
The study aimed to compare differences in oxidative stress and energy metabolism between the left and right lobe of hepatopancreas in large yellow croaker Larimichthys crocea exposed to 0 (control), 20, and 100 μM Zn for 96 h. Tipical biomarkers were examined including the proportion of white hepatopancreas, lipid content, malondialdehyde (MDA) level, glutathione (GSH) content, activity levels of enzymes (Cu/Zn-superoxide dismutase, Cu/Zn-SOD; catalase, CAT; glutathione peroxidase, GPx; glutathione reductase, GR; mitochondrial ATP synthase, F-ATPase; malate dehydrogenase, MDH; succinate dehydrogenase, SDH; hepatic lipase, HTGL; lipoprotein lipase, LPL), mRNA levels of genes encoding these enzymes (sod1, cat, gpx1a, gr, atp5b, mdh, sdh, htgl, and lpl), and gene expression of signaling molecules the NF-E2-related nuclear factor 2 (nrf2) and Kelch-like ECH-associated protein 1 (keap1). A whitish color in the left lobe of hepatopancreas was observed in the control and Zn-exposed fish. Contrarily, the right lobe of hepatopancreas tended towards red with increasing Zn levels. The phenomenon was further confirmed by that lipid content was reduced in the right lobe and was not significantly affected in the left lobe by Zn. The right lobe showed higher energy consumption than the left lobe as reflected by the up-regulation of activity levels of HTGL, LPL, F-ATPase, MDH, and SDH. Lipid peroxidation declined by 20 μM Zn and was unchanged by 100 μM Zn in both lobes, which could be explained by increased activity levels of Cu/Zn-SOD and GPx. However, the magnitude of increase in Cu/Zn-SOD activity was greater in the right lobe than that in the left one. The difference in enzyme activity between two lobes may be involved in changes in mRNA levels of sod1, gr, atp5b, sdh, htgl, lpl, and nrf2, which was further confirmed by positive relationships between enzyme activity and gene expression. Our data also showed positive correlations between nrf2 expression and mRNA levels of its target genes, suggesting that Nrf2 was required for the protracted induction of these genes. Our results demonstrated the potential molecular mechanism of Zn-induced differences between lobes of hepatopancreas, suggesting that the sampling part of hepatopancreas should be considered with caution when assessing metal contamination.
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Affiliation(s)
- Jia-Lang Zheng
- National Engineering Research Center of Marine Facilities Aquaculture, Zhejiang Ocean University, Zhoushan 316022, PR China.
| | - Li-Bin Peng
- National Engineering Research Center of Marine Facilities Aquaculture, Zhejiang Ocean University, Zhoushan 316022, PR China
| | - Qing-Ling Zhu
- National Engineering Research Center of Marine Facilities Aquaculture, Zhejiang Ocean University, Zhoushan 316022, PR China
| | - Xiao-Lin Zhang
- National Engineering Research Center of Marine Facilities Aquaculture, Zhejiang Ocean University, Zhoushan 316022, PR China
| | - Wei Hu
- School of Animal Science, Yangtze University, Jingzhou, 424020, PR China
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Ferri F, Lai Q, Molinaro A, Poli E, Parlati L, Lattanzi B, Mennini G, Melandro F, Pugliese F, Maldarelli F, Corsi A, Riminucci M, Merli M, Rossi M, Ginanni Corradini S. Donor Small-Droplet Macrovesicular Steatosis Affects Liver Transplant Outcome in HCV-Negative Recipients. Can J Gastroenterol Hepatol 2019; 2019:5862985. [PMID: 31187028 PMCID: PMC6521523 DOI: 10.1155/2019/5862985] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2019] [Accepted: 04/03/2019] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND No data are available on liver transplantation (LT) outcome and donor liver steatosis, classified as large droplet macrovesicular (Ld-MaS), small-droplet macrovesicular (Sd-MaS), and true microvesicular (MiS), taking into account the recipient Hepatitis C virus (HCV) status. AIM We investigate the impact of allograft steatosis reclassified according to the Brunt classification on early graft function and survival after LT. METHODS We retrospectively reviewed 204 consecutive preischemia biopsies of grafts transplanted in our center during the period 2001-2011 according to recipient HCV status. RESULTS The median follow-up after LT was 7.5 years (range: 0.0-16.7). In negative recipients (n=122), graft loss was independently associated with graft Sd-MaS, in multivariable Cox regression models comprehending only pre-/intraoperative variables (HR=1.03, 95%CI=1.01-1.05; P=0.003) and when including indexes of early postoperative graft function (HR=1.04, 95%CI=1.02-1.06; P=0.001). Graft Sd-MaS>15% showed a risk for graft loss > 2.5-folds in both the models. Graft Sd-MaS>15% was associated with reduced graft ATP content and, only in HCV- recipients, with higher early post-LT serum AST peaks. CONCLUSIONS In HCV-negative recipients, allografts with >15% Sd-MaS have significantly reduced graft survival and show low ATP and higher AST peaks in the immediate posttransplant period. Donors with >15% Sd-MaS have significantly higher BMI, longer ICU stays, and lower PaO2.
