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Yamaguchi R, Oda T, Nagashima K. Comparison of the diagnostic accuracy of shear wave elastography with transient elastography in adult nonalcoholic fatty liver disease: a systematic review and network meta-analysis of diagnostic test accuracy. Abdom Radiol (NY) 2025; 50:734-746. [PMID: 39240377 PMCID: PMC11794403 DOI: 10.1007/s00261-024-04546-8] [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: 06/05/2024] [Revised: 08/17/2024] [Accepted: 08/21/2024] [Indexed: 09/07/2024]
Abstract
PURPOSE To compare the diagnostic test accuracy (DTA) of shear wave elastography (SWE) to that of transient elastography (TE) for liver fibrosis grade assessment in nonalcoholic fatty liver disease adults. METHODS MEDLINE, The Cochrane Library, and Web of Science were searched. Inclusion criteria were primary studies examining DTA of TE, point SWE (pSWE), two-dimensional SWE (2D-SWE), or magnetic resonance elastography (MRE) with liver biopsy. Network meta-analysis was conducted using a Bayesian bivariate mixed-effects model. RESULTS For fibrosis grade 2 or higher, 15 studies with 25 observations (16 observations for TE, 1 for MRE, 4 for pSWE and 2D-SWE; 2,066 patients) were included; the pooled sensitivity and specificity were 0.79 (95% credible interval (CrI) 0.70-0.86; 95% prediction interval (PI) 0.36-0.96) and 0.73 (95% CrI 0.62-0.82; 95% PI 0.23-0.96) for TE, 0.68 (95% CrI 0.48-0.83; 95% PI 0.23-0.94) and 0.75 (95% CrI 0.53-0.88; 95% PI 0.24-0.97) for pSWE, 0.85 (95% CrI 0.70-0.93; 95% PI 0.40-0.98) and 0.72 (95% CrI 0.49-0.86; 95% PI 0.20-0.96) for 2D-SWE, respectively. The proportion of studies classified as unclear in QUADAS-2 was high, and the results were heterogeneous. CONCLUSION 2D-SWE could be recommended as TE is for liver fibrosis assessment. The protocol of this systematic review and network meta-analysis has been registered in PROSPERO (CRD42022327249). All included primary papers have already been published and the information and data can be used freely.
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Affiliation(s)
- Ruri Yamaguchi
- Department of Investigative Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryomachi, Aobaku, Sendai, 980-8575, Japan.
| | - Tetsuro Oda
- Chugai Pharmaceutical Co., Ltd., Tokyo, Japan
| | - Kengo Nagashima
- Biostatistics Unit, Clinical and Translational Research Center, Keio University Hospital, Tokyo, 160-8582, Japan
- Department of Bioregulation, Graduate School of Medicine, Nippon Medical School, Tokyo, 113-8602, Japan
- Division of Cancer Therapeutics, National Cancer Center Research Institute, Tokyo, 104-0045, Japan
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2
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Duarte-Rojo A, Taouli B, Leung DH, Levine D, Nayfeh T, Hasan B, Alsawaf Y, Saadi S, Majzoub AM, Manolopoulos A, Haffar S, Dundar A, Murad MH, Rockey DC, Alsawas M, Sterling RK. Imaging-based noninvasive liver disease assessment for staging liver fibrosis in chronic liver disease: A systematic review supporting the AASLD Practice Guideline. Hepatology 2025; 81:725-748. [PMID: 38489521 DOI: 10.1097/hep.0000000000000852] [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] [Received: 11/09/2023] [Accepted: 01/19/2024] [Indexed: 03/17/2024]
Abstract
BACKGROUND AND AIMS Transient elastography (TE), shear wave elastography, and/or magnetic resonance elastography (MRE), each providing liver stiffness measurement (LSM), are the most studied imaging-based noninvasive liver disease assessment (NILDA) techniques. To support the American Association for the Study of Liver Diseases guidelines on NILDA, we summarized the evidence on the accuracy of these LSM methods to stage liver fibrosis (F). APPROACH AND RESULTS A comprehensive search for studies assessing LSM by TE, shear wave elastography, or MRE for the identification of significant fibrosis (F2-4), advanced fibrosis (F3-4), or cirrhosis (F4), using histopathology as the standard of reference by liver disease etiology in adults or children from inception to April 2022 was performed. We excluded studies with <50 patients with a single disease entity and mixed liver disease etiologies (with the exception of HCV/HIV coinfection). Out of 9447 studies, 240 with 61,193 patients were included in this systematic review. In adults, sensitivities for the identification of F2-4 ranged from 51% to 95%, for F3-4 from 70% to 100%, and for F4 from 60% to 100% across all techniques/diseases, whereas specificities ranged from 36% to 100%, 74% to 100%, and 67% to 99%, respectively. The largest body of evidence available was for TE; MRE appeared to be the most accurate method. Imaging-based NILDA outperformed blood-based NILDA in most comparisons, particularly for the identification of F3-4/F4. In the pediatric population, imaging-based NILDA is likely as accurate as in adults. CONCLUSIONS LSM from TE, shear wave elastography, and MRE shows acceptable to outstanding accuracy for the detection of liver fibrosis across various liver disease etiologies. Accuracy increased from F2-4 to F3-4 and was the highest for F4. Further research is needed to better standardize the use of imaging-based NILDA, particularly in pediatric liver diseases.
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Affiliation(s)
- Andres Duarte-Rojo
- Division of Gastroenterology and Hepatology, Northwestern Medicine and Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
| | - Bachir Taouli
- Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Daniel H Leung
- Department of Pediatrics, Baylor College of Medicine and Division of Gastroenterology, Hepatology and Nutrition, Texas Children's Hospital, Houston, Texas, USA
| | - Deborah Levine
- Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Tarek Nayfeh
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Bashar Hasan
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Yahya Alsawaf
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Samer Saadi
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | | | | | - Samir Haffar
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Ayca Dundar
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - M Hassan Murad
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Don C Rockey
- Digestive Disease Research Center, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Mouaz Alsawas
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Richard K Sterling
- Section of Hepatology, Department of Medicine, Virginia Commonwealth University, Richmond, Virginia, USA
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3
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Gurjar S, Bhat A R, Upadhya R, Shenoy RP. Extracellular vesicle-mediated approaches for the diagnosis and therapy of MASLD: current advances and future prospective. Lipids Health Dis 2025; 24:5. [PMID: 39773634 PMCID: PMC11705780 DOI: 10.1186/s12944-024-02396-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Accepted: 12/05/2024] [Indexed: 01/11/2025] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is an asymptomatic, multifaceted condition often associated with various risk factors, including fatigue, obesity, insulin resistance, metabolic syndrome, and sleep apnea. The increasing burden of MASLD underscores the critical need for early diagnosis and effective therapies. Owing to the lack of efficient therapies for MASLD, early diagnosis is crucial. Consequently, noninvasive biomarkers and imaging techniques are essential for analyzing disease risk and play a pivotal role in the global diagnostic process. The use of extracellular vesicles has emerged as promising for early diagnosis and therapy of various liver ailments. Herein, a comprehensive summary of the current diagnostic modalities for MASLD is presented, highlighting their advantages and limitations while exploring the potential of extracellular vesicles (EVs) as innovative diagnostic and therapeutic tools for MASLD. With this aim, this review emphasizes an in-depth understanding of the origin of EVs and the pathophysiological alterations of these ectosomes and exosomes in various liver diseases. This review also explores the therapeutic potential of EVs as key components in the future management of liver disease. The dual role of EVs as biomarkers and their therapeutic utility in MASLD essentially highlights their clinical integration to improve MASLD diagnosis and treatment. While EV-based therapies are still in their early stages of development and require substantial research to increase their therapeutic value before they can be used clinically, the diagnostic application of EVs has been extensively explored. Moving forward, developing diagnostic devices leveraging EVs will be crucial in advancing MASLD diagnosis. Thus, the literature summarized provides suitable grounds for clinicians and researchers to explore EVs for devising diagnostic and treatment strategies for MASLD.
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Affiliation(s)
- Swasthika Gurjar
- Department of Biochemistry, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Karnataka, 576104, Manipal, India
| | - Ramanarayana Bhat A
- Manipal Centre for Biotherapeutics Research, Manipal, Manipal Academy of Higher Education, Karnataka, 576104, Manipal, India
| | - Raghavendra Upadhya
- Manipal Centre for Biotherapeutics Research, Manipal, Manipal Academy of Higher Education, Karnataka, 576104, Manipal, India.
| | - Revathi P Shenoy
- Department of Biochemistry, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Karnataka, 576104, Manipal, India.
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Thakral N, Desalegn H, Diaz LA, Cabrera D, Loomba R, Arrese M, Arab JP. A Precision Medicine Guided Approach to the Utilization of Biomarkers in MASLD. Semin Liver Dis 2024; 44:273-286. [PMID: 38991536 DOI: 10.1055/a-2364-2928] [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] [Indexed: 07/13/2024]
Abstract
The new nomenclature of metabolic dysfunction-associated steatotic liver disease (MASLD) emphasizes a positive diagnosis based on cardiometabolic risk factors. This definition is not only less stigmatizing but also allows for subclassification and stratification, thereby addressing the heterogeneity of what was historically referred to as nonalcoholic fatty liver disease. The heterogeneity within this spectrum is influenced by several factors which include but are not limited to demographic/dietary factors, the amount of alcohol use and drinking patterns, metabolic status, gut microbiome, genetic predisposition together with epigenetic factors. The net effect of this dynamic and intricate system-level interaction is reflected in the phenotypic presentation of MASLD. Therefore, the application of precision medicine in this scenario aims at complex phenotyping with consequent individual risk prediction, development of individualized preventive strategies, and improvements in the clinical trial designs. In this review, we aim to highlight the importance of precision medicine approaches in MASLD, including the use of novel biomarkers of disease, and its subsequent utilization in future study designs.
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Affiliation(s)
- Nimish Thakral
- Division of Gastroenterology and Hepatology, University of Kentucky, Lexington, Kentucky
| | - Hailemichael Desalegn
- Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University, London, Ontario, Canada
| | - Luis Antonio Diaz
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Daniel Cabrera
- Centro de Investigación e Innovación Biomédica (CiiB), Universidad de los Andes, Santiago, Chile
- Escuela de Medicina, Facultad de Ciencias Medicas, Universidad Bernardo O'Higgins, Santiago, Chile
| | - Rohit Loomba
- Division of Gastroenterology and Hepatology, MASLD Research Center, University of California San Diego, San Diego, California
| | - Marco Arrese
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Juan Pablo Arab
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, Virginia
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Meroueh C, Warasnhe K, Tizhoosh HR, Shah VH, Ibrahim SH. Digital pathology and spatial omics in steatohepatitis: Clinical applications and discovery potentials. Hepatology 2024:01515467-990000000-00815. [PMID: 38517078 PMCID: PMC11669472 DOI: 10.1097/hep.0000000000000866] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2024] [Accepted: 02/26/2024] [Indexed: 03/23/2024]
Abstract
Steatohepatitis with diverse etiologies is the most common histological manifestation in patients with liver disease. However, there are currently no specific histopathological features pathognomonic for metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, or metabolic dysfunction-associated steatotic liver disease with increased alcohol intake. Digitizing traditional pathology slides has created an emerging field of digital pathology, allowing for easier access, storage, sharing, and analysis of whole-slide images. Artificial intelligence (AI) algorithms have been developed for whole-slide images to enhance the accuracy and speed of the histological interpretation of steatohepatitis and are currently employed in biomarker development. Spatial biology is a novel field that enables investigators to map gene and protein expression within a specific region of interest on liver histological sections, examine disease heterogeneity within tissues, and understand the relationship between molecular changes and distinct tissue morphology. Here, we review the utility of digital pathology (using linear and nonlinear microscopy) augmented with AI analysis to improve the accuracy of histological interpretation. We will also discuss the spatial omics landscape with special emphasis on the strengths and limitations of established spatial transcriptomics and proteomics technologies and their application in steatohepatitis. We then highlight the power of multimodal integration of digital pathology augmented by machine learning (ML)algorithms with spatial biology. The review concludes with a discussion of the current gaps in knowledge, the limitations and premises of these tools and technologies, and the areas of future research.
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Affiliation(s)
- Chady Meroueh
- Department of Laboratory Medicine & Pathology, Mayo Clinic, Rochester, Minnesota, USA
| | - Khaled Warasnhe
- Division of Gastroenterology & Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - H. R. Tizhoosh
- Department of Artificial Intelligence & Informatics, Mayo Clinic, Rochester, Minnesota, USA
| | - Vijay H. Shah
- Division of Gastroenterology & Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Samar H. Ibrahim
- Division of Gastroenterology & Hepatology, Mayo Clinic, Rochester, Minnesota, USA
- Division of Pediatric Gastroenterology & Hepatology, Mayo Clinic, Rochester, Minnesota, USA
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López Tórrez SM, Ayala CO, Ruggiro PB, Costa CAD, Wagner MB, Padoin AV, Mattiello R. Accuracy of prognostic serological biomarkers in predicting liver fibrosis severity in people with metabolic dysfunction-associated steatotic liver disease: a meta-analysis of over 40,000 participants. Front Nutr 2024; 11:1284509. [PMID: 38419854 PMCID: PMC10899345 DOI: 10.3389/fnut.2024.1284509] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Accepted: 01/25/2024] [Indexed: 03/02/2024] Open
Abstract
Introduction A prognostic model to predict liver severity in people with metabolic dysfunction-associated steatotic liver disease (MASLD) is very important, but the accuracy of the most commonly used tools is not yet well established. Objective The meta-analysis aimed to assess the accuracy of different prognostic serological biomarkers in predicting liver fibrosis severity in people with MASLD. Methods Adults ≥18 years of age with MASLD were included, with the following: liver biopsy and aspartate aminotransferase-to-platelet ratio (APRI), fibrosis index-4 (FIB-4), non-alcoholic fatty liver disease fibrosis score (NFS), body mass index, aspartate aminotransferase/alanine aminotransferase ratio, diabetes score (BARD score), FibroMeter, FibroTest, enhanced liver fibrosis (ELF), Forns score, and Hepascore. Meta-analyses were performed using a random effects model based on the DerSimonian and Laird methods. The study's risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2. Results In total, 138 articles were included, of which 86 studies with 46,514 participants met the criteria for the meta-analysis. The results for the summary area under the receiver operating characteristic (sAUROC) curve, according to the prognostic models, were as follows: APRI: advanced fibrosis (AF): 0.78, any fibrosis (AnF): 0.76, significant fibrosis (SF): 0.76, cirrhosis: 0.72; FIB-4: cirrhosis: 0.83, AF: 0.81, AnF: 0.77, SF: 0.75; NFS: SF: 0.81, AF: 0.81, AnF: 0.71, cirrhosis: 0.69; BARD score: SF: 0.77, AF: 0.73; FibroMeter: SF: 0.88, AF: 0.84; FibroTest: SF: 0.86, AF: 0.78; and ELF: AF: 0.87. Conclusion The results of this meta-analysis suggest that, when comparing the scores of serological biomarkers with liver biopsies, the following models showed better diagnostic accuracy in predicting liver fibrosis severity in people with MASLD: FIB-4 for any fibrosis, FibroMeter for significant fibrosis, ELF for advanced fibrosis, and FIB-4 for cirrhosis.Clinical trial registration: [https://clinicaltrials.gov/], identifier [CRD 42020180525].
