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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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Maino C, Vernuccio F, Cannella R, Cristoferi L, Franco PN, Carbone M, Cortese F, Faletti R, De Bernardi E, Inchingolo R, Gatti M, Ippolito D. Non-invasive imaging biomarkers in chronic liver disease. Eur J Radiol 2024; 181:111749. [PMID: 39317002 DOI: 10.1016/j.ejrad.2024.111749] [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: 07/28/2024] [Revised: 08/20/2024] [Accepted: 09/17/2024] [Indexed: 09/26/2024]
Abstract
Chronic liver disease (CLD) is a global and worldwide clinical challenge, considering that different underlying liver entities can lead to hepatic dysfunction. In the past, blood tests and clinical evaluation were the main noninvasive tools used to detect, diagnose and follow-up patients with CLD; in case of clinical suspicion of CLD or unclear diagnosis, liver biopsy has been considered as the reference standard to rule out different chronic liver conditions. Nowadays, noninvasive tests have gained a central role in the clinical pathway. Particularly, liver stiffness measurement (LSM) and cross-sectional imaging techniques can provide transversal information to clinicians, helping them to correctly manage, treat and follow patients during time. Cross-sectional imaging techniques, namely computed tomography (CT) and magnetic resonance imaging (MRI), have plenty of potential. Both techniques allow to compute the liver surface nodularity (LSN), associated with CLDs and risk of decompensation. MRI can also help quantify fatty liver infiltration, mainly with the proton density fat fraction (PDFF) sequences, and detect and quantify fibrosis, especially thanks to elastography (MRE). Advanced techniques, such as intravoxel incoherent motion (IVIM), T1- and T2- mapping are promising tools for detecting fibrosis deposition. Furthermore, the injection of hepatobiliary contrast agents has gained an important role not only in liver lesion characterization but also in assessing liver function, especially in CLDs. Finally, the broad development of radiomics signatures, applied to CT and MR, can be considered the next future approach to CLDs. The aim of this review is to provide a comprehensive overview of the current advancements and applications of both invasive and noninvasive imaging techniques in the evaluation and management of CLD.
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Affiliation(s)
- Cesare Maino
- Department of Diagnostic Radiology, Fondazione IRCCS San Gerardo dei Tintori, Via Pergolesi 33, 20900 Monza, MB, Italy.
| | - Federica Vernuccio
- Section of Radiology - Department of Biomedicine, Neuroscience and Advanced Diagnostics (BiND), University of Palermo, Via del Vespro 129, Palermo 90127, Italy
| | - Roberto Cannella
- Section of Radiology - Department of Biomedicine, Neuroscience and Advanced Diagnostics (BiND), University of Palermo, Via del Vespro 129, Palermo 90127, Italy
| | - Laura Cristoferi
- Department of Gastroenterlogy, Fondazione IRCCS San Gerardo dei Tintori, Via Pergolesi 33, 20900 Monza, MB, Italy
| | - Paolo Niccolò Franco
- Department of Diagnostic Radiology, Fondazione IRCCS San Gerardo dei Tintori, Via Pergolesi 33, 20900 Monza, MB, Italy
| | - Marco Carbone
- Department of Gastroenterlogy, ASST Grande Ospedale Metropolitano Niguarda, Pizza dell'Ospedale Maggiore 3, 20100 Milano, MI, Italy
| | - Francesco Cortese
- Interventional Radiology Unit, "F. Miulli" General Hospital, Acquaviva delle Fonti 70021, Italy
| | - Riccardo Faletti
- Department of Surgical Sciences, University of Turin, Turin 10126, Italy
| | - Elisabetta De Bernardi
- Department of Medicine and Surgery - University of Milano Bicocca, Via Cadore 33, 20090 Monza, MB, Italy
| | - Riccardo Inchingolo
- Interventional Radiology Unit, "F. Miulli" General Hospital, Acquaviva delle Fonti 70021, Italy
| | - Marco Gatti
- Department of Surgical Sciences, University of Turin, Turin 10126, Italy
| | - Davide Ippolito
- Department of Diagnostic Radiology, Fondazione IRCCS San Gerardo dei Tintori, Via Pergolesi 33, 20900 Monza, MB, Italy; Department of Medicine and Surgery - University of Milano Bicocca, Via Cadore 33, 20090 Monza, MB, Italy
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3
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Zhang Y, Rao Y, Lu J, Wang J, Ker DFE, Zhou J, Wang DM. The influence of biophysical niche on tumor-associated macrophages in liver cancer. Hepatol Commun 2024; 8:e0569. [PMID: 39470328 PMCID: PMC11524744 DOI: 10.1097/hc9.0000000000000569] [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: 03/04/2024] [Accepted: 08/30/2024] [Indexed: 10/30/2024] Open
Abstract
HCC, the most common type of primary liver cancer, is a leading cause of cancer-related mortality worldwide. Although the advancement of immunotherapies by immune checkpoint inhibitors (ICIs) that target programmed cell death 1 or programmed cell death 1-ligand 1 has revolutionized the treatment for HCC, the majority is still not beneficial. Accumulating evidence has pointed out that the potent immunosuppressive tumor microenvironment in HCC poses a great challenge to ICI therapeutic efficacy. As a key component in tumor microenvironment, tumor-associated macrophages (TAMs) play vital roles in HCC development, progression, and ICI low responsiveness. Mechanistically, TAM can promote cancer invasion and metastasis, angiogenesis, epithelial-mesenchymal transition, maintenance of stemness, and most importantly, immunosuppression. Targeting TAMs, therefore, represents an opportunity to enhance the ICI therapeutic efficacy in patients with HCC. While previous research has primarily focused on biochemical cues influencing macrophages, emerging evidence highlights the critical role of biophysical signals, such as substrate stiffness, topography, and external forces. In this review, we summarize the influence of biophysical characteristics within the tumor microenvironment that regulate the phenotype and function of TAMs in HCC pathogenesis and progression. We also explore the possible mechanisms and discuss the potential of manipulating biophysical cues in regulating TAM for HCC therapy. By gaining a deeper understanding of how macrophages sense and respond to mechanical forces, we may potentially usher in a path toward a curative approach for combinatory cancer immunotherapies.
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Affiliation(s)
- Ying Zhang
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong, SAR, China
- Institute of Tissue Engineering and Regenerative Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong, SAR, China
- Institute of Precision Medicine, Jining Medical University, Jining, China
| | - Ying Rao
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong, SAR, China
- Institute of Tissue Engineering and Regenerative Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong, SAR, China
| | - Jiahuan Lu
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong, SAR, China
- Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Sha Tin, Hong Kong, SAR, China
| | - Jiyu Wang
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong, SAR, China
- Institute of Tissue Engineering and Regenerative Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong, SAR, China
| | - Dai Fei Elmer Ker
- Center for Neuromusculoskeletal Restorative Medicine, Hong Kong Science Park, Sha Tin, Hong Kong, SAR, China
- Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, SAR, China
| | - Jingying Zhou
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong, SAR, China
| | - Dan Michelle Wang
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong, SAR, China
- Institute of Tissue Engineering and Regenerative Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong, SAR, China
- Center for Neuromusculoskeletal Restorative Medicine, Hong Kong Science Park, Sha Tin, Hong Kong, SAR, China
- Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Sha Tin, Hong Kong, SAR, China
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Petroni ML, Perazza F, Marchesini G. Breakthrough in the Treatment of Metabolic Associated Steatotic Liver Disease: Is it all over? Dig Liver Dis 2024; 56:1442-1451. [PMID: 38972788 DOI: 10.1016/j.dld.2024.04.021] [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: 04/11/2024] [Accepted: 04/22/2024] [Indexed: 07/09/2024]
Abstract
On March 14, 2024, after more than 25 years of intense research and a long series of failures, the Food and Drug Administration approved resmetirom as first drug for the treatment of non-alcoholic steatohepatitis (NASH) with fibrosis (now Metabolic-Associated Steatotic Liver Disease - MASLD). The present review covers this difficult process, finally providing a drug to complement lifestyle intervention, that has long been the sole approved therapeutic intervention. However, the availability of a drug shown to reduce disease progression in advanced stages of diseases opens a series of questions that deserve even more intense research. How to continue ongoing trials? How to generate an appropriate use of resmetirom in the community, limiting treatment according to predefined criteria and according to individual risk assessment? How to guarantee that both hepatic and non-hepatic comorbidities are appropriately targeted? How to define cost-effective strategies that might prevent the generation of unacceptable differences within the population, given the high costs of novel drugs and the extremely high numbers of candidates to treatment? Only a close surveillance of drug use in the real world, generated by insurance databases and national healthcare system registries, might provide adequate answers to these compelling questions.
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Affiliation(s)
- Maria Letizia Petroni
- Unit of Clinical Nutrition and Metabolism, IRCCS-Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Federica Perazza
- Unit of Clinical Nutrition and Metabolism, IRCCS-Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; Alma Mater University, Bologna, Italy
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Duarte-Rojo A, Patel K, Rockey DC. Noninvasive assessment of liver fibrosis and portal hypertension. Curr Opin Gastroenterol 2024; 40:148-155. [PMID: 38547334 DOI: 10.1097/mog.0000000000001019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/04/2024]
Abstract
PURPOSE OF REVIEW The result of ongoing liver injury - and disease, regardless of cause - is fibrosis, and fibrosis appears to be a critically important result of ongoing injury. Further, in a number of different liver diseases, the presence of fibrosis has prognostic value. Therefore, the assessment of fibrosis is of critical clinical importance. Given the importance of fibrosis, there has been a rapid evolution in the use of noninvasive liver tests. This review highlights a number of the core principles surrounding. RECENT FINDINGS The use of noninvasive test has progressed rapidly over the last decade and data are rapidly accumulating. New terminology has been adapted by the American Association for the Study of Liver Disease (AASLD) for noninvasive assessment of liver disease and termed 'NILDA' (Non-Invasive Liver Disease Assessment). Blood based such as APRI and or FIB-4 and imaging tests such as liver stiffness measurement (LSM) have moderate to high degrees of accuracy for detection of advanced liver fibrosis (≥ F2) and even higher accuracy for detection of severe fibrosis (F4 or cirrhosis). NILDA are particularly effective at the ends of the liver disease spectrum. For example, a very low LSM (less than 7 kPa) essentially excludes significant fibrosis or portal hypertension, and a very high LSM (> 25 kPa) makes significant fibrosis with portal hypertension (cirrhosis) highly likely. SUMMARY NILDA are currently front and center in terms of assessment of the severity of liver disease. In all patients with known or suspected liver disease, noninvasive blood tests, including APRI and or FIB-4, should be the initial choice to assess the severity of liver fibrosis and/or portal hypertension. In most patients, these tests should be followed with imaging evaluation. The most commonly available imaging is LSM, which appears to be more accurate in predicting fibrosis severity, and is superior to blood tests in the assessment of portal hypertension. In situations in which there is diagnostic uncertainly, liver biopsy with or without HVPG remains an important consideration.
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Affiliation(s)
- Andres Duarte-Rojo
- Division of Gastroenterology and Hepatology, Northwestern Medicine, Feinberg School of Medicine, Chicago, Illinois
| | - Keyur Patel
- Division of Gastroenterology and Hepatology, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Don C Rockey
- Medical University of South Carolina Digestive Disease Research Center and the Medical University of South Carolina, Charleston, South Carolina, USA
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6
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Bazerbachi F, Baroud S, Levy MJ, Maselli DB, Vargas EJ, Bofill-Garcia A, Law RJ, Chandrasekhara V, Storm AC, Gleeson FC, Rajan E, Iyer PG, Watt KD, Abu Dayyeh BK. Celiac artery mesenteric fat measurement with endosonography (CAMEUS) reliably correlates with obesity and related comorbidities. Gastroenterol Rep (Oxf) 2024; 12:goae039. [PMID: 38681751 PMCID: PMC11052652 DOI: 10.1093/gastro/goae039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Revised: 02/29/2024] [Accepted: 03/20/2024] [Indexed: 05/01/2024] Open
Abstract
Background Visceral fat represents a metabolically active entity linked to adverse metabolic sequelae of obesity. We aimed to determine if celiac artery mesenteric fat thickness can be reliably measured during endoscopic ultrasound (EUS), and if these measurements correlate with metabolic disease burden. Methods This was a retrospective analysis of patients who underwent celiac artery mesenteric fat measurement with endosonography (CAMEUS) measurement at a tertiary referral center, and a validation prospective trial of patients with obesity and nonalcoholic steatohepatitis who received paired EUS exams with CAMEUS measurement before and after six months of treatment with an intragastric balloon. Results CAMEUS was measured in 154 patients [56.5% females, mean age 56.5 ± 18.0 years, body mass index (BMI) 29.8 ± 8.0 kg/m2] and was estimated at 14.7 ± 6.5 mm. CAMEUS better correlated with the presence of non-alcoholic fatty liver disease (NAFLD) (R2 = 0.248, P < 0.001) than BMI (R2 = 0.153, P < 0.001), and significantly correlated with metabolic parameters and diseases. After six months of intragastric balloon placement, the prospective cohort experienced 11.7% total body weight loss, 1.3 points improvement in hemoglobin A1c (P = 0.001), and a 29.4% average decrease in CAMEUS (-6.4 ± 5.2 mm, P < 0.001). CAMEUS correlated with improvements in weight (R2 = 0.368), aspartate aminotransferase to platelet ratio index (R2 = 0.138), and NAFLD activity score (R2 = 0.156) (all P < 0.05). Conclusions CAMEUS is a novel measure that is significantly correlated with critical metabolic indices and can be easily captured during routine EUS to risk-stratify susceptible patients. This station could allow for EUS access to sampling and therapeutics of this metabolic region.
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Affiliation(s)
- Fateh Bazerbachi
- CentraCare, Interventional Endoscopy Program, St Cloud Hospital, St. Cloud, MN, USA
- Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, Minneapolis, MN, USA
| | - Serge Baroud
- Department of Internal Medicine, MetroHealth Medical Center and Case Western Reserve University, Cleveland, OH, USA
| | - Michael J Levy
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Daniel B Maselli
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Eric J Vargas
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | | | - Ryan J Law
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | | | - Andrew C Storm
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Ferga C Gleeson
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Elizabeth Rajan
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Prasad G Iyer
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Kymberly D Watt
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Barham K Abu Dayyeh
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
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Zoncapè M, Liguori A, Tsochatzis EA. Non-invasive testing and risk-stratification in patients with MASLD. Eur J Intern Med 2024; 122:11-19. [PMID: 38246813 DOI: 10.1016/j.ejim.2024.01.013] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Revised: 01/12/2024] [Accepted: 01/14/2024] [Indexed: 01/23/2024]
Abstract
The development and validation of non-invasive fibrosis tests (NITs) has changed clinical practice in Hepatology over the last 15 years. Metabolic associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is the most prevalent liver disease in western countries, with up to a third of the unselected adult population affected. In this article, we review the use of NITs in the diagnosis and staging of MASLD. We discuss their use in the diagnosis of steatosis, steatohepatitis and fibrosis and critically evaluate recently published data. These NITs include a variety of approaches, such as serum markers like FIB-4, pro-C3 and ELF, imaging techniques like Fibroscan® and MRE, and combined scores like Agile 3+ and Agile 4, offering a range of options for healthcare providers. Furthermore, these non-invasive tests also serve as valuable prognostic tools, allowing for better risk assessment and improved patient management, particularly in predicting liver-related events and overall mortality.
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Affiliation(s)
- Mirko Zoncapè
- Sheila Sherlock Liver Unit, Royal Free Hospital, London, UK; UCL Institute for Liver and Digestive Health, University College London, UK; Liver Unit, Department of Medicine, University of Verona and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Antonio Liguori
- Sheila Sherlock Liver Unit, Royal Free Hospital, London, UK; UCL Institute for Liver and Digestive Health, University College London, UK; Medical and Surgical Sciences Department, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Emmanuel A Tsochatzis
- Sheila Sherlock Liver Unit, Royal Free Hospital, London, UK; UCL Institute for Liver and Digestive Health, University College London, UK.
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Gioia S, Baiocchini A, d'Amati G, Tavano D, Ridola L, Nardelli S, de Felice I, Lapenna L, Merli M, Pellicelli A, Giannelli V, Riggio O. Porto-sinusoidal vascular disorder (PSVD): Application of new diagnostic criteria in a multicenter cohort of patients. Dig Liver Dis 2024; 56:291-296. [PMID: 37550100 DOI: 10.1016/j.dld.2023.07.023] [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: 05/29/2023] [Revised: 07/14/2023] [Accepted: 07/21/2023] [Indexed: 08/09/2023]
Abstract
BACKGROUND AND AIM The term porto-sinusoidal vascular disorder (PSVD) was recently proposed to replace that of idiopathic non-cirrhotic portal hypertension (INCPH) to describe patients with typical histological lesions in absence of cirrhosis, irrespective of the presence/absence of portal hypertension (PH), and new diagnostic criteria were defined. The study aimed to compare the applicability between the diagnostic criteria of PSVD and those of INCPH. MATERIALS AND METHODS 53 patients affected by PSVD were enrolled. Biochemical, clinical, ultrasound and histological data, the presence and type of associated diseases were recorded in a database. According to the new criteria, histological data and signs of PH were divided into specific and non-specific. Percutaneous and transjugular biopsies were compared to establish the usability of the two methods for diagnostic purposes. RESULTS In 85% of the patients the diagnosis of PSVD was obtained by applying the first criterion (25 had specific histological signs with specific signs of PH); one patient presented with specific histological signs but no PH. In 8 patients the diagnosis was obtained by applying the second criterion. 19% of patients had portal vein thrombosis. Finally, the prevalence of the various histological lesions was similar between the patients submitted to percutaneous and transjugular liver biopsy. CONCLUSIONS The study confirms that the diagnostic criteria of PSVD lead to the inclusion of a greater number of patients than INCPH.
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Affiliation(s)
- Stefania Gioia
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy.
| | - Andrea Baiocchini
- Department of Pathology, San Camillo Forlanini Hospital, Rome, Italy
| | - Giulia d'Amati
- Department of Radiological, Oncological, and Pathological Sciences, Sapienza University of Rome, Rome, Italy
| | - Daniele Tavano
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Lorenzo Ridola
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Silvia Nardelli
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Ilaria de Felice
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Lucia Lapenna
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Manuela Merli
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Adriano Pellicelli
- Liver Unit, Department of Liver Transplant, Azienda Ospedaliera San Camillo Forlanini, Rome, Italy
| | - Valerio Giannelli
- Liver Unit, Department of Liver Transplant, Azienda Ospedaliera San Camillo Forlanini, Rome, Italy
| | - Oliviero Riggio
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
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9
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Marti-Aguado D, Arnouk J, Liang JX, Lara-Romero C, Behari J, Furlan A, Jimenez-Pastor A, Ten-Esteve A, Alfaro-Cervello C, Bauza M, Gallen-Peris A, Gimeno-Torres M, Merino-Murgui V, Perez-Girbes A, Benlloch S, Pérez-Rojas J, Puglia V, Ferrández-Izquierdo A, Aguilera V, Giesteira B, França M, Monton C, Escudero-García D, Alberich-Bayarri Á, Serra MA, Bataller R, Romero-Gomez M, Marti-Bonmati L. Development and validation of an image biomarker to identify metabolic dysfunction associated steatohepatitis: MR-MASH score. Liver Int 2024; 44:202-213. [PMID: 37904633 DOI: 10.1111/liv.15766] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Revised: 09/11/2023] [Accepted: 10/08/2023] [Indexed: 11/01/2023]
Abstract
BACKGROUND AND AIMS Diagnosis of metabolic dysfunction-associated steatohepatitis (MASH) requires histology. In this study, a magnetic resonance imaging (MRI) score was developed and validated to identify MASH in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Secondarily, a screening strategy for MASH diagnosis was investigated. METHODS This prospective multicentre study included 317 patients with biopsy-proven MASLD and contemporaneous MRI. The discovery cohort (Spain, Portugal) included 194 patients. NAFLD activity score (NAS) and fibrosis were assessed with the NASH-CRN histologic system. MASH was defined by the presence of steatosis, lobular inflammation, and ballooning, with NAS ≥4 with or without fibrosis. An MRI-based composite biomarker of Proton Density Fat Fraction and waist circumference (MR-MASH score) was developed. Findings were afterwards validated in an independent cohort (United States, Spain) with different MRI protocols. RESULTS In the derivation cohort, 51% (n = 99) had MASH. The MR-MASH score identified MASH with an AUC = .88 (95% CI .83-.93) and strongly correlated with NAS (r = .69). The MRI score lower cut-off corresponded to 88% sensitivity with 86% NPV, while the upper cut-off corresponded to 92% specificity with 87% PPV. MR-MASH was validated with an AUC = .86 (95% CI .77-.92), 91% sensitivity (lower cut-off) and 87% specificity (upper cut-off). A two-step screening strategy with sequential MR-MASH examination performed in patients with indeterminate-high FIB-4 or transient elastography showed an 83-84% PPV to identify MASH. The AUC of MR-MASH was significantly higher than that of the FAST score (p < .001). CONCLUSIONS The MR-MASH score has clinical utility in the identification and management of patients with MASH at risk of progression.