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Affiliation(s)
- Flaminia Ferri
- Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy
| | - Quirino Lai
- Hepato-Bilio-Pancreatic and Liver Transplant Unit Department of Surgery, Sapienza University of Rome, 00161 Rome, Italy
| | - Antonio Molinaro
- Department of Molecular and Clinical Medicine, University of Gothenburg, and Sahlgrenska University Hospital, 405 30 Gothenburg, Sweden
| | - Edoardo Poli
- Centre Hepato-Biliaire, Hôpital Paul Brousse, AP-HP, 94800 Villejuif, France
| | - Lucia Parlati
- Hepatology Department, Université Paris Descartes, Cochin Hospital, AP-HP, 75014 Paris, France
| | - Barbara Lattanzi
- Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy
| | - Gianluca Mennini
- Hepato-Bilio-Pancreatic and Liver Transplant Unit Department of Surgery, Sapienza University of Rome, 00161 Rome, Italy
| | - Fabio Melandro
- Hepato-Bilio-Pancreatic and Liver Transplant Unit Department of Surgery, Sapienza University of Rome, 00161 Rome, Italy
| | - Francesco Pugliese
- Department of Anaesthesiology Critical Care Medicine and Pain Therapy, Sapienza University of Rome, 00161 Rome, Italy
| | - Federica Maldarelli
- Department of Anaesthesiology Critical Care Medicine and Pain Therapy, Sapienza University of Rome, 00161 Rome, Italy
| | - Alessandro Corsi
- Department of Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy
| | - Mara Riminucci
- Department of Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy
| | - Manuela Merli
- Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy
| | - Massimo Rossi
- Hepato-Bilio-Pancreatic and Liver Transplant Unit Department of Surgery, Sapienza University of Rome, 00161 Rome, Italy
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Hanafy AS, Seleem WM, El-Kalla F, AbdAlkhalik Basha M, Abd-Elsalam S. Efficacy of a non-invasive model in predicting the cardiovascular morbidity and histological severity in non-alcoholic fatty liver disease. Diabetes Metab Syndr 2019; 13:2272-2278. [PMID: 31235168 DOI: 10.1016/j.dsx.2019.05.032] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2019] [Accepted: 05/24/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND Insulin resistance (IR) in cases of non-alcoholic fatty liver disease (NAFLD) is connected to remarkable liver cell inflammation and cardiovascular complications. Given the prevalence of NAFLD and its association with potential sequels, there is a strong need for an accurate non-invasive tool to monitor the progression of NAFLD. METHODS 272 patients with NAFLD and cardio-metabolic risk factors were tested for HOMA-IR, mean platelet volume (MPV), neutrophil-lymphocyte ratio (NLR), uric acid, ferritin, lipid profile, liver stiffness measurement (LSM), controlled attenuation parameter (CAP) by fibroscan and carotid intima media thickness (CIMT). Liver biopsy was performed to validate the results.100 healthy controls were selected. A score was constructed and applied to a validation group (n = 61). RESULTS Logistic regression revealed that significant fibrosis and cardiovascular risk in NAFLD were independently associated with AST/ALT ratio (p = 0.000), GGT (p = 0.000), CIMT (p = 0.001), uric acid (p = 0.000), VLDL (p = 0.000), HOMA-IR (p = 0.000), ferritin (p = 0.000) CAP (p = 0.000), LSM (p0.000). A non-invasive model was formulated by which a value > 15 was accurate in identification of advanced fibrosis and cardiovascular risk with a sensitivity of 97.3%, specificity 97%. CONCLUSION The score correlated well with the results of liver biopsy and can be repeated with great flexibility to assess severity of NAFLD.
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Affiliation(s)
- Amr Shaaban Hanafy
- Internal Medicine Department, Hepato-gastroenterology, Zagazig University, Egypt
| | - Waseem M Seleem
- Internal Medicine Department, Hepato-gastroenterology, Zagazig University, Egypt
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31
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Khurana S, Butt W, Khara HS, Johal AS, West SF, Chen ZME, Berger AL, Diehl DL. Bi-lobar liver biopsy via EUS enhances the assessment of disease severity in patients with non-alcoholic steatohepatitis. Hepatol Int 2019; 13:323-329. [PMID: 30993598 DOI: 10.1007/s12072-019-09945-4] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2018] [Accepted: 03/27/2019] [Indexed: 12/13/2022]
Abstract
BACKGROUND In patients with non-alcoholic fatty liver disease (NAFLD), all-cause mortality increases with fibrosis stage. Liver biopsy (LB), performed predominantly in the right lobe, assesses fibrosis, however, right lobe LB may not be sufficient due to histological variation in different lobes. Endoscopic ultrasound (EUS) allows for biopsy of right and left liver lobes in the same setting. METHODS This retrospective study assessed for histologic variability amongst left and right liver lobe (L:R) specimens obtained via EUS at a tertiary care center. Between January 2012 and December 2015, 38 NAFLD patients underwent LB, in whom both lobes were sampled. RESULTS L:R agreement was near-perfect for steatosis (κ = 0.816, 95% CI 0.674, 0.958), good for ballooning (κ = 0.740, 95% CI 0.565, 0.916) and moderate for lobular inflammation (κ = 0.401 95% CI 0.110, 0.692) and fibrosis (κ = 0.473, 95% CI 0.275, 0.672). Intra-observer variability assessed by blinded repeat slide readings was almost perfect for fibrosis and steatosis (κ = 1, 95% CI 1, 1 and κ = 0.939, 95% CI 0.881, 0.997 respectively) and substantial for lobular inflammation (κ = 0.725, 95% CI 0.584, 0.866). Only right lobe assessment underestimated fibrosis in 21%, inflammation in 13%, and steatosis and ballooning in 8% cases. CONCLUSIONS These data indicate that in NAFLD, due to regional variation, EUS-guided bi-lobar LB improves assessment of disease activity and fibrosis.
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Affiliation(s)
- Sandeep Khurana
- Department of Gastroenterology and Hepatology, Geisinger Medical Center, 100 N Academy Ave, Danville, PA, 18702, USA.
| | - Waseem Butt
- Department of Gastroenterology and Hepatology, Geisinger Medical Center, 100 N Academy Ave, Danville, PA, 18702, USA
| | - Harshit S Khara
- Department of Gastroenterology and Hepatology, Geisinger Medical Center, 100 N Academy Ave, Danville, PA, 18702, USA
| | - Amitpal S Johal
- Department of Gastroenterology and Hepatology, Geisinger Medical Center, 100 N Academy Ave, Danville, PA, 18702, USA
| | - Sara F West
- Department of Gastroenterology and Hepatology, Geisinger Medical Center, 100 N Academy Ave, Danville, PA, 18702, USA
| | - Zong-Ming E Chen
- Department of Pathology, Geisinger Medical Center, Danville, PA, USA
| | - Andrea L Berger
- Department of Biostatistics, Geisinger Medical Center, Danville, PA, USA
| | - David L Diehl
- Department of Gastroenterology and Hepatology, Geisinger Medical Center, 100 N Academy Ave, Danville, PA, 18702, USA
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32
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Abstract
There remains an important role for liver biopsy in the management of liver disorders. Image-guided liver biopsy can be obtained with percutaneous or transjugular approaches. Real-time image-guided liver biopsy can be accomplished with endoscopic ultrasound (EUS). EUS-guided liver biopsy (EUS-LB) has emerged as a safe means of obtaining liver biopsy. EUS-LB confers several advantages over other methods, including the ability to target both lobes of the liver, increased patient comfort and decreased apprehension during the procedure, and shorter recovery time after the biopsy. Future development of technology that allows for EUS-guided portal pressure measurement could further drive EUS-LB use.
