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Cathcart J, Barrett R, Bowness JS, Mukhopadhya A, Lynch R, Dillon JF. Accuracy of Non-Invasive Imaging Techniques for the Diagnosis of MASH in Patients With MASLD: A Systematic Review. Liver Int 2025; 45:e16127. [PMID: 39400428 DOI: 10.1111/liv.16127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2024] [Revised: 09/14/2024] [Accepted: 09/27/2024] [Indexed: 10/15/2024]
Abstract
BACKGROUND AND AIMS Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing public health problem. The secondary stage in MASLD is steatohepatitis (MASH), the co-existence of steatosis and inflammation, a leading cause of progression to fibrosis and mortality. MASH resolution alone improves survival. Currently, MASH diagnosis is via liver biopsy. This study sought to evaluate the accuracy of imaging-based tests for MASH diagnosis, which offer a non-invasive method of diagnosis. METHODS Eight academic literature databases were searched and references of previous systematic reviews and included papers were checked for additional papers. Liver biopsy was used for reference standard. RESULTS We report on 69 imaging-based studies. There were 31 studies on MRI, 27 on ultrasound, five on CT, 13 on transient elastography, eight on controlled attenuation parameter (CAP) and two on scintigraphy. The pathological definition of MASH was inconsistent, making it difficult to compare studies. 55/69 studies (79.71%) were deemed high-risk of bias as they had no preset thresholds and no validation. The two largest groups of imaging papers were on MRI and ultrasound. AUROCs were up to 0.93 for MRE, 0.90 for MRI, 1.0 for magnetic resonance spectroscopy (MRS) and 0.94 for ultrasound-based studies. CONCLUSIONS Our study found that the most promising imaging tools are MRI techniques or ultrasound-based scores and confirmed there is potential to utilise these for MASH diagnosis. However, many publications are single studies without independent prospective validation. Without this, there is no clear imaging tool or score currently available that is reliably tested to diagnose MASH.
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Affiliation(s)
- Jennifer Cathcart
- Division of Molecular and Clinical Medicine, University of Dundee, Dundee, UK
- Gastroenterology Department, Aberdeen Royal Infirmary, Aberdeen, UK
| | - Rachael Barrett
- Division of Molecular and Clinical Medicine, University of Dundee, Dundee, UK
| | - James S Bowness
- University College London Hospitals NHS Foundation Trust, London, UK
- Department of Targeting Intervention, University College London, London, UK
| | | | - Ruairi Lynch
- Division of Molecular and Clinical Medicine, University of Dundee, Dundee, UK
| | - John F Dillon
- Division of Molecular and Clinical Medicine, University of Dundee, Dundee, UK
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Diaz LA, Arab JP, Idalsoaga F, Perelli J, Vega J, Dirchwolf M, Carreño J, Samith B, Valério C, Moreira RO, Acevedo M, Brahm J, Hernández N, Gadano A, Oliveira CP, Arrese M, Castro-Narro G, Pessoa MG. Updated recommendations for the management of metabolic dysfunction-associated steatotic liver disease (MASLD) by the Latin American working group. Ann Hepatol 2025:101903. [PMID: 40089151 DOI: 10.1016/j.aohep.2025.101903] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2024] [Revised: 02/04/2025] [Accepted: 02/07/2025] [Indexed: 03/17/2025]
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the leading causes of chronic liver disease globally. Based on the 2023 definition, MASLD is characterized by the presence of metabolic dysfunction and limited alcohol consumption (<140 grams/week for women, <210 grams/week for men). Given the significant burden of MASLD in Latin America, this guidance was developed by the Latin American Association for the Study of the Liver (ALEH) Working Group to address key aspects of its clinical assessment and therapeutic strategies. In Latin America, ultrasonography is recommended as the initial screening tool for hepatic steatosis due to its accessibility, while Fibrosis-4 (FIB-4) is preferred for fibrosis risk stratification, with further evaluation using more specific techniques (i.e., vibration-controlled transient elastography or Enhanced Liver Fibrosis [ELF] test). A Mediterranean diet is advised for all MASLD patients, with a target of 7-10% weight loss for those with excess weight. Complete alcohol abstinence is recommended for patients with significant fibrosis, and smoking cessation is encouraged regardless of fibrosis stage. Pharmacological options should be tailored based on the presence of steatohepatitis, liver fibrosis, excess weight, and diabetes, including resmetirom, incretin-based therapies, pioglitazone, and sodium-glucose cotransporter-2 inhibitors. Bariatric surgery may be considered for MASLD patients with obesity unresponsive to lifestyle and medical interventions. Hepatocellular carcinoma screening is advised for all cirrhotic patients, with consideration given to those with advanced fibrosis based on individual risk. Finally, routine cardiovascular risk assessment and proper diabetes prevention and management remain crucial for all patients with MASLD.