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Affiliation(s)
- David Marti-Aguado
- Digestive Disease Department, Clinic University Hospital, INCLIVA Health Research Institute, Valencia, Spain
- Biomedical Imaging Research Group (GIBI230), La Fe Health Research Institute, and Imaging La Fe node at Distributed Network for Biomedical Imaging (ReDIB) Unique Scientific and Technical Infrastructures (ICTS), Valencia, Spain
| | - Joud Arnouk
- Division of Gastroenterology, Hepatology and Nutrition, Center for Liver Diseases, Pittsburgh Liver Research Center, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Jia-Xu Liang
- Digestive Diseases Department, CIBERehd, Virgen del Rocio University Hospital, Seville, Spain
- Institute of Biomedicine of Seville (HUVR/CSIC/US), Department of Medicine, University of Seville, Seville, Spain
| | - Carmen Lara-Romero
- Digestive Diseases Department, CIBERehd, Virgen del Rocio University Hospital, Seville, Spain
- Institute of Biomedicine of Seville (HUVR/CSIC/US), Department of Medicine, University of Seville, Seville, Spain
| | - Jaideep Behari
- Division of Gastroenterology, Hepatology and Nutrition, Center for Liver Diseases, Pittsburgh Liver Research Center, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Alessandro Furlan
- Division of Abdominal Imaging, Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Ana Jimenez-Pastor
- Biomedical Imaging Research Group (GIBI230), La Fe Health Research Institute, and Imaging La Fe node at Distributed Network for Biomedical Imaging (ReDIB) Unique Scientific and Technical Infrastructures (ICTS), Valencia, Spain
- Quantitative Imaging Biomarkers in Medicine, QUIBIM SL, Valencia, Spain
| | - Amadeo Ten-Esteve
- Biomedical Imaging Research Group (GIBI230), La Fe Health Research Institute, and Imaging La Fe node at Distributed Network for Biomedical Imaging (ReDIB) Unique Scientific and Technical Infrastructures (ICTS), Valencia, Spain
| | - Clara Alfaro-Cervello
- Pathology Department, Clinic University Hospital, INCLIVA Health Research Institute, Valencia, Spain
- Faculty of Medicine, University of Valencia, Valencia, Spain
| | - Mónica Bauza
- Pathology Department, La Fe University and Polytechnic Hospital, Valencia, Spain
| | - Ana Gallen-Peris
- Digestive Disease Department, Hospital Arnau de Vilanova, Valencia, Spain
| | - Marta Gimeno-Torres
- Digestive Disease Department, La Fe University and Polytechnic Hospital, Valencia, Spain
| | - Víctor Merino-Murgui
- Digestive Disease Department, Clinic University Hospital, INCLIVA Health Research Institute, Valencia, Spain
| | - Alexandre Perez-Girbes
- Biomedical Imaging Research Group (GIBI230), La Fe Health Research Institute, and Imaging La Fe node at Distributed Network for Biomedical Imaging (ReDIB) Unique Scientific and Technical Infrastructures (ICTS), Valencia, Spain
- Radiology Department, La Fe University and Polytechnic Hospital, Valencia, Spain
| | - Salvador Benlloch
- Digestive Disease Department, Hospital Arnau de Vilanova, Valencia, Spain
- CIBERehd, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Madrid, Spain
| | - Judith Pérez-Rojas
- Pathology Department, La Fe University and Polytechnic Hospital, Valencia, Spain
| | - Víctor Puglia
- Pathology Department, Hospital Arnau de Vilanova, Valencia, Spain
| | - Antonio Ferrández-Izquierdo
- Pathology Department, Clinic University Hospital, INCLIVA Health Research Institute, Valencia, Spain
- Faculty of Medicine, University of Valencia, Valencia, Spain
| | - Victoria Aguilera
- CIBERehd, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Madrid, Spain
- Hepatology and Liver Transplantation Unit, La Fe University and Polytechnic Hospital, Valencia, Spain
| | - Bruno Giesteira
- Radiology Department, Centro Hospitalar Universitário do Porto, Instituto de Ciências Biomédicas de Abel Salazar, University of Porto, Porto, Portugal
| | - Manuela França
- Radiology Department, Centro Hospitalar Universitário do Porto, Instituto de Ciências Biomédicas de Abel Salazar, University of Porto, Porto, Portugal
| | - Cristina Monton
- Digestive Disease Department, Clinic University Hospital, INCLIVA Health Research Institute, Valencia, Spain
| | - Desamparados Escudero-García
- Digestive Disease Department, Clinic University Hospital, INCLIVA Health Research Institute, Valencia, Spain
- Faculty of Medicine, University of Valencia, Valencia, Spain
| | - Ángel Alberich-Bayarri
- Biomedical Imaging Research Group (GIBI230), La Fe Health Research Institute, and Imaging La Fe node at Distributed Network for Biomedical Imaging (ReDIB) Unique Scientific and Technical Infrastructures (ICTS), Valencia, Spain
- Quantitative Imaging Biomarkers in Medicine, QUIBIM SL, Valencia, Spain
| | - Miguel A Serra
- Digestive Disease Department, Clinic University Hospital, INCLIVA Health Research Institute, Valencia, Spain
- Faculty of Medicine, University of Valencia, Valencia, Spain
| | - Ramon Bataller
- Division of Gastroenterology, Hepatology and Nutrition, Center for Liver Diseases, Pittsburgh Liver Research Center, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Manuel Romero-Gomez
- Digestive Diseases Department, CIBERehd, Virgen del Rocio University Hospital, Seville, Spain
- Institute of Biomedicine of Seville (HUVR/CSIC/US), Department of Medicine, University of Seville, Seville, Spain
- University of Seville, Seville, Spain
| | - Luis Marti-Bonmati
- Biomedical Imaging Research Group (GIBI230), La Fe Health Research Institute, and Imaging La Fe node at Distributed Network for Biomedical Imaging (ReDIB) Unique Scientific and Technical Infrastructures (ICTS), Valencia, Spain
- Radiology Department, La Fe University and Polytechnic Hospital, Valencia, Spain
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Felli E, Selicean S, Guixé-Muntet S, Wang C, Bosch J, Berzigotti A, Gracia-Sancho J. Mechanobiology of portal hypertension. JHEP Rep 2023; 5:100869. [PMID: 37841641 PMCID: PMC10568428 DOI: 10.1016/j.jhepr.2023.100869] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Revised: 06/28/2023] [Accepted: 07/03/2023] [Indexed: 10/17/2023] Open
Abstract
The interplay between mechanical stimuli and cellular mechanobiology orchestrates the physiology of tissues and organs in a dynamic balance characterized by constant remodelling and adaptative processes. Environmental mechanical properties can be interpreted as a complex set of information and instructions that cells read continuously, and to which they respond. In cirrhosis, chronic inflammation and injury drive liver cells dysfunction, leading to excessive extracellular matrix deposition, sinusoidal pseudocapillarization, vascular occlusion and parenchymal extinction. These pathological events result in marked remodelling of the liver microarchitecture, which is cause and result of abnormal environmental mechanical forces, triggering and sustaining the long-standing and progressive process of liver fibrosis. Multiple mechanical forces such as strain, shear stress, and hydrostatic pressure can converge at different stages of the disease until reaching a point of no return where the fibrosis is considered non-reversible. Thereafter, reciprocal communication between cells and their niches becomes the driving force for disease progression. Accumulating evidence supports the idea that, rather than being a passive consequence of fibrosis and portal hypertension (PH), mechanical force-mediated pathways could themselves represent strategic targets for novel therapeutic approaches. In this manuscript, we aim to provide a comprehensive review of the mechanobiology of PH, by furnishing an introduction on the most important mechanisms, integrating these concepts into a discussion on the pathogenesis of PH, and exploring potential therapeutic strategies.
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Affiliation(s)
- Eric Felli
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland
- Department for BioMedical Research, Visceral Surgery and Medicine, University of Bern, Switzerland
| | - Sonia Selicean
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland
- Department for BioMedical Research, Visceral Surgery and Medicine, University of Bern, Switzerland
| | - Sergi Guixé-Muntet
- Liver Vascular Biology Research Group, IDIBAPS Biomedical Research Institute, CIBEREHD, Spain
| | - Cong Wang
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland
- Department for BioMedical Research, Visceral Surgery and Medicine, University of Bern, Switzerland
| | - Jaume Bosch
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland
- Department for BioMedical Research, Visceral Surgery and Medicine, University of Bern, Switzerland
- Liver Vascular Biology Research Group, IDIBAPS Biomedical Research Institute, CIBEREHD, Spain
| | - Annalisa Berzigotti
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland
- Department for BioMedical Research, Visceral Surgery and Medicine, University of Bern, Switzerland
| | - Jordi Gracia-Sancho
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland
- Department for BioMedical Research, Visceral Surgery and Medicine, University of Bern, Switzerland
- Liver Vascular Biology Research Group, IDIBAPS Biomedical Research Institute, CIBEREHD, Spain
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11
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Man S, Deng Y, Ma Y, Fu J, Bao H, Yu C, Lv J, Liu H, Wang B, Li L. Prevalence of Liver Steatosis and Fibrosis in the General Population and Various High-Risk Populations: A Nationwide Study With 5.7 Million Adults in China. Gastroenterology 2023; 165:1025-1040. [PMID: 37380136 DOI: 10.1053/j.gastro.2023.05.053] [Citation(s) in RCA: 64] [Impact Index Per Article: 32.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Revised: 05/15/2023] [Accepted: 05/22/2023] [Indexed: 06/30/2023]
Abstract
BACKGROUND & AIMS This study aimed to estimate the prevalence of liver steatosis and fibrosis in the general population and populations with potential risk factors in China, so as to inform policies for the screening and management of fatty liver disease and liver fibrosis in general and high-risk populations. METHODS This cross-sectional, population-based, nationwide study was based on the database of the largest health check-up chain in China. Adults from 30 provinces who underwent a check-up between 2017 and 2022 were included. Steatosis and fibrosis were assessed and graded by transient elastography. Overall and stratified prevalence was estimated among the general population and various subpopulations with demographic, cardiovascular, and chronic liver disease risk factors. A mixed effect regression model was used to examine predictors independently associated with steatosis and fibrosis. RESULTS In 5,757,335 participants, the prevalence of steatosis, severe steatosis, advanced fibrosis, and cirrhosis was 44.39%, 10.57%, 2.85%, and 0.87%, respectively. Participants who were male, with obesity, diabetes, hypertension, dyslipidemia, metabolic syndrome, or elevated alanine aminotransferase or aspartate aminotransferase had a significantly higher prevalence of all grades of steatosis and fibrosis, and those with fatty liver, decreased albumin or platelet count, and hepatitis B virus infection also had a significantly higher prevalence of fibrosis than their healthy counterparts. Most cardiovascular and chronic liver disease risk factors were independent predictors for steatosis and fibrosis, except for dyslipidemia for fibrosis. CONCLUSIONS A substantial burden of liver steatosis and fibrosis was found in China. Our study provides evidence for shaping future pathways for screening and risk stratification of liver steatosis and fibrosis in the general population. The findings of this study highlight that fatty liver and liver fibrosis should be included in disease management programs as targets for screening and regular monitoring in high-risk populations, especially in those with diabetes.
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Affiliation(s)
- Sailimai Man
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China; Meinian Institute of Health, Beijing, China; Peking University Health Science Center Meinian Public Health Institute, Beijing, China; Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing, China
| | - Yuhan Deng
- Meinian Institute of Health, Beijing, China; Department of Social Medicine and Health Education, School of Public Health, Peking University, Beijing, China
| | - Yuan Ma
- Meinian Institute of Health, Beijing, China; School of Population Medicine and Public Health, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jingzhu Fu
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China; Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing, China
| | - Heling Bao
- Institute of Medical Information, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Canqing Yu
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China; Peking University Health Science Center Meinian Public Health Institute, Beijing, China; Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing, China; Peking University Center for Public Health and Epidemic Preparedness & Response, Beijing, China
| | - Jun Lv
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China; Peking University Health Science Center Meinian Public Health Institute, Beijing, China; Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing, China; Peking University Center for Public Health and Epidemic Preparedness & Response, Beijing, China
| | - Hui Liu
- Institute of Medical Information, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
| | - Bo Wang
- Meinian Institute of Health, Beijing, China; Peking University Health Science Center Meinian Public Health Institute, Beijing, China; Peking University Center for Public Health and Epidemic Preparedness & Response, Beijing, China.
| | - Liming Li
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China; Peking University Health Science Center Meinian Public Health Institute, Beijing, China; Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing, China; Peking University Center for Public Health and Epidemic Preparedness & Response, Beijing, China.
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12
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Serra-Burriel M, Juanola A, Serra-Burriel F, Thiele M, Graupera I, Pose E, Pera G, Grgurevic I, Caballeria L, Piano S, van Kleef L, Reichert M, Roulot D, Pericàs JM, Schattenberg JM, Tsochatztis EA, Guha IN, Garcia-Retortillo M, Hernández R, Hoyo J, Fuentes M, Expósito C, Martínez A, Such P, Madir A, Detlefsen S, Tonon M, Martini A, Ma AT, Pich J, Bonfill E, Juan M, Soria A, Carol M, Gratacós-Ginès J, Morillas RM, Toran P, Navarrete JM, Torrejón A, Fournier C, Llorca A, Arslanow A, de Koning HJ, Cucchietti F, Manns M, Newsome PN, Hernáez R, Allen A, Angeli P, de Knegt RJ, Karlsen TH, Galle P, Wong VWS, Fabrellas N, Castera L, Krag A, Lammert F, Kamath PS, Ginès P. Development, validation, and prognostic evaluation of a risk score for long-term liver-related outcomes in the general population: a multicohort study. Lancet 2023; 402:988-996. [PMID: 37572680 DOI: 10.1016/s0140-6736(23)01174-1] [Citation(s) in RCA: 51] [Impact Index Per Article: 25.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Revised: 04/04/2023] [Accepted: 06/05/2023] [Indexed: 08/14/2023]
Abstract
BACKGROUND Liver cirrhosis is a major cause of death worldwide. Cirrhosis develops after a long asymptomatic period of fibrosis progression, with the diagnosis frequently occurring late, when major complications or cancer develop. Few reliable tools exist for timely identification of individuals at risk of cirrhosis to allow for early intervention. We aimed to develop a novel score to identify individuals at risk for future liver-related outcomes. METHODS We derived the LiverRisk score from an international prospective cohort of individuals from six countries without known liver disease from the general population, who underwent liver fibrosis assessment by transient elastography. The score included age, sex, and six standard laboratory variables. We created four groups: minimal risk, low risk, medium risk, and high risk according to selected cutoff values of the LiverRisk score (6, 10, and 15). The model's discriminatory accuracy and calibration were externally validated in two prospective cohorts from the general population. Moreover, we ascertained the prognostic value of the score in the prediction of liver-related outcomes in participants without known liver disease with median follow-up of 12 years (UK Biobank cohort). FINDINGS We included 14 726 participants: 6357 (43·2%) in the derivation cohort, 4370 (29·7%) in the first external validation cohort, and 3999 (27·2%) in the second external validation cohort. The score accurately predicted liver stiffness in the development and external validation cohorts, and was superior to conventional serum biomarkers of fibrosis, as measured by area under the receiver-operating characteristics curve (AUC; 0·83 [95% CI [0·78-0·89]) versus the fibrosis-4 index (FIB-4; 0·68 [0·61-0·75] at 10 kPa). The score was effective in identifying individuals at risk of liver-related mortality, liver-related hospitalisation, and liver cancer, thereby allowing stratification to different risk groups for liver-related outcomes. The hazard ratio for liver-related mortality in the high-risk group was 471 (95% CI 347-641) compared with the minimal risk group, and the overall AUC of the score in predicting 10-year liver-related mortality was 0·90 (0·88-0·91) versus 0.84 (0·82-0·86) for FIB-4. INTERPRETATION The LiverRisk score, based on simple parameters, predicted liver fibrosis and future development of liver-related outcomes in the general population. The score might allow for stratification of individuals according to liver risk and thus guide preventive care. FUNDING European Commission under the H20/20 programme; Fondo de Investigación Sanitaria de Salud; Instituto de Salud Carlos III; Spanish Ministry of Economy, Industry, and Competitiveness; the European Regional Development Fund; and the German Ministry of Education and Research (BMBF).