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Affiliation(s)
- David L Diehl
- Department of Gastroenterology and Nutrition, Geisinger Medical Center, 100 North Academy Avenue, 21-11, Danville, PA 17822, USA.
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Udelsman BV, Corey KE, Lindvall C, Gee DW, Meireles OR, Hutter MM, Chang DC, Witkowski ER. Risk factors and prevalence of liver disease in review of 2557 routine liver biopsies performed during bariatric surgery. Surg Obes Relat Dis 2019; 15:843-849. [PMID: 31014948 DOI: 10.1016/j.soard.2019.01.035] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2018] [Revised: 01/21/2019] [Accepted: 01/30/2019] [Indexed: 01/22/2023]
Abstract
BACKGROUND Obesity is a known risk factor for nonalcoholic fatty liver disease (NAFLD). However, among individuals undergoing bariatric surgery, the prevalence and risk factors for NAFLD, as well as distinct phenotypes of steatosis, nonalcoholic steatohepatitis (NASH), and fibrosis remain incompletely understood. OBJECTIVES To determine the prevalence and risk factors for steatosis, NASH, and fibrosis in individuals undergoing routine bariatric surgery. SETTING Academic medical center in the United States. METHODS Liver wedge biopsies were performed at the time of surgery between 2001 and 2017. Pathology reports were reviewed, and individuals were grouped by NAFLD phenotype. Covariates including demographic characteristics, co-morbidities, and preoperative laboratory values were compared between groups using Student's t test, Pearson's χ2, and logistic regression. RESULTS Liver biopsies were obtained in 97.7% of first-time bariatric procedures, representing 2557 patients. Mean age was 45.6 years, mean body mass index was 46.7, and most were non-Hispanic white (76.1%) and female (71.6%). On histologic review 61.2% had steatosis and 30.9% NASH. Fibrosis was identified in 29.3% of individuals, and 7.8% had stage ≥2 fibrosis. On logistic regression, elevated aspartate aminotransferase (odds ratio [OR] 1.87; P < .001) and elevated alanine aminotransferase (OR 1.62; P < .001) were independently associated with fibrosis. Elevated hemoglobin A1C of 5.7% to 6.5% (OR 1.29; P < .01) and >6.5% (OR 3.23; P < .001) were also associated with fibrosis. A similar trend was seen for NASH. CONCLUSIONS NASH and/or fibrosis is present in nearly one third of patients undergoing routine bariatric surgery. Risk factors include diabetes, elevated liver enzymes, and diabetes. Risk assessment and aggressive screening should be considered in patients undergoing bariatric surgery.
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Affiliation(s)
- Brooks V Udelsman
- Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts.
| | - Kathleen E Corey
- Harvard Medical School, Boston, Massachusetts; Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts
| | - Charlotta Lindvall
- Department of Psychosocial Oncology and Palliative Care, Dana-Farber Cancer Institute, Boston, Massachusetts; Division of Palliative Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts
| | - Denise W Gee
- Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts
| | - Ozanan R Meireles
- Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts
| | - Matthew M Hutter
- Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts
| | - David C Chang
- Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts
| | - Elan R Witkowski
- Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts
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Reistad N, Nilsson JH, Bergenfeldt M, Rissler P, Sturesson C. Intraoperative liver steatosis characterization using diffuse reflectance spectroscopy. HPB (Oxford) 2019; 21:175-180. [PMID: 30049643 DOI: 10.1016/j.hpb.2018.06.1809] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2018] [Revised: 06/03/2018] [Accepted: 06/24/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND Liver steatosis is associated with poor outcome after liver transplantation and liver resection. There is a need for an accurate and reliable intraoperative tool to identify and quantify steatosis. This study aimed to investigate whether surface diffuse reflectance spectroscopy (DRS) measurements could detect liver steatosis on humans during liver surgery. METHODS The DRS instrumentation setup consists of a computer, a high-power tungsten halogen light source and two spectrometers, connected through a trifurcated optical fiber to a hand-held probe. Patients scheduled for open resection for liver tumors were considered for inclusion. Multiple DRS measurements were performed on the liver surface after mobilization. RESULTS In total, 1210 DRS spectra originated from 38 patients, were analyzed. When applying the data to an analytical model the volumetric absorption ratio factor of fat and water specified an explicit distinction between mild to moderate, and moderate to severe steatosis (p < 0.001). There were significant differences between none-to-mild and moderate-to-severe steatosis grade for the following parameters: reduced scattering coefficient (p < 0.001), Mie to total scattering fraction (p < 0.001), Mie slope (p = 0.003), lipid/(lipid + water) (p < 0.001), blood volume (p = 0.044) and bile volume (p < 0.001). CONCLUSION This study shows that it is possible to evaluate steatosis grades with hepatic surface diffuse reflectance spectroscopy measurements.
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Affiliation(s)
- Nina Reistad
- Department of Physics, Lund University, Lund, Sweden
| | - Jan H Nilsson
- Department of Surgery, Clinical Sciences Lund, Lund University and Skåne University Hospital, Lund, Sweden
| | - Magnus Bergenfeldt
- Department of Surgery, Clinical Sciences Lund, Lund University and Skåne University Hospital, Lund, Sweden
| | - Pehr Rissler
- Department of Pathology, Clinical Sciences Lund, Lund University and Skåne University Hospital, Lund, Sweden
| | - Christian Sturesson
- Department of Surgery, Clinical Sciences Lund, Lund University and Skåne University Hospital, Lund, Sweden.
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Abstract
OBJECTIVE Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are major causes of chronic liver disease characterized by steatosis, inflammation, and fibrosis. Diagnosis of inflammation is limited by the need for liver biopsy. Dynamic PET with the widely used radiotracer 18F-FDG provides a novel method for evaluating spatial and temporal changes in liver inflammation. MATERIALS AND METHODS Patients with NAFLD or NASH underwent dynamic FDG PET and MRI within 6 months of undergoing liver biopsy. Liver time-activity curves were extracted to estimate kinetic parameters representing various rate constants of FDG transport using tracer kinetic modeling. Liver biopsy specimens were scored on the basis of NASH Clinical Research Network criteria. RESULTS This pilot study included 22 patients, 14 of whom were women. Patient age ranged from 18 to 70 years, and the mean body mass index (weight in kilograms divided by the square of height in meters) was 33.2 (range, 24-43.1). The K1 value, which represents the rate of FDG transport from blood to hepatic tissue, was significantly correlated with inflammation (r = -0.7284; p = 0.0001) and the overall NAFLD activity score (NAS; r = -0.6750; p = 0.0006). K1 values were inversely related to the hepatic inflammation score and NAS. Although heterogeneity in K1 values across eight liver segments was noted, distinct segregation existed among segmental K1 values dependent on the histologic inflammation score (p = 0.022) or NAS (p = 0.0091). K1 had a strong association with both inflammation (ROC AUC value, 0.88) and the NAS (ROC AUC value, 0.89), with K1 = 1.02 (mL/min/mL) corresponding to a sensitivity and specificity of 93% and 88%, respectively, for the NAS. CONCLUSION Dynamic FDG PET with tracer kinetic modeling has the potential to determine liver inflammation in patients with NAFLD and NASH and can fill an essential gap in diagnosis.