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Affiliation(s)
- Luis Antonio Diaz
- MASLD Research Center, Division of Gastroenterology and Hepatology, University of California San Diego, San Diego, CA, USA; Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
| | - Juan Pablo Arab
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile; Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, VA, USA
| | - Francisco Idalsoaga
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile; Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University & London Health Sciences Centre, London, Ontario, Canada
| | - Javiera Perelli
- Unidad de Diabetes y Nutrición Clínica, Clínica Universidad de los Andes, Santiago, Chile
| | - Javier Vega
- Departamento de Nutrición, Diabetes y Metabolismo, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | | | - Javiera Carreño
- Asociación Latinoamericana para el Estudio del Hígado (ALEH), Santiago, Chile
| | - Bárbara Samith
- Departamento de Nutrición, Diabetes y Metabolismo, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Cynthia Valério
- Instituto Estadual de Diabetes e Endocrinologia Luiz Capriglione, Rio de Janeiro, RJ, Brasil
| | - Rodrigo Oliveira Moreira
- Instituto Estadual de Diabetes e Endocrinologia Luiz Capriglione, Rio de Janeiro, RJ, Brasil; Faculdade de Medicina de Valença, Centro Universitário de Valença, Valença, RJ, Brasil; Faculdade de Medicina, Centro Universitário Presidente Antônio Carlos, Juiz de Fora, MG, Brasil
| | - Mónica Acevedo
- División de Enfermedades Cardiovasculares, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Javier Brahm
- Unidad de Gastroenterología, Clínica Universidad de los Andes, Santiago, Chile
| | - Nelia Hernández
- Asociación Latinoamericana para el Estudio del Hígado (ALEH), Santiago, Chile; Hospital de Clínicas, Universidad de la República, Montevideo, Uruguay
| | - Adrian Gadano
- Liver Unit, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina; Department of Research, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Claudia P Oliveira
- Gastroenterology Department, Hospital das Clínicas (LIM07) HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brasil
| | - Marco Arrese
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile; Asociación Latinoamericana para el Estudio del Hígado (ALEH), Santiago, Chile
| | - Graciela Castro-Narro
- Asociación Latinoamericana para el Estudio del Hígado (ALEH), Santiago, Chile; Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Mexico City, Mexico; Medica Sur Clinic & Foundation, Mexico City, Mexico
| | - Mario G Pessoa
- Asociación Latinoamericana para el Estudio del Hígado (ALEH), Santiago, Chile; Gastroenterology Department, Hospital das Clínicas (LIM07) HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brasil
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Jin HY, Noh ES, Jeong H, Hwang IIT. Prediction of hepatic fibrosis using the aspartate transaminase-to-platelet ratio index in children and adolescents with metabolic dysfunction-associated steatotic liver disease. BMC Pediatr 2024; 24:788. [PMID: 39614232 DOI: 10.1186/s12887-024-05263-3] [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: 09/03/2024] [Accepted: 11/19/2024] [Indexed: 12/01/2024] Open
Abstract
BACKGROUND Aspartate transaminase-to-platelet ratio index (APRI) is an easy and useful predictor of hepatic fibrosis in patients with chronic hepatic disease, and it significantly correlates with the degree of hepatic fibrosis in adult patients with metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to evaluate the use of APRI in assessing the severity of MASLD in children and adolescents. METHODS Medical records of 115 patients (males: 78; females: 37) with MASLD were retrospectively reviewed. The correlations between the APRI and clinical parameters that indicate the severity of MASLD were analyzed. Their ages ranged between 7.3 and 18.8 years old. Patients with hepatitis B or C infections were excluded from the study. The APRI score was calculated, and transient elastography for liver stiffness measurement (LSM) was performed for all the patients. RESULTS The mean APRI score was 0.46 ± 0.26, ranging between 0.16 and 1.57. The LSM values ranged between 2.94 and 7.72 kPa. Body mass index-standard deviation score, transaminase levels, and HbA1c levels were higher in a group with abnormal LSM when divided into two groups according to LSM. The APRI score was greater in the group with abnormal LSM (0.40 ± 0.17 vs. 0.64 ± 0.40, P < 0.001). The APRI score was associated with LSM (r = 0.354, P < 0.001). Area under the curve of APRI for predicting abnormal LSM was 0.650 (95% confidence interval, 0.517-0.784) with a cutoff value of 0.74. CONCLUSIONS APRI score showed weak correlation with LSM. Further study encompassing various severity of hepatic fibrosis is needed for identifying better and sensitive non-invasive indicators in pediatric MASLD.