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Affiliation(s)
- Miquel Serra-Burriel
- Epidemiology, Statistics, and Prevention Institute, University of Zurich, Zurich, Switzerland
| | - Adrià Juanola
- Liver Unit Hospital Clínic, University of Barcelona, Barcelona, Catalonia, Spain; Institut D'Investigacions Biomèdiques August Pi I Sunyer, Barcelona, Catalonia, Spain; Centro de Investigación En Red de Enfermedades Hepáticas Y Digestivas, Barcelona, Spain
| | | | - Maja Thiele
- Centre for Liver Research, Department of Gastroenterology and Hepatology, Odense University Hospital, and Institute for Clinical Research, University of Southern Denmark Odense, Odense, Denmark
| | - Isabel Graupera
- Liver Unit Hospital Clínic, University of Barcelona, Barcelona, Catalonia, Spain; Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Catalonia, Spain; Institut D'Investigacions Biomèdiques August Pi I Sunyer, Barcelona, Catalonia, Spain; Centro de Investigación En Red de Enfermedades Hepáticas Y Digestivas, Barcelona, Spain
| | - Elisa Pose
- Liver Unit Hospital Clínic, University of Barcelona, Barcelona, Catalonia, Spain; Institut D'Investigacions Biomèdiques August Pi I Sunyer, Barcelona, Catalonia, Spain; Centro de Investigación En Red de Enfermedades Hepáticas Y Digestivas, Barcelona, Spain
| | - Guillem Pera
- Unitat de Suport a la Recerca Metropolitana Nord, Institut Universitari d'Investigació en Atenció Primària Jordi Gol, Mataró, Barcelona, Spain
| | - Ivica Grgurevic
- Department of Gastroenterology, Hepatology and Clinical Nutrition, University Hospital Dubrava, University of Zagreb School of Medicine and Faculty of Pharmacy and Biochemistry, Zagreb, Croatia
| | - Llorenç Caballeria
- Unitat de Suport a la Recerca Metropolitana Nord, Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Metropolitana Nord, IDIAP Jordi Gol, ICS Institut Català de la Salut, Barcelona, Spain
| | - Salvatore Piano
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, Padova, Italy
| | - Laurens van Kleef
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Centre, Rotterdam, Netherlands
| | - Mathias Reichert
- Department of Medicine II, Saarland University Medical Center, Homburg, Germany
| | - Dominique Roulot
- Unité d'Hépatologie, Hôpital Avicenne, AP-HP, Université Paris 13, Bobigny, France
| | - Juan M Pericàs
- Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain; Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Jörn M Schattenberg
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
| | - Emmanuel A Tsochatztis
- UCL Institute for Liver and Digestive Health, Royal Free Hospital, University College of London, London, UK
| | - Indra Neil Guha
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
| | | | - Rosario Hernández
- Institut Catala de la Salut, BCN, Ambit d'Atencio Primaria, Barcelona, Spain
| | - Jordi Hoyo
- Institut Catala de la Salut, BCN, Ambit d'Atencio Primaria, Barcelona, Spain
| | - Matilde Fuentes
- Institut Catala de la Salut, BCN, Ambit d'Atencio Primaria, Barcelona, Spain
| | - Carmen Expósito
- Unitat de Suport a la Recerca Metropolitana Nord, Institut Universitari d'Investigació en Atenció Primària Jordi Gol, Mataró, Barcelona, Spain
| | - Alba Martínez
- Unitat de Suport a la Recerca Metropolitana Nord, Institut Universitari d'Investigació en Atenció Primària Jordi Gol, Mataró, Barcelona, Spain
| | - Patricia Such
- Health, Safety and Emergencies of SEAT, CUPRA and the Volkswagen Group Companies in Spain, Martorell, Spain
| | - Anita Madir
- Department of Gastroenterology, Hepatology and Clinical Nutrition, University Hospital Dubrava, University of Zagreb School of Medicine and Faculty of Pharmacy and Biochemistry, Zagreb, Croatia
| | - Sönke Detlefsen
- Department of Pathology, Odense University Hospital, and Institute for Clinical Research, University of Southern Denmark Odense, Odense, Denmark
| | - Marta Tonon
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, Padova, Italy
| | - Andrea Martini
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, Padova, Italy
| | - Ann T Ma
- Liver Unit Hospital Clínic, University of Barcelona, Barcelona, Catalonia, Spain; Institut D'Investigacions Biomèdiques August Pi I Sunyer, Barcelona, Catalonia, Spain; Centro de Investigación En Red de Enfermedades Hepáticas Y Digestivas, Barcelona, Spain
| | - Judith Pich
- Clinical Trial Unit, Hospital Clínic, Barcelona, Spain
| | - Eva Bonfill
- Clinical Trial Unit, Hospital Clínic, Barcelona, Spain
| | - Marta Juan
- Clinical Trial Unit, Hospital Clínic, Barcelona, Spain
| | - Anna Soria
- Liver Unit Hospital Clínic, University of Barcelona, Barcelona, Catalonia, Spain; Institut D'Investigacions Biomèdiques August Pi I Sunyer, Barcelona, Catalonia, Spain; Centro de Investigación En Red de Enfermedades Hepáticas Y Digestivas, Barcelona, Spain
| | - Marta Carol
- Liver Unit Hospital Clínic, University of Barcelona, Barcelona, Catalonia, Spain; Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Catalonia, Spain; Institut D'Investigacions Biomèdiques August Pi I Sunyer, Barcelona, Catalonia, Spain; Centro de Investigación En Red de Enfermedades Hepáticas Y Digestivas, Barcelona, Spain
| | - Jordi Gratacós-Ginès
- Liver Unit Hospital Clínic, University of Barcelona, Barcelona, Catalonia, Spain; Institut D'Investigacions Biomèdiques August Pi I Sunyer, Barcelona, Catalonia, Spain; Centro de Investigación En Red de Enfermedades Hepáticas Y Digestivas, Barcelona, Spain
| | - Rosa M Morillas
- Liver Unit, Hospital Germans Trias i Pujol, IGTP, Badalona, Spain
| | - Pere Toran
- Unitat de Suport a la Recerca Metropolitana Nord, Institut Universitari d'Investigació en Atenció Primària Jordi Gol, Mataró, Barcelona, Spain
| | - J M Navarrete
- Health, Safety and Emergencies of SEAT, CUPRA and the Volkswagen Group Companies in Spain, Martorell, Spain
| | - Antoni Torrejón
- Health, Safety and Emergencies of SEAT, CUPRA and the Volkswagen Group Companies in Spain, Martorell, Spain
| | | | | | - Anita Arslanow
- Liver Unit Hospital Clínic, University of Barcelona, Barcelona, Catalonia, Spain; Institut D'Investigacions Biomèdiques August Pi I Sunyer, Barcelona, Catalonia, Spain
| | - Harry J de Koning
- Department of Public Health, Erasmus MC University Medical Centre, Rotterdam, Netherlands
| | | | - Michael Manns
- Health Sciences, Hannover Medical School MHH, Hannover, Germany
| | - Phillip N Newsome
- National Institute for Health Research Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham, Birmingham, UK
| | - Rubén Hernáez
- Division of Gastroenterology and Hepatology, Department of Medicine, Michael E DeBakey Veterans Affairs Medical Center, Houston, TX, USA; Center for Innovations in Quality, Effectiveness and Safety, Michael E DeBakey Veterans Affairs Medical Center, Houston, TX, USA; Division of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA
| | - Alina Allen
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA
| | - Paolo Angeli
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, Padova, Italy
| | - Robert J de Knegt
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Centre, Rotterdam, Netherlands
| | - Tom H Karlsen
- Section of Gastroenterology, Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, Oslo University Hospital, Oslo, Norway; Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway
| | - Peter Galle
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Núria Fabrellas
- Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Catalonia, Spain; Institut D'Investigacions Biomèdiques August Pi I Sunyer, Barcelona, Catalonia, Spain; Centro de Investigación En Red de Enfermedades Hepáticas Y Digestivas, Barcelona, Spain
| | - Laurent Castera
- Department of Hepatology, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy, Université de Paris, Paris, France
| | - Aleksander Krag
- Centre for Liver Research, Department of Gastroenterology and Hepatology, Odense University Hospital, and Institute for Clinical Research, University of Southern Denmark Odense, Odense, Denmark
| | - Frank Lammert
- Department of Medicine II, Saarland University Medical Center, Homburg, Germany; Institute for Occupational Medicine and Public Health, Saarland University, Homburg, Germany; Hannover Medical School, Hannover, Germany
| | - Patrick S Kamath
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA
| | - Pere Ginès
- Liver Unit Hospital Clínic, University of Barcelona, Barcelona, Catalonia, Spain; Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Catalonia, Spain; Institut D'Investigacions Biomèdiques August Pi I Sunyer, Barcelona, Catalonia, Spain; Centro de Investigación En Red de Enfermedades Hepáticas Y Digestivas, Barcelona, Spain.
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13
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Liang JX, Ampuero J, Niu H, Imajo K, Noureddin M, Behari J, Lee DH, Ehman RL, Rorsman F, Vessby J, Lacalle JR, Mózes FE, Pavlides M, Anstee QM, Harrison SA, Castell J, Loomba R, Romero-Gómez M. An individual patient data meta-analysis to determine cut-offs for and confounders of NAFLD-fibrosis staging with magnetic resonance elastography. J Hepatol 2023; 79:592-604. [PMID: 37121437 PMCID: PMC10623141 DOI: 10.1016/j.jhep.2023.04.025] [Citation(s) in RCA: 30] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Revised: 03/23/2023] [Accepted: 04/12/2023] [Indexed: 05/02/2023]
Abstract
BACKGROUND & AIMS We conducted an individual patient data meta-analysis to establish stiffness cut-off values for magnetic resonance elastography (MRE) in staging liver fibrosis and to assess potential confounding factors. METHODS A systematic review of the literature identified studies reporting MRE data in patients with NAFLD. Data were obtained from the corresponding authors. The pooled diagnostic cut-off value for the various fibrosis stages was determined in a two-stage meta-analysis. Multilevel modelling methods were used to analyse potential confounding factors influencing the diagnostic accuracy of MRE in staging liver fibrosis. RESULTS Eight independent cohorts comprising 798 patients were included in the meta-analysis. The area under the receiver operating characteristic curve (AUROC) for MRE in detecting significant fibrosis was 0.92 (sensitivity, 79%; specificity, 89%). For advanced fibrosis, the AUROC was 0.92 (sensitivity, 87%; specificity, 88%). For cirrhosis, the AUROC was 0.94 (sensitivity, 88%, specificity, 89%). Cut-offs were defined to explore concordance between MRE and histopathology: ≥F2, 3.14 kPa (pretest probability, 39.4%); ≥F3, 3.53 kPa (pretest probability, 24.1%); and F4, 4.45 kPa (pretest probability, 8.7%). In generalized linear mixed model analysis, histological steatohepatitis with higher inflammatory activity (odds ratio 2.448, 95% CI 1.180-5.079, p <0.05) and high gamma-glutamyl transferase (GGT) concentration (>120U/L) (odds ratio 3.388, 95% CI 1.577-7.278, p <0.01] were significantly associated with elevated liver stiffness, and thus affecting accuracy in staging early fibrosis (F0-F1). Steatosis, as measured by magnetic resonance imaging proton density fat fraction, and body mass index(BMI) were not confounders. CONCLUSIONS MRE has excellent diagnostic performance for significant, advanced fibrosis and cirrhosis in patients with NAFLD. Elevated inflammatory activity and GGT level may lead to overestimation of early liver fibrosis, but anthropometric measures such as BMI or the degree of steatosis do not. IMPACT AND IMPLICATIONS This individual patient data meta-analysis of eight international cohorts, including 798 patients, demonstrated that MRE achieves excellent diagnostic accuracy for significant, advanced fibrosis and cirrhosis in patients with NAFLD. Cut-off values (significant fibrosis, 3.14 kPa; advanced fibrosis, 3.53 kPa; and cirrhosis, 4.45 kPa) were established. Elevated inflammatory activity and gamma-glutamyltransferase level may affect the diagnostic accuracy of MRE, leading to overestimation of liver fibrosis in early stages. We observed no impact of diabetes, obesity, or any other metabolic disorder on the diagnostic accuracy of MRE.
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Affiliation(s)
- Jia-Xu Liang
- Digestive Diseases Unit and CIBERehd, Virgen del Rocío University Hospital, Seville, Spain; Institute of Biomedicine of Seville (HUVR/CSIC/US), University of Seville, Seville, Spain; Department of Diagnostic Radiology, The Fifth Clinical Medical College of Henan University of Chinese Medicine (Zhengzhou People's Hospital), Zhengzhou, China
| | - Javier Ampuero
- Digestive Diseases Unit and CIBERehd, Virgen del Rocío University Hospital, Seville, Spain; Institute of Biomedicine of Seville (HUVR/CSIC/US), University of Seville, Seville, Spain
| | - Hao Niu
- Digestive System and Clinical Pharmacology Unit, Virgen de la Victoria University Hospital, Biomedical Research Institute of Malaga and Nanomedicine Platform-IBIMA (Plataforma BIONAND), University of Malaga, Málaga, Spain; Biomedical Research Network Center for Hepatic and Digestive Diseases (CIBERehd), Carlos III Health Institute, Madrid, Spain
| | - Kento Imajo
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine; Yokohama, Japan
| | - Mazen Noureddin
- Fatty Liver Program, Division of Digestive and Liver Diseases, Comprehensive Transplant Program, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Jaideep Behari
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Center for Liver Diseases, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Dae Ho Lee
- Department of Internal Medicine, Gachon University College of Medicine (Gachon University Gil Medical Center), Incheon, South Korea
| | - Richard L Ehman
- Department of Diagnostic Radiology, Mayo Clinic College of Medicine, Rochester, MN, USA
| | - Fredrik Rorsman
- Department of Medical Sciences, Section of Gastroenterology and Hepatology, Uppsala University, Uppsala, Sweden
| | - Johan Vessby
- Department of Medical Sciences, Section of Gastroenterology and Hepatology, Uppsala University, Uppsala, Sweden
| | - Juan R Lacalle
- Biostatistics Unit, Department of Preventive Medicine and Public Health, University of Seville, Seville, Spain
| | - Ferenc E Mózes
- Oxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK
| | - Michael Pavlides
- Oxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK; Translational Gastroenterology Unit, University of Oxford, Oxford, UK
| | - Quentin M Anstee
- Translational and Clinical Research Institute; Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, UK; Newcastle NIHR Biomedical Research Centre, Newcastle Upon Tyne Hospitals, NHS Trust, Newcastle Upon Tyne, UK
| | - Stephen A Harrison
- Oxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK
| | - Javier Castell
- Department of Radiology, Virgen del Rocío University Hospital, Seville, Spain
| | - Rohit Loomba
- Division of Epidemiology, Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA, USA; NAFLD Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, CA, USA
| | - Manuel Romero-Gómez
- Digestive Diseases Unit and CIBERehd, Virgen del Rocío University Hospital, Seville, Spain; Institute of Biomedicine of Seville (HUVR/CSIC/US), University of Seville, Seville, Spain.
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14
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Castera L, Cusi K. Diabetes and cirrhosis: Current concepts on diagnosis and management. Hepatology 2023; 77:2128-2146. [PMID: 36631005 DOI: 10.1097/hep.0000000000000263] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Accepted: 10/03/2022] [Indexed: 01/13/2023]
Abstract
Type 2 diabetes mellitus is often associated with cirrhosis as comorbidities, acute illness, medications, and other conditions profoundly alter glucose metabolism. Both conditions are closely related in NAFLD, the leading cause of chronic liver disease, and given its rising burden worldwide, management of type 2 diabetes mellitus in cirrhosis will be an increasingly common dilemma. Having diabetes increases cirrhosis-related complications, including HCC as well as overall mortality. In the absence of effective treatments for cirrhosis, patients with type 2 diabetes mellitus should be systematically screened as early as possible for NAFLD-related fibrosis/cirrhosis using noninvasive tools, starting with a FIB-4 index followed by transient elastography, if available. In people with cirrhosis, an early diagnosis of diabetes is critical for an optimal management strategy (ie, nutritional goals, and glycemic targets). Diagnosis of diabetes may be missed if based on A1C in patients with cirrhosis and impaired liver function (Child-Pugh B-C) as anemia may turn the test unreliable. Clinicians must also become aware of their high risk of hypoglycemia, especially in decompensated cirrhosis where insulin is the only therapy. Care should be within multidisciplinary teams (nutritionists, obesity management teams, endocrinologists, hepatologists, and others) and take advantage of novel glucose-monitoring devices. Clinicians should become familiar with the safety and efficacy of diabetes medications for patients with advanced fibrosis and compensated cirrhosis. Management is conditioned by whether the patient has either compensated or decompensated cirrhosis. This review gives an update on the complex relationship between cirrhosis and type 2 diabetes mellitus, with a focus on its diagnosis and treatment, and highlights knowledge gaps and future directions.
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Affiliation(s)
- Laurent Castera
- Departement of Hepatology, Hospital Beaujon, Assistance Publique-Hôpitaux de Paris, INSERM UMR 1149, Université Paris Cité, Clichy, France
| | - Kenneth Cusi
- Division of Endocrinology, Diabetes and Metabolism, The University of Florida, Gainesville, Florida, USA
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15
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Parikh NS, Kamel H, Zhang C, Gupta A, Cohen DE, de Leon MJ, Gottesman RF, Iadecola C. Association of liver fibrosis with cognitive test performance and brain imaging parameters in the UK Biobank study. Alzheimers Dement 2023; 19:1518-1528. [PMID: 36149265 PMCID: PMC10033462 DOI: 10.1002/alz.12795] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2022] [Revised: 08/05/2022] [Accepted: 08/09/2022] [Indexed: 11/11/2022]
Abstract
INTRODUCTION We hypothesized that liver fibrosis is associated with worse cognitive performance and corresponding brain imaging changes. METHODS We examined the association of liver fibrosis with cognition and brain imaging parameters in the UK Biobank study. Liver fibrosis was assessed using the Fibrosis-4 (FIB-4) score. The primary cognitive outcome was the digit symbol substitution test (DSST); secondary outcomes were additional executive function/processing speed and memory tests. Imaging outcomes were hippocampal, total brain, and white matter hyperintensity (WMH) volumes. RESULTS We included 105,313 participants with cognitive test data, and 41,982 with magnetic resonance imaging (MRI). In adjusted models, liver fibrosis was associated with worse performance on the DSST and tests of executive function but not memory. Liver fibrosis was associated with lower hippocampal and total brain volumes, without compelling association with WMH volume. DISCUSSION Liver fibrosis is associated with worse performance on select cognitive tests and lower hippocampal and total brain volumes. HIGHLIGHTS It is increasingly recognized that chronic liver conditions impact brain health. We performed an analysis of data from the UK Biobank prospective cohort study. Liver fibrosis was associated with worse performance on executive function tests. Liver fibrosis was not associated with memory impairment. Liver fibrosis was associated with lower hippocampal and total brain volumes.
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Affiliation(s)
- Neal S Parikh
- Clinical and Translational Neuroscience Unit, Feil Family Brain and Mind Research Institute and Department of Neurology, Weill Cornell Medicine, New York, New York, USA
| | - Hooman Kamel
- Clinical and Translational Neuroscience Unit, Feil Family Brain and Mind Research Institute and Department of Neurology, Weill Cornell Medicine, New York, New York, USA
| | - Cenai Zhang
- Clinical and Translational Neuroscience Unit, Feil Family Brain and Mind Research Institute and Department of Neurology, Weill Cornell Medicine, New York, New York, USA
| | - Ajay Gupta
- Department of Radiology, Weill Cornell Medicine, New York, New York, USA
| | - David E Cohen
- Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Mony J de Leon
- Department of Radiology, Weill Cornell Medicine, New York, New York, USA
| | - Rebecca F Gottesman
- Stroke Branch, National Institute of Neurological Disorders and Stroke Intramural Research Program, Bethesda, Maryland, USA
| | - Costantino Iadecola
- Clinical and Translational Neuroscience Unit, Feil Family Brain and Mind Research Institute and Department of Neurology, Weill Cornell Medicine, New York, New York, USA
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16
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van Kleef LA, Sonneveld MJ, Zhu F, Ikram MA, Kavousi M, de Knegt RJ. Liver stiffness is associated with excess mortality in the general population driven by heart failure: The Rotterdam Study. Liver Int 2023; 43:1000-1007. [PMID: 36744819 DOI: 10.1111/liv.15538] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Revised: 01/31/2023] [Accepted: 02/02/2023] [Indexed: 02/07/2023]
Abstract
BACKGROUND Elevated liver stiffness reflects hepatic fibrosis but can also be secondary to venous congestion. We aimed to study the association between liver stiffness and mortality in the general population, stratified for heart failure and/or coronary heart disease (CHD). METHODS We analysed individuals enrolled in the ongoing prospective population-based Rotterdam Study who attended a visit between 2009-2014 that included liver stiffness measurement. Exclusion criteria for the primary analysis were incomplete data on heart failure, unreliable liver stiffness, alcohol abuse and viral hepatitis, leaving 4.153 participants (aged 67.5 ± 8.4 years, 44.2% male) for analysis with a median follow-up of 6.0 (interquartile range: 5.1-7.0) years. Secondary analysis included participants with viral hepatitis, alcohol abuse and/or unreliable measurement. The association between liver stiffness and mortality was assessed using Cox regression. Associations between heart failure, CHD, and echocardiographic characteristics and liver stiffness were quantified with linear regression. RESULTS Liver stiffness ≥8.0 kPa was associated with mortality (aHR: 1.37, 95%CI: 1.00-1.89). However, this was driven by participants with heart failure (aHR: 2.48, 95%CI: 1.15-5.35), since high liver stiffness was not associated with mortality in participants without heart failure and/or CHD (aHR: 1.07, 95%CI: 0.70-1.64). Results were consistent when individuals with viral hepatitis, alcohol abuse or unreliable liver stiffness measurement were not excluded. Several cardiovascular characteristics were significantly associated with higher liver stiffness, e.g. heart failure, moderate/poor diastolic dysfunction, and right atrium diameter > 4.5 cm. CONCLUSION In our cohort of community-dwelling elderly, high liver stiffness was associated with excess mortality, primarily explained by participants with heart failure. Moreover, heart failure and its indicators were associated with increased liver stiffness.