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Hong CW, Wolfson T, Sy EZ, Schlein AN, Hooker JC, Dehkordy SF, Hamilton G, Reeder SB, Loomba R, Sirlin CB. Optimization of region-of-interest sampling strategies for hepatic MRI proton density fat fraction quantification. J Magn Reson Imaging 2018; 47:988-994. [PMID: 28842937 PMCID: PMC5826828 DOI: 10.1002/jmri.25843] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2017] [Accepted: 08/07/2017] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Clinical trials utilizing proton density fat fraction (PDFF) as an imaging biomarker for hepatic steatosis have used a laborious region-of-interest (ROI) sampling strategy of placing an ROI in each hepatic segment. PURPOSE To identify a strategy with the fewest ROIs that consistently achieves close agreement with the nine-ROI strategy. STUDY TYPE Retrospective secondary analysis of prospectively acquired clinical research data. POPULATION A total of 391 adults (173 men, 218 women) with known or suspected NAFLD. FIELD STRENGTH/SEQUENCE Confounder-corrected chemical-shift-encoded 3T MRI using a 2D multiecho gradient-recalled echo technique. ASSESSMENT An ROI was placed in each hepatic segment. Mean nine-ROI PDFF and segmental PDFF standard deviation were computed. Segmental and lobar PDFF were compared. PDFF was estimated using every combinatorial subset of ROIs and compared to the nine-ROI average. STATISTICAL TESTING Mean nine-ROI PDFF and segmental PDFF standard deviation were summarized descriptively. Segmental PDFF was compared using a one-way analysis of variance, and lobar PDFF was compared using a paired t-test and a Bland-Altman analysis. The PDFF estimated by every subset of ROIs was informally compared to the nine-ROI average using median intraclass correlation coefficients (ICCs) and Bland-Altman analyses. RESULTS The study population's mean whole-liver PDFF was 10.1 ± 8.9% (range: 1.1-44.1%). Although there was no significant difference in average segmental (P = 0.452) or lobar (P = 0.154) PDFF, left and right lobe PDFF differed by at least 1.5 percentage points in 25.1% (98/391) of patients. Any strategy with ≥4 ROIs had ICC >0.995. 115 of 126 four-ROI strategies (91%) had limits of agreement (LOA) <1.5%, including four-ROI strategies with two ROIs from each lobe, which all had LOA <1.5%. 14/36 (39%) of two-ROI strategies and 74/84 (88%) of three-ROI strategies had ICC >0.995, and 2/36 (6%) of two-ROI strategies and 46/84 (55%) of three-ROI strategies had LOA <1.5%. DATA CONCLUSION Four-ROI sampling strategies with two ROIs in the left and right lobes achieve close agreement with nine-ROI PDFF. LEVEL OF EVIDENCE 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:988-994.
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Affiliation(s)
- Cheng William Hong
- Liver Imaging Group, Department of Radiology, University of California San Diego, San Diego, California, USA
| | - Tanya Wolfson
- Computational and Applied Statistics Laboratory, University of California San Diego, San Diego, California, USA
| | - Ethan Z. Sy
- Liver Imaging Group, Department of Radiology, University of California San Diego, San Diego, California, USA
| | - Alexandra N. Schlein
- Liver Imaging Group, Department of Radiology, University of California San Diego, San Diego, California, USA
| | - Jonathan C. Hooker
- Liver Imaging Group, Department of Radiology, University of California San Diego, San Diego, California, USA
| | - Soudabeh Fazeli Dehkordy
- Liver Imaging Group, Department of Radiology, University of California San Diego, San Diego, California, USA
| | - Gavin Hamilton
- Liver Imaging Group, Department of Radiology, University of California San Diego, San Diego, California, USA
| | - Scott B. Reeder
- Departments of Radiology, Medical Physics, Biomedical Engineering, Medicine, and Emergency Medicine, University of Wisconsin Madison, Madison, Wisconsin, USA
| | - Rohit Loomba
- NAFLD Research Center, Division of Gastroenterology, Department of Medicine, University of California San Diego, San Diego, California, USA
| | - Claude B. Sirlin
- Liver Imaging Group, Department of Radiology, University of California San Diego, San Diego, California, USA
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Hua B, Hakkarainen A, Zhou Y, Lundbom N, Yki-Järvinen H. Fat accumulates preferentially in the right rather than the left liver lobe in non-diabetic subjects. Dig Liver Dis 2018; 50:168-174. [PMID: 28964678 DOI: 10.1016/j.dld.2017.08.030] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2017] [Revised: 07/19/2017] [Accepted: 08/14/2017] [Indexed: 12/11/2022]
Abstract
AIMS To examine the distribution of liver fat (LFAT) in non-diabetic subjects and test whether the fat in the right as compared to the left lobe correlates better with components of the metabolic syndrome or not. METHODS In this cross sectional study, we determined LFAT by 1H-MRS in the right lobe (LFAT%MRS), and by MRI (LFAT%MRI) in four regions of interest (ROIs 1-4, two in the right and two in the left lobe) in 97 non-diabetic subjects (age range 22-74 years, BMI 18-41kg/m2) and compared the accuracy of LFATMRI in the different ROIs in diagnosing non-alcoholic fatty liver disease (NAFLD) using areas under the receiver operator characteristic (AUROC) curves. RESULTS 38% of the subjects had NAFLD (LFAT%MRS). LFAT%MRI was significantly higher in the right (5.7±0.5%) than the left (5.1±0.4%) lobe (p<0.02). The AUROC for LFAT%MRI in the right lobe for diagnosing NAFLD was significantly better than that in the left lobe. The relationships between several metabolic parameters and LFAT%MRI in the left lobe were significantly worse than those for LFAT%MRS while there was no difference between LFAT%MRS and right lobe ROIs. CONCLUSIONS Liver right lobe contains more fat and correlates better with components of the metabolic syndrome than the left in non-diabetic subjects.