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Affiliation(s)
- Hye Young Jin
- Department of Pediatrics, Kangdong Sacred Heart hospital, Hallym University College of Medicine, 150, Seongan-ro, Gangdong-gu, Seoul, 05355, Republic of Korea
| | - Eu Seon Noh
- Department of Pediatrics, Kangdong Sacred Heart hospital, Hallym University College of Medicine, 150, Seongan-ro, Gangdong-gu, Seoul, 05355, Republic of Korea
| | - Hwalrim Jeong
- Department of Pediatrics, Soonchunhyang University, Cheonan hospital, Cheonan, Korea
| | - I I Tae Hwang
- Department of Pediatrics, Kangdong Sacred Heart hospital, Hallym University College of Medicine, 150, Seongan-ro, Gangdong-gu, Seoul, 05355, Republic of Korea.
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Wu Y, Zhou J, Zhang J, Li H. Cytokeratin 18 in nonalcoholic fatty liver disease: value and application. Expert Rev Mol Diagn 2024; 24:1009-1022. [PMID: 39387822 DOI: 10.1080/14737159.2024.2413941] [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: 02/07/2024] [Accepted: 10/04/2024] [Indexed: 10/15/2024]
Abstract
INTRODUCTION Nonalcoholic fatty liver disease (NAFLD) is a common metabolism-related disease worldwide. Although studies have shown that some medications may be effective for treating NAFLD, they do not satisfy the medical requirements, and lifestyle changes are the most basic strategy. Thus, early detection of NAFLD and timely lifestyle interventions are highly important. AREAS COVERED The traditional diagnostic methods for NAFLD are limited by accuracy, cost, and security issues. Cytokeratin 18 (CK18), which is a marker of apoptosis and overall cell death, is an excellent biomarker for NAFLD. Liver fat accumulation in NAFLD triggers the activation of caspases, which increases the CK18 cleavage and its release into the blood. CK18 can help diagnose different stages of NAFLD, especially the nonalcoholic steatohepatitis (NASH) stage. In evaluating the efficacy of the NAFLD treatment and predicting the risk of NAFLD-related diseases, CK18 plays a significant role. EXPERT OPINION CK18 can non-invasively monitor the pathological conditions of NAFLD patients and provide new hope for the early diagnosis of NAFLD. Adding CK18 to the NAFLD diagnostic criteria that are widely used in clinical settings may be efficient for the detection of NAFLD and early effective intervention.
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Affiliation(s)
- Yuan Wu
- School of Medicine, The 2nd Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
- Liver Disease Department of Integrative Medicine, Ningbo No. 2 Hospital, Ningbo, China
| | - Jing Zhou
- Liver Disease Department of Integrative Medicine, Ningbo No. 2 Hospital, Ningbo, China
| | - Jun Zhang
- Liver Disease Department of Integrative Medicine, Ningbo No. 2 Hospital, Ningbo, China
| | - Hongshan Li
- School of Medicine, The 2nd Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
- Liver Disease Department of Integrative Medicine, Ningbo No. 2 Hospital, Ningbo, China
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Zheng S, Li D, Shi Z, Yang Y, Li L, Chen P, A bulimiti X, Li F. Development and validation of a nomogram for nonalcoholic fatty liver disease in Western Xinjiang, China. Eur J Gastroenterol Hepatol 2024; 36:1220-1229. [PMID: 38916218 PMCID: PMC11361349 DOI: 10.1097/meg.0000000000002807] [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: 02/21/2024] [Accepted: 04/11/2024] [Indexed: 06/26/2024]
Abstract
OBJECTIVE The aim of this study was to establish a simple, nonalcoholic fatty liver disease (NAFLD) screening model using readily available variables to identify high-risk individuals in Western Xinjiang, China. METHODS A total of 40 033 patients from the National Health Examination were divided into a training group (70%) and a validation group (30%). Univariate regression and least absolute shrinkage and selection operator models optimized feature selection, while a multivariate logistic regression analysis constructed the prediction model. The model's performance was evaluated using the area under the receiver operating characteristic curve, and its clinical utility was assessed through decision curve analysis. RESULTS The nomogram assessed NAFLD risk based on factors such as sex, age, diastolic blood pressure, waist circumference, BMI, fasting plasma glucose, alanine aminotransferase, platelet count, total cholesterol, triglycerides, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol. The area under the receiver operating characteristic curves were 0.829 for men and 0.859 for women in the development group, and 0.817 for men and 0.865 for women in the validation group. The decision curve analysis confirmed the nomogram's clinical usefulness, with consistent findings in the validation set. CONCLUSION A user-friendly nomogram prediction model for NAFLD risk was successfully developed and validated for Western Xinjiang, China.
