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Azizi N, Naghibi H, Shakiba M, Morsali M, Zarei D, Abbastabar H, Ghanaati H. Evaluation of MRI proton density fat fraction in hepatic steatosis: a systematic review and meta-analysis. Eur Radiol 2025; 35:1794-1807. [PMID: 39254718 DOI: 10.1007/s00330-024-11001-1] [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: 02/10/2024] [Revised: 06/24/2024] [Accepted: 07/15/2024] [Indexed: 09/11/2024]
Abstract
BACKGROUND Amidst the global rise of metabolic dysfunction-associated steatotic liver disease (MASLD), driven by increasing obesity rates, there is a pressing need for precise, non-invasive diagnostic tools. Our research aims to validate MRI Proton Density Fat Fraction (MRI-PDFF) utility, compared to liver biopsy, in grading hepatic steatosis in MASLD. METHODS A systematic search was conducted across Embase, PubMed/Medline, Scopus, and Web of Science until January 13, 2024, selecting studies that compare MRI-PDFF with liver biopsy for hepatic steatosis grading, defined as grades 0 (< 5% steatosis), 1 (5-33% steatosis), 2 (34-66% steatosis), and 3 (> 66% steatosis). RESULTS Twenty-two studies with 2844 patients were included. The analysis showed high accuracy of MRI-PDFF with AUCs of 0.97 (95% CI = 0.96-0.98) for grade 0 vs ≥ 1, 0.91 (95% CI = 0.88-0.93) for ≤ 1 vs ≥ 2, and 0.91 (95% CI = 0.88-0.93) for ≤ 2 vs 3, diagnostic odds ratio (DOR) from 98.74 (95% CI = 58.61-166.33) to 23.36 (95% CI = 13.76-39.68), sensitivity and specificity from 0.93 (95% CI = 0.88-0.96) to 0.76 (95% CI = 0.63-0.85) and 0.93 (95% CI = 0.88-0.96) to 0.89 (95% CI = 0.84-0.93), respectively. Likelihood ratio (LR) + ranged from 13.3 (95% CI = 7.4-24.0) to 7.2 (95% CI = 4.9-10.5), and LR - from 0.08 (95% CI = 0.05-0.13) to 0.27 (95% CI = 0.17-0.42). The proposed MRI-PDFF threshold of 5.7% for liver fat content emerges as a potential cut-off for the discrimination between grade 0 vs ≥ 1 (p = 0.075). CONCLUSION MRI-PDFF is a precise non-invasive technique for diagnosing and grading hepatic steatosis, warranting further studies to establish its diagnostic thresholds. CLINICAL RELEVANCE STATEMENT This study underscores the high diagnostic accuracy of MRI-PDFF for distinguishing between various grades of hepatic steatosis for early detection and management of MASLD, though further research is necessary for broader application. KEY POINTS MRI-PDFF offers precision in diagnosing and monitoring hepatic steatosis. The diagnostic accuracy of MRI-PDFF decreases as the grade of hepatic steatosis advances. A 5.7% MRI-PDFF threshold differentiates steatotic from non-steatotic livers.
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Affiliation(s)
- Narges Azizi
- Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Tehran University of Medical Science, Tehran, Iran
| | - Hamed Naghibi
- Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Tehran University of Medical Science, Tehran, Iran
| | - Madjid Shakiba
- Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Tehran University of Medical Science, Tehran, Iran
| | - Mina Morsali
- Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Tehran University of Medical Science, Tehran, Iran
| | - Diana Zarei
- Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Tehran University of Medical Science, Tehran, Iran
| | - Hedayat Abbastabar
- Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Tehran University of Medical Science, Tehran, Iran
| | - Hossein Ghanaati
- Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Tehran University of Medical Science, Tehran, Iran.
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Barazesh M, Jalili S, Akhzari M, Faraji F, Khorramdin E. Recent Progresses on Pathophysiology, Diagnosis, Therapeutic Modalities,
and Management of Non-alcoholic Fatty Liver Disorder. CURRENT DRUG THERAPY 2024; 19:20-48. [DOI: 10.2174/1574885518666230417111247] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Revised: 01/30/2023] [Accepted: 02/06/2023] [Indexed: 01/03/2025]
Abstract
Abstract:
Non-alcoholic fatty liver disease (NAFLD) is currently the utmost common chronic liver
disorder that happens through all age groups and is identified to occur in 14%-30% of the general
population, demonstrating a critical and grossing clinical issue because of the growing incidence of
obesity and overweight. From the histological aspect, it looks like alcoholic liver damage, but it happens in patients who avoid remarkable alcohol usage. NAFLD comprises a broad spectrum, ranging
from benign hepatocellular steatosis to inflammatory nonalcoholic steatohepatitis (NASH), different
levels of fibrosis, and cirrhosis. Patients with NASH are more susceptible to more rapid progression to
cirrhosis and hepatocellular carcinoma. There is no single factor that drives proceeding from simple
steatosis to NASH. However, a combination of multi parameters such as genetic background, gut microflora, intake of high fat/ fructose dietary contents or methionine/choline-deficient diet, and consequently accumulated hepatocellular lipids mainly including triglycerides and also other bio-analytes,
such as free fatty acids, cholesterol, and phospholipids display a crucial role in disease promotion.
NAFLD is related to overweight and insulin resistance (IR) and is regarded as the hepatic presentation
of the metabolic syndrome, an amalgamation of medical statuses such as hyperlipidemia, hypertension, type 2 diabetes, and visceral obesity. Despite the increasing prevalence of this disease, which
imposes a remarkable clinical burden, most affected patients remain undiagnosed in a timely manner,
largely related to the asymptomatic entity of NAFLD patients and the unavailability of accurate and
efficient noninvasive diagnostic tests. However, liver biopsy is considered a gold standard for NAFLD
diagnosis, but due to being expensive and invasiveness is inappropriate for periodic disease screening.
Some noninvasive monitoring approaches have been established recently for NAFLD assessment. In
addition to the problem of correct disease course prediction, no effective therapeutic modalities are
approved for disease treatment. Imaging techniques can commonly validate the screening and discrimination of NAFLD; nevertheless, staging the disease needs a liver biopsy. The present therapeutic approaches depend on weight loss, sports activities, and dietary modifications, although different insulin-sensitizing drugs, antioxidants, and therapeutic agents seem hopeful. This review aims to focus on
the current knowledge concerning epidemiology, pathogenesis, and different biochemical experiments
and imaging modalities applied to diagnose the different grades of NAFLD and its management, as
well as new data about pharmacological therapies for this disorder.