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Affiliation(s)
- Bian Hua
- Minerva Foundation Institute for Medical Research, Helsinki, Finland; Department of Endocrinology, Zhongshan Hosipital, Fudan University, Shanghai, China.
| | - Antti Hakkarainen
- Department of Radiology, Helsinki Medical Imaging Center, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland
| | - You Zhou
- Minerva Foundation Institute for Medical Research, Helsinki, Finland; Systems Immunity University Research Institute and Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, United Kingdom
| | - Nina Lundbom
- Department of Radiology, Helsinki Medical Imaging Center, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland
| | - Hannele Yki-Järvinen
- Minerva Foundation Institute for Medical Research, Helsinki, Finland; Department of Medicine, University of Helsinki, Helsinki, Finland
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Chalasani N, Younossi Z, Lavine JE, Charlton M, Cusi K, Rinella M, Harrison SA, Brunt EM, Sanyal AJ. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatology 2018; 67:328-357. [PMID: 28714183 DOI: 10.1002/hep.29367] [Citation(s) in RCA: 4866] [Impact Index Per Article: 695.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2017] [Accepted: 06/29/2017] [Indexed: 02/06/2023]
Affiliation(s)
| | - Zobair Younossi
- Center for Liver Disease and Department of Medicine, Inova Fairfax Hospital, Falls Church, VA
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Cheah MCC, McCullough AJ, Goh GBB. Current Modalities of Fibrosis Assessment in Non-alcoholic Fatty Liver Disease. J Clin Transl Hepatol 2017; 5:261-271. [PMID: 28936407 PMCID: PMC5606972 DOI: 10.14218/jcth.2017.00009] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2017] [Revised: 04/13/2017] [Accepted: 04/29/2017] [Indexed: 12/12/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a burgeoning global health concern. In the subset of NAFLD patients with non-alcoholic steatohepatitis (NASH), the presence of significant fibrosis at index assessment is associated with poor prognosis and increased mortality. Hence, there is a growing need to accurately assess and stage fibrosis. Liver biopsy, the current gold standard, has limitations with sampling error and is invasive, with associated inherent risk. This has led to a host of non-invasive means of assessing fibrosis, which has garnered relevance in a disease that requires serial assessment of fibrosis longitudinally over time. This review discusses, comprehensively, the various tools available to the clinician for the assessment of fibrosis, including the various scoring systems used in liver biopsy, the non-invasive means of serum biomarkers, such as the highly-validated NAFLD fibrosis score, and the imaging-based modalities, such as transient elastography and magnetic resonance elastography.
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Affiliation(s)
- Mark CC Cheah
- Department of Gastroenterology & Hepatology, Singapore General Hospital, Singapore
| | - Arthur J McCullough
- Department of Gastroenterology, Cleveland Clinic, Ohio, USA
- Department of Pathobiology, Cleveland Clinic, Ohio, USA
| | - George Boon-Bee Goh
- Department of Gastroenterology & Hepatology, Singapore General Hospital, Singapore
- Duke-NUS Medical School, Singapore
- *Correspondence to: Dr George Boon-Bee Goh, Department of Gastroenterology & Hepatology, Singapore General Hospital, 20 College Road, Singapore 169856, Singapore. Tel: +65-62223322, Fax: +65-62273623, E-mail:
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Controlled attenuation parameter for diagnosing steatosis in bariatric surgery candidates with suspected nonalcoholic fatty liver disease. Eur J Gastroenterol Hepatol 2017; 29:1022-1030. [PMID: 28570343 DOI: 10.1097/meg.0000000000000919] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
INTRODUCTION Steatosis in patients with nonalcoholic fatty liver disease (NAFLD) is often benign, but may progress to fibrosis. The accurate diagnosis of hepatic steatosis is therefore important for clinical decision-making and prognostic assessments. The controlled attenuation parameter (CAP), a noninvasive measurement obtained with Fibro-Scan, has been developed for liver steatosis assessment. CAP performs poorly in patients with high BMI. The XL probe was initially developed for measuring liver stiffness in overweight patients. We assessed the diagnostic value of CAP in candidates for bariatric surgery with suspected NAFLD examined with the XL probe. PATIENTS AND METHODS For the retrospective group, raw ultrasonic radiofrequency signals were stored prospectively in the Fibro-Scan examination file for offline CAP calculation in 194 consecutive obese patients undergoing liver stiffness measurement in the 15 days before liver biopsy. For the prospective group, CAP was calculated automatically and prospectively from the XL probe in 123 obese patients. RESULTS In the retrospective group, the diagnostic accuracy of CAP was satisfactory for differentiating S3 from S0-S1-S2 (0.79±0.03; 95% confidence interval: 0.71-0.84) and S3 from S0 (0.85±0.05; 95% confidence interval: 0.73-0.92). The Obuchowski measure demonstrated a very good discriminatory performance: 0.87±0.02 in the retrospective group and 0.91±0.02 in the prospective group. CONCLUSION CAP calculations from XL probe measurements efficiently detected severe steatosis in morbidly obese patients with suspected NAFLD. However, the cutoff values should now be confirmed in a larger prospective cohort.
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Dulai PS, Sirlin CB, Loomba R. MRI and MRE for non-invasive quantitative assessment of hepatic steatosis and fibrosis in NAFLD and NASH: Clinical trials to clinical practice. J Hepatol 2016; 65:1006-1016. [PMID: 27312947 PMCID: PMC5124376 DOI: 10.1016/j.jhep.2016.06.005] [Citation(s) in RCA: 260] [Impact Index Per Article: 28.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2016] [Revised: 05/19/2016] [Accepted: 06/06/2016] [Indexed: 02/07/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) represents one of the most common causes of chronic liver disease, and its prevalence is rising worldwide. The occurrence of non-alcoholic steatohepatitis (NASH) is associated with a substantial increase in disease related morbidity and mortality. Accordingly, there has been a surge of innovation surrounding drug development in an effort to off-set the natural progression and long-term risks of this disease. Disease assessment within clinical trials and clinical practice for NAFLD is currently done with liver biopsies. Liver biopsy-based assessments, however, remain imprecise and are not without cost or risk. This carries significant implications for the feasibility and costs of bringing therapeutic interventions to market. A need therefore arises for reliable and highly accurate surrogate end-points that can be used in phase 2 and 3 clinical trials to reduce trial size requirements and costs, while improving feasibility and ease of implementation in clinical practice. Significant advances have now been made in magnetic resonance technology, and magnetic resonance imaging (MRI) and elastrography (MRE) have been demonstrated to be highly accurate diagnostic tools for the detection of hepatic steatosis and fibrosis. In this review article, we will summarize the currently available evidence regarding the use of MRI and MRE among NAFLD patients, and the evolving role these surrogate biomarkers will play in the rapidly advancing arena of clinical trials in NASH and hepatic fibrosis. Furthermore, we will highlight how these tools can be readily applied to routine clinical practice, where the growing burden of NAFLD will need to be met with enhanced monitoring algorithms.