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Affiliation(s)
- Shuaiyin Zheng
- Xinjiang Second Medical College
- Xinjiang Key Laboratory of Clinical Gene Testing and Biomedical Information
| | - Di Li
- Xinjiang Key Laboratory of Clinical Gene Testing and Biomedical Information
- Department of Public Health, Karamay Hospital of People’s Hospital of Xinjiang Uygur Autonomous Region
- Xinjiang Digestive System Tumor Precision Medical Clinical Medical Research Center, Karamay
| | - Zhuoyue Shi
- Department of Public Health, Xinjiang Medical University, Urumqi
| | - Ying Yang
- Department of Public Health, Xinjiang Medical University, Urumqi
| | | | | | | | - Fuye Li
- Department of Public Health, Xinjiang Medical University, Urumqi
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Fouad Y, Alboraie M, Shiha G. Epidemiology and diagnosis of metabolic dysfunction-associated fatty liver disease. Hepatol Int 2024; 18:827-833. [PMID: 38967907 PMCID: PMC11450050 DOI: 10.1007/s12072-024-10704-3] [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: 02/08/2024] [Accepted: 06/01/2024] [Indexed: 07/06/2024]
Abstract
The most common chronic liver illness worldwide is metabolic dysfunction linked to fatty liver disease (MAFLD), which is poorly understood by doctors and patients. Many people with this disease develop steatohepatitis, cirrhosis and its consequences, as well as extrahepatic manifestations; these conditions are particularly common if they are linked to diabetes mellitus or obesity. A breakthrough with numerous benefits is the switch from NAFLD to MAFLD in terms of terminology and methodology. The diagnosis of MAFLD is based on affirmative criteria; unlike NAFLD, it is no longer based on exclusion. The diagnosis of MAFLD and the evaluation of steatosis and fibrosis is achieved using liver biopsy and non-invasive laboratory or radiographic techniques. We briefly address the most recent developments in MAFLD epidemiology and diagnosis.
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Affiliation(s)
- Yasser Fouad
- Department of Gastroenterology, Hepatology and Endemic Medicine, Faculty of Medicine, Minia University, Minia, Egypt.
| | - Mohamed Alboraie
- Department of Internal Medicine, Al-Azhar University, Cairo, Egypt
| | - Gamal Shiha
- Egyptian Liver Research Institute and Hospital, Mansoura, Egypt
- Hepatology and Gastroenterology Unit, Internal Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
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Kim B, Jin HY, Yoon JS, Noh ES, Hwang IT. Triglyceride Glucose Index is Associated with Ultrasonographic Fatty Liver Indicator in Children and Adolescents with Non-alcoholic Fatty Liver Disease. J Clin Res Pediatr Endocrinol 2024; 16:306-313. [PMID: 38664989 PMCID: PMC11590764 DOI: 10.4274/jcrpe.galenos.2024.2024-2-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2024] [Accepted: 03/25/2024] [Indexed: 09/06/2024] Open
Abstract
Objective Non-alcoholic fatty liver disease (NAFLD) is defined as chronic hepatic steatosis and is becoming prevalent, along with the increasing trend for obesity in children and adolescents. A non-invasive and reliable tool is needed to differentiate non-alcoholic steatohepatitis from simple steatosis. This study evaluated the association between the triglyceride glucose (TyG) index and the ultrasonographic fatty liver indicator (US-FLI), and the possibility of using the TyG index for prediction of severity of pediatric NAFLD. Methods One hundred and twenty one patients who were diagnosed with NAFLD by ultrasonography were included. They were categorized into three groups according to body mass index (BMI). Ninety-two were obese, and 19 and 10 were overweight and normal weight, respectively. Results The homeostatic model assessment for insulin resistance (HOMA-IR) was highest in the group with obesity (p=0.044). The TyG index and US-FLI did not differ significantly among the three BMI groups (p=0.186). Fourteen (11.6%) of the 121 patients had US-FLI ≥6, in whom the BMI-SDS and TyG index were higher (p=0.017, p=0.004), whereas HOMA-IR did not differ significantly from the group with US-FLI <6 (p=0.366). US-FLI was associated with BMI-SDS and the TyG index. TyG index was significantly associated with US-FLI after adjustment for BMI-SDS. The cut-off value for the TyG index for predicting US-FLI ≥6 was 8.91, with an area under the curve of 0.785. Conclusion TyG index was associated with the degree of hepatic steatosis, suggesting that it might be a useful tool for predicting the severity of pediatric NAFLD.