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Affiliation(s)
- Sergio M. López Tórrez
- School of Medicine, Graduate Program in Medicine and Health Sciences, Pontifícia Universidade Católica de Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
| | - Camila O. Ayala
- School of Medicine, Postgraduate Program in Pediatrics and Child Health, Pontifícia Universidade Católica de Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
| | - Paula Bayer Ruggiro
- School of Medicine, Pontifícia Universidade Católica de Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
| | - Caroline Abud Drumond Costa
- School of Medicine, Postgraduate Program in Pediatrics and Child Health, Pontifícia Universidade Católica de Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
| | - Mario B. Wagner
- School of Medicine, Graduate Program in Medicine and Health Sciences, Pontifícia Universidade Católica de Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
- School Medicine, Universidade Federal de Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
| | - Alexandre Vontobel Padoin
- School of Medicine, Graduate Program in Medicine and Health Sciences, Pontifícia Universidade Católica de Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
| | - Rita Mattiello
- School Medicine, Universidade Federal de Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
- School of Medicine, Postgraduate Program in Epidemiology, Universidade Federal de Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
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7
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Castagneto-Gissey L, Bornstein SR, Mingrone G. Can liquid biopsies for MASH help increase the penetration of metabolic surgery? A narrative review. Metabolism 2024; 151:155721. [PMID: 37923007 DOI: 10.1016/j.metabol.2023.155721] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Revised: 10/30/2023] [Accepted: 10/30/2023] [Indexed: 11/07/2023]
Abstract
This narrative review highlights current evidence on non-invasive tests to predict the presence or absence as well as the severity of metabolic dysfunction-associated steatohepatitis (MASH) and liver fibrosis. Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common condition characterized by fat accumulation in the liver that affects 32 % of the world population. The most severe form of MASLD is MASH in which hepatocyte ballooning and inflammation are present together with steatosis; MASH is often associated with liver fibrosis. MASH diagnosis is determined by invasive liver biopsy. Hence, there is a critical need for non-invasive MASH tests. Plasma biomarkers for MASH diagnosis generally have low sensitivity (62-66 %), and specificity (78-82 %). Monocyte levels of Perilipin2 (PLIN2) predict MASH with an accuracy of 92-93 %, and sensitivity and specificity of 90-95 % and 88-100 %, respectively. This liquid biopsy test can facilitate the study of MASH prevalence in general populations and also monitor the effects of lifestyle, surgical, and pharmacological interventions. Without any FDA-approved MASH therapeutic, and with metabolic surgery markedly surpassing the efficacy of lifestyle modification, an accurate and reliable liquid biopsy could help more people choose surgery as a treatment for MASH.
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Affiliation(s)
| | - Stefan R Bornstein
- Department of Medicine III, Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden, Dresden, Germany; Division of Diabetes & Nutritional Sciences, School of Cardiovascular and Metabolic Medicine & Sciences, King's College London, London, United Kingdom
| | - Geltrude Mingrone
- Division of Diabetes & Nutritional Sciences, School of Cardiovascular and Metabolic Medicine & Sciences, King's College London, London, United Kingdom; Università Cattolica del Sacro Cuore, Rome, Italy; Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
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8
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Kaya E, Yilmaz Y. Noninvasive, serum-based evaluation of liver fibrosis in metabolic (dysfunction)-associated fatty liver disease. METABOLIC STEATOTIC LIVER DISEASE 2024:137-150. [DOI: 10.1016/b978-0-323-99649-5.00012-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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9
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Zhang X, Li G, Lin H, Wong VWS, Wong GLH. Noninvasive evaluation of liver fibrosis in MASLD—Imaging/elastography based. METABOLIC STEATOTIC LIVER DISEASE 2024:151-166. [DOI: 10.1016/b978-0-323-99649-5.00005-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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10
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El-Eshmawy MM. Impact of obesity on liver function tests: is nonalcoholic fatty liver disease the only player? A review article. Porto Biomed J 2023; 8:e228. [PMID: 37846300 PMCID: PMC10575409 DOI: 10.1097/j.pbj.0000000000000228] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Revised: 07/21/2023] [Accepted: 07/24/2023] [Indexed: 10/18/2023] Open
Abstract
Objectives Obesity and nonalcoholic fatty liver disease (NAFLD) are common worldwide health problems with a strong relationship in between. NAFLD is currently the most common cause of abnormal liver function tests (LFT) because of obesity pandemic. The question is NAFLD the only player of abnormal LFT in obesity? Methodology This article reviews the most important topics regarding the derangements of LFT in obesity through a PubMed search strategy for all English-language literature. Results The reported abnormal LFT in obesity were increased serum levels of transaminases (alanine aminotransaminase, aspartate aminotransaminase), gamma glutamyl transferase, and alkaline phosphatase and decreased serum levels of bilirubin and albumin. Besides novel potential hepatic markers of NAFLD/NASH such as triglycerides/high-density lipoprotein cholesterol ratio, sex hormone-binding globulin, fibroblast growth factor 21, and markers of hepatocyte apoptosis i.e. cytokeratin 18 and microribonucleic acids (miRNAs). Beyond NAFLD, there are other underlying players for the abnormal LFT in obesity such as oxidative stress, inflammation, and insulin resistance. Conclusion Derangements of LFT in obesity are attributed to NAFLD but also to obesity itself and its related oxidative stress, insulin resistance, and chronic inflammatory state. Abnormal LFT predict more than just liver disease.
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Affiliation(s)
- Mervat M. El-Eshmawy
- Department of Internal Medicine, Mansoura Specialized Medical Hospital, Faculty of Medicine, Mansoura University, Egypt
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11
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Villani R, Lupo P, Sangineto M, Romano AD, Serviddio G. Liver Ultrasound Elastography in Non-Alcoholic Fatty Liver Disease: A State-of-the-Art Summary. Diagnostics (Basel) 2023; 13:1236. [PMID: 37046454 PMCID: PMC10093430 DOI: 10.3390/diagnostics13071236] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 03/21/2023] [Accepted: 03/23/2023] [Indexed: 03/29/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a chronic disease which is currently the most common hepatic disorder affecting up to 38% of the general population with differences according to age, country, ethnicity and sex. Both genetic and acquired risk factors such as a high-calorie diet or high intake of saturated fats have been associated with obesity, diabetes and, finally, NAFLD. A liver biopsy has always been considered essential for the diagnosis of NAFLD; however, due to several limitations such as the potential occurrence of major complications, sampling variability and the poor repeatability in clinical practice, it is considered an imperfect option for the evaluation of liver fibrosis over time. For these reasons, a non-invasive assessment by serum biomarkers and the quantification of liver stiffness is becoming the new frontier in the management of patients with NAFLD and liver fibrosis. We present a state-of-the-art summary addressing the methods for the non-invasive evaluation of liver fibrosis in NAFLD patients, particularly the ultrasound-based techniques (transient elastography, ARFI techniques and strain elastography) and their optimal cut-off values for the staging of liver fibrosis.
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Affiliation(s)
- Rosanna Villani
- Liver Unit, C.U.R.E. (University Centre for Liver Disease Research and Treatment), Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy
| | - Pierluigi Lupo
- Department of Radiology, University of Foggia, 71122 Foggia, Italy
| | - Moris Sangineto
- Liver Unit, C.U.R.E. (University Centre for Liver Disease Research and Treatment), Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy
| | - Antonino Davide Romano
- Liver Unit, C.U.R.E. (University Centre for Liver Disease Research and Treatment), Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy
| | - Gaetano Serviddio
- Liver Unit, C.U.R.E. (University Centre for Liver Disease Research and Treatment), Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy
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12
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Chee D, Ng CH, Chan KE, Huang DQ, Teng M, Muthiah M. The Past, Present, and Future of Noninvasive Test in Chronic Liver Diseases. Med Clin North Am 2023; 107:397-421. [PMID: 37001944 DOI: 10.1016/j.mcna.2022.12.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/22/2023]
Abstract
Chronic liver disease is a major global health threat and is the 11th leading cause of death globally. A liver biopsy is frequently required in assessing the degree of steatosis and fibrosis, information that is important in diagnosis, management, and prognostication. However, liver biopsies have limitations and carry a considerable risk, leading to the development of various modalities of noninvasive testing tools. These tools have been developed in recent years and have improved markedly in diagnostic accuracy. Moving forward, they may change the practice of hepatology.
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Affiliation(s)
- Douglas Chee
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Tower Block Level 10, 1E Kent Ridge Road, Singapore 119228, Singapore
| | - Cheng Han Ng
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Tower Block Level 10, 1E Kent Ridge Road, Singapore 119228, Singapore
| | - Kai En Chan
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Tower Block Level 10, 1E Kent Ridge Road, Singapore 119228, Singapore
| | - Daniel Q Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Tower Block Level 10, 1E Kent Ridge Road, Singapore 119228, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Tower Block Level 10, 1E Kent Ridge Road, Singapore 119228, Singapore; National University Centre for Organ Transplantation, National University Health System, Tower Block Level 10, 1E Kent Ridge Road, Singapore 119228, Singapore
| | - Margaret Teng
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Tower Block Level 10, 1E Kent Ridge Road, Singapore 119228, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Tower Block Level 10, 1E Kent Ridge Road, Singapore 119228, Singapore; National University Centre for Organ Transplantation, National University Health System, Tower Block Level 10, 1E Kent Ridge Road, Singapore 119228, Singapore
| | - Mark Muthiah
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Tower Block Level 10, 1E Kent Ridge Road, Singapore 119228, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Tower Block Level 10, 1E Kent Ridge Road, Singapore 119228, Singapore; National University Centre for Organ Transplantation, National University Health System, Tower Block Level 10, 1E Kent Ridge Road, Singapore 119228, Singapore.
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Contreras D, González-Rocha A, Clark P, Barquera S, Denova-Gutiérrez E. Diagnostic accuracy of blood biomarkers and non-invasive scores for the diagnosis of NAFLD and NASH: Systematic review and meta-analysis. Ann Hepatol 2023; 28:100873. [PMID: 36371077 DOI: 10.1016/j.aohep.2022.100873] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Revised: 10/12/2022] [Accepted: 10/13/2022] [Indexed: 11/11/2022]
Abstract
INTRODUCTION AND OBJECTIVES Fatty liver disease is an important public health problem. Early diagnosis is critical to lower its rate of progression to irreversible/terminal stages. This study aimed to evaluate the accuracy of non-invasive prediction scores for fatty liver disease (NAFLD and NASH) diagnosis in adults. MATERIALS AND METHODS A search was conducted in 10 databases, a qualitative synthesis of 45 studies, and quantitative analysis of the six most common scores. There were 23 risk scores found for NAFLD diagnosis and 32 for NASH diagnosis. The most used were Fatty Liver Index (FLI), aspartate aminotransferase (AST) to Platelet Ratio Index, Fibrosis-4 Index (FIB-4), AST/alanine aminotransferase (ALT) ratio, BARD score, and NAFLD fibrosis score (NFS). RESULTS The results from the meta-analysis for FLI: Area under the curve (AUC) of 0.76 (95% Confidence Interval [CI] 0.73, 0.80), sensitivity 0.67 (CI 95% 0.62, 0.72) and specificity 0.78 (CI 95% 0.74, 0.83). The AST to Platelet Ratio Index: AUC 0.83 (CI 95% 0.80, 0.86), sensitivity 0.45 (95% CI 0.29, 0.62), and specificity of 0.89 (95% CI 0.83, 0.92). The NFS: AUC of 0.82 (CI 95% 0.78, 0.85), sensitivity 0.30 (CI 95% 0.27, 0.33) and specificity 0.96 (CI 95% 0.95,0.96). CONCLUSIONS The FLI for NAFLD and AST to Platelet Ratio Index for NASH were the risk scores with the highest prognostic value in the included studies. Further research is needed for the application of new diagnostic risk scores for NAFLD and NASH.
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Affiliation(s)
- Daniela Contreras
- Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico
| | | | - Patricia Clark
- Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico; Clinical Epidemiology Research Unit, Children Hospital of Mexico "Federico Gómez", Mexico City, Mexico
| | - Simón Barquera
- Nutrition, and Health Research Center, National Institute of Public Health, Cuernavaca, Mexico
| | - Edgar Denova-Gutiérrez
- Nutrition, and Health Research Center, National Institute of Public Health, Cuernavaca, Mexico.
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14
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Cao YT, Xiang LL, Qi F, Zhang YJ, Chen Y, Zhou XQ. Accuracy of controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) for assessing steatosis and fibrosis in non-alcoholic fatty liver disease: A systematic review and meta-analysis. EClinicalMedicine 2022; 51:101547. [PMID: 35844772 PMCID: PMC9284399 DOI: 10.1016/j.eclinm.2022.101547] [Citation(s) in RCA: 62] [Impact Index Per Article: 20.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2022] [Revised: 06/16/2022] [Accepted: 06/20/2022] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease, and among the non-invasive tests, controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) have shown better diagnostic performance in NAFLD. This meta-analysis aimed to evaluate the performance of CAP and LSM for assessing steatosis and fibrosis in NAFLD. METHODS We searched the PubMed, Web of Science, Cochrane Library, and Embase databases for relevant articles published up to February 13th, 2022, and selected studies that met the inclusion and exclusion criteria, and evaluated the quality of evidence. Then we pooled sensitivity (SE), specificity (SP), and area under receiver operating characteristic (AUROC) curves. A random effect model was applied regardless of heterogeneity. Meta-regression analysis and subgroup analysis were performed to explore heterogeneity, and Fagan plot analysis was used to evaluate clinical utility. This meta-analysis was completed in Nanjing, Jiangsu and registered on PROSPERO (CRD42022309965). FINDINGS A total of 10537 patients from 61 studies were included in our meta-analysis. The AUROC of CAP were 0·924, 0·794 and 0·778 for steatosis grades ≥ S1, ≥ S2 and = S3, respectively, and the AUROC of LSM for detecting fibrosis stages ≥ F1, ≥ F2, ≥ F3, and = F4 were 0·851, 0·830, 0·897 and 0·925, respectively. Subgroup analysis revealed that BMI ≥ 30 kg/m² had lower accuracy for diagnosing S ≥ S1, ≥ S2 than BMI<30 kg/m². For the mean cut-off values, significant differences were found in CAP values among different body mass index (BMI) populations and LSM values among different regions. For diagnosing S ≥ S1, ≥ S2 and = S3, the mean CAP cut-off values for BMI ≥ 30 kg/m² were 30·7, 28·2, and 27·9 dB/m higher than for BMI < 30 kg/m² (P = 0·001, 0·001 and 0·018, respectively). For diagnosing F ≥ F2 and = F4, the mean cut-off values of Europe and America were 0·96 and 2·03 kPa higher than Asia (P = 0·027, P = 0·034), respectively. In addition, the results did not change significantly after sensitivity analysis and the trim and fill method to correct for publication bias, proving that the conclusions are robust. INTERPRETATION The good performance of CAP and LSM for the diagnosis of mild steatosis (S ≥ S1), advanced liver fibrosis (F ≥ F3), and cirrhosis (F = F4) can be used to screen for NAFLD in high-risk populations. Of note, the accuracy of CAP for the detection of steatosis in patients with obesity is reduced and requires specific diagnostic values. For LSM, the same diagnostic values can be used when the appropriate probes are selected based on BMI and the automated probe selection tool. The performance of CAP and LSM in assessing steatosis in patients with obesity, moderate to severe steatosis, and low-grade fibrosis should be further validated and improved in the future. FUNDING The study was funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).