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Affiliation(s)
- Mahdi Barazesh
- School of Paramedical, Gerash University of Medical Sciences, Gerash, Iran
| | - Sajad Jalili
- Department of Orthopedics, School of
Medicine, Ahvaz Jundishapour University of Medical Sciences, Ahvaz, Iran
| | - Morteza Akhzari
- School of Nursing, Larestan University of
Medical Sciences, Larestan, Iran
| | - Fouzieyeh Faraji
- School of Paramedical, Gerash University of Medical Sciences, Gerash, Iran
| | - Ebrahim Khorramdin
- Department of Orthopedics, School of
Medicine, Ahvaz Jundishapour University of Medical Sciences, Ahvaz, Iran
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Three segments sampling strategy for the assessment of liver steatosis using magnetic resonance imaging proton density fat fraction. Eur J Radiol 2023; 159:110653. [PMID: 36563563 DOI: 10.1016/j.ejrad.2022.110653] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2022] [Revised: 10/28/2022] [Accepted: 12/12/2022] [Indexed: 12/23/2022]
Abstract
PURPOSE This research aims to determine the best liver segments representing the whole-liver fat fraction (FF) in magnetic resonance imaging (MRI)-based measurement of the proton density fat fraction (PDFF). METHOD This retrospective study included 989 adult subjects who underwent MRI-PDFF from March 2018 to January 2021. Three regions of interest (ROI) were measured and averaged for each hepatic segment and the volume-weighted hepatic FF was calculated. Intrahepatic fat variability was assessed by standard deviation between all ROIs. Univariate and multivariate linear regression analyses were done for the factors associated with intrahepatic fat variability among clinical characteristics, blood parameters and the volume-weighted FF. The arithmetic means of specific hepatic segments that were the closest to the volume-weighted FF were identified in all subjects and those with moderate or severe fatty liver. RESULTS The volume-weighted FF was 8.18% and variability was 1.33%. Volume-weighted FF was the only associated factor with intrahepatic variability. The arithmetic mean of segments V, VI, and IV was closest to the volume-weighted FF in all subjects and in subjects with moderate or severe fatty liver. CONCLUSIONS There was considerable heterogeneity in hepatic steatosis between each segment of the liver, and the variability was significantly affected by the volume-weighted FF. The mean hepatic FF from segments V, VI, and IV could be used to estimate the volume-weighted FF of the whole liver, not only in the general population but also in patients with moderate or severe fatty liver.
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Bischoff SC, Barazzoni R, Busetto L, Campmans-Kuijpers M, Cardinale V, Chermesh I, Eshraghian A, Kani HT, Khannoussi W, Lacaze L, Léon-Sanz M, Mendive JM, Müller MW, Ockenga J, Tacke F, Thorell A, Vranesic Bender D, Weimann A, Cuerda C. European guideline on obesity care in patients with gastrointestinal and liver diseases - Joint ESPEN/UEG guideline. Clin Nutr 2022; 41:2364-2405. [PMID: 35970666 DOI: 10.1016/j.clnu.2022.07.003] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Accepted: 07/03/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND Patients with chronic gastrointestinal (GI) disease such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), celiac disease, gastroesophageal reflux disease (GERD), pancreatitis, and chronic liver disease (CLD) often suffer from obesity because of coincidence (IBD, IBS, celiac disease) or related pathophysiology (GERD, pancreatitis and CLD). It is unclear if such patients need a particular diagnostic and treatment that differs from the needs of lean GI patients. The present guideline addresses this question according to current knowledge and evidence. OBJECTIVE The objective of the guideline is to give advice to all professionals working in the field of gastroenterology care including physicians, surgeons, dietitians and others how to handle patients with GI disease and obesity. METHODS The present guideline was developed according to the standard operating procedure for ESPEN guidelines, following the Scottish Intercollegiate Guidelines Network (SIGN) grading system (A, B, 0, and good practice point (GPP)). The procedure included an online voting (Delphi) and a final consensus conference. RESULTS In 100 recommendations (3x A, 33x B, 24x 0, 40x GPP, all with a consensus grade of 90% or more) care of GI patients with obesity - including sarcopenic obesity - is addressed in a multidisciplinary way. A particular emphasis is on CLD, especially fatty liver disease, since such diseases are closely related to obesity, whereas liver cirrhosis is rather associated with sarcopenic obesity. A special chapter is dedicated to obesity care in patients undergoing bariatric surgery. The guideline focuses on adults, not on children, for whom data are scarce. Whether some of the recommendations apply to children must be left to the judgment of the experienced pediatrician. CONCLUSION The present guideline offers for the first time evidence-based advice how to care for patients with chronic GI diseases and concomitant obesity, an increasingly frequent constellation in clinical practice.
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Affiliation(s)
- Stephan C Bischoff
- Institute of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.
| | - Rocco Barazzoni
- Department of Medical, Technological and Translational Sciences, University of Trieste, Ospedale di Cattinara, Trieste, Italy.
| | - Luca Busetto
- Department of Medicine, University of Padova, Padova, Italy.
| | - Marjo Campmans-Kuijpers
- Department of Gastroenterology and Hepatology, University Medical Centre Groningen, Groningen, the Netherlands.
| | - Vincenzo Cardinale
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy.
| | - Irit Chermesh
- Department of Gastroenterology, Rambam Health Care Campus, Affiliated with Technion-Israel Institute of Technology, Haifa, Israel.
| | - Ahad Eshraghian
- Department of Gastroenterology and Hepatology, Avicenna Hospital, Shiraz, Iran.
| | - Haluk Tarik Kani
- Department of Gastroenterology, Marmara University, School of Medicine, Istanbul, Turkey.
| | - Wafaa Khannoussi
- Hepato-Gastroenterology Department, Mohammed VI University Hospital, Oujda, Morocco; Laboratoire de Recherche des Maladies Digestives (LARMAD), Mohammed the First University, Oujda, Morocco.
| | - Laurence Lacaze
- Department of General Surgery, Mantes-la-Jolie Hospital, Mantes-la-Jolie, France; Department of Clinical Nutrition, Paul-Brousse-Hospital, Villejuif, France.
| | - Miguel Léon-Sanz
- Department of Endocrinology and Nutrition, University Hospital Doce de Octubre, Medical School, University Complutense, Madrid, Spain.
| | - Juan M Mendive
- La Mina Primary Care Academic Health Centre, Catalan Institute of Health (ICS), University of Barcelona, Barcelona, Spain.
| | - Michael W Müller
- Department of General and Visceral Surgery, Regionale Kliniken Holding, Kliniken Ludwigsburg-Bietigheim GGmbH, Krankenhaus Bietigheim, Bietigheim-Bissingen, Germany.
| | - Johann Ockenga
- Medizinische Klinik II, Klinikum Bremen-Mitte, Bremen FRG, Bremen, Germany.
| | - Frank Tacke
- Department of Hepatology & Gastroenterology, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, Berlin, Germany.
| | - Anders Thorell
- Department of Clinical Science, Danderyds Hospital, Karolinska Institutet & Department of Surgery, Ersta Hospital, Stockholm, Sweden.
| | - Darija Vranesic Bender
- Unit of Clinical Nutrition, Department of Internal Medicine, University Hospital Centre Zagreb, Zagreb, Croatia.
| | - Arved Weimann
- Department of General, Visceral and Oncological Surgery, St. George Hospital, Leipzig, Germany.