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Affiliation(s)
- Laurens A van Kleef
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands
| | - Milan J Sonneveld
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands
| | - Fang Zhu
- Department of Cardiology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands
| | - M Arfan Ikram
- Department of Epidemiology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands
| | - Maryam Kavousi
- Department of Cardiology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands
| | - Robert J de Knegt
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands
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17
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Belfort-DeAguiar R, Lomonaco R, Cusi K. Approach to the Patient With Nonalcoholic Fatty Liver Disease. J Clin Endocrinol Metab 2023; 108:483-495. [PMID: 36305273 DOI: 10.1210/clinem/dgac624] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Revised: 10/13/2022] [Indexed: 01/20/2023]
Abstract
CONTEXT Nonalcoholic fatty liver disease (NAFLD) is associated with obesity and type 2 diabetes (T2D), causing substantial burden from hepatic and extrahepatic complications. However, endocrinologists often follow people who are at the highest risk of its more severe form with nonalcoholic steatohepatitis or NASH (i.e., T2D or obesity with cardiometabolic risk factors). Endocrinologists are in a unique position to prevent cirrhosis in this population with early diagnosis and treatment. OBJECTIVE This work aims to offer endocrinologists a practical approach for the management of patients with NAFLD, including diagnosis, fibrosis risk stratification, and referral to hepatologists. PATIENTS (1) An asymptomatic patient with obesity and cardiometabolic risk factors, found to have hepatic steatosis; (2) a patient with T2D and NASH with clinically significant liver fibrosis; and (3) a liver transplant recipient with a history of NASH cirrhosis, with significant weight regain and with recurrent NAFLD on the transplanted organ. CONCLUSION NASH can be reversed with proper management of obesity and of T2D. While no agents are currently approved for the treatment of NASH, treatment should include lifestyle changes and a broader use of structured weight-loss programs, obesity pharmacotherapy, and bariatric surgery. Diabetes medications such as pioglitazone and some glucagon-like peptide 1 receptor agonists may also improve liver histology and cardiometabolic health. Sodium-glucose cotransporter-2 inhibitors and insulin may ameliorate steatosis, but their effect on steatohepatitis remains unclear. Awareness by endocrinologists about, establishing an early diagnosis of fibrosis (ie, FIB-4, liver elastography) in patients at high-risk of cirrhosis, long-term monitoring, and timely referral to the hepatologist are all critical to curve the looming epidemic of cirrhosis from NAFLD.
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Affiliation(s)
- Renata Belfort-DeAguiar
- Internal Medicine Department, Endocrinology Section, Yale University, New Haven, Connecticut 06520, USA
| | - Romina Lomonaco
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, Florida 32610, USA
| | - Kenneth Cusi
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, Florida 32610, USA
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18
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Alcohol consumption and metabolic syndrome: Clinical and epidemiological impact on liver disease. J Hepatol 2023; 78:191-206. [PMID: 36063967 DOI: 10.1016/j.jhep.2022.08.030] [Citation(s) in RCA: 120] [Impact Index Per Article: 60.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Revised: 08/04/2022] [Accepted: 08/19/2022] [Indexed: 02/01/2023]
Abstract
Alcohol use and metabolic syndrome are highly prevalent in the population and frequently co-exist. Both are implicated in a large range of health problems, including chronic liver disease, hepatocellular carcinoma, and liver-related outcomes (i.e. decompensation or liver transplantation). Studies have yielded mixed results regarding the effects of mild-moderate alcohol consumption on the risk of metabolic syndrome and fatty liver disease, possibly due to methodological differences. The few available prospective studies have indicated that mild-moderate alcohol use is associated with an increase in liver-related outcomes. This conclusion was substantiated by systems biology analyses suggesting that alcohol and metabolic syndrome may play a similar role in fatty liver disease, potentiating an already existing dysregulation of common vital homeostatic pathways. Alcohol and metabolic factors are independently and jointly associated with liver-related outcomes. Indeed, metabolic syndrome increases the risk of liver-related outcomes, regardless of alcohol intake. Moreover, the components of metabolic syndrome appear to have additive effects when it comes to the risk of liver-related outcomes. A number of population studies have implied that measures of central/abdominal obesity, such as the waist-to-hip ratio, can predict liver-related outcomes more accurately than BMI, including in individuals who consume harmful quantities of alcohol. Many studies even point to synergistic interactions between harmful alcohol use and many metabolic components. This accumulating evidence showing independent, combined, and modifying effects of alcohol and metabolic factors on the onset and progression of chronic liver disease highlights the multifactorial background of liver disease in the population. The available evidence suggests that more holistic approaches could be useful for risk prediction, diagnostics and treatment planning.
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19
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Bhadauria DS, Kumar P, Tiwari P, Kaul A, Negi TS, Rai P, Shanmugam S, Veeranki V, Prasad N, Goel A. Liver Stiffness is Reduced to Normal After Successful Renal Transplantation: A Prospective Cohort Study. J Clin Exp Hepatol 2022; 12:1445-1450. [PMID: 36340304 PMCID: PMC9630024 DOI: 10.1016/j.jceh.2022.06.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Accepted: 06/02/2022] [Indexed: 12/12/2022] Open
Abstract
Background Liver stiffness (LS) may be falsely elevated in patients on maintenance hemodialysis (MHD) due to fluid overload. We measured LS change by transient elastography (TE) in MHD patients before and after successful renal transplantation. Method Adults on ≥2 years of MHD, without additional risk factors for liver fibrosis or fluid overload, and planned for renal transplantation were prospectively recruited. LS was measured on two occasions, i.e., within two weeks before transplantation (pre-Tx LS) and after ≥ 3 months after successful transplantation (post-Tx LS). The participants with pre-Tx LS ≤ 7.0 KPa and >7.0 KPa were classified as "Group I" and "Group II," respectively. Categorical and numerical data are expressed as ratio/proportions and mean (SD), respectively. Results Paired data from 43 participants (males 42 [97.7%]; age 32 [11] years) were analyzed. The pre-Tx and post-Tx LS of the entire cohort, measured at 307 (198) days of interval, were 8.5 (7.3) KPa and 6.7 (3.1) KPa, respectively. Before transplantation, 21 (49%) participants belonged to Group II and 22 (51%) to Group I. Among the Group II participants, 12 (57%) showed LS normalization after 312 (182) days of transplantation. Of the 22 participants in Group I, three (13.6%) showed LS elevation to >7.0 KPa after 303 (217) days of transplantation. The mean LS changes among the overall cohort, Group II, and Group I were -1.8 KPa, -4.1 KPa, and +0.2 KPa, respectively. Conclusion LS in people on MHD may be falsely elevated, which is likely to normalize after successful renal transplantation.
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Affiliation(s)
- Dharmendra S. Bhadauria
- Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Pankaj Kumar
- Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Prachi Tiwari
- Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Anupma Kaul
- Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Tajwar S. Negi
- Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Praveer Rai
- Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Sabrinath Shanmugam
- Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Vamsidhar Veeranki
- Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Narayan Prasad
- Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Amit Goel
- Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
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20
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Zhuang RH, Weinstock AK, Ganesh S, Behari J, Malik SM, Bataller R, Furlan A, Hughes CB, Humar A, Duarte-Rojo A. Characterization of hepatic steatosis using controlled attenuation parameter and MRI-derived proton density fat fraction in living donor liver transplantation. Clin Transplant 2022; 36:e14786. [PMID: 35993599 DOI: 10.1111/ctr.14786] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2022] [Revised: 07/14/2022] [Accepted: 07/15/2022] [Indexed: 12/15/2022]
Abstract
BACKGROUND The increasingly favorable outcomes of live donor liver transplant warrant development of screening techniques to expand current donor pool. Transient elastography (TE) with controlled attenuation parameter (CAP) is accessible and has promising diagnostic performance in non-obese individuals. Here, we demonstrate its utility in grading donor steatosis for risk assessment in living liver donors (LLD). STUDY DESIGN In a prospective study of LLD and recipients, accuracy was determined using MRI-derived proton density fat fraction (PDFF) as reference. RESULTS One hundred and one LLD underwent TE, 95 of whom had available PDFF. Median CAP and MRI-PDFF were 233 dB/m (206-270) and 2.9% (2.3-4.0), respectively. A CAP threshold of 270 dB/m captured all steatosis which was present in 13 (13%) LLD (AUROC .942, 100% sensitivity and 83% specificity). Performance further improved when excluding obese LLD and limiting analysis to M-probe (AUROC .971 and .974, respectively, with 87% specificity). There was no difference in CAP and MRI-PDFF between LLD and nondonors (P = .26 and .21, respectively). Early allograft dysfunction was observed in one recipient (CAP 316, PDFF 9.5%), zero underwent retransplant, and one died from sepsis. CONCLUSION The specific role of CAP in living liver donation warrants further study, beginning with its use as screening tool across peripheral clinics.
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Affiliation(s)
- Rachel H Zhuang
- Internal Medicine Program, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, USA
| | - Allison K Weinstock
- Department of Radiology, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, USA
| | - Swaytha Ganesh
- Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, USA.,Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, USA
| | - Jaideep Behari
- Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, USA.,Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, USA
| | - Shahid M Malik
- Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, USA.,Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, USA
| | - Ramon Bataller
- Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, USA.,Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, USA
| | - Alessandro Furlan
- Department of Radiology, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, USA
| | - Christopher B Hughes
- Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, USA.,Department of Surgery, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, USA
| | - Abhinav Humar
- Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, USA.,Department of Surgery, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, USA
| | - Andres Duarte-Rojo
- Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, USA.,Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, USA
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21
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van Kleef LA, Lu Z, Ikram MA, de Groot NMS, Kavousi M, de Knegt RJ. Liver stiffness not fatty liver disease is associated with atrial fibrillation: The Rotterdam study. J Hepatol 2022; 77:931-938. [PMID: 35688226 DOI: 10.1016/j.jhep.2022.05.030] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Revised: 04/05/2022] [Accepted: 05/22/2022] [Indexed: 02/01/2023]
Abstract
BACKGROUND & AIMS Fatty liver disease has become the most prevalent chronic liver disease globally and is linked to cardiovascular disease, including arrhythmias. However, there have been inconsistent reports on the association between fatty liver disease and atrial fibrillation, while the role of liver stiffness in this association remains unclear. METHODS Within the Rotterdam Study, a large prospective ongoing cohort, participants attending the abdominal ultrasound program between 2009-2014 were included. Exclusion criteria were no atrial fibrillation data or >20% missing data across analysis variables. Steatosis was assessed by ultrasound, liver stiffness by transient elastography and atrial fibrillation by 12-lead electrocardiograms. Incident atrial fibrillation was based on medical records and complete until 2014. Logistic and Cox-regression were used to quantify associations between fatty liver disease and atrial fibrillation. RESULTS We included 5,825 participants (aged 69.5±9.1, 42.9% male), 35.7% had steatosis, liver stiffness measurement was available in 73.3%, and 7.0% had prevalent atrial fibrillation. Steatosis was not associated with prevalent atrial fibrillation in fully adjusted models (odds ratio [OR] 0.80; 95% CI 0.62-1.03), findings were consistent for non-alcoholic or metabolic dysfunction-associated fatty liver disease. Liver stiffness was significantly associated with prevalent atrial fibrillation (OR 1.09 per kPa, 95% CI 1.03-1.16); however, this was only persistent among those without steatosis (OR 1.18 per kPa, 95% CI 1.08-1.29). Lastly, no associations were found between steatosis (hazard ratio 0.88; 95% CI 0.59-1.33; follow-up 2.1 [1.1-3.2] years) and incident atrial fibrillation. CONCLUSIONS Fatty liver disease was not associated with prevalent or incident atrial fibrillation, while liver stiffness was significantly associated with atrial fibrillation, especially among those without steatosis. This association might be driven by venous congestion instead of fibrogenesis, but this awaits further validation. We recommend assessing cardiovascular health in participants with high liver stiffness, especially in the absence of overt liver disease. CLINICAL TRIAL NUMBER NTR6831. LAY SUMMARY There have been inconsistent reports about the potential links between fatty liver disease and atrial fibrillation (an irregular and often very fast heart rhythm). Herein, we show that liver stiffness (which is a marker of liver fibrosis), but not fatty liver disease, was associated with a higher prevalence of atrial fibrillation. We hypothesis that atrial fibrillation, rather than fibrosis, may be the cause of increased liver stiffness in participants without overt liver disease.
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Affiliation(s)
- Laurens A van Kleef
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Zuolin Lu
- Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - M Arfan Ikram
- Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Natasja M S de Groot
- Department of Cardiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Maryam Kavousi
- Department of Cardiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Robert J de Knegt
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
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22
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Association between arterial hypertension and liver outcomes using polygenic risk scores: a population-based study. Sci Rep 2022; 12:15581. [PMID: 36114231 PMCID: PMC9481629 DOI: 10.1038/s41598-022-20084-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Accepted: 09/08/2022] [Indexed: 12/03/2022] Open
Abstract
Arterial hypertension (HTA) is associated with liver disease, but causality remains unclear. We investigated whether genetic predisposition to HTA is associated with liver disease in the population, and if antihypertensive medication modifies this association. Participants of the Finnish health-examination surveys, FINRISK 1992–2012 and Health 2000 (n = 33,770), were linked with national electronic healthcare registers for liver-related outcomes (K70-K77, C22.0) and with the drug reimbursement registry for new initiation of antihypertensive medication during follow-up. Genetic predisposition to HTA was defined by polygenic risk scores (PRSs). During a median 12.9-year follow-up (409,268.9 person-years), 441 liver-related outcomes occurred. In the fully-adjusted Cox-regression models, both measured systolic blood pressure and clinically defined HTA were associated with liver-related outcomes. PRSs for systolic and diastolic blood pressure were significantly associated with liver-related outcomes (HR/SD 1.19, 95% CI 1.01–1.24, and 1.12, 95% CI 1.01–1.25, respectively). In the highest quintile of the systolic blood pressure PRS, new initiation of antihypertensive medication was associated with reduced rates of liver-related outcomes (HR 0.55, 95% CI 0.31–0.97). HTA and a genetic predisposition for HTA are associated with liver-related outcomes in the population. New initiation of antihypertensive medication attenuates this association in persons with high genetic risk for HTA.
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23
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Marti-Aguado D, Clemente-Sanchez A, Bataller R. Cigarette smoking and liver diseases. J Hepatol 2022; 77:191-205. [PMID: 35131406 DOI: 10.1016/j.jhep.2022.01.016] [Citation(s) in RCA: 72] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Revised: 01/14/2022] [Accepted: 01/25/2022] [Indexed: 01/27/2023]
Abstract
Cigarette smoking is a preventable risk factor for premature morbidity and mortality. A history of smoking is observed in approximately 40% of patients with liver disease, while a growing number of studies are investigating the potential impact of smoking in chronic liver diseases. This review discusses the effects of smoking on liver diseases, at multiple levels, with a focus on its potential causal role. Clinical evidence indicates that cigarette smoking negatively impacts the incidence and severity of fatty liver disease, fibrosis progression, hepatocellular carcinoma development, and the outcomes of patients with advanced liver disease. The underlying mechanisms are complex and involve different pathophysiological pathways including oxidative stress and oncogenic signals. Importantly, smoking promotes cardiovascular disease and extrahepatic cancers in patients with steatohepatitis and in transplant recipients. We discuss how promoting smoking cessation could improve the rates of treatment response (in clinical trials) and fibrosis regression, while reducing the risk of hepatocellular carcinoma and improving liver transplant outcomes. Finally, we discuss current challenges such as the referral of smokers to specialised units for smoking cessation.
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Affiliation(s)
- David Marti-Aguado
- Digestive Disease Department, Clinic University Hospital, INCLIVA Health Research Institute, Valencia, Spain; Center for Liver Diseases, Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Pittsburgh Liver Research Center, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Ana Clemente-Sanchez
- Center for Liver Diseases, Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Pittsburgh Liver Research Center, University of Pittsburgh Medical Center, Pittsburgh, PA, USA; Liver Unit and Digestive Department, Hospital General Universitario Gregorio Marañon, CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
| | - Ramon Bataller
- Center for Liver Diseases, Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Pittsburgh Liver Research Center, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
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24
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Giri S, Ingawale S. PHAT Score for Prediction of Clinically Significant Portal Hypertension: Old Wine in a New Bottle. J Clin Gastroenterol 2022; 56:464. [PMID: 35220376 DOI: 10.1097/mcg.0000000000001682] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Affiliation(s)
- Suprabhat Giri
- Department of Gastroenterology Nizam's Institute of Medical Sciences Hyderabad, Telangana
| | - Sushrut Ingawale
- Department of General Medicine, Seth GS Medical College and KEM Hospital Mumbai, Maharashtra, India
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25
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Cusi K, Isaacs S, Barb D, Basu R, Caprio S, Garvey WT, Kashyap S, Mechanick JI, Mouzaki M, Nadolsky K, Rinella ME, Vos MB, Younossi Z. American Association of Clinical Endocrinology Clinical Practice Guideline for the Diagnosis and Management of Nonalcoholic Fatty Liver Disease in Primary Care and Endocrinology Clinical Settings: Co-Sponsored by the American Association for the Study of Liver Diseases (AASLD). Endocr Pract 2022; 28:528-562. [PMID: 35569886 DOI: 10.1016/j.eprac.2022.03.010] [Citation(s) in RCA: 512] [Impact Index Per Article: 170.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Revised: 03/11/2022] [Accepted: 03/11/2022] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To provide evidence-based recommendations regarding the diagnosis and management of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) to endocrinologists, primary care clinicians, health care professionals, and other stakeholders. METHODS The American Association of Clinical Endocrinology conducted literature searches for relevant articles published from January 1, 2010, to November 15, 2021. A task force of medical experts developed evidence-based guideline recommendations based on a review of clinical evidence, expertise, and informal consensus, according to established American Association of Clinical Endocrinology protocol for guideline development. RECOMMENDATION SUMMARY This guideline includes 34 evidence-based clinical practice recommendations for the diagnosis and management of persons with NAFLD and/or NASH and contains 385 citations that inform the evidence base. CONCLUSION NAFLD is a major public health problem that will only worsen in the future, as it is closely linked to the epidemics of obesity and type 2 diabetes mellitus. Given this link, endocrinologists and primary care physicians are in an ideal position to identify persons at risk on to prevent the development of cirrhosis and comorbidities. While no U.S. Food and Drug Administration-approved medications to treat NAFLD are currently available, management can include lifestyle changes that promote an energy deficit leading to weight loss; consideration of weight loss medications, particularly glucagon-like peptide-1 receptor agonists; and bariatric surgery, for persons who have obesity, as well as some diabetes medications, such as pioglitazone and glucagon-like peptide-1 receptor agonists, for those with type 2 diabetes mellitus and NASH. Management should also promote cardiometabolic health and reduce the increased cardiovascular risk associated with this complex disease.