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Affiliation(s)
- Yu-tian Cao
- The first clinical medical college of Nanjing University of Chinese Medicine, Nanjing, China
- Department of Endocrinology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China
| | - Liu-lan Xiang
- The first clinical medical college of Nanjing University of Chinese Medicine, Nanjing, China
- Department of Endocrinology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China
| | - Fang Qi
- The first clinical medical college of Nanjing University of Chinese Medicine, Nanjing, China
- Department of Endocrinology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China
| | - Yu-juan Zhang
- The first clinical medical college of Nanjing University of Chinese Medicine, Nanjing, China
- Department of Endocrinology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China
| | - Yi Chen
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Xi-qiao Zhou
- Department of Endocrinology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China
- Corresponding author at: Department of Endocrinology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, China.
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15
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Mózes FE, Lee JA, Selvaraj EA, Jayaswal ANA, Trauner M, Boursier J, Fournier C, Staufer K, Stauber RE, Bugianesi E, Younes R, Gaia S, Lupșor-Platon M, Petta S, Shima T, Okanoue T, Mahadeva S, Chan WK, Eddowes PJ, Hirschfield GM, Newsome PN, Wong VWS, de Ledinghen V, Fan J, Shen F, Cobbold JF, Sumida Y, Okajima A, Schattenberg JM, Labenz C, Kim W, Lee MS, Wiegand J, Karlas T, Yılmaz Y, Aithal GP, Palaniyappan N, Cassinotto C, Aggarwal S, Garg H, Ooi GJ, Nakajima A, Yoneda M, Ziol M, Barget N, Geier A, Tuthill T, Brosnan MJ, Anstee QM, Neubauer S, Harrison SA, Bossuyt PM, Pavlides M. Diagnostic accuracy of non-invasive tests for advanced fibrosis in patients with NAFLD: an individual patient data meta-analysis. Gut 2022; 71:1006-1019. [PMID: 34001645 PMCID: PMC8995830 DOI: 10.1136/gutjnl-2021-324243] [Citation(s) in RCA: 288] [Impact Index Per Article: 96.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 04/23/2021] [Accepted: 04/29/2021] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Liver biopsy is still needed for fibrosis staging in many patients with non-alcoholic fatty liver disease. The aims of this study were to evaluate the individual diagnostic performance of liver stiffness measurement by vibration controlled transient elastography (LSM-VCTE), Fibrosis-4 Index (FIB-4) and NAFLD (non-alcoholic fatty liver disease) Fibrosis Score (NFS) and to derive diagnostic strategies that could reduce the need for liver biopsies. DESIGN Individual patient data meta-analysis of studies evaluating LSM-VCTE against liver histology was conducted. FIB-4 and NFS were computed where possible. Sensitivity, specificity and area under the receiver operating curve (AUROC) were calculated. Biomarkers were assessed individually and in sequential combinations. RESULTS Data were included from 37 primary studies (n=5735; 45% women; median age: 54 years; median body mass index: 30 kg/m2; 33% had type 2 diabetes; 30% had advanced fibrosis). AUROCs of individual LSM-VCTE, FIB-4 and NFS for advanced fibrosis were 0.85, 0.76 and 0.73. Sequential combination of FIB-4 cut-offs (<1.3; ≥2.67) followed by LSM-VCTE cut-offs (<8.0; ≥10.0 kPa) to rule-in or rule-out advanced fibrosis had sensitivity and specificity (95% CI) of 66% (63-68) and 86% (84-87) with 33% needing a biopsy to establish a final diagnosis. FIB-4 cut-offs (<1.3; ≥3.48) followed by LSM cut-offs (<8.0; ≥20.0 kPa) to rule out advanced fibrosis or rule in cirrhosis had a sensitivity of 38% (37-39) and specificity of 90% (89-91) with 19% needing biopsy. CONCLUSION Sequential combinations of markers with a lower cut-off to rule-out advanced fibrosis and a higher cut-off to rule-in cirrhosis can reduce the need for liver biopsies.
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Affiliation(s)
- Ferenc Emil Mózes
- Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK
| | - Jenny A Lee
- Department of Epidemiology and Data Science, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Emmanuel Anandraj Selvaraj
- Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK,Translational Gastroenterology Unit, University of Oxford, Oxford, Oxfordshire, UK,NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust and the University of Oxford, Oxford, UK
| | | | - Michael Trauner
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Jerome Boursier
- Laboratoire HIFIH, UPRES EA 3859, SFR ICAT 4208, Universite d'Angers, Angers, Pays de la Loire, France,Service d'Hepato-Gastroenterologie et Oncologie Digestive, Centre Hospitalier Universitaire d'Angers, Angers, Pays de la Loire, France
| | | | - Katharina Staufer
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria,Department of Visceral Surgery and Medicine, Inselspital University Hospital Bern, Bern, Switzerland,Department of Surgery, Division of Transplantation, Medical University of Vienna, Vienna, Austria
| | - Rudolf E Stauber
- Department of Internal Medicine, Medical University of Graz, Graz, Austria
| | | | - Ramy Younes
- Boehringer Ingelheim International GmbH, Ingelheim, Rheinland-Pfalz, Germany
| | - Silvia Gaia
- Medical Sciences, University of Turin, Torino, Italy
| | - Monica Lupșor-Platon
- Department of Ultrasonography, University of Medicine and Pharmacy, Regional Institute of Gastroenterology and Hepatology “Prof. Dr. Octavian Fodor”, Cluj Napoca, Romania
| | - Salvatore Petta
- Section of Gastroenterology and Hepatology, PROMISE, Palermo, Italy
| | - Toshihide Shima
- Hepatology Center, Saiseikai Suita Hospital, Suita, Osaka, Japan
| | - Takeshi Okanoue
- Hepatology Center, Saiseikai Suita Hospital, Suita, Osaka, Japan
| | - Sanjiv Mahadeva
- Faculty of Medicine, Department of Medicine, University of Malaya, Kuala Lumpur, Wilayah Persekutuan, Malaysia
| | - Wah-Kheong Chan
- Faculty of Medicine, Department of Medicine, University of Malaya, Kuala Lumpur, Wilayah Persekutuan, Malaysia
| | - Peter J Eddowes
- NIHR Biomedical Research Centre, University of Birmingham, Birmingham, UK,NIHR Nottingham Biomedical Research Centre, University of Nottingham, Nottingham, Nottinghamshire, UK
| | - Gideon M Hirschfield
- Toronto Centre for Liver Disease, University Health Network, Toronto, Ontario, Canada
| | - Philip Noel Newsome
- NIHR Biomedical Research Centre, University of Birmingham, Birmingham, UK,Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK,Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong, Hong Kong
| | - Victor de Ledinghen
- Centre d'Investigation de la Fibrose Hépatique, Hopital Haut-Leveque, Pessac, France,INSERM1053, Universite de Bordeaux, Talence, Aquitaine, France
| | - Jiangao Fan
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Feng Shen
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jeremy F Cobbold
- Translational Gastroenterology Unit, University of Oxford, Oxford, Oxfordshire, UK,NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust and the University of Oxford, Oxford, UK
| | - Yoshio Sumida
- Department of Internal Medicine, Aichi Medical University, Nagakute, Aichi, Japan
| | - Akira Okajima
- Department of Gastroenterology, Koseikai Takeda Hospital, Kyoto, Japan
| | - Jörn M Schattenberg
- Department of Internal Medicine I, University Medical Centre of the Johannes Gutenberg-University Mainz, Mainz, Rhineland-Palatinate, Germany
| | - Christian Labenz
- Department of Internal Medicine I, University Medical Centre of the Johannes Gutenberg-University Mainz, Mainz, Rhineland-Palatinate, Germany
| | - Won Kim
- Department of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, South Korea
| | - Myoung Seok Lee
- Department of Radiology, Seoul National University Seoul Metropolitan Government Boramae Medical Center, Dongjak-gu, Seoul, The Republic of Korea
| | - Johannes Wiegand
- Department of Medicine II, Leipzig University Medical Center, Leipzig, Sachsen, Germany
| | - Thomas Karlas
- Department of Medicine II, Leipzig University Medical Center, Leipzig, Sachsen, Germany
| | - Yusuf Yılmaz
- Department of Gastroenterology, Marmara University School of Medicine, Istanbul, Turkey,Institute of Gastroenterology, Marmara University, Istanbul, Turkey
| | - Guruprasad Padur Aithal
- NIHR Nottingham Biomedical Research Centre, University of Nottingham, Nottingham, Nottinghamshire, UK,Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK
| | - Naaventhan Palaniyappan
- NIHR Nottingham Biomedical Research Centre, University of Nottingham, Nottingham, Nottinghamshire, UK,Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK
| | - Christophe Cassinotto
- Diagnostic and Interventional Radiology, University Hospital Centre Montpellier, Montpellier, Languedoc-Roussillon, France
| | - Sandeep Aggarwal
- Department of Surgical Disciplines, AIIMS, New Delhi, Delhi, India
| | - Harshit Garg
- Department of Surgical Disciplines, AIIMS, New Delhi, Delhi, India
| | - Geraldine J Ooi
- Department of Surgery, Monash University, Prahran, Victoria, Australia
| | - Atsushi Nakajima
- Department of Gastroenterology and Hepatology, Yokohama City University, Yokohama, Kanagawa, Japan
| | - Masato Yoneda
- Department of Gastroenterology and Hepatology, Yokohama City University, Yokohama, Kanagawa, Japan
| | - Marianne Ziol
- Service d'Anatomie Pathologique et Centre de Ressources Biologiques, Hopital Jean Verdier, Paris, France
| | - Nathalie Barget
- Centre de Ressources Biologiques, Hopitaux Universitaires Paris-Seine-Saint-Denis, Bondy, Île-de-France, France
| | - Andreas Geier
- Division of Hepatology, University Hospital Wurzburg, Wurzburg, Bayern, Germany
| | - Theresa Tuthill
- Internal Medicine Research Unit, Pfizer Inc, Cambridge, Massachusetts, USA
| | - M. Julia Brosnan
- Internal Medicine Research Unit, Pfizer Inc, Cambridge, Massachusetts, USA
| | - Quentin Mark Anstee
- Translational and Clinical Research Institute, Faculty of Medicine, Newcastle University, Newcastle upon Tyne, Tyne and Wear, UK
| | - Stefan Neubauer
- Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK
| | - Stephen A. Harrison
- Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK
| | - Patrick M Bossuyt
- Department of Epidemiology and Data Science, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Michael Pavlides
- Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK .,Translational Gastroenterology Unit, University of Oxford, Oxford, Oxfordshire, UK.,NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust and the University of Oxford, Oxford, UK
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16
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Li G, Zhang X, Lin H, Liang LY, Wong GLH, Wong VWS. Non-invasive tests of non-alcoholic fatty liver disease. Chin Med J (Engl) 2022; 135:532-546. [PMID: 35089884 PMCID: PMC8920457 DOI: 10.1097/cm9.0000000000002027] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Indexed: 11/26/2022] Open
Abstract
ABSTRACT For the detection of steatosis, quantitative ultrasound imaging techniques have achieved great progress in past years. Magnetic resonance imaging proton density fat fraction is currently the most accurate test to detect hepatic steatosis. Some blood biomarkers correlate with non-alcoholic steatohepatitis, but the accuracy is modest. Regarding liver fibrosis, liver stiffness measurement by transient elastography (TE) has high accuracy and is widely used across the world. Magnetic resonance elastography is marginally better than TE but is limited by its cost and availability. Several blood biomarkers of fibrosis have been used in clinical trials and hold promise for selecting patients for treatment and monitoring treatment response. This article reviews new developments in the non-invasive assessment of non-alcoholic fatty liver disease (NAFLD). Accumulating evidence suggests that various non-invasive tests can be used to diagnose NAFLD, assess its severity, and predict the prognosis. Further studies are needed to determine the role of the tests as monitoring tools. We cannot overemphasize the importance of context in selecting appropriate tests.
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Affiliation(s)
- Guanlin Li
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong, China
| | - Xinrong Zhang
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong, China
| | - Huapeng Lin
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong, China
| | - Lilian Yan Liang
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong, China
| | - Grace Lai-Hung Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong, China
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong, China
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17
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Zachou K, Lygoura V, Arvaniti P, Giannoulis G, Gatselis NK, Koukoulis GK, Dalekos GN. FibroMeter scores for the assessment of liver fibrosis in patients with autoimmune liver diseases. Ann Hepatol 2021; 22:100285. [PMID: 33157268 DOI: 10.1016/j.aohep.2020.10.013] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2020] [Revised: 10/12/2020] [Accepted: 10/21/2020] [Indexed: 02/08/2023]
Abstract
INTRODUCTION AND OBJECTIVES We assessed FibroMeter virus (FMvirus) and FibroMeter vibration-controlled transient elastography (FMVCTE) in 134 patients with autoimmune liver diseases [ALD, autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC)], in order to assess new potential non-invasive biomarkers of liver fibrosis in patients with ALD, as similar data are missing. PATIENTS AND METHODS The following groups were included: group 1: n = 78 AIH; group 2: n = 56 PBC. FMvirus and FMVCTE were determined in all 134 patients who underwent liver biopsy and TE the same day with sera collection. In addition, APRI and FIB-4 scores were calculated. RESULTS The AUCs for TE and FMVCTE were significantly better (0.809; p < 0.001 and 0.772; p = 0.001, respectively for AIH and 0.997; p < 0.001 and 1; p < 0.001, for PBC) than the other three markers in predicting ≥ F3 fibrosis irrespective of the biochemical activity. FMVCTE and TE had good diagnostic accuracy (75.6% and 73%, respectively) for predicting severe fibrosis in AIH and performed even better in PBC (94.6% and 96.4%, respectively). The cut-offs of TE and FMVCTE had the best sensitivity and specificity in predicting ≥ F3 fibrosis in both AIH and PBC. CONCLUSIONS FMVCTE seems to detect severe fibrosis equally to TE in patients with ALD but with better specificity. Biochemical disease activity did not seem to affect their diagnostic accuracy in ALD and therefore, could be helpful for the assessment of fibrosis, especially if they are performed sequentially (first TE with the best sensitivity and then FMVCTE with the best specificity).
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Affiliation(s)
- Kalliopi Zachou
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece
| | - Vasiliki Lygoura
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece
| | - Pinelopi Arvaniti
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece
| | - Georgios Giannoulis
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece
| | - Nikolaos K Gatselis
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece
| | - George K Koukoulis
- Department of Pathology, Medical School, University of Thessaly, Larissa, Greece
| | - George N Dalekos
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece.
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18
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Clinical and Molecular Biomarkers for Diagnosis and Staging of NAFLD. Int J Mol Sci 2021; 22:ijms222111905. [PMID: 34769333 PMCID: PMC8585051 DOI: 10.3390/ijms222111905] [Citation(s) in RCA: 55] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Revised: 10/30/2021] [Accepted: 10/30/2021] [Indexed: 12/16/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common hepatic pathology in industrialized countries, affecting about 25% of the general population. NAFLD is a benign condition, however, it could evolve toward more serious diseases, including non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and finally, hepatocellular carcinoma (HCC). Liver biopsy is still the gold standard for NAFLD diagnosis. Due to the risks associated with liver biopsy and the impossibility to apply it on a large scale, it is now necessary to identify non-invasive biomarkers, which may reliably identify patients at higher risk of progression. Therefore, several lines of research have tried to address this issue by identifying novel biomarkers using omics approaches, including lipidomics, metabolomics and RNA molecules' profiling. Thus, in this review, we firstly report the conventional biomarkers used in clinical practice for NAFL and NASH diagnosis as well as fibrosis staging, and secondly, we pay attention to novel biomarkers discovered through omics approaches with a particular focus on RNA biomarkers (microRNAs, long-noncoding RNAs), showing promising diagnostic performance for NAFL/NASH diagnosis and fibrosis staging.