| | - Cristina Cuerda
- Departamento de Medicina, Universidad Complutense de Madrid, Nutrition Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
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Bischoff SC, Barazzoni R, Busetto L, Campmans‐Kuijpers M, Cardinale V, Chermesh I, Eshraghian A, Kani HT, Khannoussi W, Lacaze L, Léon‐Sanz M, Mendive JM, Müller MW, Ockenga J, Tacke F, Thorell A, Vranesic Bender D, Weimann A, Cuerda C. European guideline on obesity care in patients with gastrointestinal and liver diseases - Joint European Society for Clinical Nutrition and Metabolism / United European Gastroenterology guideline. United European Gastroenterol J 2022; 10:663-720. [PMID: 35959597 PMCID: PMC9486502 DOI: 10.1002/ueg2.12280] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Accepted: 07/07/2022] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Patients with chronic gastrointestinal (GI) disease such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), celiac disease, gastroesophageal reflux disease (GERD), pancreatitis, and chronic liver disease (CLD) often suffer from obesity because of coincidence (IBD, IBS, celiac disease) or related pathophysiology (GERD, pancreatitis and CLD). It is unclear if such patients need a particular diagnostic and treatment that differs from the needs of lean GI patients. The present guideline addresses this question according to current knowledge and evidence. OBJECTIVE The objective of the guideline is to give advice to all professionals working in the field of gastroenterology care including physicians, surgeons, dietitians and others how to handle patients with GI disease and obesity. METHODS The present guideline was developed according to the standard operating procedure for European Society for Clinical Nutrition and Metabolism guidelines, following the Scottish Intercollegiate Guidelines Network grading system (A, B, 0, and good practice point [GPP]). The procedure included an online voting (Delphi) and a final consensus conference. RESULTS In 100 recommendations (3x A, 33x B, 24x 0, 40x GPP, all with a consensus grade of 90% or more) care of GI patients with obesity - including sarcopenic obesity - is addressed in a multidisciplinary way. A particular emphasis is on CLD, especially fatty liver disease, since such diseases are closely related to obesity, whereas liver cirrhosis is rather associated with sarcopenic obesity. A special chapter is dedicated to obesity care in patients undergoing bariatric surgery. The guideline focuses on adults, not on children, for whom data are scarce. Whether some of the recommendations apply to children must be left to the judgment of the experienced pediatrician. CONCLUSION The present guideline offers for the first time evidence-based advice how to care for patients with chronic GI diseases and concomitant obesity, an increasingly frequent constellation in clinical practice.
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Affiliation(s)
| | - Rocco Barazzoni
- Department of Medical, Technological and Translational SciencesUniversity of TriesteTriesteItaly
| | - Luca Busetto
- Department of MedicineUniversity of PadovaPadovaItaly
| | - Marjo Campmans‐Kuijpers
- Department of Gastroenterology and HepatologyUniversity Medical Centre GroningenGroningenThe Netherlands
| | - Vincenzo Cardinale
- Department of Medico‐Surgical Sciences and BiotechnologiesSapienza University of RomeRomeItaly
| | - Irit Chermesh
- Department of GastroenterologyRambam Health Care CampusAffiliated with Technion‐Israel Institute of TechnologyHaifaIsrael
| | - Ahad Eshraghian
- Department of Gastroenterology and HepatologyAvicenna HospitalShirazIran
| | - Haluk Tarik Kani
- Department of GastroenterologyMarmara UniversitySchool of MedicineIstanbulTurkey
| | - Wafaa Khannoussi
- Hepato‐Gastroenterology DepartmentMohammed VI University HospitalOujdaMorocco
- Laboratoire de Recherche des Maladies Digestives (LARMAD)Mohammed the First UniversityOujdaMorocco
| | - Laurence Lacaze
- Department of NutritionRennes HospitalRennesFrance
- Department of general surgeryMantes‐la‐Jolie HospitalFrance
- Department of clinical nutritionPaul Brousse‐Hospital, VillejuifFrance
| | - Miguel Léon‐Sanz
- Department of Endocrinology and NutritionUniversity Hospital Doce de OctubreMedical SchoolUniversity ComplutenseMadridSpain
| | - Juan M. Mendive
- La Mina Primary Care Academic Health Centre. Catalan Institute of Health (ICS)University of BarcelonaBarcelonaSpain
| | - Michael W. Müller
- Department of General and Visceral SurgeryRegionale Kliniken HoldingKliniken Ludwigsburg‐Bietigheim gGmbHBietigheim‐BissingenGermany
| | - Johann Ockenga
- Medizinische Klinik IIKlinikum Bremen‐MitteBremenGermany
| | - Frank Tacke
- Department of Hepatology & GastroenterologyCharité Universitätsmedizin BerlinCampus Virchow‐Klinikum and Campus Charité MitteBerlinGermany
| | - Anders Thorell
- Department of Clinical ScienceDanderyds HospitalKarolinska InstitutetStockholmSweden
- Department of SurgeryErsta HospitalStockholmSweden
| | - Darija Vranesic Bender
- Department of Internal MedicineUnit of Clinical NutritionUniversity Hospital Centre ZagrebZagrebCroatia
| | - Arved Weimann
- Department of General, Visceral and Oncological SurgerySt. George HospitalLeipzigGermany
| | - Cristina Cuerda
- Departamento de MedicinaUniversidad Complutense de MadridNutrition UnitHospital General Universitario Gregorio MarañónMadridSpain
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Haam JH, Lee YK, Suh E, Kim YS. Characteristics of Urine Organic Acid Metabolites in Nonalcoholic Fatty Liver Disease Assessed Using Magnetic Resonance Imaging with Elastography in Korean Adults. Diagnostics (Basel) 2022; 12:diagnostics12051199. [PMID: 35626354 PMCID: PMC9140840 DOI: 10.3390/diagnostics12051199] [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: 04/23/2022] [Revised: 05/05/2022] [Accepted: 05/09/2022] [Indexed: 02/01/2023] Open
Abstract
The liver is an essential organ that manufactures energy through various metabolic pathways; thus, exploring the intermediate metabolites in nonalcoholic fatty liver disease (NAFLD) may help discover novel parameters in hepatic steatosis or fibrosis. The present study aimed to investigate the traits of urine organic acid metabolites in participants with hepatic steatosis and fibrosis in nonalcoholic Korean adults. Hepatic steatosis and fibrosis, in 68 men and 65 women, were evaluated using quantification by proton density fat fraction with magnetic resonance (MR) imaging and MR elastography, respectively. Urine metabolites were obtained using a high-performance liquid chromatography–mass spectrometry analysis. The candidate metabolites were included in the logistic regression models for hepatic steatosis and fibrosis. The association between high p-hydroxyphenyllactate levels and hepatic steatosis was not independent of body mass index and Homeostatic Model Assessment-insulin resistance. High ethylmalonate, β-hydroxybutyrate, and sulfate levels were significantly related to a low probability of hepatic fibrosis, independent of covariates. In conclusion, urine metabolites were not related to hepatic steatosis independent of obesity and insulin resistance, while several metabolites were specifically associated with hepatic fibrosis. Further study is required to verify the diagnostic value of the metabolites in a population with wide-spectrum NAFLD.
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Affiliation(s)
- Ji-Hee Haam
- Chaum Life Center, CHA University, Seoul 06062, Korea; (J.-H.H.); (Y.K.L.); (E.S.)
| | - Yun Kyong Lee
- Chaum Life Center, CHA University, Seoul 06062, Korea; (J.-H.H.); (Y.K.L.); (E.S.)
| | - Eunkyung Suh
- Chaum Life Center, CHA University, Seoul 06062, Korea; (J.-H.H.); (Y.K.L.); (E.S.)
| | - Young-Sang Kim
- Department of Family Medicine, CHA Bundang Medical Center, CHA University, Seongnam 13496, Korea
- Correspondence:
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Paul J. Recent advances in non-invasive diagnosis and medical management of non-alcoholic fatty liver disease in adult. EGYPTIAN LIVER JOURNAL 2020. [DOI: 10.1186/s43066-020-00043-x] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Abstract
Background
Number of non-alcoholic fatty liver disease (NAFLD) cases is increasing over time due to alteration of food habit, increase incidence of metabolic syndrome, and lack of exercise. Liver biopsy is the test for diagnosis and staging of NAFLD, but nowadays several biochemical markers, scoring systems, and imaging studies are available to diagnose and stage NAFLD which is linked to end-stage liver disease, hepatocellular cancer, and elevated cardiovascular- and cancer-related morbidity and mortality. Therefore urgent diagnosis and management are required to avoid complications related to NAFLD. This review summarizes recent advances in diagnosis and medical management of non-alcoholic fatty liver disease.