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Affiliation(s)
- Parambir S Dulai
- Division of Gastroenterology, Department of Medicine, University of California at San Diego, La Jolla, CA, United States
| | - Claude B Sirlin
- Liver Imaging Group, Department of Radiology, University of California at San Diego, La Jolla, CA, United States
| | - Rohit Loomba
- Division of Gastroenterology, Department of Medicine, University of California at San Diego, La Jolla, CA, United States; NAFLD Research Center, Department of Medicine, University of California at San Diego, La Jolla, CA, United States.
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Pineda JJ, Diehl DL, Miao CL, Johal AS, Khara HS, Bhanushali A, Chen EZ. EUS-guided liver biopsy provides diagnostic samples comparable with those via the percutaneous or transjugular route. Gastrointest Endosc 2016; 83:360-365. [PMID: 26301407 DOI: 10.1016/j.gie.2015.08.025] [Citation(s) in RCA: 91] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2015] [Accepted: 08/07/2015] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS Liver biopsy (LB) traditionally has been performed via a percutaneous (PC), transjugular (TJ), or surgical approach. EUS-guided LB (EUS-LB) is an emerging method that has shown promise in terms of tissue yield and procedural safety. Comparison of histologic yield of EUS-LB with other methods of LB has not been done. This study aimed to compare tissue yield of different LB methods. METHODS EUS-LB, TJ-LB, and PC-LB were identified retrospectively. EUS-LB was obtained via transgastric and transduodenal biopsy, or via transgastric (left lobe) biopsy alone using a 19-gauge FNA needle (non-Trucut). TJ-LB specimens were obtained with an 18- or 19-gauge needle, and PC-LB specimens with an 18- or 20-gauge needle. Stained slides were digitized on a whole slide scanner, and the total specimen length (TSL) and the count of complete portal triads (CPTs) were determined. Comparisons of TSL and CPT among the 3 groups were done with Wilcoxon rank sum tests. RESULTS Wilcoxon rank sum tests indicated that EUS-LB of both liver regions produced significantly more tissue in terms of both TSL and CPTs compared with a PC-LB (P = .0000 and .0006). EUS-LB produced significantly longer TSL than TJ-LB (P = .01) and similar CPTs (P = .22). Those EUS-LB cases in which the left lobe only was sampled were not statistically different compared with PC-LB and TJ-LB. CONCLUSION EUS-guided-LB produces specimens at least comparable to, and in some cases better than, PC-LB or TJ-LB. Widely separated liver regions can be easily sampled, which may have some benefit. The role of EUS-LB is likely to increase in the future.
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Affiliation(s)
- Jonh J Pineda
- Department of Gastroenterology and Nutrition, Geisinger Medical Center, Danville, Pennsylvania, USA
| | - David L Diehl
- Department of Gastroenterology and Nutrition, Geisinger Medical Center, Danville, Pennsylvania, USA
| | - Chuan L Miao
- Department of Gastroenterology and Nutrition, Geisinger Medical Center, Danville, Pennsylvania, USA
| | - Amitpal S Johal
- Department of Gastroenterology and Nutrition, Geisinger Medical Center, Danville, Pennsylvania, USA
| | - Harshit S Khara
- Department of Gastroenterology and Nutrition, Geisinger Medical Center, Danville, Pennsylvania, USA
| | - Ashok Bhanushali
- Department of Interventional Radiology, Geisinger Medical Center, Danville, Pennsylvania, USA
| | - Eric Z Chen
- Department of Pathology, Geisinger Medical Center, Danville, Pennsylvania, USA
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Brunt EM. Nonalcoholic Fatty Liver Disease: Pros and Cons of Histologic Systems of Evaluation. Int J Mol Sci 2016; 17:E97. [PMID: 26771611 PMCID: PMC4730339 DOI: 10.3390/ijms17010097] [Citation(s) in RCA: 59] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2015] [Revised: 01/06/2016] [Accepted: 01/07/2016] [Indexed: 12/12/2022] Open
Abstract
The diagnostic phenotype of nonalcoholic fatty liver disease (NAFLD)--in particular, the most significant form in terms of prognosis, nonalcoholic steatohepatitis (NASH)--continues to rely on liver tissue evaluation, in spite of remarkable advances in non-invasive algorithms developed from serum-based tests and imaging-based or sonographically-based tests for fibrosis or liver stiffness. The most common tissue evaluation remains percutaneous liver biopsy; considerations given to the needle size and the location of the biopsy have the potential to yield the most representative tissue for evaluation. The pathologist's efforts are directed to not only global diagnosis, but also assessment of severity of injury. Just as in other forms of chronic liver disease, these assessments can be divided into necroinflammatory activity, and fibrosis with parenchymal remodeling, in order to separately analyze potentially reversible (grade) and non-reversible (stage) lesions. These concepts formed the bases for current methods of evaluating the lesions that collectively comprise the phenotypic spectra of NAFLD. Four extant methods have specific applications; there are pros and cons to each, and this forms the basis of the review.
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Affiliation(s)
- Elizabeth M Brunt
- Department of Pathology and Immunology, Washington University School of Medicine, Campus Box 8118, St. Louis, MO 63110, USA.