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19
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Selvaraj EA, Mózes FE, Jayaswal ANA, Zafarmand MH, Vali Y, Lee JA, Levick CK, Young LAJ, Palaniyappan N, Liu CH, Aithal GP, Romero-Gómez M, Brosnan MJ, Tuthill TA, Anstee QM, Neubauer S, Harrison SA, Bossuyt PM, Pavlides M. Diagnostic accuracy of elastography and magnetic resonance imaging in patients with NAFLD: A systematic review and meta-analysis. J Hepatol 2021; 75:770-785. [PMID: 33991635 DOI: 10.1016/j.jhep.2021.04.044] [Citation(s) in RCA: 189] [Impact Index Per Article: 47.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Revised: 03/15/2021] [Accepted: 04/25/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Vibration-controlled transient elastography (VCTE), point shear wave elastography (pSWE), 2-dimensional shear wave elastography (2DSWE), magnetic resonance elastography (MRE), and magnetic resonance imaging (MRI) have been proposed as non-invasive tests for patients with non-alcoholic fatty liver disease (NAFLD). This study evaluated their diagnostic accuracy for liver fibrosis and non-alcoholic steatohepatitis (NASH). METHODS PubMED/MEDLINE, EMBASE and the Cochrane Library were searched for studies examining the diagnostic accuracy of these index tests, against histology as the reference standard, in adult patients with NAFLD. Two authors independently screened and assessed methodological quality of studies and extracted data. Summary estimates of sensitivity, specificity and area under the curve (sAUC) were calculated for fibrosis stages and NASH, using a random effects bivariate logit-normal model. RESULTS We included 82 studies (14,609 patients). Meta-analysis for diagnosing fibrosis stages was possible in 53 VCTE, 11 MRE, 12 pSWE and 4 2DSWE studies, and for diagnosing NASH in 4 MRE studies. sAUC for diagnosis of significant fibrosis were: 0.83 for VCTE, 0.91 for MRE, 0.86 for pSWE and 0.75 for 2DSWE. sAUC for diagnosis of advanced fibrosis were: 0.85 for VCTE, 0.92 for MRE, 0.89 for pSWE and 0.72 for 2DSWE. sAUC for diagnosis of cirrhosis were: 0.89 for VCTE, 0.90 for MRE, 0.90 for pSWE and 0.88 for 2DSWE. MRE had sAUC of 0.83 for diagnosis of NASH. Three (4%) studies reported intention-to-diagnose analyses and 15 (18%) studies reported diagnostic accuracy against pre-specified cut-offs. CONCLUSIONS When elastography index tests are acquired successfully, they have acceptable diagnostic accuracy for advanced fibrosis and cirrhosis. The potential clinical impact of these index tests cannot be assessed fully as intention-to-diagnose analyses and validation of pre-specified thresholds are lacking. LAY SUMMARY Non-invasive tests that measure liver stiffness or use magnetic resonance imaging (MRI) have been suggested as alternatives to liver biopsy for assessing the severity of liver scarring (fibrosis) and fatty inflammation (steatohepatitis) in patients with non-alcoholic fatty liver disease (NAFLD). In this study, we summarise the results of previously published studies on how accurately these non-invasive tests can diagnose liver fibrosis and inflammation, using liver biopsy as the reference. We found that some techniques that measure liver stiffness had a good performance for the diagnosis of severe liver scarring.
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Affiliation(s)
- Emmanuel Anandraj Selvaraj
- Oxford Centre for Clinical Magnetic Resonance Research, Radcliffe Department of Medicine, University of Oxford, Oxford, UK; Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust and the University of Oxford, Oxford, UK
| | - Ferenc Emil Mózes
- Oxford Centre for Clinical Magnetic Resonance Research, Radcliffe Department of Medicine, University of Oxford, Oxford, UK
| | - Arjun Narayan Ajmer Jayaswal
- Oxford Centre for Clinical Magnetic Resonance Research, Radcliffe Department of Medicine, University of Oxford, Oxford, UK
| | - Mohammad Hadi Zafarmand
- Department of Epidemiology and Data Science, Amsterdam UMC, University of Amsterdam, The Netherlands
| | - Yasaman Vali
- Department of Epidemiology and Data Science, Amsterdam UMC, University of Amsterdam, The Netherlands
| | - Jenny A Lee
- Department of Epidemiology and Data Science, Amsterdam UMC, University of Amsterdam, The Netherlands
| | - Christina Kim Levick
- Oxford Centre for Clinical Magnetic Resonance Research, Radcliffe Department of Medicine, University of Oxford, Oxford, UK
| | - Liam Arnold Joseph Young
- Oxford Centre for Clinical Magnetic Resonance Research, Radcliffe Department of Medicine, University of Oxford, Oxford, UK
| | - Naaventhan Palaniyappan
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
| | - Chang-Hai Liu
- UCM Digestive Diseases. Virgen del Rocio University Hospital. Institute of Biomedicine of Seville, University of Seville, Sevilla, Spain; Center for Infectious Diseases, West China Hospital of Sichuan University; Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Disease, West China Hospital, Sichuan University, Chengdu, China
| | - Guruprasad Padur Aithal
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
| | - Manuel Romero-Gómez
- UCM Digestive Diseases. Virgen del Rocio University Hospital. Institute of Biomedicine of Seville, University of Seville, Sevilla, Spain
| | - M Julia Brosnan
- Internal Medicine Research Unit, Pfizer Inc, Cambridge, MA, USA
| | | | - Quentin M Anstee
- Liver Research Group, Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK; NIHR Newcastle Biomedical Research Centre, Newcastle upon Tyne Hospitals, NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Stefan Neubauer
- Oxford Centre for Clinical Magnetic Resonance Research, Radcliffe Department of Medicine, University of Oxford, Oxford, UK
| | - Stephen A Harrison
- Oxford Centre for Clinical Magnetic Resonance Research, Radcliffe Department of Medicine, University of Oxford, Oxford, UK
| | - Patrick M Bossuyt
- Department of Epidemiology and Data Science, Amsterdam UMC, University of Amsterdam, The Netherlands
| | - Michael Pavlides
- Oxford Centre for Clinical Magnetic Resonance Research, Radcliffe Department of Medicine, University of Oxford, Oxford, UK; Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust and the University of Oxford, Oxford, UK.
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20
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Van Dijk AM, Vali Y, Mak AL, Lee J, Tushuizen ME, Zafarmand MH, Anstee QM, Brosnan MJ, Nieuwdorp M, Bossuyt PM, Holleboom AG. Systematic Review with Meta-Analyses: Diagnostic Accuracy of FibroMeter Tests in Patients with Non-Alcoholic Fatty Liver Disease. J Clin Med 2021; 10:jcm10132910. [PMID: 34209858 PMCID: PMC8269151 DOI: 10.3390/jcm10132910] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Revised: 06/11/2021] [Accepted: 06/14/2021] [Indexed: 12/14/2022] Open
Abstract
Early detection of liver fibrosis is crucial to select the correct care path for patients with non-alcoholic fatty liver disease (NAFLD). Here, we systematically review the evidence on the performance of FibroMeter versions in detecting different levels of fibrosis in patients with NAFLD. We searched four databases (Medline, Embase, the Cochrane library, and Web of Science) to find studies that included adults with NAFLD and biopsy-confirmed fibrosis (F1 to F4), compared with any version of FibroMeter. Two independent researchers screened the references, collected the data, and assessed the methodological quality of the included studies. We used a bivariate logit-normal random effects model to produce meta-analyses. From 273 references, 12 studies were eligible for inclusion, encompassing data from 3425 patients. Meta-analyses of the accuracy in detecting advanced fibrosis (F ≥ 3) were conducted for FibroMeter Virus second generation (V2G), NAFLD, and vibration controlled transient elaFS3stography (VCTE). FibroMeter VCTE showed the best diagnostic accuracy in detecting advanced fibrosis (sensitivity: 83.5% (95%CI 0.58–0.94); specificity: 91.1% (95%CI 0.89–0.93)), followed by FibroMeter V2G (sensitivity: 83.1% (95%CI 0.73–0.90); specificity: 84.4% (95%CI 0.62–0.95)) and FibroMeter NAFLD (sensitivity: 71.7% (95%CI 0.63–0.79); specificity: 82.8% (95%CI 0.71–0.91)). No statistically significant differences were found between the different FibroMeter versions. FibroMeter tests showed acceptable sensitivity and specificity in detecting advanced fibrosis in patients with NAFLD, but an urge to conduct head-to-head comparison studies in patients with NAFLD of the different FibroMeter tests remains.
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Affiliation(s)
- Anne-Marieke Van Dijk
- Department of Internal and Vascular Medicine, Amsterdam University Medical Centres, Location AMC, 1105AZ Amsterdam, The Netherlands; (A.L.M.); (M.N.); (A.G.H.)
- Correspondence: ; Tel.: +31-205665973
| | - Yasaman Vali
- Department of Epidemiology and Data Science, Amsterdam University Medical Centres, Location AMC, 1105AZ Amsterdam, The Netherlands; (Y.V.); (J.L.); (M.H.Z.); (P.M.B.)
| | - Anne Linde Mak
- Department of Internal and Vascular Medicine, Amsterdam University Medical Centres, Location AMC, 1105AZ Amsterdam, The Netherlands; (A.L.M.); (M.N.); (A.G.H.)
| | - Jenny Lee
- Department of Epidemiology and Data Science, Amsterdam University Medical Centres, Location AMC, 1105AZ Amsterdam, The Netherlands; (Y.V.); (J.L.); (M.H.Z.); (P.M.B.)
| | - Maarten E. Tushuizen
- Department of Gastroenterology and Hepatology, Leiden University Medical Centre, 2333ZA Leiden, The Netherlands;
| | - Mohammad Hadi Zafarmand
- Department of Epidemiology and Data Science, Amsterdam University Medical Centres, Location AMC, 1105AZ Amsterdam, The Netherlands; (Y.V.); (J.L.); (M.H.Z.); (P.M.B.)
| | - Quentin M. Anstee
- Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE1 7RU, UK;
| | - M. Julia Brosnan
- Internal Medicine Research Unit, Pfizer Inc., Cambridge, MA 02139, USA;
| | - Max Nieuwdorp
- Department of Internal and Vascular Medicine, Amsterdam University Medical Centres, Location AMC, 1105AZ Amsterdam, The Netherlands; (A.L.M.); (M.N.); (A.G.H.)
| | - Patrick M. Bossuyt
- Department of Epidemiology and Data Science, Amsterdam University Medical Centres, Location AMC, 1105AZ Amsterdam, The Netherlands; (Y.V.); (J.L.); (M.H.Z.); (P.M.B.)
| | - Adriaan G. Holleboom
- Department of Internal and Vascular Medicine, Amsterdam University Medical Centres, Location AMC, 1105AZ Amsterdam, The Netherlands; (A.L.M.); (M.N.); (A.G.H.)
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21
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Kim MN, Han K, Yoo J, Ha Y, Chon YE, Lee JH, Simon TG, Chan AT, Hwang SG. Body weight variability and the risk of cardiovascular outcomes in patients with nonalcoholic fatty liver disease. Sci Rep 2021; 11:9154. [PMID: 33911167 PMCID: PMC8080815 DOI: 10.1038/s41598-021-88733-3] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Accepted: 04/13/2021] [Indexed: 02/06/2023] Open
Abstract
We investigated the association between body weight variability and the risks of cardiovascular disease and mortality in patients with nonalcoholic fatty liver disease (NAFLD) using large-scale, nationwide cohort data. We included 726,736 individuals with NAFLD who underwent a health examination between 2009 and 2010. NAFLD was defined as a fatty liver index ≥ 60, after excluding significant alcohol intake, viral hepatitis, and liver cirrhosis. Body weight variability was assessed using four indices, including variability independent of the mean (VIM). During a median 8.1-year follow-up, we documented 11,358, 14,714, and 22,164 cases of myocardial infarction (MI), stroke, and all-cause mortality, respectively. Body weight variability was associated with an increased risk of MI, stroke, and mortality after adjusting for confounding variables. The hazard ratios (HRs) (95% confidence intervals) for the highest quartile, compared with the lowest quartile, of VIM for body weight were 1.15 (1.10-1.20), 1.22 (1.18-1.26), and 1.56 (1.53-1.62) for MI, stroke, and all-cause mortality, respectively. Body weight variability was associated with increased risks of MI, stroke, and all-cause mortality in NAFLD patients. Appropriate interventions to maintain a stable weight could positively affect health outcomes in NAFLD patients.
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Affiliation(s)
- Mi Na Kim
- Division of Gastroenterology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, 59 Yatap-ro, Bundang-gu, Seongnam, 13496, Republic of Korea.
- Clinical and Translational Hepatology Laboratory, Seongnam, Republic of Korea.
| | - Kyungdo Han
- Department of Statistics and Actuarial Science, Soongsil University, Seoul, Republic of Korea
| | - Juhwan Yoo
- Department of Biomedicine and Health Science, The Catholic University of Korea, Seoul, Republic of Korea
| | - Yeonjung Ha
- Division of Gastroenterology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, 59 Yatap-ro, Bundang-gu, Seongnam, 13496, Republic of Korea
| | - Young Eun Chon
- Division of Gastroenterology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, 59 Yatap-ro, Bundang-gu, Seongnam, 13496, Republic of Korea
| | - Ju Ho Lee
- Division of Gastroenterology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, 59 Yatap-ro, Bundang-gu, Seongnam, 13496, Republic of Korea
| | - Tracey G Simon
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Liver Center, Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Andrew T Chan
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Seong Gyu Hwang
- Division of Gastroenterology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, 59 Yatap-ro, Bundang-gu, Seongnam, 13496, Republic of Korea.
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22
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Mikolasevic I, Domislovic V, Klapan M, Juric T, Lukic A, Krznaric-Zrnic I, Fuckar-Cupic D, Stimac D, Filipec Kanizaj T, Krznaric Z, Radic-Kristo D, Milic S, Martinovic M, Grubesic A, Grgurevic I. Accuracy of Controlled Attenuation Parameter and Liver Stiffness Measurement in Patients with Non-alcoholic Fatty Liver Disease. ULTRASOUND IN MEDICINE & BIOLOGY 2021; 47:428-437. [PMID: 33358052 DOI: 10.1016/j.ultrasmedbio.2020.11.015] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Revised: 11/12/2020] [Accepted: 11/16/2020] [Indexed: 06/12/2023]
Abstract
We evaluated the diagnostic accuracy of the controlled attenuation parameter (CAP) and liver stiffness measurements (LSM) measured with either an M or XL probe against liver biopsy (LB) in patients with non-alcoholic fatty liver disease (NAFLD). This study was a cross-sectional prospective study that included 179 NAFLD patients. With a cutoff value for CAP ≥345, we can exclude significant steatosis in 87% (79.4%-92.5%) of our population. With respect to the LSM, the highest accuracy was obtained for F ≥ F3 (area under the receiver operating characteristic curve [AUROC] = 0.98) and F = F4 (AUROC = 0.98). In a multivariable linear regression model, significant predictors influencing LSM were fibrosis stage (β = 2.6, p < 0.001) as a positive predictor and lobular inflammation (β = -0.68, p = 0.04) as a negative predictor, without significant influence after adjustment for CAP and probe type. We found that CAP is a satisfactory method for excluding advanced steatosis, while LSM is a good non-invasive marker for the exclusion of fibrosis.