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Affiliation(s)
- Kenneth Cusi
- Guideine and Algorithm Task Forces Co-Chair, Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, Florida
| | - Scott Isaacs
- Guideline and Algorithm Task Forces Co-Chair, Division of Endocrinology, Emory University School of Medicine, Atlanta, Georgia
| | - Diana Barb
- University of Florida, Gainesville, Florida
| | - Rita Basu
- Division of Endocrinology, University of Virginia School of Medicine, Charlottesville, Virginia
| | - Sonia Caprio
- Yale University School of Medicine, New Haven, Connecticut
| | - W Timothy Garvey
- Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, Alabama
| | | | - Jeffrey I Mechanick
- The Marie-Josee and Henry R. Kravis Center for Cardiovascular Health at Mount Sinai Heart, Icahn School of Medicine at Mount Sinai
| | | | - Karl Nadolsky
- Michigan State University College of Human Medicine, Grand Rapids, Michigan
| | - Mary E Rinella
- AASLD Representative, University of Pritzker School of Medicine, Chicago, Illinois
| | - Miriam B Vos
- Center for Clinical and Translational Research, Emory University School of Medicine, Children's Healthcare of Atlanta, Atlanta, Georgia
| | - Zobair Younossi
- AASLD Representative, Inova Medicine, Inova Health System, Falls Church, Virginia
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26
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Mosbah H, Donadille B, Vatier C, Janmaat S, Atlan M, Badens C, Barat P, Béliard S, Beltrand J, Ben Yaou R, Bismuth E, Boccara F, Cariou B, Chaouat M, Charriot G, Christin-Maitre S, De Kerdanet M, Delemer B, Disse E, Dubois N, Eymard B, Fève B, Lascols O, Mathurin P, Nobécourt E, Poujol-Robert A, Prevost G, Richard P, Sellam J, Tauveron I, Treboz D, Vergès B, Vermot-Desroches V, Wahbi K, Jéru I, Vantyghem MC, Vigouroux C. Dunnigan lipodystrophy syndrome: French National Diagnosis and Care Protocol (PNDS; Protocole National de Diagnostic et de Soins). Orphanet J Rare Dis 2022; 17:170. [PMID: 35440056 PMCID: PMC9019936 DOI: 10.1186/s13023-022-02308-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Accepted: 03/24/2022] [Indexed: 11/29/2022] Open
Abstract
Dunnigan syndrome, or Familial Partial Lipodystrophy type 2 (FPLD2; ORPHA 2348), is a rare autosomal dominant disorder due to pathogenic variants of the LMNA gene. The objective of the French National Diagnosis and Care Protocol (PNDS; Protocole National de Diagnostic et de Soins), is to provide health professionals with a guide to optimal management and care of patients with FPLD2, based on a critical literature review and multidisciplinary expert consensus. The PNDS, written by members of the French National Reference Center for Rare Diseases of Insulin Secretion and Insulin Sensitivity (PRISIS), is available on the French Health Authority website (in French). Dunnigan syndrome is characterized by a partial atrophy of the subcutaneous adipose tissue and by an insulin resistance syndrome, associated with a risk of metabolic, cardiovascular and muscular complications. Its prevalence, assessed at 1/100.000 in Europe, is probably considerably underestimated. Thorough clinical examination is key to diagnosis. Biochemical testing frequently shows hyperinsulinemia, abnormal glucose tolerance and hypertriglyceridemia. Elevated hepatic transaminases (hepatic steatosis) and creatine phosphokinase, and hyperandrogenism in women, are common. Molecular analysis of the LMNA gene confirms diagnosis and allows for family investigations. Regular screening and multidisciplinary monitoring of the associated complications are necessary. Diabetes frequently develops from puberty onwards. Hypertriglyceridemia may lead to acute pancreatitis. Early atherosclerosis and cardiomyopathy should be monitored. In women, polycystic ovary syndrome is common. Overall, the management of patients with Dunnigan syndrome requires the collaboration of several health care providers. The attending physician, in conjunction with the national care network, will ensure that the patient receives optimal care through regular follow-up and screening. The various elements of this PNDS are described to provide such a support.
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Affiliation(s)
- H Mosbah
- Endocrinology, Diabetology and Reproductive Endocrinology Department, Assistance Publique-Hôpitaux de Paris, Saint-Antoine University Hospital, National Reference Center for Rare Diseases of Insulin Secretion and Insulin Sensitivity (PRISIS), Paris, France.,Sorbonne University, Inserm UMR_S938, Saint-Antoine Research Centre, Institute of Cardiometabolism and Nutrition, Paris, France
| | - B Donadille
- Endocrinology, Diabetology and Reproductive Endocrinology Department, Assistance Publique-Hôpitaux de Paris, Saint-Antoine University Hospital, National Reference Center for Rare Diseases of Insulin Secretion and Insulin Sensitivity (PRISIS), Paris, France
| | - C Vatier
- Endocrinology, Diabetology and Reproductive Endocrinology Department, Assistance Publique-Hôpitaux de Paris, Saint-Antoine University Hospital, National Reference Center for Rare Diseases of Insulin Secretion and Insulin Sensitivity (PRISIS), Paris, France.,Sorbonne University, Inserm UMR_S938, Saint-Antoine Research Centre, Institute of Cardiometabolism and Nutrition, Paris, France
| | - S Janmaat
- Endocrinology, Diabetology and Reproductive Endocrinology Department, Assistance Publique-Hôpitaux de Paris, Saint-Antoine University Hospital, National Reference Center for Rare Diseases of Insulin Secretion and Insulin Sensitivity (PRISIS), Paris, France.,Sorbonne University, Inserm UMR_S938, Saint-Antoine Research Centre, Institute of Cardiometabolism and Nutrition, Paris, France
| | - M Atlan
- Sorbonne University, Inserm UMR_S938, Saint-Antoine Research Centre, Institute of Cardiometabolism and Nutrition, Paris, France.,Plastic Surgery Department, Assistance Publique-Hôpitaux de Paris, Tenon Hospital, Paris, France
| | - C Badens
- Department of Genetics, Assistance Publique-Hôpitaux de Marseille, Marseille, France
| | - P Barat
- Pediatric Endocrinology Unit, Bordeaux University Hospitals, Bordeaux, France
| | - S Béliard
- Nutrition Department, Assistance Publique-Hôpitaux de Marseille, La Conception Hospital, Marseille, France
| | - J Beltrand
- Paediatric Endocrinology Department, Assistance Publique-Hôpitaux de Paris, Necker Hospital, Paris University, Paris, France
| | - R Ben Yaou
- Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Myology Institute, Sorbonne University, Paris, France
| | - E Bismuth
- Paediatric Endocrinology Department, Assistance Publique-Hôpitaux de Paris, Robert Debré Hospital, Paris University, Paris, France
| | - F Boccara
- Cardiology Department, Assistance Publique-Hôpitaux de Paris, St Antoine Hospital, Sorbonne University, Paris, France
| | - B Cariou
- Endocrinology Department, Nantes University Hospitals, Guillaume et René Laennec Hospital, Nantes University, Nantes, France
| | - M Chaouat
- Plastic Surgery Department, Assistance Publique-Hôpitaux de Paris, St Louis Hospital, Paris University, Paris, France
| | - G Charriot
- French Lipodystrophy Association (AFLIP; Association Française des Lipodystrophies), Pierrevert, France
| | - S Christin-Maitre
- Endocrinology, Diabetology and Reproductive Endocrinology Department, Assistance Publique-Hôpitaux de Paris, Saint-Antoine University Hospital, National Reference Center for Rare Diseases of Insulin Secretion and Insulin Sensitivity (PRISIS), Paris, France.,Sorbonne University, Inserm UMR_S938, Saint-Antoine Research Centre, Institute of Cardiometabolism and Nutrition, Paris, France.,Sorbonne University, Inserm UMR_S933, Paris, France
| | - M De Kerdanet
- Paediatric Endocrinology Department, Rennes University Hospitals, South Hospital, Rennes, France
| | - B Delemer
- Endocrinology Department, Reims University Hospitals, Robert Debré Hospital, Reims, France
| | - E Disse
- Endocrinology Department, Lyon University Hospitals, South Lyon Civil Hospital, Lyon University, Pierre Benite, France
| | - N Dubois
- Nutrition Department, Assistance Publique-Hôpitaux de Marseille, La Conception Hospital, Marseille, France
| | - B Eymard
- Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Myology Institute, Sorbonne University, Paris, France
| | - B Fève
- Endocrinology, Diabetology and Reproductive Endocrinology Department, Assistance Publique-Hôpitaux de Paris, Saint-Antoine University Hospital, National Reference Center for Rare Diseases of Insulin Secretion and Insulin Sensitivity (PRISIS), Paris, France.,Sorbonne University, Inserm UMR_S938, Saint-Antoine Research Centre, Institute of Cardiometabolism and Nutrition, Paris, France
| | - O Lascols
- Sorbonne University, Inserm UMR_S938, Saint-Antoine Research Centre, Institute of Cardiometabolism and Nutrition, Paris, France.,Molecular Biology and Genetics Department, Assistance Publique-Hôpitaux de Paris, Saint-Antoine University Hospital, Paris, France
| | - P Mathurin
- Hepatology Department, Lille 2 University Hospitals, Lille University, Lille, France
| | - E Nobécourt
- Endocrinology Department, La Reunion University Hospitals, Reunion South Hospital, St Pierre de la Reunion, France
| | - A Poujol-Robert
- Hepatology Department, Assistance Publique-Hôpitaux de Paris, Saint-Antoine Hospital, Sorbonne University, Paris, France
| | - G Prevost
- Endocrinology Department, Rouen University Hospitals, Bois-Guillaume Hospital, Rouen, France
| | - P Richard
- Cardiogenetics and Myogenetics Department, Assistance Publique-Hôpitaux de Paris, Pitie Salpêtrière Hospital, Sorbonne University, Paris, France
| | - J Sellam
- Sorbonne University, Inserm UMR_S938, Saint-Antoine Research Centre, Institute of Cardiometabolism and Nutrition, Paris, France.,Rhumatology Department, Assistance Publique-Hôpitaux de Paris, Saint-Antoine Hospital, Sorbonne University, Paris, France
| | - I Tauveron
- Endocrinology Department, Clermont-Ferrand University Hospital, Clermont Auvergne University, Clermont-Ferrand, France
| | - D Treboz
- French Lipodystrophy Association (AFLIP; Association Française des Lipodystrophies), Pierrevert, France
| | - B Vergès
- Endocrinology-Diabetology Department, Dijon University Hospital, François Mitterand Hospital, Bourgogne University, Dijon, France
| | - V Vermot-Desroches
- Endocrinology, Diabetology and Reproductive Endocrinology Department, Assistance Publique-Hôpitaux de Paris, Saint-Antoine University Hospital, National Reference Center for Rare Diseases of Insulin Secretion and Insulin Sensitivity (PRISIS), Paris, France
| | - K Wahbi
- Cardiology Department, Assistance Publique-Hôpitaux de Paris, Cochin Hospital, Paris University, Paris, France
| | - I Jéru
- Sorbonne University, Inserm UMR_S938, Saint-Antoine Research Centre, Institute of Cardiometabolism and Nutrition, Paris, France.,Molecular Biology and Genetics Department, Assistance Publique-Hôpitaux de Paris, Saint-Antoine University Hospital, Paris, France
| | - M C Vantyghem
- Endocrinology Department, Lille 2 University Hospitals, Lille University, Lille, France
| | - C Vigouroux
- Endocrinology, Diabetology and Reproductive Endocrinology Department, Assistance Publique-Hôpitaux de Paris, Saint-Antoine University Hospital, National Reference Center for Rare Diseases of Insulin Secretion and Insulin Sensitivity (PRISIS), Paris, France. .,Sorbonne University, Inserm UMR_S938, Saint-Antoine Research Centre, Institute of Cardiometabolism and Nutrition, Paris, France. .,Molecular Biology and Genetics Department, Assistance Publique-Hôpitaux de Paris, Saint-Antoine University Hospital, Paris, France.
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27
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Stockdale AJ, Kreuels B, Shawa IT, Meiring JE, Thindwa D, Silungwe NM, Chetcuti K, Joekes E, Mbewe M, Mbale B, Patel P, Kachala R, Patel PD, Malewa J, Finch P, Davis C, Shah R, Tong L, da Silva Filipe A, Thomson EC, Geretti AM, Gordon MA. A clinical and molecular epidemiological survey of hepatitis C in Blantyre, Malawi, suggests a historic mechanism of transmission. J Viral Hepat 2022; 29:252-262. [PMID: 35075742 PMCID: PMC9305194 DOI: 10.1111/jvh.13646] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Accepted: 01/06/2022] [Indexed: 12/09/2022]
Abstract
Hepatitis C virus (HCV) is a leading cause of liver disease worldwide. There are no previous representative community HCV prevalence studies from Southern Africa, and limited genotypic data. Epidemiological data are required to inform an effective public health response. We conducted a household census-based random sampling serological survey, and a prospective hospital-based study of patients with cirrhosis and hepatocellular carcinoma (HCC) in Blantyre, Malawi. We tested participants with an HCV antigen/antibody ELISA (Monolisa, Bio-Rad), confirmed with PCR (GeneXpert, Cepheid) and used line immunoassay (Inno-LIA, Fujiribio) for RNA-negative participants. We did target-enrichment whole-genome HCV sequencing (NextSeq, Illumina). Among 96,386 censused individuals, we randomly selected 1661 people aged ≥16 years. Population-standardized HCV RNA prevalence was 0.2% (95% CI 0.1-0.5). Among 236 patients with cirrhosis and HCC, HCV RNA prevalence was 1.9% and 5.0%, respectively. Mapping showed that HCV RNA+ patients were from peri-urban areas surrounding Blantyre. Community and hospital HCV RNA+ participants were older than comparator HCV RNA-negative populations (median 53 vs 30 years for community, p = 0.01 and 68 vs 40 years for cirrhosis/HCC, p < 0.001). Endemic HCV genotypes (n = 10) were 4v (50%), 4r (30%) and 4w (10%). In this first census-based community serological study in Southern Africa, HCV was uncommon in the general population, was centred on peri-urban regions and was attributable for <5% of liver disease. HCV infection was observed only among older people, suggesting a historic mechanism of transmission. Genotype 4r, which has been associated with treatment failure with ledipasvir and daclatasvir, is endemic.
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Affiliation(s)
- Alexander J Stockdale
- Malawi-Liverpool-Wellcome Trust Programme, Blantyre, Malawi.,Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK
| | - Benno Kreuels
- Department of Tropical Medicine, Bernhard Nocht Institute for Tropical Medicine and 1st Department of Medicine, University Medical Centre, Hamburg-Eppendorf, Hamburg, Germany.,Kamuzu University of Health Sciences, Blantyre, Malawi
| | - Isaac T Shawa
- Malawi-Liverpool-Wellcome Trust Programme, Blantyre, Malawi.,Kamuzu University of Health Sciences, Blantyre, Malawi
| | - James E Meiring
- Malawi-Liverpool-Wellcome Trust Programme, Blantyre, Malawi.,Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK
| | - Deus Thindwa
- Malawi-Liverpool-Wellcome Trust Programme, Blantyre, Malawi.,Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK
| | | | - Karen Chetcuti
- Malawi-Liverpool-Wellcome Trust Programme, Blantyre, Malawi.,Kamuzu University of Health Sciences, Blantyre, Malawi
| | | | - Maurice Mbewe
- Malawi-Liverpool-Wellcome Trust Programme, Blantyre, Malawi
| | | | | | - Rabson Kachala
- Malawi Ministry of Health, Capitol Hill, Lilongwe, Malawi
| | | | - Jane Malewa
- Kamuzu University of Health Sciences, Blantyre, Malawi.,Department of Medicine, Queen Elizabeth Central Hospital, Blantyre, Malawi
| | - Peter Finch
- Kamuzu University of Health Sciences, Blantyre, Malawi.,Department of Medicine, Queen Elizabeth Central Hospital, Blantyre, Malawi
| | - Chris Davis
- MRC - University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK
| | - Rajiv Shah
- MRC - University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK
| | - Lily Tong
- MRC - University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK
| | - Ana da Silva Filipe
- MRC - University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK
| | - Emma C Thomson
- MRC - University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK
| | - Anna Maria Geretti
- Department of Infectious Diseases, Fondazione PTV, Faculty of Medicine, University of Rome Tor Vergata, Rome, Italy
| | - Melita A Gordon
- Malawi-Liverpool-Wellcome Trust Programme, Blantyre, Malawi.,Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.,Kamuzu University of Health Sciences, Blantyre, Malawi
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28
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Unalp-Arida A, Ruhl CE. Transient Elastography-Assessed Hepatic Steatosis and Fibrosis Are Associated With Body Composition in the United States. Clin Gastroenterol Hepatol 2022; 20:e808-e830. [PMID: 33549867 DOI: 10.1016/j.cgh.2021.02.009] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Revised: 01/28/2021] [Accepted: 02/02/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS We examined transient elastography assessed hepatic steatosis and fibrosis distributions and relationships with body composition in a representative United States population sample. METHODS Liver stiffness and controlled attenuation parameter (CAP) were assessed on 4870 non-Hispanic White, non-Hispanic Black, non-Hispanic Asian, and Hispanic men and women aged 20 years and over in the National Health and Nutrition Examination Survey (NHANES) 2017-2018. Participants underwent anthropometry and dual-energy x-ray absorptiometry (DXA). RESULTS Compared to women, men had higher mean CAP (274.2 dB/m vs 254.4 dB/m) and liver stiffness (6.4 kPa vs 5.5 kPa). CAP and liver stiffness increased through middle age and markedly with BMI. In multivariate-adjusted analysis, CAP in the upper quartile was associated with increased age, BMI, waist-to-hip ratio, diabetes, hypertension, alanine aminotransferase (ALT) and C-reactive protein and decreased HDL cholesterol. After adjustment, non-Hispanic Blacks had lower CAP and non-Hispanic Asians had higher CAP. In multivariate-adjusted analysis, liver stiffness in the upper quartile was associated with male sex, increased age, BMI, diabetes, hepatitis C virus positivity, ALT and CAP. Lower stiffness among Non-Hispanic Asians was not significant after adjustment for BMI. DXA trunk and extremity fat mass were positively related to both CAP and liver stiffness with multivariate adjustment (P < .001 for each). Results were similar with CAP and liver stiffness as continuous characteristics. CONCLUSIONS In the United States population, increased anthropometric and DXA body composition measures were associated with higher CAP and liver stiffness. Racial-ethnic differences observed merit further research to elucidate the burden of obesity and liver health disparities.
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Affiliation(s)
- Aynur Unalp-Arida
- National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland
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Rojas-Suárez J, Contreras-Arrieta S, Santacruz J, Julio J, Cueter M, Carrasquilla D, Anichiarico W, Yepes I. Residual Liver Stiffness in the Postpartum Period in Women with Preeclampsia and Healthy Women: A Case-Control Study. Pregnancy Hypertens 2022; 28:156-161. [DOI: 10.1016/j.preghy.2022.04.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Revised: 04/09/2022] [Accepted: 04/11/2022] [Indexed: 02/07/2023]
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Lee DH, Sung SU, Lee YK, Lim IH, Jang H, Joo SK, Park JH, Chang MS, So YH, Kim W. A sequential approach using the age-adjusted fibrosis-4 index and vibration-controlled transient elastography to detect advanced fibrosis in Korean patients with non-alcoholic fatty liver disease. Aliment Pharmacol Ther 2022; 55:994-1007. [PMID: 35005800 DOI: 10.1111/apt.16766] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Revised: 09/02/2021] [Accepted: 12/24/2021] [Indexed: 12/09/2022]
Abstract
BACKGROUND AND AIMS Vibration-controlled transient elastography (VCTE) has shown good diagnostic performance in predicting fibrosis stages in patients with non-alcoholic fatty liver disease (NAFLD). However, an optimal diagnostic approach to detect advanced fibrosis in patients with NAFLD has not been established. APPROACH AND RESULTS We prospectively collected data from 539 subjects who underwent liver biopsy at a single centre between January 2014 and December 2019. Diagnostic performance was estimated using the area under the receiver-operating characteristic curve (AUROC). Several models combining the fibrosis 4 index (FIB-4) score and liver stiffness measurement (LSM) were analysed to reduce the need for unnecessary liver biopsies. We observed significant fibrosis (≥F2), advanced fibrosis (≥F3) and cirrhosis (F4) in 173 (32.1%), 74 (13.7%) and 46 subjects (8.5%), respectively. The AUROCs (95% CI) for LSMs to diagnose ≥F2, ≥F3 and F4 were 0.82 (0.78-0.85), 0.92 (0.89-0.94) and 0.95 (0.93-0.97), respectively. Optimal LSM cut-off values were 6.7 (≥F2), 8.3 (≥F3) and 9.8 (F4) kPa. LSMs were affected by waist circumference, serum albumin and fibrosis stage (R2 = 0.315). Abdominal obesity, elevated transaminase, diabetes mellitus and high IQR/Median were associated with the discordance of ≥2 fibrosis stages between LSMs and histologic data. The sequential use of the age-adjusted FIB-4 and LSMs yielded the least uncertainty (5.3%) in classifying disease severity with the highest diagnostic accuracy (81%) among a variety of non-invasive test combinations. CONCLUSIONS The sequential approach of age-adjusted FIB-4 and VCTE could represent a practical diagnostic strategy to detect advanced fibrosis in NAFLD (ClinicalTrials.gov #NCT02206841).