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Xanthakos SA, Jenkins TM, Kleiner DE, Boyce TW, Mourya R, Karns R, Brandt ML, Harmon CM, Helmrath MA, Michalsky MP, Courcoulas AP, Zeller MH, Inge TH. High Prevalence of Nonalcoholic Fatty Liver Disease in Adolescents Undergoing Bariatric Surgery. Gastroenterology 2015; 149:623-34.e8. [PMID: 26026390 PMCID: PMC4654456 DOI: 10.1053/j.gastro.2015.05.039] [Citation(s) in RCA: 104] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2014] [Revised: 05/14/2015] [Accepted: 05/20/2015] [Indexed: 12/16/2022]
Abstract
BACKGROUND & AIMS Little is known about the prevalence of nonalcoholic fatty liver disease (NAFLD) among severely obese adolescents or factors that determine its development. We investigated the prevalence of NAFLD in a multicenter cohort of adolescents undergoing bariatric surgery and the factors associated with it. METHODS We enrolled 242 adolescents undergoing bariatric surgery between March 2007 and February 2012 at 5 tertiary care centers into a multicenter, prospective observational cohort study. Intraoperative core liver biopsies were collected from 165 subjects; 17 were excluded because of insufficient liver tissue or use of hepatotoxic medications, so 148 remained in the study (mean age, 16.8 ± 1.6 years; median body mass index = 52 kg/m(2)). Liver tissues were analyzed by histology using validated criteria. Hepatic gene expression was analyzed in 67 samples. RESULTS NAFLD was present in 59% of this predominantly female (72%), white (68%), non-Hispanic (91%) cohort. Of subjects with NAFLD, 24% had borderline and 10% had definite nonalcoholic steatohepatitis (NASH). Mild fibrosis (stage 2 or lower) was observed in 18% of liver biopsies and stage 3 was observed in 0.7%, but cirrhosis was not detected. Dyslipidemia was present in 78% of subjects, hypertension in 44%, and diabetes in 14%. More severe NAFLD was associated with increasing levels of alanine aminotransferase, fasting glucose level, hypertension (each P < .01), and white blood cell count (P = .04). Only diabetes was associated with detection of fibrosis (odds ratio = 3.56; 95% confidence interval: 1.93-6.56). Microarray analysis associated presence of NASH with altered expression of genes that regulate macrophage chemotaxis, cholesterol absorption, and fatty acid binding. CONCLUSIONS More than half of adolescents undergoing bariatric surgery in this cohort had NAFLD, yet the prevalence of severe or fibrotic NASH was low. Increasing severity of NAFLD was associated with level of alanine aminotransferase and cardiometabolic risk factors, but not body mass index. Based on gene expression analysis, borderline and definite NASH were associated with abnormal immune function, intestinal cholesterol absorption, and lipid metabolism.
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Affiliation(s)
- Stavra A Xanthakos
- Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio.
| | - Todd M Jenkins
- Division of Pediatric Surgery, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio
| | - David E Kleiner
- Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
| | - Tawny W Boyce
- University of New Mexico Cancer Center, Biostatistics Shared Resource, Albuquerque, New Mexico
| | - Reena Mourya
- Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio
| | - Rebekah Karns
- Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio
| | - Mary L Brandt
- Division of Pediatric Surgery, Texas Children's Hospital, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas
| | - Carroll M Harmon
- Division of Pediatric Surgery, Women & Children's Hospital of Buffalo, University of Buffalo School of Medicine and Biomedical Sciences, Buffalo, New York
| | - Michael A Helmrath
- Division of Pediatric Surgery, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio
| | - Marc P Michalsky
- Department of Pediatric Surgery, The Ohio State University College of Medicine and Nationwide Children's Hospital, Columbus, Ohio
| | - Anita P Courcoulas
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - Meg H Zeller
- Division of Behavioral Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Thomas H Inge
- Division of Pediatric Surgery, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio
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Parekh PJ, Majithia R, Diehl DL, Baron TH. Endoscopic ultrasound-guided liver biopsy. Endosc Ultrasound 2015; 4:85-91. [PMID: 26020041 PMCID: PMC4445181 DOI: 10.4103/2303-9027.156711] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2015] [Accepted: 03/30/2015] [Indexed: 12/13/2022] Open
Abstract
Liver biopsy remains the cornerstone in the diagnosis and management of liver disorders. Results of liver biopsy can often drive therapeutic decision-making. Unfortunately, studies have shown conventional biopsy techniques to carry significant sampling variability that can potentially impact patient care. Endoscopic ultrasound (EUS) is gaining traction as an alternative method of biopsy. For parenchymal disease, it can decrease sampling variability. It offers a more targeted approach for focal lesions. Its diagnostic yield and limited adverse event profile make it a promising approach for liver biopsy.
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Affiliation(s)
- Parth J Parekh
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Tulane University, New Orleans, Louisiana, USA
| | - Raj Majithia
- Division of Gastroenterology and Hepatology, University of North Carolina - Johnston Healthcare, Smithfield, USA
| | - David L Diehl
- Department of Gastroenterology and Nutrition, Geisinger Medical Center, Danville, Pennsylvania, USA
| | - Todd H Baron
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, North Carolina, USA
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Papandreou D, Andreou E. Role of diet on non-alcoholic fatty liver disease: An updated narrative review. World J Hepatol 2015; 7:575-582. [PMID: 25848481 PMCID: PMC4381180 DOI: 10.4254/wjh.v7.i3.575] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2014] [Revised: 11/26/2014] [Accepted: 12/31/2014] [Indexed: 02/06/2023] Open
Abstract
The purpose of this article review is to update what is known about the role of diet on non-alcoholic fatty liver disease (NAFLD). NAFLD is the most common cause of chronic liver disease in the developed world and is considered to be a spectrum, ranging from fatty infiltration of the liver alone (steatosis), which may lead to fatty infiltration with inflammation known as non alcoholic steatohepatitis While the majority of individuals with risk factors like obesity and insulin resistance have steatosis, only few people may develop steatohepatitis. Current treatment relies on weight loss and exercise, although various insulin-sensitizing medications appear promising. Weight loss alone by dietary changes has been shown to lead to histological improvement in fatty liver making nutrition therapy to become a cornerstone of treatment for NAFLD. Supplementation of vitamin E, C and omega 3 fatty acids are under consideration with some conflicting data. Moreover, research has been showed that saturated fat, trans-fatty acid, carbohydrate, and simple sugars (fructose and sucrose) may play significant role in the intrahepatic fat accumulation. However, true associations with specific nutrients yet to be clarified.