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Affiliation(s)
- Ivana Mikolasevic
- Department of Gastroenterology, University Hospital Center Rijeka, Rijeka, Croatia; Department of Gastroenterology, University Hospital Merkur, Zagreb, Croatia; Faculty of medicine, Rijeka, Croatia.
| | - Viktor Domislovic
- Department of Gastroenterology and Hepatology, University Hospital Center Zagreb, Zagreb, Croatia
| | | | | | | | - Irena Krznaric-Zrnic
- Department of Gastroenterology, University Hospital Center Rijeka, Rijeka, Croatia
| | - Dora Fuckar-Cupic
- Department of Gastroenterology, University Hospital Merkur, Zagreb, Croatia; Clinical Department of Pathology and Cytology, University Hospital Center Rijeka, Rijeka, Croatia
| | - Davor Stimac
- Department of Gastroenterology, University Hospital Center Rijeka, Rijeka, Croatia; Faculty of medicine, Rijeka, Croatia
| | - Tajana Filipec Kanizaj
- Department of Gastroenterology, University Hospital Merkur, Zagreb, Croatia; Faculty of Medicine, Zagreb, Croatia; Faculty of Medicine, Zagreb, Croatia
| | - Zeljko Krznaric
- Department of Gastroenterology and Hepatology, University Hospital Center Zagreb, Zagreb, Croatia; Faculty of Medicine, Zagreb, Croatia
| | | | - Sandra Milic
- Department of Gastroenterology, University Hospital Center Rijeka, Rijeka, Croatia; Faculty of medicine, Rijeka, Croatia
| | - Marko Martinovic
- Department of Hematology, University Hospital Center Rijeka, Rijeka, Croatia
| | - Aron Grubesic
- Faculty of medicine, Rijeka, Croatia; Department of Hematology, University Hospital Center Rijeka, Rijeka, Croatia
| | - Ivica Grgurevic
- Faculty of Medicine, Zagreb, Croatia; Department of Gastroenterology, Hepatology and Clinical Nutrition, University Hospital Dubrava, Zagreb, Croatia
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Lee JI, Lee HW, Lee KS, Lee HS, Park JY. Effects of Statin Use on the Development and Progression of Nonalcoholic Fatty Liver Disease: A Nationwide Nested Case-Control Study. Am J Gastroenterol 2021; 116:116-124. [PMID: 33027082 DOI: 10.14309/ajg.0000000000000845] [Citation(s) in RCA: 71] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Accepted: 06/03/2020] [Indexed: 02/06/2023]
Abstract
INTRODUCTION The use of statins in nonalcoholic fatty liver disease (NAFLD) may reduce cardiovascular morbidity, although their effect on NAFLD itself is not well known. We aimed to investigate the role of statins on the development of de novo NAFLD and progression of significant liver fibrosis. METHODS This study included 11,593,409 subjects from the National Health Information Database of the Republic of Korea entered in 2010 and followed up until 2016. NAFLD was diagnosed by calculating fatty liver index (FLI), and significant liver fibrosis was evaluated using the BARD score. Controls were randomly selected at a ratio of 1:5 from individuals who were at risk of becoming the case subjects at the time of selection. RESULTS Among 5,339,901 subjects that had a FLI < 30 and included in the non-NAFLD cohort, 164,856 subjects eventually had NAFLD developed. The use of statin was associated with a reduced risk of NAFLD development (adjusted odds ratio [AOR] 0.66; 95% confidence interval [CI] 0.65-0.67) and was independent of associated diabetes mellitus (DM) (with DM: AOR 0.44; 95% CI 0.41-0.46, without DM: AOR 0.71; 95% CI 0.69-0.72). From 712,262 subjects with a FLI > 60 and selected in the NAFLD cohort, 111,257 subjects showed a BARD score ≥ 2 and were defined as liver fibrosis cases. The use of statins reduced the risk of significant liver fibrosis (AOR 0.43; 95% CI 0.42-0.44), independent of DM (with DM: AOR 0.31; 95% CI 0.31-0.32, without DM: AOR 0.52; 95% CI 0.51-0.52). DISCUSSION In this large population-based study, statin use decreased the risk of NAFLD occurrence and the risk of liver fibrosis once NAFLD developed.
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Affiliation(s)
- Jung Il Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seodaemun-gu, Seoul, South Korea
- Gangnam Severance Hospital, Yonsei University College of Medicine, Gangnam-Gu, Seoul, South Korea
| | - Hyun Woong Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seodaemun-gu, Seoul, South Korea
- Gangnam Severance Hospital, Yonsei University College of Medicine, Gangnam-Gu, Seoul, South Korea
| | - Kwan Sik Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seodaemun-gu, Seoul, South Korea
- Gangnam Severance Hospital, Yonsei University College of Medicine, Gangnam-Gu, Seoul, South Korea
| | - Hye Sun Lee
- Biostatistics Collaboration Unit, Yonsei University College of Medicine, Gangnam-Gu, Seoul, South Korea
| | - Ju-Young Park
- Biostatistics Collaboration Unit, Yonsei University College of Medicine, Gangnam-Gu, Seoul, South Korea
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24
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Garbuzenko D. Non-invasive diagnosis of liver fibrosis associated with nonalcoholic steatohepatitis. DOKAZATEL'NAYA GASTROENTEROLOGIYA 2021; 10:75. [DOI: 10.17116/dokgastro20211004175] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Kazankov K, Rosso C, Younes R, Armandi A, Hagström H, Møller HJ, Stål P, Bugianesi E, Grønbæk H. Macrophage Markers Do Not Add to the Prediction of Liver Fibrosis by Transient Elastography in Patients With Metabolic Associated Fatty Liver Disease. Front Med (Lausanne) 2020; 7:616212. [PMID: 33392234 PMCID: PMC7775526 DOI: 10.3389/fmed.2020.616212] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2020] [Accepted: 11/27/2020] [Indexed: 12/15/2022] Open
Abstract
Background and Aims: Non-invasive fibrosis staging is essential in metabolic associated fatty liver disease (MAFLD). Transient elastography (TE) is a well-established method for liver fibrosis assessment. We have previously shown that the macrophage marker sCD163 is an independent predictor for fibrosis in MAFLD. In the present study we tested whether the combination of macrophage markers and TE improves fibrosis prediction. Methods: We measured macrophage markers soluble (s)CD163 and mannose receptor (sMR) in two independent cohorts from Italy (n = 141) and Sweden (n = 70) with biopsy-proven MAFLD and available TE. Results: In the Italian cohort, TE and sCD163 showed similar moderate associations with liver fibrosis (rho = 0.56, p < 0.001 and rho = 0.42, p < 0.001, respectively). TE had an area under the Receiver Operating Characteristics curve (AUROC, with 95% CI) for fibrosis; F ≥ 2 = 0.79 (0.72-0.86), F ≥ 3 = 0.81 (0.73-0.89), F4 = 0.95 (0.90-1.0). sCD163 also predicted fibrosis well [F ≥ 2 = 0.71 (0.63-0.80), F ≥ 3 = 0.82 (0.74-0.90), F4 = 0.89 (0.76-1.0)]. However, combining sCD163 and TE did not improve the AUROCs significantly [F ≥ 2 = 0.79 (0.72-0.86), F ≥ 3 = 0.85 (0.78-0.92), F4 = 0.97 (0.93-1.0)]. In the Swedish cohort, TE showed a closer association with fibrosis (rho = 0.73, p < 0.001) than sCD163 (rho = 0.43, p < 0.001) and sMR (rho = 0.46, p < 0.001). TE predicted fibrosis well [F ≥ 2 = 0.88 (0.80-0.97), F ≥ 3 = 0.90 (0.83-0.97), F4 = 0.87 (0.78-0.96)], whereas sCD163 did not (best AUROC 0.75). sMR showed a better prediction [F ≥ 2 = 0.68 (0.56-0.81), F ≥ 3 = 0.82 (0.71-0.92), F4 = 0.79 (0.66-0.93)], but the addition of sMR did not further improve the prediction of fibrosis by TE. Conclusion: In these cohorts of MAFLD patients, TE was superior to macrophage markers for fibrosis prediction and in contrast to our hypothesis the addition of these markers to TE did not improve its predictive capability.
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Affiliation(s)
- Konstantin Kazankov
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.,Institute of Liver and Digestive Health, University College London, London, United Kingdom
| | - Chiara Rosso
- Department of Medical Sciences, Division of Gastroenterology and Hepatology, University of Turin, Turin, Italy
| | - Ramy Younes
- Boehringer Ingelheim International, Gesellschaft mit beschränkter Haftung, Ingelheim, Germany
| | - Angelo Armandi
- Department of Medical Sciences, Division of Gastroenterology and Hepatology, University of Turin, Turin, Italy
| | - Hannes Hagström
- Department of Upper GI, Unit of Hepatology, Karolinska University Hospital, Stockholm, Sweden.,Department of Medicine, Clinical Epidemiology Unit, Solna, Karolinska Institutet, Stockholm, Sweden.,Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden
| | - Holger Jon Møller
- Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark
| | - Per Stål
- Department of Upper GI, Unit of Hepatology, Karolinska University Hospital, Stockholm, Sweden.,Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden
| | - Elisabetta Bugianesi
- Department of Medical Sciences, Division of Gastroenterology and Hepatology, University of Turin, Turin, Italy
| | - Henning Grønbæk
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
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26
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Hanif H, Khan MM, Ali MJ, Shah PA, Satiya J, Lau DT, Aslam A. A New Endemic of Concomitant Nonalcoholic Fatty Liver Disease and Chronic Hepatitis B. Microorganisms 2020; 8:1526. [PMID: 33020450 PMCID: PMC7601829 DOI: 10.3390/microorganisms8101526] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Revised: 09/28/2020] [Accepted: 09/30/2020] [Indexed: 12/12/2022] Open
Abstract
Hepatitis B virus (HBV) infection remains a global public problem despite the availability of an effective vaccine. In the past decades, nonalcoholic fatty liver disease (NAFLD) has surpassed HBV as the most common cause of chronic liver disease worldwide. The prevalence of concomitant chronic hepatitis B (CHB) and NAFLD thus reaches endemic proportions in geographic regions where both conditions are common. Patients with CHB and NAFLD are at increased risk of liver disease progression to cirrhosis and hepatocellular carcinoma. Due to the complexity of the pathogenesis, accurate diagnosis of NAFLD in CHB patients can be challenging. Liver biopsy is considered the gold standard for diagnosing and determining disease severity, but it is an invasive procedure with potential complications. There is a growing body of literature on the application of novel noninvasive serum biomarkers and advanced radiological modalities to diagnose and evaluate NAFLD, but most have not been adequately validated, especially for patients with CHB. Currently, there is no approved therapy for NAFLD, although many new agents are in different phases of development. This review provides a summary of the epidemiology, clinical features, diagnosis, and management of the NAFLD and highlights the unmet needs in the areas of CHB and NAFLD coexistence.
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Affiliation(s)
- Hira Hanif
- Liver Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; (H.H.); (M.M.K.); (M.J.A.); (P.A.S.); (J.S.)
| | - Muzammil M. Khan
- Liver Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; (H.H.); (M.M.K.); (M.J.A.); (P.A.S.); (J.S.)
| | - Mukarram J. Ali
- Liver Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; (H.H.); (M.M.K.); (M.J.A.); (P.A.S.); (J.S.)
| | - Pir A. Shah
- Liver Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; (H.H.); (M.M.K.); (M.J.A.); (P.A.S.); (J.S.)
- Department of Internal Medicine, University of Texas, San Antonio, TX 78229, USA
| | - Jinendra Satiya
- Liver Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; (H.H.); (M.M.K.); (M.J.A.); (P.A.S.); (J.S.)
| | - Daryl T.Y. Lau
- Liver Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; (H.H.); (M.M.K.); (M.J.A.); (P.A.S.); (J.S.)
| | - Aysha Aslam
- Department of Medicine, Louis A Weiss Memorial Hospital, Chicago, IL 60640, USA
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Lee HW, Wong GLH, Kwok R, Choi KC, Chan CKM, Shu SST, Leung JKY, Chim AML, Luk AOY, Ma RCW, Chan HLY, Chan JCN, Kong APS, Wong VWS. Serial Transient Elastography Examinations to Monitor Patients With Type 2 Diabetes: A Prospective Cohort Study. Hepatology 2020; 72:1230-1241. [PMID: 31991487 DOI: 10.1002/hep.31142] [Citation(s) in RCA: 58] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2019] [Accepted: 12/23/2019] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIMS Type 2 diabetes is an important risk factor for nonalcoholic fatty liver disease (NAFLD) and advanced fibrosis. Current international guidelines recommend the use of noninvasive tests as initial assessments for NAFLD, but the role of noninvasive tests as monitoring tools has not been established. We aimed to study the role of transient elastography as a monitoring tool in patients with type 2 diabetes. APPROACH AND RESULTS We recruited patients with type 2 diabetes without viral hepatitis or excessive alcohol intake from a complication screening facility in Hong Kong in 2013-2014 and repeated the assessments in 2016-2018. The primary endpoint was an increase of liver stiffness measurement (LSM) to ≥10 kPa. The secondary endpoint was the change in the controlled attenuation parameter (CAP). A total of 611 patients with type 2 diabetes and a valid LSM (mean age, 57.7 ± 10.9 years; 342 men [56.0%]) were included in this study (568 also had a valid CAP). Overall, there was moderate correlation between the baseline and follow-up LSM (r = 0.689, P < 0.001). Among 487 patients with a baseline LSM <10 kPa, 21 (4.3%) had a follow-up LSM ≥10 kPa. Baseline body mass index, alanine aminotransferase (ALT), and ∆ALT were independent factors associated with LSM increase. Among 124 patients with a baseline LSM ≥10 kPa, 70 (56.5%) had a follow-up LSM <10 kPa. Among 198 patients with a CAP <248 dB/m at baseline, 103 (52.0%) had a CAP increased to ≥248 dB/m. CONCLUSIONS The prevalence and incidence of NAFLD in patients with type 2 diabetes are high. Although advanced fibrosis is common in this population, few patients progress to advanced fibrosis in 3 years. Future studies should define the optimal surveillance interval in patients with diabetes.
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Affiliation(s)
- Hye Won Lee
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.,Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.,Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, South Korea
| | - Grace Lai-Hung Wong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.,Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Raymond Kwok
- Department of Gastroenterology, Blacktown Hospital, Sydney, Australia
| | - Kai Chow Choi
- Nethersole School of Nursing, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Carmen Ka-Man Chan
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.,Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Sally She-Ting Shu
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.,Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Julie Ka-Yu Leung
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.,Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Angel Mei-Ling Chim
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.,Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Andrea On-Yan Luk
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.,Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.,Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Ronald Ching-Wan Ma
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.,Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.,Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Henry Lik-Yuen Chan
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.,Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Juliana Chung-Ngor Chan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.,Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.,Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Alice Pik-Shan Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.,Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.,Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Vincent Wai-Sun Wong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.,Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
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Puthenpura MM, Patel V, Fam J, Katz L, Tichansky DS, Myers S. The Use of Transient Elastography Technology in the Bariatric Patient: a Review of the Literature. Obes Surg 2020; 30:5108-5116. [PMID: 32981002 DOI: 10.1007/s11695-020-05002-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2020] [Revised: 09/17/2020] [Accepted: 09/22/2020] [Indexed: 12/17/2022]
Abstract
Transient elastography (TE) is a non-invasive technology that demonstrates promise in assessing liver steatosis and fibrosis without the risks of traditional percutaneous liver biopsy. Many studies have examined its reliability in respect to liver biopsy, but fewer have examined using TE in obese and bariatric surgery patients. With evidence showing that bariatric surgery can lead to improvement of liver steatosis and fibrosis, TE has the potential to provide a simple avenue of hepatic assessment in patients before and after procedures. This review article investigates what is known about the reliability of TE and its implementation in obese and bariatric surgery patients.