Main text
Recently published studies from PubMed, Red Cross, Copernicus, and also various previous studies were reviewed. We have discussed various non-invasive methods for detection of non-alcoholic fatty liver disease, non-alcoholic steatohepatitis (NASH), and hepatic fibrosis. Non pharmacological therapies for NAFLD, indications, and approved medications for NAFLD and other commonly used non-approved medications have been discussed in this review article.
Conclusions
Multiple non-invasive tests are available for diagnosis of NAFLD, and its different stages however gold standard test is liver biopsy. NALFD without NASH and significant fibrosis is treated by lifestyle modifications which include moderate to vigorous exercise and diet modification. To improve hepatic steatosis, minimum of 3–5% of body weight loss is necessary, but > 7–10% weight reductions is required for histological improvement in NASH and fibrosis. Pharmacotherapy is indicated when patient is having NASH with significant fibrosis.
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Diagnostic Accuracy of Noninvasive Markers of Steatosis, NASH, and Liver Fibrosis in HIV-Monoinfected Individuals at Risk of Nonalcoholic Fatty Liver Disease (NAFLD): Results From the ECHAM Study. J Acquir Immune Defic Syndr 2019; 80:e86-e94. [PMID: 30570529 DOI: 10.1097/qai.0000000000001936] [Citation(s) in RCA: 48] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND HIV-monoinfected individuals are at high risk of nonalcoholic fatty liver disease. Noninvasive tests of steatosis, nonalcoholic steatohepatitis (NASH), and fibrosis have been poorly assessed in this population. Using liver biopsy (LB) as a reference, we assessed the accuracy of noninvasive methods for their respective diagnosis: magnetic resonance imaging proton-density-fat-fraction (MRI-PDFF), FibroScan/controlled attenuation parameter (CAP), and biochemical tests. METHODS We enrolled antiretroviral therapy-controlled participants with persistently elevated transaminases and/or metabolic syndrome, and/or lipodystrophy. All had hepatic MRI-PDFF, FibroScan/CAP, FibroTest/NashTest/SteatoTest, APRI, FIB-4, and nonalcoholic fatty liver disease-fibrosis score. A LB was indicated if suspected significant fibrosis (FibroScan ≥7.1 kPa and/or FibroTest ≥0.49). Performance was considered as good if area under a receiver operating characteristic curves (AUROCs) was >0.80. RESULTS Among the 140 patients with suspected significant fibrosis out of the 402 eligible patients, 49 had had a LB: median age of 54 years (53-65), body mass index: 26 kg/m (24-30), steatosis in 37 (76%), NASH in 23 (47%), and fibrosis in 31 (63%) patients [F2: 7 (14%); F3: 6 (12%); and F4: 2 (4%)]. Regarding steatosis, MRI-PDFF had excellent and CAP good performances with AUROCs at 0.98 (95% confidence interval: 0.96 to 1.00) and 0.88 (0.76 to 0.99), respectively, whereas the AUROCs of SteatoTest was 0.68 (0.51 to 0.85). Regarding fibrosis (≥F2), APRI and FIB-4 had good performance with AUROCs at 0.86 (0.74 to 0.98) and 0.81 (0.67 to 0.95). By contrast, FibroScan and FibroTest had poor AUROCs [0.61 (0.43 to 0.79) and 0.61 (0.44 to 0.78)], with very low specificity. Regarding NASH, alanine aminotransferase ≥36 IU/L had good performance with AUROCs of 0.83 (0.71 to 0.94), whereas the NashTest had an AUROC of 0.60 (0.44 to 0.76). CONCLUSIONS In HIV-monoinfected patients, MRI-PDFF and FibroScan/CAP are highly accurate for the diagnosis of steatosis. The alanine aminotransferase level and APRI should be considered for the detection of NASH and fibrosis.
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Matos J, Paparo F, Bacigalupo L, Cenderello G, Mussetto I, De Cesari M, Bernardi SP, Cevasco L, Forni GL, Cassola G, Rollandi GA. Noninvasive liver fibrosis assessment in chronic viral hepatitis C: agreement among 1D transient elastography, 2D shear wave elastography, and magnetic resonance elastography. Abdom Radiol (NY) 2019; 44:4011-4021. [PMID: 31696266 DOI: 10.1007/s00261-019-02295-7] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
PURPOSE To assess the agreement of one-dimensional transient elastography (1D-TE), two-dimensional shear wave elastography (2D-SWE), and magnetic resonance elastography (MRE) in a consecutive cohort of patients affected by hepatitis C virus (HCV) and to understand which patient-related factors are associated with disagreement. METHODS Ninety-one consecutive patients with current or previous chronic HCV infection were enrolled between March 2017 and September 2018. We assessed the correlation between stiffness measurements expressed in kilopascals (kPa). After converting kPa values in three groups of increasing fibrosis burden using validated cut-off values, we assessed the agreement among the different techniques. Factors influencing inter-modality disagreement were examined by employing multivariate logistic regression analysis. RESULTS Seventy-seven patients met the inclusion criteria and had reliable measurements by all stiffness imaging techniques. At the quantitative analysis, a strong correlation between stiffness measurements was found (Spearman's rho values ranging from 0.7 to 0.89 in all pairs of techniques). Complete concordance among MRE, 1D-TE, and 2D-SWE was found in 64.9% of patients, and the agreement was highest between MRE and 1D-TE, with κ value of 0.801. In only 2/77 patients (2.6%), there was complete disagreement. High body mass index (BMI) was the only factor significantly associated with inter-modality discordance. CONCLUSIONS MRE, 1D-TE, and 2D-SWE assigned the majority of patients to the same fibrosis group. The agreement was at least good, and there was a strong correlation between kPa values in all three pairs of techniques. Highest agreement was found between MRE and 1D-TE. High BMI was associated with discordance among the techniques.
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Affiliation(s)
- João Matos
- Unit of Radiology, Department of Diagnostic Imaging, E.O. Ospedali Galliera, Mura delle Cappuccine 14, 16128, Genoa, Italy.
- DISSAL - Department of Health Sciences, University of Genoa, Via Antonio Pastore, 1, 16132, Genoa, Italy.