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Affiliation(s)
- Dong Hyeon Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of Korea
| | - Se Un Sung
- Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Yun Kyu Lee
- Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Ik Hyeon Lim
- Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Heejoon Jang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of Korea
| | - Sae Kyoung Joo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of Korea
| | - Jeong Hwan Park
- Department of Pathology, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of Korea
| | - Mee Soo Chang
- Department of Pathology, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of Korea
| | - Young Ho So
- Department of Radiology, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of Korea
| | - Won Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of Korea
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31
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Siegel L, Murad MH, Riley RD, Bazerbachi F, Wang Z, Chu H. A Guide to Estimating the Reference Range From a Meta-Analysis Using Aggregate or Individual Participant Data. Am J Epidemiol 2022; 191:948-956. [PMID: 35102410 DOI: 10.1093/aje/kwac013] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Revised: 12/09/2021] [Accepted: 01/21/2022] [Indexed: 12/16/2022] Open
Abstract
Clinicians frequently must decide whether a patient's measurement reflects that of a healthy "normal" individual. Thus, the reference range is defined as the interval in which some proportion (frequently 95%) of measurements from a healthy population is expected to fall. One can estimate it from a single study or preferably from a meta-analysis of multiple studies to increase generalizability. This range differs from the confidence interval for the pooled mean and the prediction interval for a new study mean in a meta-analysis, which do not capture natural variation across healthy individuals. Methods for estimating the reference range from a meta-analysis of aggregate data that incorporates both within- and between-study variations were recently proposed. In this guide, we present 3 approaches for estimating the reference range: one frequentist, one Bayesian, and one empirical. Each method can be applied to either aggregate or individual-participant data meta-analysis, with the latter being the gold standard when available. We illustrate the application of these approaches to data from a previously published individual-participant data meta-analysis of studies measuring liver stiffness by transient elastography in healthy individuals between 2006 and 2016.
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32
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Valenti L, Pelusi S, Bianco C, Ceriotti F, Berzuini A, Iogna Prat L, Trotti R, Malvestiti F, D'Ambrosio R, Lampertico P, Colli A, Colombo M, Tsochatzis EA, Fraquelli M, Prati D. Definition of Healthy Ranges for Alanine Aminotransferase Levels: A 2021 Update. Hepatol Commun 2021; 5:1824-1832. [PMID: 34520121 PMCID: PMC8557310 DOI: 10.1002/hep4.1794] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Revised: 06/22/2021] [Accepted: 07/02/2021] [Indexed: 12/12/2022] Open
Abstract
The changing epidemiology of liver disease, and modifications in the recommended analytical methodology call for a re-evaluation of the upper reference limits (URLs) of alanine aminotransferase (ALT) levels. Using the same approach consolidated 20 years ago to define the healthy population, we defined the URL for the newly recommended International Federation of Clinical Chemistry (IFCC) standardized test. In a cross-sectional study, we examined 21,296 apparently healthy blood donors (age 18-65 years) and calculated the sex-specific URL by the 95th percentile in individuals without risk factors for liver disease. These were tested for the ability to predict liver damage in a subset of 745 participants with dysmetabolism, in an independent cohort of 977 unselected donors, and in 899 patients with chronic liver disease. ALT levels were measured by the IFCC test. Male sex, body mass index, glucose, lipids, ferritin, hypertension, and younger age were independent ALT predictors (P < 0.001). Updated URLs were identified at 42/30 U/L in males/females, approximately 30% lower than those currently recommended by the IFCC. Due to improved sensitivity, they conferred the ability to detect steatosis and significant fibrosis in individuals with dysmetabolism (odds ratio [OR] = 2.31, range 1.40-3.80, P = 0.001; and OR = 3.35, range 1.19-9.42, P = 0.021; respectively), although with a limited accuracy, and significant fibrosis in unselected donors (OR = 2.32, 1.02-5.31, P = 0.045). Updated URLs had a moderate to high accuracy to discriminate liver conditions (area under the receiver operating characteristic curve = 0.81, range 0.78-0.91). Conclusion: Updated URLs by the IFCC method were lower than those calculated in initial studies, but higher than those in use with the recommended old, nonstandardized method, and were able to better predict liver disease. The limited awareness that different techniques are still in use should be regarded as a possible source of medical errors.
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Affiliation(s)
- Luca Valenti
- Department of Pathophysiology and TransplantationUniversità degli Studi di MilanoMilanItaly.,Department of Transfusion Medicine and HaematologyFondazione IRCCS Ca' Granda Ospedale Maggiore PoliclinicoMilanItaly
| | - Serena Pelusi
- Department of Pathophysiology and TransplantationUniversità degli Studi di MilanoMilanItaly.,Department of Transfusion Medicine and HaematologyFondazione IRCCS Ca' Granda Ospedale Maggiore PoliclinicoMilanItaly
| | - Cristiana Bianco
- Department of Transfusion Medicine and HaematologyFondazione IRCCS Ca' Granda Ospedale Maggiore PoliclinicoMilanItaly.,Department of MedicineUdine HospitalUdineItaly
| | - Ferruccio Ceriotti
- Clinical LaboratoryFondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico MilanMilanItaly
| | - Alessandra Berzuini
- Department of Transfusion Medicine and HaematologyFondazione IRCCS Ca' Granda Ospedale Maggiore PoliclinicoMilanItaly
| | - Laura Iogna Prat
- UCL Institute for Liver and Digestive HealthRoyal Free Hospital and UCLLondonUnited Kingdom
| | - Roberta Trotti
- Department of Transfusion Medicine and HaematologyFondazione IRCCS Ca' Granda Ospedale Maggiore PoliclinicoMilanItaly
| | - Francesco Malvestiti
- Department of Pathophysiology and TransplantationUniversità degli Studi di MilanoMilanItaly.,Department of Transfusion Medicine and HaematologyFondazione IRCCS Ca' Granda Ospedale Maggiore PoliclinicoMilanItaly
| | - Roberta D'Ambrosio
- Division of Gastroenterology and HepatologyFondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico MilanMilanItaly
| | - Pietro Lampertico
- Division of Gastroenterology and HepatologyFondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico MilanMilanItaly.,CRC "A. M. and A. Migliavacca" Center for Liver DiseaseDepartment of Pathophysiology and TransplantationUniversity of MilanMilanItaly
| | - Agostino Colli
- Department of Transfusion Medicine and HaematologyFondazione IRCCS Ca' Granda Ospedale Maggiore PoliclinicoMilanItaly
| | | | - Emmanuel A Tsochatzis
- UCL Institute for Liver and Digestive HealthRoyal Free Hospital and UCLLondonUnited Kingdom
| | - Mirella Fraquelli
- Department of Gastroenterology and EndoscopyFondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico MilanMilanItaly
| | - Daniele Prati
- Department of Transfusion Medicine and HaematologyFondazione IRCCS Ca' Granda Ospedale Maggiore PoliclinicoMilanItaly
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Francque SM, Marchesini G, Kautz A, Walmsley M, Dorner R, Lazarus JV, Zelber-Sagi S, Hallsworth K, Busetto L, Frühbeck G, Dicker D, Woodward E, Korenjak M, Willemse J, Koek GH, Vinker S, Ungan M, Mendive JM, Lionis C. Non-alcoholic fatty liver disease: A patient guideline. JHEP Rep 2021; 3:100322. [PMID: 34693236 PMCID: PMC8514420 DOI: 10.1016/j.jhepr.2021.100322] [Citation(s) in RCA: 131] [Impact Index Per Article: 32.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Accepted: 06/08/2021] [Indexed: 02/07/2023] Open
Abstract
This patient guideline is intended for all patients at risk of or living with non-alcoholic fatty liver disease (NAFLD). NAFLD is the most frequent chronic liver disease worldwide and comes with a high disease burden. Yet, there is a lot of unawareness. Furthermore, many aspects of the disease are still to be unravelled, which has an important impact on the information that is given (or not) to patients. Its management requires a close interaction between patients and their many healthcare providers. It is important for patients to develop a full understanding of NAFLD in order to enable them to take an active role in their disease management. This guide summarises the current knowledge relevant to NAFLD and its management. It has been developed by patients, patient representatives, clinicians and scientists and is based on current scientific recommendations, intended to support patients in making informed decisions.
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Key Words
- ALD, alcohol-related or alcoholic liver disease
- ASH, alcoholic steatohepatitis
- BMI, body mass index
- CAP, controlled attenuation parameter
- CT, computed tomography
- CVD, cardiovascular disease
- EASD, European Association for the Study of Diabetes
- EASL, European Association for the Study of the Liver
- EASO, European Association for the Study of Obesity
- FIB-4, fibrosis-4 index
- FXR, farnesoid X receptor
- GLP-1 RAs, glucagon-like receptor 1 agonists
- GP, general practitioner
- HCC, hepatocellular carcinoma
- HDL, high-density lipoprotein
- LDL, low-density lipoproteins
- MRE, magnetic resonance elastography
- MRI, magnetic resonance imaging
- NAFL, non-alcoholic fatty liver
- NAFLD, non-alcoholic fatty liver disease
- NASH CRN, NASH Clinical Research Network
- NASH, non-alcoholic steatohepatitis
- NIT, non-invasive test
- SMART, specific, measurable, achievable, relevant, timely
- T1D, type 1 diabetes
- T2D, type 2 diabetes
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Affiliation(s)
- Sven M. Francque
- Department of Gastroenterology and Hepatology, Antwerp University Hospital, Antwerp, Belgium
- Laboratory of Experimental Medicine and Paediatrics (LEMP), Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
- InflaMed Centre of Excellence, University of Antwerp, Antwerp, Belgium
- Translational Sciences in Inflammation and Immunology, University of Antwerp, Antwerp, Belgium
| | - Giulio Marchesini
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy
- Department of Medical and Surgical Sciences, “Alma Mater” University, Bologna, Italy
| | | | | | | | - Jeffrey V. Lazarus
- Barcelona Institute for Global Health (ISGlobal), Hospital Clínic, University of Barcelona, Spain
| | - Shira Zelber-Sagi
- School of Public Health, Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa, Israel
- Department of Gastroenterology and Hepatology, The Tel-Aviv Medical Center, Tel-Aviv, Israel
| | - Kate Hallsworth
- Newcastle NIHR Biomedical Research Centre, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
| | - Luca Busetto
- Department of Medicine, University of Padova, Italy
- European Association for the Study of Obesity
| | - Gema Frühbeck
- Department of Endocrinology & Nutrition, University of Navarra Clinic, IdiSNA, CIBEROBN, Pamplona, Spain
- European Association for the Study of Obesity
| | - Dror Dicker
- Department of Internal Medicine, Rabin Medical Center Hasharon Hospital, Tikva, Israel
- European Association for the Study of Obesity
| | | | | | | | - Gerardus H. Koek
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre, Maastricht, the Netherlands
- School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands
| | - Shlomo Vinker
- Department of Family Medicine, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- World Organization of Family Doctors (WONCA)
- European General Practice Research Network (EGPRN)
- Israel Association of Family Physicians, Israel
- Leumit Health Services, Tel Aviv, Israel
| | | | - Juan M. Mendive
- Training Unit of Family Medicine, Catalan Institute of Health, Barcelona, Spain
- European Society for Primary Care Gastroenterology
| | - Christos Lionis
- European Society for Primary Care Gastroenterology
- Clinic of Social and Family Medicine, School of Medicine, University of Crete, Heraklion, Greece
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34
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Cao W, Siegel L, Zhou J, Zhu M, Tong T, Chen Y, Chu H. Estimating the reference interval from a fixed effects meta-analysis. Res Synth Methods 2021; 12:630-640. [PMID: 33864652 PMCID: PMC8924903 DOI: 10.1002/jrsm.1488] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Revised: 03/14/2021] [Accepted: 03/30/2021] [Indexed: 11/09/2022]
Abstract
A reference interval provides a basis for physicians to determine whether a measurement is typical of a healthy individual. It can be interpreted as a prediction interval for a new individual from the overall population. However, a reference interval based on a single study may not be representative of the broader population. Meta-analysis can provide a general reference interval based on the overall population by combining results from multiple studies. Methods for estimating the reference interval from a random effects meta-analysis have been recently proposed to incorporate the within and between-study variation, but a random effects model may give imprecise estimates of the between-study variation with only few studies. In addition, the normal distribution of underlying study-specific means, and equal within-study variance assumption in these methods may be inappropriate in some settings. In this article, we aim to estimate the reference interval based on the fixed effects model assuming study effects are unrelated, which is useful for a meta-analysis with only a few studies (e.g., ≤5). We propose a mixture distribution method only assuming parametric distributions (e.g., normal) for individuals within each study and integrating them to form the overall population distribution. This method is compared to an empirical method only assuming a parametric overall population distribution. Simulation studies have shown that both methods can estimate a reference interval with coverage close to the targeted value (i.e., 95%). Meta-analyses of women daytime urination frequency and frontal subjective postural vertical measurements are reanalyzed to demonstrate the application of our methods.
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Affiliation(s)
- Wenhao Cao
- Division of Biostatistics, University of Minnesota, Minneapolis, Minnesota, USA
| | - Lianne Siegel
- Division of Biostatistics, University of Minnesota, Minneapolis, Minnesota, USA
| | - Jincheng Zhou
- Center for Design & Analysis, Amgen Inc., Thousand Oaks, California, USA
| | - Motao Zhu
- The Center for Injury Research and Policy, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, Ohio, USA
| | - Tiejun Tong
- Department of Mathematics, Hong Kong Baptist University, Kowloon Tong, Hong Kong
| | - Yong Chen
- Department of Biostatistics, Epidemiology and Informatics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Haitao Chu
- Division of Biostatistics, University of Minnesota, Minneapolis, Minnesota, USA
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35
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Foschi FG, Domenicali M, Giacomoni P, Dall'Aglio AC, Conti F, Borghi A, Bevilacqua V, Napoli L, Mirici F, Cucchetti A, Ercolani G, Gardini AC, Bellentani S, Gastaldelli A, Giuffrè M, Tiribelli C, Bedogni G. Is there an association between commonly employed biomarkers of liver fibrosis and liver stiffness in the general population? Ann Hepatol 2021; 19:380-387. [PMID: 32451205 DOI: 10.1016/j.aohep.2020.04.003] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2020] [Revised: 04/29/2020] [Accepted: 04/29/2020] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND OBJECTIVES Surrogate biomarkers of liver fibrosis developed in tertiary care are increasingly used in general populations. We evaluated the association between liver stiffness (LS) and five continuous (AST/ALT, APRI, Forns Index, FIB-4, GGT) and two discrete biomarkers (BARD, BAAT) in a general population. PATIENTS AND METHODS 636 (29%) of the 2159 citizens of the Bagnacavallo Study had LS measured by transient elastography. Using linear regression with univariate multiple imputation, we evaluated the association of LS with the above biomarkers in the total sample of 2159 citizens. RESULTS The mean change of LS between the 5th and 95th internal percentile of any continuous biomarker was ≤1kPa. The mean change of LS between scores 0 and 3 of BARD and scores 0 and ≥3 of BAAT was >1kPa but of doubtful clinical relevance. CONCLUSION We found a modest association between LS and seven biomarkers of liver fibrosis in a general population.
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Affiliation(s)
| | - Marco Domenicali
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | | | | | - Fabio Conti
- Department of Internal Medicine, Ospedale di Faenza, AUSL Romagna, Italy
| | - Alberto Borghi
- Department of Internal Medicine, Ospedale di Faenza, AUSL Romagna, Italy
| | | | - Lucia Napoli
- Department of Internal Medicine, Ospedale di Faenza, AUSL Romagna, Italy
| | - Federica Mirici
- Department of Internal Medicine, Ospedale di Faenza, AUSL Romagna, Italy
| | - Alessandro Cucchetti
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Giorgio Ercolani
- Department of Internal Medicine, Ospedale di Faenza, AUSL Romagna, Italy
| | - Andrea Casadei Gardini
- Department of Oncology and Hematology, Division of Oncology, University of Modena and Reggio Emilia, Modena, Italy
| | | | - Amalia Gastaldelli
- Institute of Clinical Physiology, National Research Council, Pisa, Italy
| | - Mauro Giuffrè
- Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy
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Stadlbauer V, Negrean I, Posch A, Streit A, Feldbacher N, Stauber RE, Horvath A. Fibroscan® probe selection for lean adults. JGH OPEN 2021; 5:750-753. [PMID: 34263068 PMCID: PMC8264238 DOI: 10.1002/jgh3.12579] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/02/2021] [Revised: 05/10/2021] [Accepted: 05/18/2021] [Indexed: 11/19/2022]
Abstract
Background and Aim Fibroscan® is used to assess fibrosis and steatosis of the liver noninvasively. The company suggests to use the S+‐probe in people <18 years with a thoracic circumference (TC) between 45 and 75 cm and the M+‐probe in children with a TC >75 cm and adults with a skin–liver capsule distance <2.5 cm. For lean adults with a TC ≤75 cm, no comparative studies have been performed. Furthermore, it is unclear whether lean adults need to be fasted before assessment. Methods We compared liver stiffness (LS) using Fibroscan® S+‐ and M+‐probes and controlled attenuation parameter (CAP; only available for M+‐probe) in healthy volunteers with a TC ≤75 cm compared with those with a TC >75 cm in fasting state and after intake of a standardized light meal (300 kcal). Results We examined 50 volunteers (26 female, 24 ± 3 years). Twenty‐two participants were in the TC ≤75 cm group and 28 in TC >75 cm group. LS values with the S+‐probe were 15% higher than with the M+‐probe in both groups (median difference 0.6 kPa, P < 0.001). Both probes showed good agreement with minimal bias (Spearman correlation r = 0.754, P < 0.001; Interclass Correlation Coefficient 0.843, P < 0.001; Bland–Altman bias 0.6 ± 0.9 kPa, linear regression r2 = 0.557, P < 0.001). Intake of a light meal had no relevant influence on LS (S+‐ and M+‐probes) or CAP measurements (M+‐probe) in both groups. Conclusion Lean adults with a TC below 75 cm can be assessed with either the S+‐probe or the M+‐probe and may take a light meal before assessment.