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Affiliation(s)
- Bitgyeol Kim
- Hallym University College of Medicine, Kangdong Sacred Heart Hospital, Clinic of Pediatrics, Seoul, Korea
| | - Hye Young Jin
- Hallym University College of Medicine, Kangdong Sacred Heart Hospital, Clinic of Pediatrics, Seoul, Korea
| | - Jong Seo Yoon
- Hallym University College of Medicine, Kangdong Sacred Heart Hospital, Clinic of Pediatrics, Seoul, Korea
| | - Eu Seon Noh
- Hallym University College of Medicine, Kangdong Sacred Heart Hospital, Clinic of Pediatrics, Seoul, Korea
| | - Il Tae Hwang
- Hallym University College of Medicine, Kangdong Sacred Heart Hospital, Clinic of Pediatrics, Seoul, Korea
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Kim G, Yu TY, Jee JH, Bae JC, Kang M, Kim JH. Association between nonalcoholic fatty liver disease and left ventricular diastolic dysfunction: A 7-year retrospective cohort study of 3,380 adults using serial echocardiography. DIABETES & METABOLISM 2024; 50:101534. [PMID: 38608865 DOI: 10.1016/j.diabet.2024.101534] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Revised: 04/05/2024] [Accepted: 04/08/2024] [Indexed: 04/14/2024]
Abstract
AIM Left ventricular diastolic dysfunction (LVDD) has been observed in people with nonalcoholic fatty liver disease (NAFLD) in cross-sectional studies but the causal relationship is unclear. This study aimed to investigate the impact of NAFLD and the fibrotic progression of the disease on the development of LVDD, assessed by serial echocardiography, in a large population over a 7-year longitudinal setting. METHODS This retrospective cohort study included the data of 3,380 subjects from a medical health check-up program. We defined subjects having NAFLD by abdominal ultrasonography and assessed significant liver fibrosis by the aspartate transaminase (AST) to platelet ratio index (APRI), the NAFLD fibrosis score (NFS), and the fibrosis-4 (FIB-4) index. LVDD was defined using serial echocardiography. A parametric Cox proportional hazards model was used. RESULTS During 11,327 person-years of follow-up, there were 560 (16.0 %) incident cases of LVDD. After adjustment for multiple risk factors, subjects with NAFLD showed an increased adjusted hazard ratio (aHR) of 1.21 (95 % confidence interval [CI]=1.02-1.43) for incident LVDD compared to those without. The risk of LV diastolic dysfunction increased progressively with increasing degree of hepatic steatosis (P< 0.001). Compared to subjects without NAFLD, the multivariable-aHR (95 % CI) for LVDD in subjects with APRI < 0.5 and APRI ≥ 0.5 were 1.20 (1.01-1.42) and 1.36 (0.90-2.06), respectively (P= 0.036), while other fibrosis prediction models (NFS and FIB-4 index) showed insignificant results. CONCLUSIONS This study demonstrated that NAFLD was associated with an increased risk of LVDD in a large cohort. More severe forms of hepatic steatosis and/or significant liver fibrosis may increase the risk of developing LVDD.
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Affiliation(s)
- Gyuri Kim
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Tae Yang Yu
- Division of Endocrinology and Metabolism, Department of Medicine, Wonkwang Medical Center, Wonkwang University School of Medicine, Iksan, Republic of Korea
| | - Jae Hwan Jee
- Department of Health Promotion Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Ji Cheol Bae
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Republic of Korea
| | - Mira Kang
- Department of Health Promotion Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
| | - Jae Hyeon Kim
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Republic of Korea; Department of Clinical Research Design & Evaluation, SAIHST, Sungkyunkwan University, Republic of Korea.
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Tsai CC, Chiu MH, Kek HP, Yang MC, Su YT, Liu HK, Wu MS, Yeh YT. The Reduced Gut Lachnospira Species Is Linked to Liver Enzyme Elevation and Insulin Resistance in Pediatric Fatty Liver Disease. Int J Mol Sci 2024; 25:3640. [PMID: 38612453 PMCID: PMC11011648 DOI: 10.3390/ijms25073640] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2024] [Revised: 03/17/2024] [Accepted: 03/19/2024] [Indexed: 04/14/2024] Open
Abstract
The objective of this study was to investigate gut dysbiosis and its metabolic and inflammatory implications in pediatric metabolic dysfunction-associated fatty liver disease (MAFLD). This study included 105 children and utilized anthropometric measurements, blood tests, the Ultrasound Fatty Liver Index, and fecal DNA sequencing to assess the relationship between gut microbiota and pediatric MAFLD. Notable decreases in Lachnospira spp., Faecalibacterium spp., Oscillospira spp., and Akkermansia spp. were found in the MAFLD group. Lachnospira spp. was particularly reduced in children with MAFLD and hepatitis compared to controls. Both MAFLD groups showed a reduction in flavone and flavonol biosynthesis sequences. Lachnospira spp. correlated positively with flavone and flavonol biosynthesis and negatively with insulin levels and insulin resistance. Body weight, body mass index (BMI), and total cholesterol levels were inversely correlated with flavone and flavonol biosynthesis. Reduced Lachnospira spp. in children with MAFLD may exacerbate insulin resistance and inflammation through reduced flavone and flavonol biosynthesis, offering potential therapeutic targets.
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Affiliation(s)
- Ching-Chung Tsai
- Department of Pediatrics, E-Da Hospital, I-Shou University, No. 1, Yi-Da Road, Yan-Chao District, Kaohsiung City 82445, Taiwan; (C.-C.T.); (H.-P.K.); (M.-C.Y.); (Y.-T.S.); (H.-K.L.)