| | - Francesco Paparo
- Unit of Radiology, Department of Diagnostic Imaging, E.O. Ospedali Galliera, Mura delle Cappuccine 14, 16128, Genoa, Italy
| | - Lorenzo Bacigalupo
- Unit of Radiology, Department of Diagnostic Imaging, E.O. Ospedali Galliera, Mura delle Cappuccine 14, 16128, Genoa, Italy
| | - Giovanni Cenderello
- Unit of Infectious Diseases, E.O. Ospedali Galliera, Mura delle Cappuccine 14, 16128, Genoa, Italy
| | - Ilaria Mussetto
- DISSAL - Department of Health Sciences, University of Genoa, Via Antonio Pastore, 1, 16132, Genoa, Italy
| | - Matteo De Cesari
- DISSAL - Department of Health Sciences, University of Genoa, Via Antonio Pastore, 1, 16132, Genoa, Italy
| | - Silvia Perugin Bernardi
- Unit of Radiology, Department of Diagnostic Imaging, E.O. Ospedali Galliera, Mura delle Cappuccine 14, 16128, Genoa, Italy
| | - Luca Cevasco
- Unit of Radiology, Department of Diagnostic Imaging, E.O. Ospedali Galliera, Mura delle Cappuccine 14, 16128, Genoa, Italy
| | - Gian Luca Forni
- Unit of Microcitemia and Hereditary Anemias, E.O. Ospedali Galliera, Mura delle Cappuccine 14, 16128, Genoa, Italy
| | - Giovanni Cassola
- Unit of Infectious Diseases, E.O. Ospedali Galliera, Mura delle Cappuccine 14, 16128, Genoa, Italy
| | - Gian Andrea Rollandi
- Unit of Radiology, Department of Diagnostic Imaging, E.O. Ospedali Galliera, Mura delle Cappuccine 14, 16128, Genoa, Italy
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10
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Qu Y, Li M, Hamilton G, Zhang YN, Song B. Diagnostic accuracy of hepatic proton density fat fraction measured by magnetic resonance imaging for the evaluation of liver steatosis with histology as reference standard: a meta-analysis. Eur Radiol 2019; 29:5180-5189. [PMID: 30877459 DOI: 10.1007/s00330-019-06071-5] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2018] [Revised: 12/24/2018] [Accepted: 02/04/2019] [Indexed: 02/08/2023]
Abstract
OBJECTIVES The aim of this meta-analysis was to evaluate the diagnostic accuracy of hepatic magnetic resonance imaging-proton density fat fraction (MRI-PDFF) for the assessment of liver steatosis (LS) with histology as reference standard. METHODS A systematic literature search was performed to identify pertinent studies. Quality analyses were conducted by Quality Assessment of Diagnostic Accuracy Studies-2. Diagnostic data were extracted and inconsistency index was calculated for LS≥G1, LS≥G2, and LS=G3, respectively. The area under summary receiver operating characteristic curve (AUC) served as the indicator of diagnostic accuracy. The pooled sensitivity and specificity were calculated if threshold effect was absent. RESULTS Thirteen studies containing 1100 subjects were included. There was significant threshold effect for LS≥G1. The AUCs for LS≥G1, LS≥G2, and LS=G3 were 0.98 (95% confidence interval (CI) 0.76, 1.00), 0.91 (95% CI 0.89, 0.94), and 0.92 (95% CI 0.89, 0.94), respectively. The pooled sensitivities for LS≥G2 and LS=G3 were 0.83 (95% CI 0.75, 0.88) and 0.79 (95% CI 0.63, 0.90), respectively; the pooled specificities for LS≥G2 and LS=G3 were 0.89 (95% CI 0.84, 0.92) and 0.89 (95% CI 0.84, 0.92), respectively. CONCLUSIONS MRI-PDFF has high diagnostic accuracy at detecting and grading LS with histology as reference standard, suggesting that MRI-PDFF is able to provide an accurate quantification of LS in clinical trials and patient care. KEY POINT • MRI-PDFF is able to provide an accurate quantification of LS in clinical trials and patient care.
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Affiliation(s)
- Yali Qu
- Department of Radiology, West China Hospital of Sichuan University, No. 37 Guoxue Xiang, Chengdu, 610041, Sichuan, China
| | - Mou Li
- Department of Radiology, West China Hospital of Sichuan University, No. 37 Guoxue Xiang, Chengdu, 610041, Sichuan, China
| | - Gavin Hamilton
- Liver Imaging Group, Department of Radiology, University of California at San Diego, La Jolla, CA, USA
| | - Yingzhen N Zhang
- Liver Imaging Group, Department of Radiology, University of California at San Diego, La Jolla, CA, USA
| | - Bin Song
- Department of Radiology, West China Hospital of Sichuan University, No. 37 Guoxue Xiang, Chengdu, 610041, Sichuan, China.
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11
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Shi Z, Xing H, Qi C, Fang M, Fu J, Zhang X. Chinese tree shrews as a primate experimental animal eligible for the study of alcoholic liver disease: characterization and confirmation by MRI. Exp Anim 2019; 69:110-118. [PMID: 31554748 PMCID: PMC7004808 DOI: 10.1538/expanim.19-0073] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
There has been a lack of suitable fatty liver models and characterization techniques for
histopathological evaluation of alcoholic fatty liver (AFL). This work aimed to exploit an
magnetic resonance imaging (MRI) technique for characterizing an alcohol-induced fatty
liver model established in tree shrews (Tupaia belangeri chinese). The
animals were treated with 15% alcohol for two weeks instead of drinking water to induce
AFL. Blood alanine aminotransferase (ALT), aspartate aminotransferase (AST), alcohol, and
liver malondialdehyde (MDA) concentrations were determined, and the histopathology of the
liver was checked by hematoxylin & eosin (HE) and Oil red O staining on day 0 and on
the 4th, 7th and 14th days after alcohol feeding. MRI was used to trace the
histopathological changes in the liver of tree shrews in real time. Compared with the
control group, the levels of ALT, AST, and MDA significantly increased in the
alcohol-induced group and were positively correlated with the induction time. HE and Oil
red O staining revealed that a moderate fatty lesion occurred in the liver on the 4th day
and that a serious AFL was successfully induced on the 14th day. MRI further confirmed the
formation of AFL. MRI, as noninvasive examination technique, provides an alternative tool
for accurate characterization of AFL in live subjects. It is comparable to HE or Oil red O
staining for histopathological examination, but is more suitable by virtue of its high
flexibility and compliance. The AFL model of tree shrews combined with MRI
characterization can work as a platform for studying fatty liver diseases and medications
for their treatment.
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Affiliation(s)
- Zhihai Shi
- Institute of Animal Husbandry and Veterinary, Henan Academy of Agricultural Sciences, 116 Huayuan Road, Zhengzhou, Henan Province 450008, P.R. China
| | - Huijie Xing
- Institute of Laboratory Animals, Jinan University, 601 West Huangpu Avenue, Guangzhou, Guangdong Province 510632, P.R. China
| | - Chunli Qi
- Institute of Laboratory Animals, Jinan University, 601 West Huangpu Avenue, Guangzhou, Guangdong Province 510632, P.R. China
| | - Meixia Fang
- Institute of Laboratory Animals, Jinan University, 601 West Huangpu Avenue, Guangzhou, Guangdong Province 510632, P.R. China
| | - Jiangnan Fu
- Institute of Laboratory Animals, Jinan University, 601 West Huangpu Avenue, Guangzhou, Guangdong Province 510632, P.R. China
| | - Xingwang Zhang
- Department of Pharmaceutics, School of Pharmacy, Jinan University, 601 West Huangpu Avenue, Guangzhou, Guangdong Province 510632, P.R. China
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12
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Bray TJP, Chouhan MD, Punwani S, Bainbridge A, Hall-Craggs MA. Fat fraction mapping using magnetic resonance imaging: insight into pathophysiology. Br J Radiol 2018; 91:20170344. [PMID: 28936896 PMCID: PMC6223159 DOI: 10.1259/bjr.20170344] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2017] [Revised: 07/18/2017] [Accepted: 09/06/2017] [Indexed: 02/06/2023] Open
Abstract
Adipose cells have traditionally been viewed as a simple, passive energy storage depot for triglycerides. However, in recent years it has become clear that adipose cells are highly physiologically active and have a multitude of endocrine, metabolic, haematological and immune functions. Changes in the number or size of adipose cells may be directly implicated in disease (e.g. in the metabolic syndrome), but may also be linked to other pathological processes such as inflammation, malignant infiltration or infarction. MRI is ideally suited to the quantification of fat, since most of the acquired signal comes from water and fat protons. Fat fraction (FF, the proportion of the acquired signal derived from fat protons) has, therefore, emerged as an objective, image-based biomarker of disease. Methods for FF quantification are becoming increasingly available in both research and clinical settings, but these methods vary depending on the scanner, manufacturer, imaging sequence and reconstruction software being used. Careful selection of the imaging method-and correct interpretation-can improve the accuracy of FF measurements, minimize potential confounding factors and maximize clinical utility. Here, we review methods for fat quantification and their strengths and weaknesses, before considering how they can be tailored to specific applications, particularly in the gastrointestinal and musculoskeletal systems. FF quantification is becoming established as a clinical and research tool, and understanding the underlying principles will be helpful to both imaging scientists and clinicians.