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Affiliation(s)
- Vanessa Stadlbauer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine Medical University of Graz Graz Austria
| | - Iohanes Negrean
- Division of Gastroenterology and Hepatology, Department of Internal Medicine Medical University of Graz Graz Austria
| | - Andreas Posch
- Division of Gastroenterology and Hepatology, Department of Internal Medicine Medical University of Graz Graz Austria
| | - Andrea Streit
- Division of Gastroenterology and Hepatology, Department of Internal Medicine Medical University of Graz Graz Austria
| | - Nicole Feldbacher
- Division of Gastroenterology and Hepatology, Department of Internal Medicine Medical University of Graz Graz Austria.,Area 3 Cardiometabolic Health Center for Biomarker Research in Medicine (CBmed) Graz Austria
| | - Rudolf E Stauber
- Division of Gastroenterology and Hepatology, Department of Internal Medicine Medical University of Graz Graz Austria
| | - Angela Horvath
- Division of Gastroenterology and Hepatology, Department of Internal Medicine Medical University of Graz Graz Austria.,Area 3 Cardiometabolic Health Center for Biomarker Research in Medicine (CBmed) Graz Austria
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37
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Miyoshi T, Hamaguchi M, Kitagawa N, Hashimoto Y, Fukui M. Correlation between Liver Stiffness by Two-Dimensional Shear Wave Elastography and Waist Circumference in Japanese Local Citizens with Abdominal Obesity. J Clin Med 2021; 10:jcm10091971. [PMID: 34064337 PMCID: PMC8125660 DOI: 10.3390/jcm10091971] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 04/23/2021] [Accepted: 04/30/2021] [Indexed: 12/13/2022] Open
Abstract
Background: Various factors other than fibrosis could affect liver stiffness (LS), measured by two-dimensional shear wave elastography (2D-SWE). We aimed to clarify the factors affecting LS in local citizens. Methods: We performed a cross-sectional study among local citizens of a health checkup program. Abdominal obesity was defined as waist circumference ≥85 cm for men and ≥90 cm for women. We evaluated the correlation between LS by 2D-SWE (Aplio 500) and waist circumference with linear regression analyses. We selected the following items as variables in the multivariate analysis: waist circumference, sex, hypertension, diabetes, diagnostic components of metabolic syndrome, γ−glutamyl transpeptidase, total bilirubin, NAFLD fibrosis score, and an indicator of a fatty liver, evaluated ultrasonographically. Results: Overall, 345 individuals were included; 318 (181 men and 137 women; age, 63.4 years; waist circumference, 84.0 cm; LS, 5.79 kPa) were analyzed, 128 of whom had abdominal obesity and significantly higher LS than non-abdominally obese individuals. In the multivariate analysis, waist circumference was positively, independently, and significantly correlated with LS only in abdominally obese individuals. Conclusions: Liver stiffness by 2D-SWE could increase with increases in waist circumference in local citizens with abdominal obesity. Physicians should pay attention when assessing the LS of abdominally obese individuals.
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Affiliation(s)
- Tomoki Miyoshi
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan; (T.M.); (Y.H.); (M.F.)
| | - Masahide Hamaguchi
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan; (T.M.); (Y.H.); (M.F.)
- Correspondence: ; Tel.: +81-75-251-5506
| | - Noriyuki Kitagawa
- Department of Diabetology, Kameoka Municipal Hospital, Kameoka 621-8585, Japan;
| | - Yoshitaka Hashimoto
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan; (T.M.); (Y.H.); (M.F.)
| | - Michiaki Fukui
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan; (T.M.); (Y.H.); (M.F.)
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38
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Nandi N, Fraquelli M. The role of elastography in viral hepatitis and autoimmune hepatitis. Minerva Gastroenterol (Torino) 2021; 67:141-150. [PMID: 34027931 DOI: 10.23736/s2724-5985.21.02788-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The prognosis of chronic liver diseases, which represent a major public health problem, is mainly linked to the extent and progression of liver fibrosis and the subsequent risk of developing cirrhosis and related complications, mainly hepatocellular carcinoma. During the past decade many noninvasive methods and in particular electrographic techniques, have been developed to reduce the need for liver biopsy in staging fibrosis and to overcome whenever possible its limitations, mainly: invasiveness, costs, low reproducibility and poor acceptance by patients. The aim of this review was to provide a comprehensive review of the role of elastography techniques in viral chronic liver diseases and autoimmune hepatitis, with the focus on the possible advantages and limitations of these techniques and on their diagnostic accuracy in predicting the stage of liver fibrosis.
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Affiliation(s)
- Nicoletta Nandi
- Unit of Gastroenterology and Endoscopy, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
| | - Mirella Fraquelli
- Unit of Gastroenterology and Endoscopy, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy -
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Siddappa PK, Hawa F, Prokop LJ, Murad MH, Abu Dayyeh BK, Chandrasekhara V, Topazian MD, Bazerbachi F. Endoscopic pancreatic duct stenting for pain palliation in selected pancreatic cancer patients: a systematic review and meta-analysis. Gastroenterol Rep (Oxf) 2021; 9:105-114. [PMID: 34026217 PMCID: PMC8128017 DOI: 10.1093/gastro/goab001] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2020] [Revised: 01/03/2021] [Accepted: 01/05/2021] [Indexed: 12/15/2022] Open
Abstract
Background Abdominal pain is a debilitating symptom affecting ∼80% of pancreatic cancer (PC) patients. Pancreatic duct (PD) decompression has been reported to alleviate this pain, although this practice has not been widely adopted. We aimed to evaluate the role, efficacy, and safety of endoscopic PD decompression for palliation of PC post-prandial obstructive-type pain. Methods A systematic review until 7 October 2020 was performed. Two independent reviewers selected studies, extracted data, and assessed the methodological quality. Results We identified 12 publications with a total of 192 patients with PC presenting with abdominal pain, in whom PD decompression was attempted, and was successful in 167 patients (mean age 62.5 years, 58.7% males). The use of plastic stents was reported in 159 patients (95.2%). All included studies reported partial or complete improvement in pain levels after PD stenting, with an improvement rate of 93% (95% confidence interval, 79%–100%). The mean duration of pain improvement was 94 ± 16 days. Endoscopic retrograde cholangiopancreatography (ERCP)-related adverse events (AEs) were post-sphincterotomy bleeding (1.8%), post-ERCP pancreatitis (0.6%), and hemosuccus pancreaticus (0.6%). AEs were not reported in two patients who underwent endoscopic ultrasound-guided PD decompression. In the 167 patients with technical success, the stent-migration and stent-occlusion rates were 3.6% and 3.0%, respectively. No AE-related mortality was reported. The methodological quality assessment showed the majority of the studies having low or unclear quality. Conclusion In this exploratory analysis, endoscopic PD drainage may be an effective and safe option in selected patients for the management of obstructive-type PC pain. However, a randomized–controlled trial is needed to delineate the role of this invasive practice.
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Affiliation(s)
- Pradeep K Siddappa
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Fadi Hawa
- Department of Internal Medicine, St. Joseph Mercy Ann Arbor Hospital, Ypsilanti, MI, USA
| | - Larry J Prokop
- Library Public Services, Mayo Clinic, Rochester, MN, USA
| | - M Hassan Murad
- Robert D and Patricia E Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA
| | - Barham K Abu Dayyeh
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | | | - Mark D Topazian
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Fateh Bazerbachi
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
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Long MT, Zhang X, Xu H, Liu CT, Corey KE, Chung RT, Loomba R, Benjamin EJ. Hepatic Fibrosis Associates With Multiple Cardiometabolic Disease Risk Factors: The Framingham Heart Study. Hepatology 2021; 73:548-559. [PMID: 33125745 PMCID: PMC8515503 DOI: 10.1002/hep.31608] [Citation(s) in RCA: 65] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2020] [Revised: 09/21/2020] [Accepted: 10/06/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIMS NAFLD is increasing in prevalence and will soon be the most common chronic liver disease. Liver stiffness, as assessed by vibration-controlled transient elastography (VCTE), correlates with hepatic fibrosis, an important predictor of liver-related and all-cause mortality. Although liver fat is associated with cardiovascular risk factors, the association between hepatic fibrosis and cardiovascular risk factors is less clear. APPROACH AND RESULTS We performed VCTE, assessing controlled attenuation parameter (CAP; measure of steatosis) and liver stiffness measurement (LSM) in 3,276 Framingham Heart Study adult participants (53.9% women, mean age 54.3 ± 9.1 years) presenting for a routine study visit. We performed multivariable-adjusted logistic regression models to determine the association between LSM and obesity-related, vascular-related, glucose-related, and cholesterol-related cardiovascular risk factors. The prevalence of hepatic steatosis (CAP ≥ 290 dB/m) was 28.8%, and 8.8% had hepatic fibrosis (LSM ≥ 8.2 kPa). Hepatic fibrosis was associated with multiple cardiovascular risk factors, including increased odds of obesity (OR, 1.82; 95% CI, 1.35-2.47), metabolic syndrome (OR, 1.49; 95% CI 1.10-2.01), diabetes (OR, 2.67; 95% CI, 1.21-3.75), hypertension (OR, 1.52; 95% CI, 1.15-1.99), and low high-density lipoprotein cholesterol (OR, 1.47; 95% CI, 1.09-1.98), after adjustment for age, sex, smoking status, alcohol drinks/week, physical activity index, aminotransferases, and CAP. CONCLUSIONS In our community-based cohort, VCTE-defined hepatic fibrosis was associated with multiple cardiovascular risk factors, including obesity, metabolic syndrome, diabetes, hypertension, and high-density lipoprotein cholesterol, even after accounting for covariates and CAP. Additional longitudinal studies are needed to determine if hepatic fibrosis contributes to incident cardiovascular disease risk factors or events.
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Affiliation(s)
- Michelle T Long
- Section of GastroenterologyBoston Medical CenterBoston University School of MedicineBostonMA
| | - Xiaoyu Zhang
- Department of BiostatisticsBoston UniversityBostonMA
| | - Hanfei Xu
- Department of BiostatisticsBoston UniversityBostonMA
| | - Ching-Ti Liu
- Department of BiostatisticsBoston UniversityBostonMA
| | - Kathleen E Corey
- Liver CenterGastroenterology DivisionDepartment of MedicineMassachusetts General HospitalHarvard Medical SchoolBostonMA
| | - Raymond T Chung
- Liver CenterGastroenterology DivisionDepartment of MedicineMassachusetts General HospitalHarvard Medical SchoolBostonMA
| | - Rohit Loomba
- Division of GastroenterologyDepartment of Medicine and Division of EpidemiologyDepartment of Family and PreventiveUniversity of California at San DiegoLa JollaCA
| | - Emelia J Benjamin
- Evans Department of MedicineWhitaker Cardiovascular Institute and Cardiology SectionBoston University School of MedicineBostonMA
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Bazerbachi F, Vargas EJ, Rizk M, Maselli DB, Mounajjed T, Venkatesh SK, Watt KD, Port JD, Basu R, Acosta A, Hanouneh I, Gara N, Shah M, Mundi M, Clark M, Grothe K, Storm AC, Levy MJ, Abu Dayyeh BK. Intragastric Balloon Placement Induces Significant Metabolic and Histologic Improvement in Patients With Nonalcoholic Steatohepatitis. Clin Gastroenterol Hepatol 2021; 19:146-154.e4. [PMID: 32360804 PMCID: PMC8106130 DOI: 10.1016/j.cgh.2020.04.068] [Citation(s) in RCA: 83] [Impact Index Per Article: 20.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2020] [Revised: 04/17/2020] [Accepted: 04/24/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Obese patients with nonalcoholic steatohepatitis (NASH) are at risk for cirrhosis if significant weight loss is not achieved. The single fluid-filled intragastric balloon (IGB) induces meaningful weight loss and might be used in NASH treatment. We performed an open-label prospective study to evaluate the effects of IGB placement on metabolic and histologic features of NASH. METHODS Twenty-one patients with early hepatic fibrosis (81% female; mean age, 54 years; average body mass index, 44 kg/m2) underwent magnetic resonance elastography (MRE) and endoscopic ultrasound with core liver biopsy collection at time IGB placement and removal at a single center from October 2016 through March 2018. The primary outcome measure was the changes in liver histology parameters after IGB, including change in nonalcoholic fatty liver disease activity score (NAS) and fibrosis score. We also evaluated changes in weight, body mass index, waist to hip ratio, aminotransaminases, fasting levels of lipids, fasting glucose, glycosylated hemoglobin, and MRE-detected liver stiffness. RESULTS Six months after IGB, patients' mean total body weight loss was 11.7% ± 7.7%, with significant reductions in HbA1c (1.3% ± 0.5%) (P = .02). Waist circumference decreased by 14.4 ± 2.2 cm (P = .001). NAS improved in 18 of 20 patients (90%), with a median decrease of 3 points (range, 1-4 points); 16 of 20 patients (80%) had improvements of 2 points or more. Fibrosis improved by 1.17 stages in 15% of patients, and MRE-detected fibrosis improved by 1.5 stages in 10 of 20 patients (50%). Half of patients reached endpoints approved by the Food and Drug Administration of for NASH resolution and fibrosis improvement. Percent total body weight loss did not correlate with reductions in NAS or fibrosis. Other than post-procedural pain (in 5% of patients), no serious adverse events were reported. CONCLUSION In a prospective study, IGB facilitated significant metabolic and histologic improvements in NASH. IGB appears to be safe and effective for NASH management when combined with a prescribed diet and exercise program. ClinicalTrials.gov no: NCT02880189.
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Affiliation(s)
- Fateh Bazerbachi
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
| | - Eric J. Vargas
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Monika Rizk
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Daniel B. Maselli
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | | | | | - Kymberly D. Watt
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - John D. Port
- Department of Radiology, Mayo Clinic, Rochester, Minnesota
| | - Rita Basu
- Division of Endocrinology, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia
| | - Andres Acosta
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Ibrahim Hanouneh
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Naveen Gara
- Gastroenterology and Liver Institute, Escondido, California
| | - Meera Shah
- Division of Endocrinology, Mayo Clinic, Rochester, Minnesota
| | - Manpreet Mundi
- Division of Endocrinology, Mayo Clinic, Rochester, Minnesota
| | - Matthew Clark
- Division of Endocrinology, Mayo Clinic, Rochester, Minnesota
| | - Karen Grothe
- Division of Endocrinology, Mayo Clinic, Rochester, Minnesota
| | - Andrew C. Storm
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Michael J. Levy
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
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Bazerbachi F, Dobashi A, Kumar S, Misra S, Buttar NS, Wong Kee Song LM. Efficacy and safety of combined endoscopic cyanoacrylate injection and balloon-occluded retrograde transvenous occlusion (BRTOcc) of gastrorenal shunts in patients with bleeding gastric fundal varices. Gastroenterol Rep (Oxf) 2020; 9:212-218. [PMID: 34316370 PMCID: PMC8309684 DOI: 10.1093/gastro/goaa082] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Revised: 07/25/2020] [Accepted: 08/04/2020] [Indexed: 02/07/2023] Open
Abstract
Background Endoscopic cyanoacrylate (glue) injection of fundal varices may result in life-threatening embolic adverse events through spontaneous gastrorenal shunts (GRSs). Balloon-occluded retrograde transvenous occlusion (BRTOcc) of GRSs during cyanoacrylate injection may prevent serious systemic glue embolization through the shunt. This study aimed to evaluate the efficacy and safety of a combined endoscopic–interventional radiologic (BRTOcc) approach for the treatment of bleeding fundal varices. Methods We retrospectively analysed the data of patients who underwent the combined procedure for acutely bleeding fundal varices between January 2010 and April 2018. Data were extracted for patient demographics, clinical and endoscopic findings, technical details, and adverse events of the endoscopic–BRTOcc approach and patient outcomes. Results We identified 30 patients (13 [43.3%] women; median age 58 [range, 25–92] years) with gastroesophageal varices type 2 (53.3%, 16/30) and isolated gastric varices type 1 (46.7%, 14/30) per Sarin classification, and median clinical and endoscopic follow-up of 151 (range, 4–2,513) days and 98 (range, 3–2,373) days, respectively. The median volume of octyl-cyanoacrylate: Lipiodol injected was 7 (range, 4–22) mL. Procedure-related adverse events occurred in three (10.0%) patients, including transient fever, non-life-threatening pulmonary glue embolism, and an injection-site ulcer bleed. Complete gastric variceal obturation was achieved in 18 of 21 patients (85.7%) at endoscopic follow-up. Delayed variceal rebleeding was confirmed in one patient (3.3%) and suspected in two patients (6.7%). Although no procedure-related deaths occurred, the overall mortality rate was 46.7%, primarily from liver-disease progression and co-morbidities. Conclusion The combined endoscopic–BRTOcc procedure is a relatively safe and effective technique for bleeding fundal varices, with a high rate of variceal obturation and a low rate of serious adverse events.
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Affiliation(s)
- Fateh Bazerbachi
- Division of Gastroenterology, Interventional Endoscopy Program, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Akira Dobashi
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Swarup Kumar
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Sanjay Misra
- Vascular and Interventional Radiology, Mayo Clinic, Rochester, MN, USA
| | - Navtej S Buttar
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
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Abdelsameea E, Alsebaey A, Abdel-Razek W, Ehsan N, Morad W, Salama M, Waked I. Elastography and serum markers of fibrosis versus liver biopsy in 1270 Egyptian patients with hepatitis C. Eur J Gastroenterol Hepatol 2020; 32:1553-1558. [PMID: 31972660 DOI: 10.1097/meg.0000000000001672] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Chronic hepatitis C (CHC) is a leading cause of liver fibrosis. OBJECTIVE To compare utility of liver transient elastography, AST-to-platelet ratio index (APRI), fibrosis-4 index (FIB4), Forns Index and Goteborg University cirrhosis index (GUCI) in predicting fibrosis stage assessed by liver biopsy in Egyptian CHC patients. METHODS One thousand two-hundred and seventy CHC patients undergoing liver biopsy in preparation for therapy and 40 healthy potential living liver donors had transient elastography and calculation of APRI, FIB4, Forns and GUCI scores on the same day or day preceding the biopsy. RESULTS Mean age was 39.89 (17-60 years) and most were males (70.7%). All donors had F0 fibrosis, most patients had F1-F2 fibrosis (n = 1011, 79.6%) and 259 (20.4%) had F3-F4 fibrosis. Patients with F3-F4 fibrosis had higher median values of APRI (0.99 vs. 0.46), FIB4 (2.15 vs. 0.95) and Forns (7.34 vs. 4.79) indices, GUCI score (1.16 vs. 0.49) and transient elastography (19.2 vs. 6.2 kPa) (all P = 0.001). For F1 discrimination, AUROC of transient elastography was higher than both Forns and GUCI scores (P = 0.001). APRI, FIB4 and GUCI had lower AUROC than transient elastography for predicting fibrosis stage in F2 and F3 patients (P = 0.001). Transient elastography had the best area under receiver operating characteristic curve for predicting fibrosis stage in F4 patients (P = 0.001). The transient elastography cutoff values (kPa) were F1 (>4.8), F2 (>8.3), F3 (>10.1) and F4 (>13.4). Age, APRI, FIB4, Forns, GUCI and transient elastography were independent predictors of F3-F4 fibrosis. CONCLUSION Liver elastography is superior to APRI, FIB4, Forns and GUCI scores in predicting fibrosis in CHC patients.
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Affiliation(s)
| | | | | | | | - Wesam Morad
- Epidemiology and Preventive Medicine, National Liver Institute, Menoufia University, Shebeen El-Koom, Egypt
| | | | - Imam Waked
- Departments of Hepatology and Gastroenterology
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Li DK, Khan MR, Wang Z, Chongsrisawat V, Swangsak P, Teufel-Schäfer U, Engelmann G, Goldschmidt I, Baumann U, Tokuhara D, Cho Y, Rowland M, Mjelle AB, Ramm GA, Lewindon PJ, Witters P, Cassiman D, Ciuca IM, Prokop LD, Haffar S, Corey KE, Murad MH, Furuya KN, Bazerbachi F. Normal liver stiffness and influencing factors in healthy children: An individual participant data meta-analysis. Liver Int 2020; 40:2602-2611. [PMID: 32901449 DOI: 10.1111/liv.14658] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Revised: 08/20/2020] [Accepted: 08/22/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Although transient elastography (TE) is used to determine liver stiffness as a surrogate to hepatic fibrosis, the normal range in children is not well defined. We performed a systematic review and individual participant data (IPD) meta-analysis to determine the range of liver stiffness in healthy children and evaluate the influence of important biological parameters. METHODS We pooled data from 10 studies that examined healthy children using TE. We divided 1702 children into two groups: ≥3 years (older group) and < 3 years of age (younger group). Univariate and multivariate linear regression models predicting liver stiffness were conducted. RESULTS After excluding children with obesity, diabetes, or abnormal liver tests, 652 children were analysed. Among older children, mean liver stiffness was 4.45 kPa (95% confidence interval 4.34-4.56), and increased liver stiffness was associated with age, sedation status, and S probe use. In the younger group, the mean liver stiffness was 4.79 kPa (95% confidence interval 4.46-5.12), and increased liver stiffness was associated with sedation status and Caucasian race. In a subgroup analysis, hepatic steatosis on ultrasound was significantly associated with increased liver stiffness. We define a reference range for normal liver stiffness in healthy children as 2.45-5.56 kPa. CONCLUSIONS We have established TE-derived liver stiffness ranges for healthy children and propose an upper limit of liver stiffness in healthy children to be 5.56 kPa. We have identified increasing age, use of sedation, probe size, and presence of steatosis on ultrasound as factors that can significantly increase liver stiffness.