- School of Medicine for International Students, College of Medicine, I-Shou University, No. 8, Yi-Da Road, Yan-Chao District, Kaohsiung City 82445, Taiwan
| | - Min-Hsi Chiu
- Aging and Disease Prevention Research Center, Fooyin University, No. 151, Jinxue Road, Daliao District, Kaohsiung City 83102, Taiwan;
- Department of Medical Laboratory Science and Biotechnology, Fooyin University, No. 151, Jinxue Road, Daliao District, Kaohsiung City 83102, Taiwan
| | - Ho-Poh Kek
- Department of Pediatrics, E-Da Hospital, I-Shou University, No. 1, Yi-Da Road, Yan-Chao District, Kaohsiung City 82445, Taiwan; (C.-C.T.); (H.-P.K.); (M.-C.Y.); (Y.-T.S.); (H.-K.L.)
| | - Ming-Chun Yang
- Department of Pediatrics, E-Da Hospital, I-Shou University, No. 1, Yi-Da Road, Yan-Chao District, Kaohsiung City 82445, Taiwan; (C.-C.T.); (H.-P.K.); (M.-C.Y.); (Y.-T.S.); (H.-K.L.)
- School of Medicine, College of Medicine, I-Shou University, No. 8, Yi-Da Road, Yan-Chao District, Kaohsiung City 82445, Taiwan
| | - Yu-Tsun Su
- Department of Pediatrics, E-Da Hospital, I-Shou University, No. 1, Yi-Da Road, Yan-Chao District, Kaohsiung City 82445, Taiwan; (C.-C.T.); (H.-P.K.); (M.-C.Y.); (Y.-T.S.); (H.-K.L.)
- School of Medicine for International Students, College of Medicine, I-Shou University, No. 8, Yi-Da Road, Yan-Chao District, Kaohsiung City 82445, Taiwan
| | - Hsien-Kuan Liu
- Department of Pediatrics, E-Da Hospital, I-Shou University, No. 1, Yi-Da Road, Yan-Chao District, Kaohsiung City 82445, Taiwan; (C.-C.T.); (H.-P.K.); (M.-C.Y.); (Y.-T.S.); (H.-K.L.)
- School of Medicine, College of Medicine, I-Shou University, No. 8, Yi-Da Road, Yan-Chao District, Kaohsiung City 82445, Taiwan
| | - Ming-Shiang Wu
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, No. 7, Zhongshan S. Road, Zhongzheng District, Taipei City 100225, Taiwan;
| | - Yao-Tsung Yeh
- Aging and Disease Prevention Research Center, Fooyin University, No. 151, Jinxue Road, Daliao District, Kaohsiung City 83102, Taiwan;
- Department of Medical Laboratory Science and Biotechnology, Fooyin University, No. 151, Jinxue Road, Daliao District, Kaohsiung City 83102, Taiwan
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Yin H, Xiong B, Yu J, Fan Y, Zhou B, Sun Y, Wang L, Xu H, Zhu Y. Interoperator reproducibility of quantitative ultrasound analysis of hepatic steatosis in participants with suspected MASLD: A prospective study. Eur J Radiol 2024; 175:111427. [PMID: 38522397 DOI: 10.1016/j.ejrad.2024.111427] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Revised: 01/11/2024] [Accepted: 03/11/2024] [Indexed: 03/26/2024]
Abstract
OBJECTIVES To evaluate the reproducibility of tissue attenuation imaging (TAI) and tissue scatter distribution imaging (TSI) measurements in adults with suspected metabolic dysfunction-associated steatotic liver disease (MASLD) between radiologists with varying experience. MATERIALS AND METHODS Participants with suspected MASLD were prospectively recruited. TAI and TSI were performed for each participant by two radiologists with different levels of experience. Interoperability reliability was assessed on the basis of Bland-Altman analysis and intraclass correlation coefficients (ICCs). The study determined and compared the diagnostic performance of TAI and TSI with clinical prediction models using proton magnetic resonance spectroscopy (1H-MRS) as a reference. RESULTS A total of 180 participants (women, n = 56; men, n = 124, mean age, 46.98 ± 14.92 years; mean BMI, 25.81 ± 4.47) were enrolled from August 2022 to September 2022. Bland-Altman plots showed only slight deviation in the TAI and TSI results of the two radiologists; there was good interoperator reproducibility for TAI (ICC = 0.92) and TSI (ICC = 0.86). Senior and junior radiologists performed examinations labeled as TAI-1 and TSI-1, and TAI-2 and TSI-2, respectively. The areas under the curves (AUCs) of TAI-1, TAI-2, TSI-1, and TAI-2 for the detection of ≥5 % hepatic steatosis were 0.90, 0.96, 0.91 and 0.96, respectively. According to ROC analysis, the diagnostic performance of both radiologists for TAI and TSI was statistically similar and superior to that of the clinical prediction model. CONCLUSIONS TAI and TSI have good reproducibility between radiologists with different levels of experience. Meanwhile, both TAI and TSI demonstrated good diagnostic performance for hepatic steatosis (≥5%), surpassing that of clinical prediction models.