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Affiliation(s)
- Timothy JP Bray
- Centre for
Medical Imaging, University College London,University College London,
London, UK
| | - Manil D Chouhan
- Centre for
Medical Imaging, University College London,University College London,
London, UK
| | - Shonit Punwani
- Centre for
Medical Imaging, University College London,University College London,
London, UK
| | - Alan Bainbridge
- Department
of Medical Physics, University College London
Hospitals,University
College London Hospitals, London,
UK
| | - Margaret A Hall-Craggs
- Centre for
Medical Imaging, University College London,University College London,
London, UK
- Department
of Medical Physics, University College London
Hospitals,University
College London Hospitals, London,
UK
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13
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Park CC, Hooker C, Hooker JC, Bass E, Haufe W, Schlein A, Covarrubias Y, Heba E, Bydder M, Wolfson T, Gamst A, Loomba R, Schwimmer J, Hernando D, Reeder SB, Middleton M, Sirlin CB, Hamilton G. Assessment of a high-SNR chemical-shift-encoded MRI with complex reconstruction for proton density fat fraction (PDFF) estimation overall and in the low-fat range. J Magn Reson Imaging 2018; 49:229-238. [PMID: 29707848 DOI: 10.1002/jmri.26168] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2018] [Accepted: 04/04/2018] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Improving the signal-to-noise ratio (SNR) of chemical-shift-encoded MRI acquisition with complex reconstruction (MRI-C) may improve the accuracy and precision of noninvasive proton density fat fraction (PDFF) quantification in patients with hepatic steatosis. PURPOSE To assess the accuracy of high SNR (Hi-SNR) MRI-C versus standard MRI-C acquisition to estimate hepatic PDFF in adult and pediatric nonalcoholic fatty liver disease (NAFLD) using an MR spectroscopy (MRS) sequence as the reference standard. STUDY TYPE Prospective. POPULATION/SUBJECTS In all, 231 adult and pediatric patients with known or suspected NAFLD. FIELD STRENGTH/SEQUENCE PDFF estimated at 3T by three MR techniques: standard MRI-C; a Hi-SNR MRI-C variant with increased slice thickness, decreased matrix size, and no parallel imaging; and MRS (reference standard). ASSESSMENT MRI-PDFF was measured by image analysts using a region of interest coregistered with the MRS-PDFF voxel. STATISTICAL TESTS Linear regression analyses were used to assess accuracy and precision of MRI-estimated PDFF for MRS-PDFF as a function of MRI-PDFF using the standard and Hi-SNR MRI-C for all patients and for patients with MRS-PDFF <10%. RESULTS In all, 271 exams from 231 patients were included (mean MRS-PDFF: 12.6% [SD: 10.4]; range: 0.9-41.9). High agreement between MRI-PDFF and MRS-PDFF was demonstrated across the overall range of PDFF, with a regression slope of 1.035 for the standard MRI-C and 1.008 for Hi-SNR MRI-C. Hi-SNR MRI-C, compared to standard MRI-C, provided small but statistically significant improvements in the slope (respectively, 1.008 vs. 1.035, P = 0.004) and mean bias (0.412 vs. 0.673, P < 0.0001) overall. In the low-fat patients only, Hi-SNR MRI-C provided improvements in the slope (1.058 vs. 1.190, P = 0.002), mean bias (0.168 vs. 0.368, P = 0.007), intercept (-0.153 vs. -0.796, P < 0.0001), and borderline improvement in the R2 (0.888 vs. 0.813, P = 0.01). DATA CONCLUSION Compared to standard MRI-C, Hi-SNR MRI-C provides slightly higher MRI-PDFF estimation accuracy across the overall range of PDFF and improves both accuracy and precision in the low PDFF range. LEVEL OF EVIDENCE 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:229-238.
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Affiliation(s)
- Charlie C Park
- Liver Imaging Group, Department of Radiology, University of California at San Diego, La Jolla, California, USA
| | - Catherine Hooker
- Liver Imaging Group, Department of Radiology, University of California at San Diego, La Jolla, California, USA
| | - Jonathan C Hooker
- Liver Imaging Group, Department of Radiology, University of California at San Diego, La Jolla, California, USA
| | - Emily Bass
- Liver Imaging Group, Department of Radiology, University of California at San Diego, La Jolla, California, USA
| | - William Haufe
- Liver Imaging Group, Department of Radiology, University of California at San Diego, La Jolla, California, USA
| | - Alexandra Schlein
- Liver Imaging Group, Department of Radiology, University of California at San Diego, La Jolla, California, USA
| | - Yesenia Covarrubias
- Liver Imaging Group, Department of Radiology, University of California at San Diego, La Jolla, California, USA
| | - Elhamy Heba
- Liver Imaging Group, Department of Radiology, University of California at San Diego, La Jolla, California, USA
| | - Mark Bydder
- Liver Imaging Group, Department of Radiology, University of California at San Diego, La Jolla, California, USA
| | - Tanya Wolfson
- Computational and Applied Statistics Laboratory, San Diego Supercomputer Center, University of California - San Diego, San Diego, California, USA
| | - Anthony Gamst
- Computational and Applied Statistics Laboratory, San Diego Supercomputer Center, University of California - San Diego, San Diego, California, USA
| | - Rohit Loomba
- Division of Gastroenterology, Department of Medicine, University of California at San Diego, La Jolla, California, USA.,Division of Epidemiology, Department of Family Medicine and Preventive Medicine, University of California at San Diego, La Jolla, California, USA
| | - Jeffrey Schwimmer
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA.,Department of Gastroenterology, Rady Children's Hospital San Diego, California, USA
| | - Diego Hernando
- Department of Radiology, University of Wisconsin - Madison, Madison, Wisconsin, USA
| | - Scott B Reeder
- Department of Radiology, University of Wisconsin - Madison, Madison, Wisconsin, USA.,Department of Medical Physics, University of Wisconsin - Madison, Madison, Wisconsin, USA.,Department of Biomedical Engineering, University of Wisconsin - Madison, Madison, Wisconsin, USA.,Department of Medicine, University of Wisconsin - Madison, Madison, Wisconsin, USA.,Department of Emergency Medicine, University of Wisconsin - Madison, Madison, Wisconsin, USA
| | - Michael Middleton
- Liver Imaging Group, Department of Radiology, University of California at San Diego, La Jolla, California, USA
| | - Claude B Sirlin
- Liver Imaging Group, Department of Radiology, University of California at San Diego, La Jolla, California, USA
| | - Gavin Hamilton
- Liver Imaging Group, Department of Radiology, University of California at San Diego, La Jolla, California, USA
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14
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Tada T, Kumada T, Toyoda H, Sone Y, Takeshima K, Ogawa S, Goto T, Wakahata A, Nakashima M, Nakamuta M, Tanaka J. Viral eradication reduces both liver stiffness and steatosis in patients with chronic hepatitis C virus infection who received direct-acting anti-viral therapy. Aliment Pharmacol Ther 2018; 47:1012-1022. [PMID: 29424449 DOI: 10.1111/apt.14554] [Citation(s) in RCA: 57] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2017] [Revised: 12/28/2017] [Accepted: 01/16/2018] [Indexed: 12/19/2022]
Abstract
BACKGROUND Whether direct-acting anti-viral therapy can reduce liver fibrosis and steatosis in patients with chronic hepatitis C virus (HCV) infection is unclear. AIMS To evaluate changes in liver stiffness and steatosis in patients with HCV who received direct-acting anti-viral therapy and achieved sustained virological response (SVR). METHODS A total of 198 patients infected with HCV genotype 1 or 2 who achieved SVR after direct-acting anti-viral therapy were analysed. Liver stiffness as evaluated by magnetic resonance elastography, steatosis as evaluated by magnetic resonance imaging-determined proton density fat fraction (PDFF), insulin resistance, and laboratory data were assessed before treatment (baseline) and at 24 weeks after the end of treatment (SVR24). RESULTS Alanine aminotransferase and homeostatic model assessment-insulin resistance levels decreased significantly from baseline to SVR24. Conversely, platelet count, which is inversely associated with liver fibrosis, increased significantly from baseline to SVR24. In patients with high triglyceride levels (≥150 mg/dL), triglyceride levels significantly decreased from baseline to SVR24 (P = 0.004). The median (interquartile range) liver stiffness values at baseline and SVR24 were 3.10 (2.70-4.18) kPa and 2.80 (2.40-3.77) kPa respectively (P < 0.001). The PDFF values at baseline and SVR 24 were 2.4 (1.7-3.4)% and 1.9 (1.3-2.8)% respectively (P < 0.001). In addition, 68% (19/28) of patients with fatty liver at baseline (PDFF ≥5.2%; n = 28) no longer had fatty liver (PDFF <5.2%) at SVR24. CONCLUSION Viral eradication reduces both liver stiffness and steatosis in patients with chronic HCV who received direct-acting anti-viral therapy (UMIN000017020).