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Affiliation(s)
- Darrick K Li
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Muhammad Rehan Khan
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, University of Illinois College of Medicine at Peoria, Children's Hospital of Illinois, Peoria, IL, USA
| | - Zhen Wang
- Evidence-Based Practice Center, Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA
| | - Voranush Chongsrisawat
- Department of Pediatrics, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Panida Swangsak
- Department of Pediatrics, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Ulrike Teufel-Schäfer
- Department of Pediatrics and Adolescent Medicine, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | | | - Imeke Goldschmidt
- Division of Paediatric Gastroenterology and Hepatology, Hannover Medical School, Hannover, Germany
| | - Ulrich Baumann
- Division of Paediatric Gastroenterology and Hepatology, Hannover Medical School, Hannover, Germany.,Institute of Immunology and Immunotherapy, University of Birmingham, United Kingdom
| | - Daisuke Tokuhara
- Department of Pediatrics, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Yuki Cho
- Department of Pediatrics, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Marion Rowland
- School of Medicine and Medical Science, University College Dublin, Dublin, Ireland
| | - Anders B Mjelle
- Department of Pediatric and Adolescent Medicine, Haukeland University Hospital, Bergen, Norway.,Department of Clinical Medicine, University of Bergen, Bergen, Norway.,National Centre for Ultrasound in Gastroenterology, Department of Medicine, Haukeland University Hospital, Bergen, Norway
| | - Grant A Ramm
- Hepatic Fibrosis Group, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
| | - Peter J Lewindon
- Department of Gastroenterology, Hepatology and Liver Transplant, Queensland Children's Hospital, Brisbane, Australia
| | - Peter Witters
- Department of Paediatrics, University Hospitals Leuven, Leuven, Belgium
| | - David Cassiman
- Department of Gastroenterology-Hepatology and Metabolic Center, University of Leuven, Leuven, Belgium
| | - Ioana M Ciuca
- Pediatrics Department, University of Medicine and Pharmacy "Victor Babes", Timisoara, Romania
| | - Larry D Prokop
- Evidence-Based Practice Center, Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA
| | - Samir Haffar
- Digestive Center for Diagnosis and Treatment, Damascus, Syrian Arab Republic
| | - Kathleen E Corey
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - M H Murad
- Evidence-Based Practice Center, Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA
| | - Katryn N Furuya
- Department of Pediatrics, University of Wisconsin - Madison School of Medicine and Public Health, Madison, WI, USA
| | - Fateh Bazerbachi
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
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Siegel L, Murad MH, Chu H. Estimating the reference range from a meta-analysis. Res Synth Methods 2020; 12:148-160. [PMID: 32790064 DOI: 10.1002/jrsm.1442] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Revised: 06/04/2020] [Accepted: 07/30/2020] [Indexed: 12/11/2022]
Abstract
Often clinicians are interested in determining whether a subject's measurement falls within a normal range, defined as a range of values of a continuous outcome which contains some proportion (eg, 95%) of measurements from a healthy population. Several studies in the biomedical field have estimated reference ranges based on a meta-analysis of multiple studies with healthy individuals. However, the literature currently gives no guidance about how to estimate the reference range of a new subject in such settings. Instead, meta-analyses of such normative range studies typically report the pooled mean as a reference value, which does not incorporate natural variation across healthy individuals in different studies. We present three approaches to calculating the normal reference range of a subject from a meta-analysis of normally or lognormally distributed outcomes: a frequentist random effects model, a Bayesian random effects model, and an empirical approach. We present the results of a simulation study demonstrating that the methods perform well under a variety of scenarios, though users should be cautious when the number of studies is small and between-study heterogeneity is large. Finally, we apply these methods to two examples: pediatric time spent awake after sleep onset and frontal subjective postural vertical measurements.
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Affiliation(s)
- Lianne Siegel
- Division of Biostatistics, University of Minnesota, Minneapolis, Minnesota, USA
| | - M Hassan Murad
- Evidence-Based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Haitao Chu
- Division of Biostatistics, University of Minnesota, Minneapolis, Minnesota, USA
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Harrison SA, Ratziu V, Boursier J, Francque S, Bedossa P, Majd Z, Cordonnier G, Sudrik FB, Darteil R, Liebe R, Magnanensi J, Hajji Y, Brozek J, Roudot A, Staels B, Hum DW, Megnien SJ, Hosmane S, Dam N, Chaumat P, Hanf R, Anstee QM, Sanyal AJ. A blood-based biomarker panel (NIS4) for non-invasive diagnosis of non-alcoholic steatohepatitis and liver fibrosis: a prospective derivation and global validation study. Lancet Gastroenterol Hepatol 2020; 5:970-985. [PMID: 32763196 DOI: 10.1016/s2468-1253(20)30252-1] [Citation(s) in RCA: 164] [Impact Index Per Article: 32.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2020] [Revised: 05/27/2020] [Accepted: 05/29/2020] [Indexed: 01/04/2023]
Abstract
BACKGROUND Non-invasive tests that can identify patients with non-alcoholic steatohepatitis (NASH) at higher risk of disease progression are lacking. We report the development and validation of a blood-based diagnostic test to non-invasively rule in and rule out at-risk NASH (defined as non-alcoholic fatty liver disease [NAFLD] activity score [NAS] ≥4 and fibrosis stage ≥2). METHODS In this prospective derivation and global validation study, blood samples, clinical data, and liver biopsy results from three independent cohorts with suspected NAFLD were used to develop and validate a non-invasive blood-based diagnostic test, called NIS4. Derivation was done in the discovery cohort, which comprised 239 prospectively recruited patients with biopsy-confirmed NASH (NAFLD NAS ≥3; fibrosis stage 0-3) from the international GOLDEN-505 phase 2b clinical trial. A complete matrix based on 23 variables selected for univariate association with the presence of at-risk NASH and avoiding high multi-collinearity was used to derive the model in a bootstrap-based process that minimised the Akaike information criterion. The overall diagnostic performance of NIS4 was externally validated in two independent cohorts: RESOLVE-IT diag and Angers. The RESOLVE-IT diag cohort comprised the first 475 patients screened for potential inclusion into the RESOLVE-IT phase 3 clinical trial. Angers was a retrospective cohort of 227 prospectively recruited patients with suspected NAFLD and clinical risk factors for NASH or fibrosis stage 2 or more according to abnormal elastography results or abnormal liver biochemistry. Both external validation cohorts were independently analysed and were combined into a pooled validation cohort (n=702) to assess clinical performance of NIS4 and other non-invasive tests. FINDINGS The derived NIS4 algorithm comprised four independent NASH-associated biomarkers (miR-34a-5p, alpha-2 macroglobulin, YKL-40, and glycated haemoglobin; area under the receiver operating characteristics curve [AUROC] 0·80, 95% CI 0·73-0·85), and did not require adjustment for age, sex, body-mass index (BMI), or aminotransferase concentrations. Clinical cutoffs were established within the discovery cohort to optimise both rule out and rule in clinical performance while minimising indeterminate results. NIS4 was validated in the RESOLVE-IT diag cohort (AUROC 0·83, 95% CI 0·79-0·86) and the Angers cohort (0·76, 0·69-0·82). In the pooled validation cohort, patients with a NIS4 value less than 0·36 were classified as not having at-risk NASH (ruled out) with 81·5% (95% CI 76·9-85·3) sensitivity, 63·0% (57·8-68·0) specificity, and a negative predictive value of 77·9% (72·5-82·4), whereas those with a NIS4 value of more than 0·63 were classified as having at-risk NASH (ruled in) with 87·1% (83·1-90·3) specificity, 50·7% (45·3-56·1) sensitivity, and a positive predictive value of 79·2% (73·1-84·2). The diagnostic performance of NIS4 within the external validation cohorts was not influenced by age, sex, BMI, or aminotransferase concentrations. INTERPRETATION NIS4 is a novel blood-based diagnostic that provides an effective way to non-invasively rule in or rule out at-risk NASH in patients with metabolic risk factors and suspected disease. Use of NIS4 in clinical trials or in the clinic has the potential to greatly reduce unnecessary liver biopsies in patients with lower risk of disease progression. FUNDING Genfit.
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Affiliation(s)
- Stephen A Harrison
- Summit Clinical Research, San Antonio, TX, USA; Radcliffe Department of Medicine, University of Oxford, Oxford, UK
| | - Vlad Ratziu
- Sorbonne Université, Institute for Cardiometabolism and Nutrition, Hôpital Pitié-Salpêtrière, Paris, France
| | - Jérôme Boursier
- Service d'Hépato-Gastroentérologie, Centre Hospitalier Universitaire d'Angers, Angers, France; Laboratoire HIFIH, UPRES EA3859, SFR 4208, Université d'Angers, Angers, France
| | - Sven Francque
- Department of Gastroenterology and Hepatology, Antwerp University Hospital, Antwerp, Belgium; Translational Sciences in Inflammation and Immunology & InflaMed Consortium of Excellence, University of Antwerp, Antwerp, Belgium
| | - Pierre Bedossa
- Liverpat, Paris, France; Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
| | | | | | | | | | - Roman Liebe
- Genfit, Loos, France; Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Düsseldorf, Düsseldorf, Germany
| | | | | | | | | | - Bart Staels
- Université de Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011 - EGID, F-59000 Lille, France
| | | | | | | | | | | | | | - Quentin M Anstee
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK; Newcastle NIHR Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital, Newcastle upon Tyne, UK
| | - Arun J Sanyal
- Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, VA, 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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Trembling PM, Apostolidou S, Gentry-Maharaj A, Parkes J, Ryan A, Tanwar S, Burnell M, Harris S, Menon U, Rosenberg WM. The Enhanced Liver Fibrosis test is associated with liver-related outcomes in postmenopausal women with risk factors for liver disease. BMC Gastroenterol 2020; 20:104. [PMID: 32293289 PMCID: PMC7158048 DOI: 10.1186/s12876-020-01251-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2019] [Accepted: 03/30/2020] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Chronic liver disease (CLD) is usually asymptomatic but earlier detection is critical to permit life-saving interventions for those at risk due to high alcohol consumption and increased body mass index (BMI). The aim of this study was to estimate the association between the Enhanced Liver Fibrosis (ELF) test and liver-related events (LRE) and its performance in predicting LRE in postmenopausal women with risk factors in a nested case-control study within the United Kingdom Trial of Ovarian Cancer Screening (UKCTOCS). METHODS In a cohort of 95,126 we performed a case-control study measuring ELF in blinded samples from 173 participants with self-reported high alcohol use and / or BMI ≥25 kg/m2 comprising all 58 cases who developed LRE and 115 controls matched for age, alcohol and BMI who did not develop LRE during median follow-up of 8.5 years. RESULTS Using Cox regression at an ELF threshold of 10.51 hazard ratios (HR) for LRE were 4.88 (95% confidence interval (CI) 2.37-10.03) (unadjusted model) and 4.62 (95% CI 2.12-10.08) (adjusted for deprivation and self-reported hypertension, heart disease, hypercholesterolaemia and diabetes). At a threshold of 9.8 HR for LRE were 2.21 (95% CI 1.22-3.97) (unadjusted model) and 2.18 (95% CI 1.19-4.01) (adjusted). ELF was evaluated as a time dependent variable by generating time-dependent Cox models; HRs at an ELF threshold of 10.51 were 1.94 (95% CI 1.10-3.39) (unadjusted) and 2.05 (95% CI 1.16-3.64) (adjusted) and at a threshold of 9.8 HRs were 1.85 (95% CI 1.09-3.15) (unadjusted) and 1.80 (95% CI 1.04-3.13) (adjusted). Area under the receiver operating characteristic curve for recruitment ELF predicting LRE was 0.58 (95% CI 0.49-0.68), and for second subsequent ELF 0.61 (95% CI 0.52-0.71). CONCLUSION This study demonstrates the association between ELF and CLD in postmenopausal women with risk factors for liver disease, creating the opportunity to intervene to reduce liver-related mortality and morbidity. Although larger studies are required, these results demonstrate the potential of ELF as a prognostic tool in health checks in primary care. TRIAL REGISTRATION This study is nested in UKCTOCS. UKCTOCS is registered as an International Standard Randomised Controlled Trial, number ISRCTN22488978. Registered 06/04/2000.
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Affiliation(s)
- Paul M. Trembling
- Division of Medicine, University College London, Institute for Liver and Digestive Health, Royal Free Hospital, Rowland Hill Street, London, NW3 2PF UK
| | - Sophia Apostolidou
- MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, Faculty of Population Health Sciences, University College London, 2nd Floor, 90 High Holborn, London, WC1V 6LJ UK
| | - Aleksandra Gentry-Maharaj
- MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, Faculty of Population Health Sciences, University College London, 2nd Floor, 90 High Holborn, London, WC1V 6LJ UK
| | - Julie Parkes
- Primary Care and Population Sciences Academic Unit, Faculty of Medicine, University of Southampton, Level C, South Academic Block, University Hospital Southampton, Southampton, SO16 6YD UK
| | - Andy Ryan
- MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, Faculty of Population Health Sciences, University College London, 2nd Floor, 90 High Holborn, London, WC1V 6LJ UK
| | - Sudeep Tanwar
- Division of Medicine, University College London, Institute for Liver and Digestive Health, Royal Free Hospital, Rowland Hill Street, London, NW3 2PF UK
| | - Matthew Burnell
- MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, Faculty of Population Health Sciences, University College London, 2nd Floor, 90 High Holborn, London, WC1V 6LJ UK
| | - Scott Harris
- Primary Care and Population Sciences Academic Unit, Faculty of Medicine, University of Southampton, Level C, South Academic Block, University Hospital Southampton, Southampton, SO16 6YD UK
| | - Usha Menon
- MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, Faculty of Population Health Sciences, University College London, 2nd Floor, 90 High Holborn, London, WC1V 6LJ UK
| | - William M. Rosenberg
- Division of Medicine, University College London, Institute for Liver and Digestive Health, Royal Free Hospital, Rowland Hill Street, London, NW3 2PF UK
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Zhang YN, Fowler KJ, Ozturk A, Potu CK, Louie AL, Montes V, Henderson WC, Wang K, Andre MP, Samir AE, Sirlin CB. Liver fibrosis imaging: A clinical review of ultrasound and magnetic resonance elastography. J Magn Reson Imaging 2020; 51:25-42. [PMID: 30859677 PMCID: PMC6742585 DOI: 10.1002/jmri.26716] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2019] [Revised: 02/26/2019] [Accepted: 02/26/2019] [Indexed: 12/13/2022] Open
Abstract
Liver fibrosis is a histological hallmark of most chronic liver diseases, which can progress to cirrhosis and liver failure, and predisposes to hepatocellular carcinoma. Accurate diagnosis of liver fibrosis is necessary for prognosis, risk stratification, and treatment decision-making. Liver biopsy, the reference standard for assessing liver fibrosis, is invasive, costly, and impractical for surveillance and treatment response monitoring. Elastography offers a noninvasive, objective, and quantitative alternative to liver biopsy. This article discusses the need for noninvasive assessment of liver fibrosis and reviews the comparative advantages and limitations of ultrasound and magnetic resonance elastography techniques with respect to their basic concepts, acquisition, processing, and diagnostic performance. Variations in clinical contexts of use and common pitfalls associated with each technique are considered. In addition, current challenges and future directions to improve the diagnostic accuracy and clinical utility of elastography techniques are discussed. Level of Evidence: 5 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:25-42.
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Affiliation(s)
- Yingzhen N. Zhang
- Department of Radiology, Liver Imaging Group, University of California, San Diego, La Jolla, California, USA
| | - Kathryn J. Fowler
- Department of Radiology, Liver Imaging Group, University of California, San Diego, La Jolla, California, USA
| | - Arinc Ozturk
- Department of Radiology, Center for Ultrasound Research & Translation, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Chetan K. Potu
- Department of Radiology, Liver Imaging Group, University of California, San Diego, La Jolla, California, USA
| | - Ashley L. Louie
- Department of Radiology, Liver Imaging Group, University of California, San Diego, La Jolla, California, USA
| | - Vivian Montes
- Department of Radiology, Liver Imaging Group, University of California, San Diego, La Jolla, California, USA
| | - Walter C. Henderson
- Department of Radiology, Liver Imaging Group, University of California, San Diego, La Jolla, California, USA
| | - Kang Wang
- Department of Radiology, Liver Imaging Group, University of California, San Diego, La Jolla, California, USA
| | - Michael P. Andre
- Department of Radiology, University of California, San Diego, La Jolla, California, USA
| | - Anthony E. Samir
- Department of Radiology, Center for Ultrasound Research & Translation, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Claude B. Sirlin
- Department of Radiology, Liver Imaging Group, University of California, San Diego, La Jolla, California, USA
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Bazerbachi F, Vargas EJ, Matar R, Storm AC, Mounajjed TM, Topazian MD, Levy MJ, Chandrasekhara V, Abu Dayyeh BK. EUS-guided core liver biopsy sampling using a 22-gauge fork-tip needle: a prospective blinded trial for histologic and lipidomic evaluation in nonalcoholic fatty liver disease. Gastrointest Endosc 2019; 90:926-932. [PMID: 31437454 DOI: 10.1016/j.gie.2019.08.006] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2019] [Accepted: 08/04/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Diagnostic tools for nonalcoholic fatty liver disease (NAFLD) detection and prognostication are limited, with histology remaining the criterion standard. We evaluated the feasibility and safety of EUS-guided liver biopsy (EUS-LB) sampling in NAFLD staging. METHODS In a prospective cohort of NAFLD patients with steatohepatitis and early liver fibrosis based on magnetic resonance elastography (MRE), EUS-LB sampling procedures were performed using a 22-gauge fork-tip core biopsy needle. Samples were evaluated by a blinded pathologist. Total aggregate sample length (TASL), number of complete portal triads, ability to calculate NAFLD activity score, ability to stage liver fibrosis, and ability to provide enough core liver tissue for lipidomics analysis were evaluated. Performance of EUS-LB sampling was compared with MRE. RESULTS Forty-one EUS-LB samples were obtained. The median TASL was 2.4 cm (interquartile range, 2.00-2.75). The median number of complete portal triads per TASL was 26 (interquartile range, 7-62). Of the samples, 100% were adequate to convey NAFLD activity score and fibrosis stage. All samples provided enough core liver tissue to allow the application of lipidomics testing. A significant positive linear association between EUS-LB sampling-detected fibrosis and MRE-detected fibrosis was observed (r = .469, P < .005). Compared with MRE, EUS-LB sampling established early fibrosis in 13 cases that MRE classified as normal. EUS-LB sampling-related adverse events occurred in 7% and were restricted to postprocedural pain. CONCLUSIONS EUS-LB sampling is a viable technique for full NAFLD evaluation and may be superior to MRE in establishing the diagnosis of nonalcoholic steatohepatitis with early fibrosis. (Clinical trial registration number: NCT02880189.).
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Affiliation(s)
- Fateh Bazerbachi
- Division of Gastroenterology, Interventional Endoscopy Program, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Eric J Vargas
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Reem Matar
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Andrew C Storm
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Taofic M Mounajjed
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
| | - Mark D Topazian
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Michael J Levy
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Vinay Chandrasekhara
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Barham K Abu Dayyeh
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
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