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Affiliation(s)
- Max M Puthenpura
- Department of Surgery, Drexel University College of Medicine, 2900 W Queen Lane, Philadelphia, PA, 19129, USA.
| | - Vishal Patel
- The Center for Liver Disease, Tower Health Transplant Institute, 420 S 5th Ave, West Reading, PA, 19611, USA
| | - John Fam
- Department of Surgery, Drexel University College of Medicine, 2900 W Queen Lane, Philadelphia, PA, 19129, USA.,Tower Health Weight Loss Surgery and Wellness Center, 1220 Broadcasting Rd, Wyomissing, PA, 19610, USA
| | - Leon Katz
- Department of Surgery, Drexel University College of Medicine, 2900 W Queen Lane, Philadelphia, PA, 19129, USA.,Tower Health Weight Loss Surgery and Wellness Center, 1220 Broadcasting Rd, Wyomissing, PA, 19610, USA
| | - David S Tichansky
- Department of Surgery, Drexel University College of Medicine, 2900 W Queen Lane, Philadelphia, PA, 19129, USA.,Tower Health Weight Loss Surgery and Wellness Center, 1220 Broadcasting Rd, Wyomissing, PA, 19610, USA
| | - Stephan Myers
- Department of Surgery, Drexel University College of Medicine, 2900 W Queen Lane, Philadelphia, PA, 19129, USA.,Tower Health Weight Loss Surgery and Wellness Center, 1220 Broadcasting Rd, Wyomissing, PA, 19610, USA
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Performance of liver biomarkers, in patients at risk of nonalcoholic steato-hepatitis, according to presence of type-2 diabetes. Eur J Gastroenterol Hepatol 2020; 32:998-1007. [PMID: 31789950 PMCID: PMC7337110 DOI: 10.1097/meg.0000000000001606] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
OBJECTIVE There is a controversy about the performance of blood tests for the diagnostic of metabolic liver disease in patients with type-2-diabetes in comparison with patients without type-2-diabetes. These indirect comparisons assumed that the gold-standard is binary, whereas fibrosis stages, steatosis and nonalcoholic-steato-hepatitis (NASH) grades use an ordinal scale. The primary aim was to compare the diagnostic performances of FibroTest in type-2-diabetes vs. controls matched on gender, age, fibrosis stages and obesity, and taking into account the spectrum effect by Obuchowski measure. METHODS Data were retrospectively compared among patients prospectively included, with simultaneous biopsy and blindly assessed FibroTest, SteatoTest-2 and NashTest-2. The secondary aim was to construct an index (SpectrumF3F4-Index) to predict an adjusted-area under the receiver operating curve (AUROC) for F3F4 diagnosis from the prevalences of fibrosis stages, permitting to reduce the spectrum effect when performances of FibroTest, transient elastography and magnetic resonance elastography are indirectly compared. RESULTS In 505 patients at risk of NASH, the Obuchowski measures [95% confidence interval (CI)] of FibroTest, SteatoTest-2 and NashTest-2 were all equivalent in 136 type-2-diabetes cases vs. 369 matched controls: 0.871 (0.837-0.905), vs. 0.880 (0.879-0.881), 0.835 (0.797-0.873) vs. 0.806 (0.780-0.832) and 0.829 (0.793-0.865) vs. 0.855 (0.829-0.869), respectively. Standard-AUROCs (95% CI) were 0.932 (0.898-0.965), 0.872 (0.837-0.907) and 0.834 (0.699-0.969) and reduced after adjustment by SpectrumF3F4-Index to 0.794 (0.749-0.838), 0.767 (0.750-0.783) and 0.773 (0.725-0.822) for transient, magnetic resonance elastography and FibroTest, respectively. CONCLUSIONS When compared by Obuchowski measures, the performances of tests were not different in patients with T2-diabetes vs. patients without T2-diabetes. When individual data are not available, adjusted-AUROCs reduced the spectrum effect.
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Robinson A, Wong RJ. Applications and Limitations of Noninvasive Methods for Evaluating Hepatic Fibrosis in Patients With Nonalcoholic Fatty Liver Disease. Clin Liver Dis (Hoboken) 2020; 15:157-161. [PMID: 32395243 PMCID: PMC7206324 DOI: 10.1002/cld.878] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2019] [Accepted: 08/25/2019] [Indexed: 02/04/2023] Open
Abstract
http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/15-4-reading-robinson a video presentation of this article https://www.wileyhealthlearning.com/Activity/7088585/disclaimerspopup.aspx questions and earn CME.
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Affiliation(s)
- Ann Robinson
- Department of MedicineDivision of Gastroenterology and HepatologyAlameda Health System–Highland HospitalOaklandCA
| | - Robert J. Wong
- Department of MedicineDivision of Gastroenterology and HepatologyAlameda Health System–Highland HospitalOaklandCA
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31
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Shima T, Sakai K, Oya H, Katayama T, Mitsumoto Y, Mizuno M, Kanbara Y, Okanoue T. Diagnostic accuracy of combined biomarker measurements and vibration-controlled transient elastography (VCTE) for predicting fibrosis stage of non-alcoholic fatty liver disease. J Gastroenterol 2020; 55:100-112. [PMID: 31538241 DOI: 10.1007/s00535-019-01626-1] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2019] [Accepted: 08/30/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND Numerous biomarkers have been developed for assessing the presence and severity of liver fibrosis associated with non-alcoholic fatty liver disease (NAFLD). Fibrosis can be assessed by liver stiffness measurement (LSM) using vibration-controlled transient elastography (VCTE). Here we examined whether diagnostic accuracy and applicability can be further improved by combining various biomarker measurements with LSM. METHODS A total of 278 patients with biopsy-confirmed Japanese NAFLD patients were enrolled. Area under the receiver operator characteristic curve (AUROC) was evaluated for obtaining the optimum interpretation criteria for LSM by VCTE and comparing various biomarkers alone and in combination with LSM. RESULTS Liver stiffness measurements including cases with interquartile range (IQR)/median (M) < 30% or LSM ≤ 7.1 kPa demonstrated high applicability (90% of patients with NAFLD) and accuracy (AUROC: 0.891) for predicting stage ≥ 3 fibrosis. For all biomarkers tested, the AUROC values for predicting stage ≥ 3 fibrosis were increased when combined with LSM [platelet count, 0.734 vs. 0.912; type-4 collagen 7s (T4C7s), 0.894 vs. 0.921; aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT), 0.774 vs. 0.906; AST to platelet ratio index, 0.789 vs. 0.902; FIB-4 index, 0.828 vs. 0.922; NAFLD fibrosis score, 0.800 vs. 0.906; CA index-fibrosis, 0.884 vs. 0.913; FM-fibro index, 0.920 vs. 0.943; FIB-4 index + T4C7s, 0.901 vs. 0.930], demonstrating the advantage of concurrent LSM. CONCLUSIONS While VCTE has slightly limited applicability (90%) for patients with NAFLD, concurrent measurement with certain biomarkers (especially FM-fibro, T4C7s, and FIB-4) greatly improves the diagnostic accuracy.
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Affiliation(s)
- Toshihide Shima
- Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Suita, Japan
| | - Kyoko Sakai
- Clinical Laboratory, Saiseikai Suita Hospital, Suita, Japan
- Health Informatics, Kyoto University School of Public Health, Kyoto, Japan
| | - Hirohisa Oya
- Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Suita, Japan
| | - Takayuki Katayama
- Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Suita, Japan
| | - Yasuhide Mitsumoto
- Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Suita, Japan
| | - Masayuki Mizuno
- Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Suita, Japan
| | - Yoshihiro Kanbara
- Hepato-Biliary-Pancreatic Surgery, Saiseikai Suita Hospital, Suita, Japan
| | - Takeshi Okanoue
- Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Suita, Japan.
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32
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Wai JW, Fu C, Wong VWS. Confounding factors of non-invasive tests for nonalcoholic fatty liver disease. J Gastroenterol 2020; 55:731-741. [PMID: 32451628 PMCID: PMC7376510 DOI: 10.1007/s00535-020-01686-8] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Accepted: 03/27/2020] [Indexed: 02/07/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) affects at least 25% of the general adult population worldwide. Because only a fraction of the patients would develop liver-related complications, it is preferable to perform non-invasive tests as the initial assessment. This review summarizes the known and potential confounding factors that affect the performance of non-invasive tests of hepatic steatosis and fibrosis in patients with NAFLD. Clinicians may apply the knowledge and exercise caution in selecting investigations and interpreting test results when confounding factors are present.
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Affiliation(s)
- Janae Wentong Wai
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, 9/F, Prince of Wales Hospital, 30-32 Ngan Shing Street, Hong Kong, China
| | - Charmaine Fu
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, 9/F, Prince of Wales Hospital, 30-32 Ngan Shing Street, Hong Kong, China
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, 9/F, Prince of Wales Hospital, 30-32 Ngan Shing Street, Hong Kong, China ,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
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Thiele M, Lindvig KP. Elastography in Combination with Other Biomarkers: Role of Algorithms. LIVER ELASTOGRAPHY 2020:551-561. [DOI: 10.1007/978-3-030-40542-7_48] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/07/2025]
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35
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Guillaume M, Moal V, Delabaudiere C, Zuberbuhler F, Robic MA, Lannes A, Metivier S, Oberti F, Gourdy P, Fouchard-Hubert I, Selves J, Michalak S, Peron JM, Cales P, Bureau C, Boursier J. Direct comparison of the specialised blood fibrosis tests FibroMeter V2G and Enhanced Liver Fibrosis score in patients with non-alcoholic fatty liver disease from tertiary care centres. Aliment Pharmacol Ther 2019; 50:1214-1222. [PMID: 31617224 DOI: 10.1111/apt.15529] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2019] [Revised: 07/03/2019] [Accepted: 09/16/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND The Enhanced Liver Fibrosis score (ELF) and the FibroMeterV2G are two specialized blood fibrosis tests which include direct markers of liver fibrosis. They have been shown to be more accurate than the simple blood fibrosis tests FIB4 and the non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS). AIMS To directly compare the accuracies of ELF and FibroMeterV2G for the non-invasive diagnosis of liver fibrosis in NAFLD. METHODS Four hundred and seventeen patients with biopsy-proven NAFLD were enrolled from two tertiary care centres. Four blood fibrosis tests were calculated: ELF, FibroMeterV2G , NFS, and FIB4. Advanced fibrosis F3/4 on liver biopsy (NASH CRN scoring) was the primary endpoint. RESULTS Areas under the receiver operating characteristic (AUROC) curve for advanced fibrosis were not significantly different between the direct markers of liver fibrosis (hyaluronate, PIIINP, TIMP-1, alpha2-macroglobulin) and the simple blood fibrosis tests NFS and FIB4. ELF (0.793 ± 0.022) and FibroMeterV2G (0.804 ± 0.021) had significantly higher AUROC than NFS (0.722 ± 0.025, P < .010) and FIB4 (0.739 ± 0.024, P < .020). AUROC for advanced fibrosis and Obuchowski index were not significantly different between ELF and FibroMeterV2G . Algorithms using first ELF or FibroMeterV2G and then liver biopsy in case of undetermined diagnosis provided high diagnostic accuracy for advanced fibrosis: 90% sensitivity, 90% specificity, 93% negative predictive value, 85% positive predictive value, and 90% correct classification. In these algorithms, the rate of liver biopsy was 45.3% with ELF versus 39.3% with FibroMeterV2G (P = .065). CONCLUSIONS ELF and FibroMeterV2G have equal accuracy and perform better than the simple FIB4 and NFS tests for the non-invasive diagnosis of advanced liver fibrosis in patients with NAFLD from tertiary care centres.
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Affiliation(s)
- Maeva Guillaume
- Hepato-Gastroenterology Department, Toulouse University Hospital, Toulouse, France.,Institut CARDIOMET, Fédération Hospitalo-Universitaire IMPACT, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), UMR1048, INSERM/UPS, Toulouse University, Toulouse, France
| | - Valerie Moal
- Biochemistry Department, Angers University Hospital, Angers, France.,HIFIH Laboratory, UPRES 3859, SFR 4208, Angers University, Angers, France
| | | | - Floraine Zuberbuhler
- HIFIH Laboratory, UPRES 3859, SFR 4208, Angers University, Angers, France.,Hepato-Gastroenterology Department, Angers University Hospital, Angers, France
| | - Marie-Angèle Robic
- Hepato-Gastroenterology Department, Toulouse University Hospital, Toulouse, France
| | - Adrien Lannes
- HIFIH Laboratory, UPRES 3859, SFR 4208, Angers University, Angers, France.,Hepato-Gastroenterology Department, Angers University Hospital, Angers, France
| | - Sophie Metivier
- Hepato-Gastroenterology Department, Toulouse University Hospital, Toulouse, France
| | - Frederic Oberti
- HIFIH Laboratory, UPRES 3859, SFR 4208, Angers University, Angers, France.,Hepato-Gastroenterology Department, Angers University Hospital, Angers, France
| | - Pierre Gourdy
- Institut CARDIOMET, Fédération Hospitalo-Universitaire IMPACT, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), UMR1048, INSERM/UPS, Toulouse University, Toulouse, France.,Diabetology Department, Toulouse University Hospital, Toulouse, France
| | - Isabelle Fouchard-Hubert
- HIFIH Laboratory, UPRES 3859, SFR 4208, Angers University, Angers, France.,Hepato-Gastroenterology Department, Angers University Hospital, Angers, France
| | - Janick Selves
- Pathology Department, Toulouse University Hospital, Toulouse, France
| | - Sophie Michalak
- HIFIH Laboratory, UPRES 3859, SFR 4208, Angers University, Angers, France.,Pathology Department, Angers University Hospital, Angers, France
| | - Jean-Marie Peron
- Hepato-Gastroenterology Department, Toulouse University Hospital, Toulouse, France
| | - Paul Cales
- HIFIH Laboratory, UPRES 3859, SFR 4208, Angers University, Angers, France.,Hepato-Gastroenterology Department, Angers University Hospital, Angers, France
| | - Christophe Bureau
- Hepato-Gastroenterology Department, Toulouse University Hospital, Toulouse, France
| | - Jerome Boursier
- HIFIH Laboratory, UPRES 3859, SFR 4208, Angers University, Angers, France.,Hepato-Gastroenterology Department, Angers University Hospital, Angers, France
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Zhang X, Wong GLH, Wong VWS. Application of transient elastography in nonalcoholic fatty liver disease. Clin Mol Hepatol 2019; 26:128-141. [PMID: 31696690 PMCID: PMC7160347 DOI: 10.3350/cmh.2019.0001n] [Citation(s) in RCA: 80] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2019] [Accepted: 09/25/2019] [Indexed: 02/07/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is currently the most common chronic liver disease worldwide. Although it has become one of the leading causes of cirrhosis and hepatocellular carcinoma in the Western world, the proportion of NAFLD patients developing these complications is rather small. Therefore, current guidelines recommend non-invasive tests for the initial assessment of NAFLD. Among the available non-invasive tests, transient elastography by FibroScan® (Echosens, Paris, France) is commonly used by hepatologists in Europe and Asia, and the machine has been introduced to the United States in 2013 with rapid adoption. Transient elastography measures liver stiffness and the controlled attenuation parameter simultaneously and can serve as a one-stop examination for both liver steatosis and fibrosis. Liver stiffness measurement also correlates with clinical outcomes and can be used to select patients for varices screening. Although obesity is a common reason for measurement failures, the development of the XL probe allows successful measurements in the majority of obese patients. This article reviews the performance and limitations of transient elastography in NAFLD and highlights its clinical applications. We also discuss the reliability criteria for transient elastography examination and factors associated with false-positive liver stiffness measurements.