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Affiliation(s)
- T Tada
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Gifu, Japan
| | - T Kumada
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Gifu, Japan
| | - H Toyoda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Gifu, Japan
| | - Y Sone
- Department of Radiology, Ogaki Municipal Hospital, Ogaki, Gifu, Japan
| | - K Takeshima
- Department of Imaging Diagnosis, Ogaki Municipal Hospital, Ogaki, Gifu, Japan
| | - S Ogawa
- Department of Imaging Diagnosis, Ogaki Municipal Hospital, Ogaki, Gifu, Japan
| | - T Goto
- Department of Imaging Diagnosis, Ogaki Municipal Hospital, Ogaki, Gifu, Japan
| | - A Wakahata
- Department of Imaging Diagnosis, Ogaki Municipal Hospital, Ogaki, Gifu, Japan
| | - M Nakashima
- Department of Pharmacy, Ogaki Municipal Hospital, Ogaki, Gifu, Japan
| | - M Nakamuta
- Department of Gastroenterology, Kyushu Medical Center, Fukuoka, Japan
| | - J Tanaka
- Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan
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15
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Han MAT, Saouaf R, Ayoub W, Todo T, Mena E, Noureddin M. Magnetic resonance imaging and transient elastography in the management of Nonalcoholic Fatty Liver Disease (NAFLD). Expert Rev Clin Pharmacol 2017; 10:379-390. [PMID: 28277807 DOI: 10.1080/17512433.2017.1299573] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease and cirrhosis worldwide and the second most common cause of liver transplantation in major medical centers. Because liver steatosis and fibrosis severity are related to disease morbidity and mortality, the extent of disease, and disease progression, they need to be assessed and monitored. In addition, innovation with new drug developments requires disease staging and monitoring in both phase 2 and 3 clinical trials. Currently, disease assessment in both clinical practice and research is mostly performed by liver biopsy, an invasive, procedure with risks. Noninvasive, highly accurate tests are needed that could be used in clinical trials as surrogate endpoints and in clinical practice for monitoring patients. Area Covered: We discuss noninvasive tests, transient elastography (TE) with controlled attenuation parameter (CAP), magnetic resonance imaging (MRI), and MR elastography (MRE), summarize the available evidence of their usefulness for assessing steatosis and fibrosis. Therefore they could be used as clinical trials outcomes and in disease monitoring in clinical practice. Expert Commentary: TE with CAP, MRI and MRE are highly accurate noninvasive diagnostic tools for quantifying hepatic steatosis and fibrosis. Therefore they could be used as clinical trials outcomes and in disease monitoring in clinical practice.
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Affiliation(s)
- Ma Ai Thanda Han
- a Division of Digestive and Liver Diseases , Cedars-Sinai Medical Center , Los Angeles , California , USA
| | - Rola Saouaf
- b Department of Radiology , Cedars-Sinai Medical Center , Los Angeles , California , USA
| | - Walid Ayoub
- c Fatty Liver Program, Division of Digestive and Liver Diseases, Cedars-Sinai Medical Center , Los Angeles , California , USA.,d Comprehensive Transplant Center, Cedars-Sinai Medical Center , Los Angeles , California , USA
| | - Tsuyoshi Todo
- d Comprehensive Transplant Center, Cedars-Sinai Medical Center , Los Angeles , California , USA
| | - Edward Mena
- e California Liver Research Institute , Pasadena , California , USA
| | - Mazen Noureddin
- c Fatty Liver Program, Division of Digestive and Liver Diseases, Cedars-Sinai Medical Center , Los Angeles , California , USA.,d Comprehensive Transplant Center, Cedars-Sinai Medical Center , Los Angeles , California , USA
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16
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Unal E, Idilman IS, Karçaaltıncaba M. Multiparametric or practical quantitative liver MRI: towards millisecond, fat fraction, kilopascal and function era. Expert Rev Gastroenterol Hepatol 2017; 11:167-182. [PMID: 27937040 DOI: 10.1080/17474124.2017.1271710] [Citation(s) in RCA: 20] [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] [Indexed: 12/13/2022]
Abstract
New advances in liver magnetic resonance imaging (MRI) may enable diagnosis of unseen pathologies by conventional techniques. Normal T1 (550-620 ms for 1.5 T and 700-850 ms for 3 T), T2, T2* (>20 ms), T1rho (40-50 ms) mapping, proton density fat fraction (PDFF) (≤5%) and stiffness (2-3kPa) values can enable differentiation of a normal liver from chronic liver and diffuse diseases. Gd-EOB-DTPA can enable assessment of liver function by using postcontrast hepatobiliary phase or T1 reduction rate (normally above 60%). T1 mapping can be important for the assessment of fibrosis, amyloidosis and copper overload. T1rho mapping is promising for the assessment of liver collagen deposition. PDFF can allow objective treatment assessment in NAFLD and NASH patients. T2 and T2* are used for iron overload determination. MR fingerprinting may enable single slice acquisition and easy implementation of multiparametric MRI and follow-up of patients. Areas covered: T1, T2, T2*, PDFF and stiffness, diffusion weighted imaging, intravoxel incoherent motion imaging (ADC, D, D* and f values) and function analysis are reviewed. Expert commentary: Multiparametric MRI can enable biopsyless diagnosis and more objective staging of diffuse liver disease, cirrhosis and predisposing diseases. A comprehensive approach is needed to understand and overcome the effects of iron, fat, fibrosis, edema, inflammation and copper on MR relaxometry values in diffuse liver disease.