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Affiliation(s)
- Haohao Yin
- Department of Ultrasound, Institute of Ultrasound in Medicine and Engineering, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Shanghai Institute of Medical Imaging, Fudan University, Shanghai 200032, China; Institute of Ultrasound in Medicine and Engineering, Fudan University, Shanghai 200032, China
| | - Bing Xiong
- Department of Ultrasound, Institute of Ultrasound in Medicine and Engineering, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Shanghai Institute of Medical Imaging, Fudan University, Shanghai 200032, China; Institute of Ultrasound in Medicine and Engineering, Fudan University, Shanghai 200032, China
| | - Jifeng Yu
- Department of Ultrasound, Institute of Ultrasound in Medicine and Engineering, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Yunling Fan
- Department of Ultrasound, Institute of Ultrasound in Medicine and Engineering, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Boyang Zhou
- Department of Ultrasound, Institute of Ultrasound in Medicine and Engineering, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Yikang Sun
- Department of Ultrasound, Institute of Ultrasound in Medicine and Engineering, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Lifan Wang
- Department of Ultrasound, Institute of Ultrasound in Medicine and Engineering, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Huixiong Xu
- Department of Ultrasound, Institute of Ultrasound in Medicine and Engineering, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
| | - Yuli Zhu
- Department of Ultrasound, Institute of Ultrasound in Medicine and Engineering, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
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Chen PK, Hsu WF, Peng CY, Liao TL, Chang SH, Chen HH, Chen CH, Chen DY. Significant association of elevated serum galectin-9 levels with the development of non-alcoholic fatty liver disease in patients with rheumatoid arthritis. Front Med (Lausanne) 2024; 11:1347268. [PMID: 38371515 PMCID: PMC10869587 DOI: 10.3389/fmed.2024.1347268] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Accepted: 01/22/2024] [Indexed: 02/20/2024] Open
Abstract
Background Non-alcoholic fatty liver disease (NAFLD) is prevalent among rheumatoid arthritis (RA) patients, but its pathogenesis has rarely been explored. Galectin-9 (Gal-9) interacts with T cell immunoglobulin and mucin-containing-molecule-3 (TIM-3) expressed on hepatocytes and thus regulates T cell proliferation in a murine model of NAFLD. We aimed to examine the pathogenic role of the Gal-9/TIM-3 pathway in RA-NAFLD. Methods Serum levels of Gal-9, soluble TIM-3 (sTIM-3), fatty acid-binding proteins (FABP)1, and FABP4 were determined by ELISA in forty-five RA patients and eleven healthy participants. Using Oil-red O staining and immunoblotting, we examined the effects of Gal-9 and free fatty acid (FFA) on lipid accumulation in human hepatocytes and FABP1 expression. Results Serum Gal-9, sTIM-3 and FABP1 level were significantly higher in RA patients (median 5.02 ng/mL, 3.42 ng/mL, and 5.76 ng/mL, respectively) than in healthy participants (1.86 ng/mL, 0.99 ng/mL, and 0.129 ng/mL, all p < 0.001). They were also significantly higher in patients with moderate-to-severe NAFLD compared with none-to-mild NAFLD (p < 0.01; p < 0.05; and p < 0.01, respectively). Serum Gal-9 levels were positively correlated with sTIM-3, FABP1, FABP4 levels, and ultrasound-fatty liver score, respectively, in RA patients. Multivariate regression analysis revealed that Gal-9 (cut-off>3.30) was a significant predictor of NAFLD development, and Gal-9 and sTIM-3 were predictors of NAFLD severity (both p < 0.05). The cell-based assay showed that Gal-9 and FFA could upregulate FABP1 expression and enhance lipid droplet accumulation in hepatocytes. Conclusion Elevated levels of Gal-9 and sTIM3 in RA patients with NAFLD and their positive correlation with NAFLD severity suggest the pathogenic role of Gal-9 signaling in RA-related NAFLD.