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Affiliation(s)
- Xinrong Zhang
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
| | - Grace Lai-Hung Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
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Wong VWS, Irles M, Wong GLH, Shili S, Chan AWH, Merrouche W, Shu SST, Foucher J, Le Bail B, Chan WK, Chan HLY, de Ledinghen V. Unified interpretation of liver stiffness measurement by M and XL probes in non-alcoholic fatty liver disease. Gut 2019; 68:2057-2064. [PMID: 30658997 DOI: 10.1136/gutjnl-2018-317334] [Citation(s) in RCA: 127] [Impact Index Per Article: 21.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2018] [Revised: 12/03/2018] [Accepted: 12/27/2018] [Indexed: 12/11/2022]
Abstract
OBJECTIVE The latest model of vibration-controlled transient elastography (VCTE) automatically selects M or XL probe according to patients' body built. We aim to test the application of a unified interpretation of VCTE results with probes appropriate for the body mass index (BMI) and hypothesise that this approach is not affected by hepatic steatosis. DESIGN We prospectively recruited 496 patients with non-alcoholic fatty liver disease who underwent VCTE by both M and XL probes within 1 week before liver biopsy. RESULTS 391 (78.8%) and 433 (87.3%) patients had reliable liver stiffness measurement (LSM) (10 successful acquisitions and IQR:median ratio ≤0.30) by M and XL probes, respectively (p<0.001). The area under the receiver operating characteristic curves was similar between the two probes (0.75-0.88 for F2-4, 0.83-0.91 for F4). When used in the same patient, LSM by XL probe was lower than that by M probe (mean difference 2.3 kPa). In contrast, patients with BMI ≥30 kg/m2 had higher LSM regardless of the probe used. When M and XL probes were used in patients with BMI <30 and ≥30 kg/m2, respectively, they yielded nearly identical median LSM at each fibrosis stage and similar diagnostic performance. Severe steatosis did not increase LSM or the rate of false-positive diagnosis by XL probe. CONCLUSION High BMI but not severe steatosis increases LSM. The same LSM cut-offs can be used without further adjustment for steatosis when M and XL probes are used according to the appropriate BMI.
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Affiliation(s)
- Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - Marie Irles
- Centre d'Investigation de la Fibrose Hépatique, Bordeaux University Hospital, Pessac, France
| | - Grace Lai-Hung Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - Sarah Shili
- Centre d'Investigation de la Fibrose Hépatique, Bordeaux University Hospital, Pessac, France
| | - Anthony Wing-Hung Chan
- Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, New Territories, Hong Kong
| | - Wassil Merrouche
- Centre d'Investigation de la Fibrose Hépatique, Bordeaux University Hospital, Pessac, France
| | - Sally She-Ting Shu
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - Juliette Foucher
- Centre d'Investigation de la Fibrose Hépatique, Bordeaux University Hospital, Pessac, France
| | - Brigitte Le Bail
- Pathology Unit, Hôpital Pellegrin, Bordeaux University Hospital, Bordeaux, France.,INSERM U1053, Bordeaux University, Bordeaux, France
| | - Wah Kheong Chan
- Department of Medicine, Gastroenterology and Hepatology Unit, University of Malaya, Kuala Lumpur, Malaysia
| | - Henry Lik-Yuen Chan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - Victor de Ledinghen
- Centre d'Investigation de la Fibrose Hépatique, Bordeaux University Hospital, Pessac, France.,INSERM U1053, Bordeaux University, Bordeaux, France
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Zhou F, Zhou J, Wang W, Zhang XJ, Ji YX, Zhang P, She ZG, Zhu L, Cai J, Li H. Unexpected Rapid Increase in the Burden of NAFLD in China From 2008 to 2018: A Systematic Review and Meta-Analysis. Hepatology 2019; 70:1119-1133. [PMID: 31070259 DOI: 10.1002/hep.30702] [Citation(s) in RCA: 407] [Impact Index Per Article: 67.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2019] [Accepted: 05/01/2019] [Indexed: 02/06/2023]
Abstract
With rapid lifestyle transitions, the increasing burden of nonalcoholic fatty liver disease (NAFLD) in China has emerged as a major public health issue. To obtain a comprehensive overview of the status of NAFLD over the past decade, we evaluated the epidemiology, risk factors, complications, and management of NAFLD in China through a systematic review and meta-analysis. Five English literature databases and three Chinese databases were searched for relevant topics from 2008 to 2018. A total of 392 studies with a population of 2,054,554 were included. National prevalence of NAFLD was 29.2%, with a heavier disease burden among the middle-aged, males, those in northwest China and Taiwan, regions with a gross domestic product per capita greater than 100,000 yuan, and Uygur and Hui ethnic groups. Currently, original studies on natural history and complications of NAFLD in China are scarce. Several studies revealed that NAFLD is positively correlated with the incidence of extrahepatic tumors, diabetes, cardiovascular disease and metabolic syndrome. The Chinese population may have a higher hereditary risk of NAFLD due to more frequent nonsynonymous mutations in genes regulating lipid metabolism. Ultrasonography is the primary imaging tool in the detection of NAFLD in China. Serum tests and risk stratification algorithms for staging NAFLD remain under investigation. Specific pharmaceutical treatments for NAFLD are still undergoing clinical trials. It is noteworthy that the Chinese are underrepresented compared with their proportion of the NAFLD population in such trials. Conclusion: China experienced an unexpected rapid increase in the burden of NAFLD over a short period. Rising awareness and urgent actions need to be taken in order to control the NAFLD pandemic in China.
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Affiliation(s)
- Feng Zhou
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Institute of Model Animal of Wuhan University, Wuhan, China
- Basic Medical School, Wuhan University, Wuhan, China
- Medical Science Research Center, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Jianghua Zhou
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Institute of Model Animal of Wuhan University, Wuhan, China
- Basic Medical School, Wuhan University, Wuhan, China
| | - Wenxin Wang
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Institute of Model Animal of Wuhan University, Wuhan, China
- Basic Medical School, Wuhan University, Wuhan, China
| | - Xiao-Jing Zhang
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Institute of Model Animal of Wuhan University, Wuhan, China
- Basic Medical School, Wuhan University, Wuhan, China
| | - Yan-Xiao Ji
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Institute of Model Animal of Wuhan University, Wuhan, China
- Basic Medical School, Wuhan University, Wuhan, China
| | - Peng Zhang
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Institute of Model Animal of Wuhan University, Wuhan, China
- Basic Medical School, Wuhan University, Wuhan, China
| | - Zhi-Gang She
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Institute of Model Animal of Wuhan University, Wuhan, China
- Basic Medical School, Wuhan University, Wuhan, China
| | - Lihua Zhu
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Institute of Model Animal of Wuhan University, Wuhan, China
- Basic Medical School, Wuhan University, Wuhan, China
| | - Jingjing Cai
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, China
- Institute of Model Animal of Wuhan University, Wuhan, China
| | - Hongliang Li
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Institute of Model Animal of Wuhan University, Wuhan, China
- Basic Medical School, Wuhan University, Wuhan, China
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Yokoo T, Kanefuji T, Suda T, Nagayama I, Hoshi T, Abe S, Morita S, Kamimura H, Kamimura K, Tsuchiya A, Takamura M, Yagi K, Terai S. Rational arrangement of measuring shear wave speed in the liver. World J Gastroenterol 2019; 25:2503-2513. [PMID: 31171893 PMCID: PMC6543244 DOI: 10.3748/wjg.v25.i20.2503] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2018] [Revised: 11/18/2018] [Accepted: 12/27/2018] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Shear wave speed has been widely applied to quantify a degree of liver fibrosis. However, there is no standardized procedure, which makes it difficult to utilize the speed universally. AIM To provide procedural standardization of shear wave speed measurement. METHODS Point shear wave elastography (pSWE) was measured in 781 patients, and two-dimensional shear wave elastography (2dSWE) was measured on the same day in 18 cases. Regions-of-interest were placed at 12 sites, and the median and robust coefficient-of-variation (CVR) were calculated. A residual sum-of-square (Σdi 2) was computed for bootstrap values of 1000 iterations in 18 cases with each assumption of 1 to 12 measurements. The proportion of the Σdi 2 (%Σdi 2) was calculated as the ratio of Σdi 2 to pSWE after converting it based on the correlation between pSWE and 2dSWE. RESULTS The CVR showed a significantly broader distribution in the left lobe (P < 0.0001), and the smallest CVR in the right anterior segment that covered 95% cases was 40.4%. pSWE was significantly higher in the left lobe than in the right lobe (1.63 ± 0.78 m/s vs 1.61 ± 0.78 m/s, P = 0.0004), and the difference between the lobes became further discrete when the subjects were limited to the cases with a CVR less than 40.4% in any segment (1.76 ± 0.80 m/s vs 1.70 ± 0.82 m/s, P < 0.0001). The highest values of the CVR in every 0.1 m/s interval were plotted in convex upward along pSWE and peaked at 1.93 m/s. pSWE and 2dSWE were significantly correlated (P < 0.0001, r = 0.95). In 216000 resamples from 18 cases, the %Σdi 2 of 12 sites was 8.0% and gradually increased as the acquisition sites decreased to reach a significant difference with a %Σdi 2 of 7 sites (P = 0.027). CONCLUSION These data suggest that shear wave speed should be measured at 8 or more sites of spreading in both lobes.
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Affiliation(s)
- Takeshi Yokoo
- Department of Preemptive Medicine for Digestive Diseases and Healthy Active Life, Niigata University School of Medicine, Niigata, Niigata 951-8122, Japan
| | - Tsutomu Kanefuji
- Division of Gastroenterology and Hepatology, Niigata Tokamachi Hospital, Tokamachi, Niigata 948-0065, Japan
| | - Takeshi Suda
- Department of Gastroenterology and Hepatology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Minami Uonuma, Niigata 949-7302, Japan
| | - Itsuo Nagayama
- Department of Gastroenterology and Hepatology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Minami Uonuma, Niigata 949-7302, Japan
| | - Takahiro Hoshi
- Department of Gastroenterology and Hepatology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Minami Uonuma, Niigata 949-7302, Japan
| | - Satoshi Abe
- Department of Gastroenterology and Hepatology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Minami Uonuma, Niigata 949-7302, Japan
| | - Shinichi Morita
- Department of Gastroenterology and Hepatology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Minami Uonuma, Niigata 949-7302, Japan
| | - Hiroteru Kamimura
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8122, Japan
| | - Kenya Kamimura
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8122, Japan
| | - Atsunori Tsuchiya
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8122, Japan
| | - Masaaki Takamura
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8122, Japan
| | - Kazuyoshi Yagi
- Department of Gastroenterology and Hepatology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Minami Uonuma, Niigata 949-7302, Japan
| | - Shuji Terai
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8122, Japan
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Zhou JH, Cai JJ, She ZG, Li HL. Noninvasive evaluation of nonalcoholic fatty liver disease: Current evidence and practice. World J Gastroenterol 2019; 25:1307-1326. [PMID: 30918425 PMCID: PMC6429343 DOI: 10.3748/wjg.v25.i11.1307] [Citation(s) in RCA: 157] [Impact Index Per Article: 26.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2019] [Revised: 02/20/2019] [Accepted: 02/22/2019] [Indexed: 02/06/2023] Open
Abstract
With the increasing number of individuals with diabetes and obesity, nonalcoholic fatty liver disease (NAFLD) is becoming increasingly prevalent, affecting one-quarter of adults worldwide. The spectrum of NAFLD ranges from simple steatosis or nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH). NAFLD, especially NASH, may progress to fibrosis, leading to cirrhosis and hepatocellular carcinoma. NAFLD can impose a severe economic burden, and patients with NAFLD-related terminal or deteriorative liver diseases have become one of the main groups receiving liver transplantation. The increasing prevalence of NAFLD and the severe outcomes of NASH make it necessary to use effective methods to identify NAFLD. Although recognized as the gold standard, biopsy is limited by its sampling bias, poor acceptability, and severe complications, such as mortality, bleeding, and pain. Therefore, noninvasive methods are urgently needed to avoid biopsy for diagnosing NAFLD. This review discusses the current noninvasive methods for assessing NAFLD, including steatosis, NASH, and NAFLD-related fibrosis, and explores the advantages and disadvantages of measurement tools. In addition, we analyze potential noninvasive biomarkers for tracking disease processes and monitoring treatment effects, and explore effective algorithms consisting of imaging and nonimaging biomarkers for diagnosing advanced fibrosis and reducing unnecessary biopsies in clinical practice.
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Affiliation(s)
- Jiang-Hua Zhou
- Department of Cardiology, Renmin Hospital of Wuhan University, Institute of Model Animal of Wuhan University, Wuhan 430071, Hubei Province, China
| | - Jing-Jing Cai
- Department of Cardiology, The 3rd Xiangya Hospital of Central South University, Changsha 410013, Hunan Province, China
| | - Zhi-Gang She
- Department of Cardiology, Renmin Hospital of Wuhan University, Institute of Model Animal of Wuhan University, Wuhan 430071, Hubei Province, China
| | - Hong-Liang Li
- Department of Cardiology, Renmin Hospital of Wuhan University, Institute of Model Animal of Wuhan University, Wuhan 430071, Hubei Province, China
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Bernal-Reyes R, Castro-Narro G, Malé-Velázquez R, Carmona-Sánchez R, González-Huezo M, García-Juárez I, Chávez-Tapia N, Aguilar-Salinas C, Aiza-Haddad I, Ballesteros-Amozurrutia M, Bosques-Padilla F, Castillo-Barradas M, Chávez-Barrera J, Cisneros-Garza L, Flores-Calderón J, García-Compeán D, Gutiérrez-Grobe Y, Higuera de la Tijera M, Kershenobich-Stalnikowitz D, Ladrón de Guevara-Cetina L, Lizardi-Cervera J, López-Cossio J, Martínez-Vázquez S, Márquez-Guillén E, Méndez-Sánchez N, Moreno-Alcantar R, Poo-Ramírez J, Ramos-Martínez P, Rodríguez-Hernández H, Sánchez-Ávila J, Stoopen-Rometti M, Torre-Delgadillo A, Torres-Villalobos G, Trejo-Estrada R, Uribe-Esquivel M, Velarde-Ruiz Velasco J. The Mexican consensus on nonalcoholic fatty liver disease. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2019. [DOI: 10.1016/j.rgmxen.2019.02.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
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42
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Bernal-Reyes R, Castro-Narro G, Malé-Velázquez R, Carmona-Sánchez R, González-Huezo MS, García-Juárez I, Chávez-Tapia N, Aguilar-Salinas C, Aiza-Haddad I, Ballesteros-Amozurrutia MA, Bosques-Padilla F, Castillo-Barradas M, Chávez-Barrera JA, Cisneros-Garza L, Flores-Calderón J, García-Compeán D, Gutiérrez-Grobe Y, Higuera de la Tijera MF, Kershenobich-Stalnikowitz D, Ladrón de Guevara-Cetina L, Lizardi-Cervera J, López-Cossio JA, Martínez-Vázquez S, Márquez-Guillén E, Méndez-Sánchez N, Moreno-Alcantar R, Poo-Ramírez JL, Ramos-Martínez P, Rodríguez-Hernández H, Sánchez-Ávila JF, Stoopen-Rometti M, Torre-Delgadillo A, Torres-Villalobos G, Trejo-Estrada R, Uribe-Esquivel M, Velarde-Ruiz Velasco JA. The Mexican consensus on nonalcoholic fatty liver disease. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2019; 84:69-99. [PMID: 30711302 DOI: 10.1016/j.rgmx.2018.11.007] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/17/2018] [Revised: 11/06/2018] [Accepted: 11/20/2018] [Indexed: 02/06/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) affects nearly one third of the population worldwide. Mexico is one of the countries whose population has several risk factors for the disease and its prevalence could surpass 50%. If immediate action is not taken to counteract what is now considered a national health problem, the medium-term panorama will be very bleak. This serious situation prompted the Asociación Mexicana de Gastroenterología and the Asociación Mexicana de Hepatología to produce the Mexican Consensus on Fatty Liver Disease. It is an up-to-date and detailed review of the epidemiology, pathophysiology, clinical forms, diagnosis, and treatment of the disease, whose aim is to provide the Mexican physician with a useful tool for the prevention and management of nonalcoholic fatty liver disease.