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Affiliation(s)
- Emre Unal
- a Liver Imaging Team, Department of Radiology , Hacettepe University School of Medicine , Ankara , Turkey
- b Department of Radiology , Zonguldak Ataturk State Hospital , Zonguldak , Turkey
| | - Ilkay Sedakat Idilman
- a Liver Imaging Team, Department of Radiology , Hacettepe University School of Medicine , Ankara , Turkey
- c Department of Radiology , Ankara Ataturk Education and Research Hospital , Ankara , Turkey
| | - Muşturay Karçaaltıncaba
- a Liver Imaging Team, Department of Radiology , Hacettepe University School of Medicine , Ankara , Turkey
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17
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Karanjia RN, Crossey MME, Cox IJ, Fye HKS, Njie R, Goldin RD, Taylor-Robinson SD. Hepatic steatosis and fibrosis: Non-invasive assessment. World J Gastroenterol 2016; 22:9880-9897. [PMID: 28018096 PMCID: PMC5143756 DOI: 10.3748/wjg.v22.i45.9880] [Citation(s) in RCA: 62] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2016] [Revised: 10/10/2016] [Accepted: 11/16/2016] [Indexed: 02/06/2023] Open
Abstract
Chronic liver disease is a major cause of morbidity and mortality worldwide and usually develops over many years, as a result of chronic inflammation and scarring, resulting in end-stage liver disease and its complications. The progression of disease is characterised by ongoing inflammation and consequent fibrosis, although hepatic steatosis is increasingly being recognised as an important pathological feature of disease, rather than being simply an innocent bystander. However, the current gold standard method of quantifying and staging liver disease, histological analysis by liver biopsy, has several limitations and can have associated morbidity and even mortality. Therefore, there is a clear need for safe and non-invasive assessment modalities to determine hepatic steatosis, inflammation and fibrosis. This review covers key mechanisms and the importance of fibrosis and steatosis in the progression of liver disease. We address non-invasive imaging and blood biomarker assessments that can be used as an alternative to information gained on liver biopsy.
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18
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Dulai PS, Sirlin CB, Loomba R. MRI and MRE for non-invasive quantitative assessment of hepatic steatosis and fibrosis in NAFLD and NASH: Clinical trials to clinical practice. J Hepatol 2016; 65:1006-1016. [PMID: 27312947 PMCID: PMC5124376 DOI: 10.1016/j.jhep.2016.06.005] [Citation(s) in RCA: 260] [Impact Index Per Article: 28.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2016] [Revised: 05/19/2016] [Accepted: 06/06/2016] [Indexed: 02/07/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) represents one of the most common causes of chronic liver disease, and its prevalence is rising worldwide. The occurrence of non-alcoholic steatohepatitis (NASH) is associated with a substantial increase in disease related morbidity and mortality. Accordingly, there has been a surge of innovation surrounding drug development in an effort to off-set the natural progression and long-term risks of this disease. Disease assessment within clinical trials and clinical practice for NAFLD is currently done with liver biopsies. Liver biopsy-based assessments, however, remain imprecise and are not without cost or risk. This carries significant implications for the feasibility and costs of bringing therapeutic interventions to market. A need therefore arises for reliable and highly accurate surrogate end-points that can be used in phase 2 and 3 clinical trials to reduce trial size requirements and costs, while improving feasibility and ease of implementation in clinical practice. Significant advances have now been made in magnetic resonance technology, and magnetic resonance imaging (MRI) and elastrography (MRE) have been demonstrated to be highly accurate diagnostic tools for the detection of hepatic steatosis and fibrosis. In this review article, we will summarize the currently available evidence regarding the use of MRI and MRE among NAFLD patients, and the evolving role these surrogate biomarkers will play in the rapidly advancing arena of clinical trials in NASH and hepatic fibrosis. Furthermore, we will highlight how these tools can be readily applied to routine clinical practice, where the growing burden of NAFLD will need to be met with enhanced monitoring algorithms.
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Affiliation(s)
- Parambir S Dulai
- Division of Gastroenterology, Department of Medicine, University of California at San Diego, La Jolla, CA, United States
| | - Claude B Sirlin
- Liver Imaging Group, Department of Radiology, University of California at San Diego, La Jolla, CA, United States
| | - Rohit Loomba
- Division of Gastroenterology, Department of Medicine, University of California at San Diego, La Jolla, CA, United States; NAFLD Research Center, Department of Medicine, University of California at San Diego, La Jolla, CA, United States.
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19
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Bacigalupo L, Paparo F, Zefiro D, Viberti CM, Cevasco L, Gianesin B, Pinto VM, Rollandi GA, Wood JC, Forni GL. Comparison between different software programs and post-processing techniques for the MRI quantification of liver iron concentration in thalassemia patients. Radiol Med 2016; 121:751-62. [PMID: 27334009 DOI: 10.1007/s11547-016-0661-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2015] [Accepted: 06/01/2016] [Indexed: 01/19/2023]
Abstract
PURPOSE In magnetic resonance imaging (MRI) relaxometry, various software programs are available to perform R2* measurements and to estimate the liver iron concentration (LIC). The main objective of our study was to compare R2* LIC values, obtained with three different software programs based on specific decay models and calibration curves, with LIC estimates provided by R2-relaxometry (FerriScan). METHODS This retrospective study included 15 patients with 15 baseline MRIs and 34 serial examinations. R2* LIC estimates were calculated using the FuncTool, CMRtools/Thalassemia Tools and Quanta Hematology programs. Longitudinal LIC changes (ΔLIC) were calculated using the subset of 34 serial MRIs. RESULTS After Bland-Altman analysis on baseline data, Quanta Hematology, which employs the monoexponential-plus-constant fit, produced the lowest mean difference [0.01 ± 0.14 log(mg/gdw)] with the closest limits of agreement. In the longitudinal setting, Quanta Hematology again gave the lowest mean difference between R2 and R2* LIC (0.1 ± 2.6 mg/gdw). Using FerriScan as reference, the value of concordant directional ΔLIC changes was the same for all programs (27/34, 85.7 %). CONCLUSIONS R2* LICs are higher than R2 LICs at iron levels <7 mg/gdw, while R2 LIC averages higher than R2* LIC with increasing iron load. The monoexponential-plus-constant model provided the best agreement with R2 LIC estimates.
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Affiliation(s)
- Lorenzo Bacigalupo
- Radiology Unit, Department of Diagnostic Imaging, E.O. Ospedali Galliera, Mura delle Cappuccine 14, 16128, Genoa, Italy.
| | - Francesco Paparo
- Radiology Unit, Department of Diagnostic Imaging, E.O. Ospedali Galliera, Mura delle Cappuccine 14, 16128, Genoa, Italy
| | - Daniele Zefiro
- Department of Medical Physics, ASL n.5 "Spezzino", Via XXIV Maggio 139, 19124, La Spezia, Italy
| | - Carlo Maria Viberti
- Medical Physics Unit, E.O. Ospedali Galliera, Mura delle Cappuccine 14, 16128, Genoa, Italy
| | - Luca Cevasco
- Radiology Unit, Department of Diagnostic Imaging, E.O. Ospedali Galliera, Mura delle Cappuccine 14, 16128, Genoa, Italy
| | - Barbara Gianesin
- Medical Physics Unit, E.O. Ospedali Galliera, Mura delle Cappuccine 14, 16128, Genoa, Italy
| | - Valeria Maria Pinto
- Microcitemia and Hereditary Anaemias Unit, E.O. Ospedali Galliera, Mura delle Cappuccine 14, 16128, Genoa, Italy
| | - Gian Andrea Rollandi
- Radiology Unit, Department of Diagnostic Imaging, E.O. Ospedali Galliera, Mura delle Cappuccine 14, 16128, Genoa, Italy
| | - John C Wood
- Department of Radiology, Children's Hospital Los Angeles, Los Angeles, CA, USA
| | - Gian Luca Forni
- Microcitemia and Hereditary Anaemias Unit, E.O. Ospedali Galliera, Mura delle Cappuccine 14, 16128, Genoa, Italy
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