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Nilsson H, Karlgren S, Blomqvist L, Jonas E. The inhomogeneous distribution of liver function: possible impact on the prediction of post-operative remnant liver function. HPB (Oxford) 2015; 17:272-7. [PMID: 25297934 PMCID: PMC4333790 DOI: 10.1111/hpb.12348] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2014] [Accepted: 08/18/2014] [Indexed: 02/06/2023]
Abstract
BACKGROUND Previous studies have shown that liver function is inhomogeneously distributed in diseased livers, and this uneven distribution cannot be compensated for if a global liver function test is used for the prediction of post-operative remnant liver function. Dynamic Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) can assess segmental liver function, thus offering the possibility to overcome this problem. METHODS In 10 patients with liver cirrhosis and 10 normal volunteers, the contribution of individual liver segments to total liver function and volume was calculated using dynamic Gd-EOB-DTPA-enhanced MRI. Remnant liver function predictions using a segmental method and global assessment were compared for a simulated left hemihepatectomy. For the prediction based on segmental functional MRI assessment, the estimated function of the remnant liver segments was added. RESULTS Global liver function assessment overestimated the remnant liver function in 9 out of 10 patients by as much as 9.3% [median -3.5% (-9.3-3.5%)]. In the normal volunteers there was a slight underestimation of remnant function in 9 out of 10 cases [median 1.07% (-0.7-2.5%)]. DISCUSSION The present study underlines the necessity of a segmental liver function test able to compensate for the non-homogeneous nature of liver function, if the prediction of post-operative remnant liver function is to be improved.
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Affiliation(s)
- Henrik Nilsson
- Department of Clinical Sciences, Division of Surgery, Danderyd HospitalStockholm, Sweden,Correspondence, Henrik Nilsson, Division of Surgery, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, 182 88 Stockholm, Sweden. Tel: +46 8 123 550 00. Fax: +46 8 655 7766. E-mail:
| | - Silja Karlgren
- Department of Clinical Sciences, Division of Surgery, Danderyd HospitalStockholm, Sweden
| | - Lennart Blomqvist
- Department of Diagnostic Radiology, Karolinska University Hospital SolnaStockholm, Sweden,Department of Molecular Medicine and Surgery, Karolinska InstitutetStockholm, Sweden
| | - Eduard Jonas
- Department of Clinical Sciences, Division of Surgery, Danderyd HospitalStockholm, Sweden
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Lobe-specific heterogeneity in asymmetric dimethylarginine and matrix metalloproteinase levels in a rat model of obstructive cholestasis. BIOMED RESEARCH INTERNATIONAL 2014; 2014:327537. [PMID: 25013773 PMCID: PMC4075188 DOI: 10.1155/2014/327537] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/28/2014] [Revised: 05/23/2014] [Accepted: 05/26/2014] [Indexed: 12/14/2022]
Abstract
We investigated the effects of obstructive cholestasis in different hepatic lobes by evaluating asymmetric dimethylarginine (ADMA) (a nitric oxide synthase inhibitor), protein methyltransferase (PRMT) and dimethylarginine dimethylaminohydrolase (DDAH) (enzymes involved, resp., in its synthesis and degradation), the cationic transporter (CAT), and metalloproteinase (MMP) activity. Sixteen male Wistar rats underwent a 3-day cholestasis by common bile duct ligation (BDL) or sham operation. Blood samples and hepatic biopsies from left lobe (LL), median lobe (ML), and right lobe (RL) were collected. Serum hepatic enzymes, tissue ADMA, DDAH activity, CAT-2 protein, mRNA expression of DDAH and PRMT, and MMP-2 and MMP-9 activity were monitored. Cholestasis was confirmed by altered serum hepatic enzymes. Higher levels of tissue ADMA were detected in RL and ML as compared with LL. PRMT mRNA expression and DDAH activity did not differ among the lobes after BDL. CAT-2 levels are higher in the RL and ML in the sham-operated group. Higher activity in MMP-2 and MMP-9 was found in RL. In conclusion, after cholestasis an increase in hepatic ADMA in RL and ML was detected as well as tissue MMP-2 and MMP-9 activation in RL, supporting the evidence of functional heterogeneity among the liver lobes also occurring in an obstructive cholestasis model.
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50
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Jun MJ, Shim JH, Kim SY, Seo N, Kim KM, Lim YS, Lee HC, Yu E, Lee SG. Clinical implications of preoperative and intraoperative liver biopsies for evaluating donor steatosis in living related liver transplantation. Liver Transpl 2014; 20:437-45. [PMID: 24478019 DOI: 10.1002/lt.23832] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2013] [Accepted: 12/22/2013] [Indexed: 12/17/2022]
Abstract
The role of liver biopsy in selecting optimal donors is an area of continuing controversy in living donor liver transplantation (LDLT). Our aim was to assess the potential implications of preoperative and intraoperative biopsies for evaluating donor liver fat content. Three thousand eight hundred fifty-nine consecutive subjects underwent predonation needle biopsy of the right lobe, and 1766 of these subjects actually donated their livers for LDLT and underwent intraoperative wedge biopsies of paired right and left lobes. The preoperative workup protocol also included abdominal ultrasonography (USG) and computed tomography (CT). Intersample agreement on steatosis grades (<5%, 5% to <15%, 15% to <30%, and ≥30%) was calculated, and clinicometabolic factors related to sampling variability were evaluated. For detecting ≥30% steatosis in the 3859 potential donors, USG and CT had sensitivities of 84.9% and 57.3%, specificities of 76.3% and 92.7%, positive predictive values of 29.6% and 48.0%, and negative predictive values of 97.7% and 94.8%, respectively. Analyses of the 1766 actual donors showed that with respect to the total steatosis grades of intraoperative right and left biopsies versus preoperative biopsy, 36.7% and 36.0% of the pairs, respectively, differed from the weighted κ values of 0.44 and 0.40. Similar agreement levels existed for macrovesicular and microvesicular steatosis subtypes. The per-subject agreement rate for the total steatosis grade between intraoperative right and left biopsies was 83.6%. According to a multivariate analysis, independent factors affecting the variability of the total steatosis results from preoperative and intraoperative biopsies (major features) were higher systolic blood pressure, body mass index, and alanine aminotransferase values and lower high-density lipoprotein cholesterol values. In conclusion, imaging may be insufficiently sensitive for evaluating donor hepatic steatosis. Preoperative and selective intraoperative liver biopsies are mandatory for assessing donor steatosis in LDLT unless preoperative imaging demonstrates no fat.
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Affiliation(s)
- Mi-Jung Jun
- Departments of Internal Medicine, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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