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Affiliation(s)
- R Bernal-Reyes
- Sociedad Española de Beneficencia, Pachuca, Hidalgo, México.
| | - G Castro-Narro
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | - R Malé-Velázquez
- Instituto de Salud Digestiva y Hepática SA de CV, Guadalajara, Jalisco, México
| | | | - M S González-Huezo
- Servicio de Gastroenterología y Endoscopia GI, ISSSEMYM, Metepec, Estado de México, México
| | - I García-Juárez
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | - N Chávez-Tapia
- Servicio de Gastroenterología, Fundación Clínica Médica Sur, Ciudad de México, México
| | - C Aguilar-Salinas
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | - I Aiza-Haddad
- Clínica de enfermedades hepáticas, Hospital Ángeles Lómas, Ciudad de México, México
| | | | | | - M Castillo-Barradas
- Servicio de Gastroenterología, Hospital de Especialidades, Centro Médico La Raza IMSS, Ciudad de México, México
| | - J A Chávez-Barrera
- Servicio de Gastroenterología Pediátrica, Hospital General, Centro Médico La Raza, IMSS, Ciudad de México, México
| | - L Cisneros-Garza
- Servicio de Gastroenterología, Hospital Universitario de la UANL, Monterrey, Nuevo León, México
| | - J Flores-Calderón
- Servicio de Gastroenterología, Hospital de Pediatría, Centro Médico Siglo XXI, IMSS, Ciudad de México, México
| | - D García-Compeán
- Servicio de Gastroenterología, Hospital Universitario de la UANL, Monterrey, Nuevo León, México
| | - Y Gutiérrez-Grobe
- Servicio de Gastroenterología, Fundación Clínica Médica Sur, Ciudad de México, México
| | | | | | | | - J Lizardi-Cervera
- Servicio de Gastroenterología, Fundación Clínica Médica Sur, Ciudad de México, México
| | - J A López-Cossio
- Servicio de Gastroenterología y Endoscopia GI, ISSSEMYM, Metepec, Estado de México, México
| | - S Martínez-Vázquez
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | - E Márquez-Guillén
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | - N Méndez-Sánchez
- Servicio de Gastroenterología, Fundación Clínica Médica Sur, Ciudad de México, México
| | - R Moreno-Alcantar
- Servicio de Gastroenterología, Hospital de Especialidades Centro Médico Siglo XXI, IMSS, Ciudad de México, México
| | - J L Poo-Ramírez
- Centro de Innovación y Educación Ejecutiva, Tec de Monterrey, Ciudad de México, México
| | | | - H Rodríguez-Hernández
- Unidad de Investigación Biomédica AMCCI, Hospital de Especialidades, Durango, México
| | - J F Sánchez-Ávila
- Escuela de Medicina y Ciencias de la Salud, Tecnológico de Monterrey, Monterrey, Nuevo León, México
| | - M Stoopen-Rometti
- Centro de Diagnóstico CT-Scanner Lomas Altas, Ciudad de México, México
| | - A Torre-Delgadillo
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | - G Torres-Villalobos
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | | | - M Uribe-Esquivel
- Servicio de Gastroenterología, Fundación Clínica Médica Sur, Ciudad de México, México
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Chow JCL, Wong GLH, Chan AWH, Shu SST, Chan CKM, Leung JKY, Choi PCL, Chim AML, Chan HLY, Wong VWS. Repeating measurements by transient elastography in non-alcoholic fatty liver disease patients with high liver stiffness. J Gastroenterol Hepatol 2019; 34:241-248. [PMID: 29890010 DOI: 10.1111/jgh.14311] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2018] [Revised: 05/29/2018] [Accepted: 06/01/2018] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND AIM The Baveno VI Consensus recommends repeating examination in patients with high liver stiffness measurement (LSM) by transient elastography to reduce false-positive diagnosis of advanced liver disease. We tested whether repeating transient elastography can increase the overall diagnostic accuracy. METHODS Ninety-seven patients with non-alcoholic fatty liver disease who underwent two FibroScan examinations within 6 months prior to liver biopsy were evaluated. An LSM cut-off of 7.9 kPa was used to exclude F3-4 fibrosis. RESULTS Seventy-eight patients had high LSM at baseline, among whom 27 had low LSM on repeated testing; only four had F3 and none had cirrhosis. In contrast, 31 of 51 patients with high LSM at both examinations had F3-4. Nineteen patients had low LSM at baseline; none of them had F3-4 regardless of the second LSM results. If we took LSM <7.9 kPa at either examination as sufficient to exclude F3-4, the negative predictive value remained high at 91%. The positive predictive value for F3-4 increased from 45% in patients with high LSM at baseline to 61% in those with high LSM at both examinations. Sensitivity analysis using different cut-offs yielded similar results, with 76% of patients with LSM >12 kPa at both examinations having F3-4. CONCLUSIONS Transient elastography is a highly sensitive screening test to exclude F3-4 fibrosis in non-alcoholic fatty liver disease patients. One-third of patients with high LSM may have normal results on repeated examination. By repeating examination in cases with high LSM, one may spare patients from unnecessary liver biopsy.
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Affiliation(s)
- Jeremy Chak-Lun Chow
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Grace Lai-Hung Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong.,State Key laboratory of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Anthony Wing-Hung Chan
- Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Sally She-Ting Shu
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong.,State Key laboratory of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Carmen Ka-Man Chan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong.,State Key laboratory of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Julie Ka-Yu Leung
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong.,State Key laboratory of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Paul Cheung-Lung Choi
- Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Angel Mei-Ling Chim
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong.,State Key laboratory of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Henry Lik-Yuen Chan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong.,State Key laboratory of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong.,State Key laboratory of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
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Abstract
Nonalcoholic fatty liver disease (NAFLD) affects 25% of the global adult population and is the most common chronic liver disease worldwide. Nonalcoholic steatohepatitis (NASH) is the active form of NAFLD, with hepatic necroinflammation and faster fibrosis progression. With an increasing number of patients developing NASH-related end-stage liver disease and pharmacological treatments on the horizon, there is a pressing need to develop NAFLD and NASH biomarkers for prognostication, selection of patients for treatment and monitoring. This requirement is particularly true as liver biopsy utility is limited by its invasive nature, poor patient acceptability and sampling variability. This article reviews current and potential biomarkers for different features of NAFLD, namely, steatosis, necroinflammation and fibrosis. For each biomarker, we evaluate its accuracy, reproducibility, responsiveness, feasibility and limitations. We cover biochemical, imaging and genetic biomarkers and discuss biomarker discovery in the omics era.
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Wong GLH. Non-invasive assessments for liver fibrosis: The crystal ball we long for. J Gastroenterol Hepatol 2018; 33:1009-1015. [PMID: 29380413 DOI: 10.1111/jgh.14103] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2017] [Revised: 12/26/2017] [Accepted: 01/20/2018] [Indexed: 12/14/2022]
Abstract
Non-invasive assessment of liver fibrosis has been one of the most rapidly advancing fields in hepatology in the last decade. Progressive liver fibrosis results in cirrhosis, hepatocellular carcinoma (HCC), and various liver-related complications in essentially all chronic liver diseases. Assessment of liver fibrosis allows clinicians to determine the prognosis, need of treatment, disease progression, and response to treatment in patients with chronic liver disease. Liver biopsy has been the gold standard in last few decades and most adopted diagnostic tool in clinical trials. Nonetheless, it is impractical to apply the test in a large number of patients or to do it serially. Hence, various non-invasive assessments have been developed and adopted in some international management guidelines. Liver stiffness measurement (LSM) with transient elastography is one of the most widely validated non-invasive assessments for liver fibrosis. It is an accurate and reproducible method to predict advanced fibrosis in chronic hepatitis B. Using transient elastography, it is possible to perform repeated liver fibrosis assessments on a large number of asymptomatic patients. The key challenge of his tool is the confounding effect of alanine aminotransferase (ALT) level, such that decrease in LSM may only reflect ALT normalization, hence not accurate enough to indicate regression of liver fibrosis. This may be partially handled by combining LSM with a serum-based formula, which is independent of ALT such as the Forns index and enhanced liver fibrosis test. An LSM-based HCC risk score is useful to prioritize patients for HCC surveillance.
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Affiliation(s)
- Grace Lai-Hung Wong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Sha Tin, Hong Kong.,Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Sha Tin, Hong Kong.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Sha Tin, Hong Kong
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Kennedy P, Wagner M, Castéra L, Hong CW, Johnson CL, Sirlin CB, Taouli B. Quantitative Elastography Methods in Liver Disease: Current Evidence and Future Directions. Radiology 2018; 286:738-763. [PMID: 29461949 DOI: 10.1148/radiol.2018170601] [Citation(s) in RCA: 197] [Impact Index Per Article: 28.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Chronic liver diseases often result in the development of liver fibrosis and ultimately, cirrhosis. Treatment strategies and prognosis differ greatly depending on the severity of liver fibrosis, thus liver fibrosis staging is clinically relevant. Traditionally, liver biopsy has been the method of choice for fibrosis evaluation. Because of liver biopsy limitations, noninvasive methods have become a key research interest in the field. Elastography enables the noninvasive measurement of tissue mechanical properties through observation of shear-wave propagation in the tissue of interest. Increasing fibrosis stage is associated with increased liver stiffness, providing a discriminatory feature that can be exploited by elastographic methods. Ultrasonographic (US) and magnetic resonance (MR) imaging elastographic methods are commercially available, each with their respective strengths and limitations. Here, the authors review the technical basis, acquisition techniques, and results and limitations of US- and MR-based elastography techniques. Diagnostic performance in the most common etiologies of chronic liver disease will be presented. Reliability, reproducibility, failure rate, and emerging advances will be discussed. © RSNA, 2018 Online supplemental material is available for this article.
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Affiliation(s)
- Paul Kennedy
- From the Translational and Molecular Imaging Institute (P.K., B.T.) and Department of Radiology (B.T.), Icahn School of Medicine at Mount Sinai, 1470 Madison Ave, New York, NY 10029; Department of Radiology, Sorbonne Universités, UPMC, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France (M.W.); Department of Hepatology, University Paris-VII, Hôpital Beaujon, Clichy, France (L.C.); Liver Imaging Group, Department of Radiology, University of California-San Diego, San Diego, Calif (C.W.H., C.B.S.); Department of Biomedical Engineering, University of Delaware, Newark, Del (C.L.J.)
| | - Mathilde Wagner
- From the Translational and Molecular Imaging Institute (P.K., B.T.) and Department of Radiology (B.T.), Icahn School of Medicine at Mount Sinai, 1470 Madison Ave, New York, NY 10029; Department of Radiology, Sorbonne Universités, UPMC, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France (M.W.); Department of Hepatology, University Paris-VII, Hôpital Beaujon, Clichy, France (L.C.); Liver Imaging Group, Department of Radiology, University of California-San Diego, San Diego, Calif (C.W.H., C.B.S.); Department of Biomedical Engineering, University of Delaware, Newark, Del (C.L.J.)
| | - Laurent Castéra
- From the Translational and Molecular Imaging Institute (P.K., B.T.) and Department of Radiology (B.T.), Icahn School of Medicine at Mount Sinai, 1470 Madison Ave, New York, NY 10029; Department of Radiology, Sorbonne Universités, UPMC, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France (M.W.); Department of Hepatology, University Paris-VII, Hôpital Beaujon, Clichy, France (L.C.); Liver Imaging Group, Department of Radiology, University of California-San Diego, San Diego, Calif (C.W.H., C.B.S.); Department of Biomedical Engineering, University of Delaware, Newark, Del (C.L.J.)
| | - Cheng William Hong
- From the Translational and Molecular Imaging Institute (P.K., B.T.) and Department of Radiology (B.T.), Icahn School of Medicine at Mount Sinai, 1470 Madison Ave, New York, NY 10029; Department of Radiology, Sorbonne Universités, UPMC, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France (M.W.); Department of Hepatology, University Paris-VII, Hôpital Beaujon, Clichy, France (L.C.); Liver Imaging Group, Department of Radiology, University of California-San Diego, San Diego, Calif (C.W.H., C.B.S.); Department of Biomedical Engineering, University of Delaware, Newark, Del (C.L.J.)
| | - Curtis L Johnson
- From the Translational and Molecular Imaging Institute (P.K., B.T.) and Department of Radiology (B.T.), Icahn School of Medicine at Mount Sinai, 1470 Madison Ave, New York, NY 10029; Department of Radiology, Sorbonne Universités, UPMC, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France (M.W.); Department of Hepatology, University Paris-VII, Hôpital Beaujon, Clichy, France (L.C.); Liver Imaging Group, Department of Radiology, University of California-San Diego, San Diego, Calif (C.W.H., C.B.S.); Department of Biomedical Engineering, University of Delaware, Newark, Del (C.L.J.)
| | - Claude B Sirlin
- From the Translational and Molecular Imaging Institute (P.K., B.T.) and Department of Radiology (B.T.), Icahn School of Medicine at Mount Sinai, 1470 Madison Ave, New York, NY 10029; Department of Radiology, Sorbonne Universités, UPMC, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France (M.W.); Department of Hepatology, University Paris-VII, Hôpital Beaujon, Clichy, France (L.C.); Liver Imaging Group, Department of Radiology, University of California-San Diego, San Diego, Calif (C.W.H., C.B.S.); Department of Biomedical Engineering, University of Delaware, Newark, Del (C.L.J.)
| | - Bachir Taouli
- From the Translational and Molecular Imaging Institute (P.K., B.T.) and Department of Radiology (B.T.), Icahn School of Medicine at Mount Sinai, 1470 Madison Ave, New York, NY 10029; Department of Radiology, Sorbonne Universités, UPMC, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France (M.W.); Department of Hepatology, University Paris-VII, Hôpital Beaujon, Clichy, France (L.C.); Liver Imaging Group, Department of Radiology, University of California-San Diego, San Diego, Calif (C.W.H., C.B.S.); Department of Biomedical Engineering, University of Delaware, Newark, Del (C.L.J.)
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