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Affiliation(s)
- Po-Ku Chen
- Rheumatology and Immunology Center, China Medical University Hospital, Taichung, Taiwan
- Translational Medicine Laboratory, China Medical University Hospital, Taichung, Taiwan
| | - Wei-Fan Hsu
- College of Medicine, China Medical University, Taichung, Taiwan
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Cheng-Yuan Peng
- College of Medicine, China Medical University, Taichung, Taiwan
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Tsai-Ling Liao
- Ph.D. Program in Translational Medicine and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan
- Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan
- College of Medicine, National Chung Hsing University, Taichung, Taiwan
| | - Shih-Hsin Chang
- Rheumatology and Immunology Center, China Medical University Hospital, Taichung, Taiwan
- College of Medicine, China Medical University, Taichung, Taiwan
- Ph.D. Program in Translational Medicine and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan
| | - Hsin-Hua Chen
- Ph.D. Program in Translational Medicine and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan
- College of Medicine, National Chung Hsing University, Taichung, Taiwan
- Division of General Medicine, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Chu-Huang Chen
- Vascular and Medicinal Research, Texas Heart Institute, Houston, TX, United States
- Institute for Biomedical Sciences, Shinshu University, Nagano, Japan
| | - Der-Yuan Chen
- Rheumatology and Immunology Center, China Medical University Hospital, Taichung, Taiwan
- Translational Medicine Laboratory, China Medical University Hospital, Taichung, Taiwan
- College of Medicine, China Medical University, Taichung, Taiwan
- Ph.D. Program in Translational Medicine and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan
- College of Medicine, National Chung Hsing University, Taichung, Taiwan
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Harden JE, Tabacu L, Reynolds LJ. Physical activity intensity and markers of inflammation in those with non-alcoholic fatty liver disease. Diabetes Res Clin Pract 2024; 207:111047. [PMID: 38070545 DOI: 10.1016/j.diabres.2023.111047] [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: 09/01/2023] [Revised: 11/14/2023] [Accepted: 12/05/2023] [Indexed: 02/10/2024]
Abstract
AIMS To investigate associations between objectively measured light (LPA) and moderate-to-vigorous (MVPA) physical activity on plasma homocysteine and serum C-reactive protein (CRP) in individuals with Non-Alcoholic Fatty Liver Disease (NAFLD). METHODS This study was a secondary analysis using data from 2003 to 2006 National Health and Nutrition Examination Survey including a total of 983 individuals with NAFLD. Physical activity was assessed over 7 days with accelerometers. Participants were split into tertiles based on average daily minutes of LPA or MVPA and CRP and homocysteine were assessed across tertiles. RESULTS Adjusted plasma homocysteine and CRP were not different between groups regarding levels of LPA (Homocysteine: 1st tertile - 10.4 ± 0.7 µmol/L; 2nd tertile - 9.6 ± 0.4 µmol/L; 3rd tertile - 9.6 ± 0.4 µmol/L; p = 0.28; CRP: 1st tertile - 0.79 ± 0.12 mg/dL; 2nd tertile - 0.73 ± 0.09 mg/dL; 3rd tertile - 0.73 ± 0.09 mg/dL; p = 0.72). Adjusted CRP was significantly (p = 0.02) different across MVPA tertiles (1st: 0.87 ± 0.13 mg/dL; 2nd: 0.75 ± 0.10 mg/dL; 3rd:0.65 ± 0.09). CONCLUSIONS LPA does not appear to be effective at improving homocysteine or CRP levels in individuals with NAFLD. However, MVPA may be an effective therapy for decreasing CRP in NAFLD patients.
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Affiliation(s)
- Joel E Harden
- School of Exercise Science, Old Dominion University, Norfolk, VA, USA
| | - Lucia Tabacu
- Department of Mathematics and Statistics, Old Dominion University, Norfolk, VA, USA
| | - Leryn J Reynolds
- School of Exercise Science, Old Dominion University, Norfolk, VA, USA.
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Ferraioli G, Barr RG. Noninvasive assessment of liver steatosis with ultrasound techniques. MULTIPARAMETRIC ULTRASOUND FOR THE ASSESSMENT OF DIFFUSE LIVER DISEASE 2024:177-198. [DOI: 10.1016/b978-0-323-87479-3.00020-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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14
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Thomas M, Dighe M, Kolokythas O, Zecevic M, Wilson A, Erpelding T, Dubinsky TJ. Ultrasound Attenuation Imaging vs MRI-PDFF, Echogenicity and Liver Function for Assessing Degree of Steatosis in NAFLD and Non-NAFLD Patients. Ultrasound Q 2023; 39:188-193. [PMID: 37543732 DOI: 10.1097/ruq.0000000000000648] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/07/2023]
Abstract
ABSTRACT Nonalcoholic fatty liver disease (NAFLD) is a primary cause of parenchymal liver disease globally. There are currently several methods available to test the degree of steatosis in NAFLD patients, but all have drawbacks that limit their use.The objective of this study is to determine if a new technique, ultrasound (US) attenuation imaging (ATI), correlates with magnetic resonance proton density fat fraction imaging and hepatic echogenicity as seen on gray scale US imaging.Fifty-four patients were recruited at the University of Washington Medical Center from individuals who had already been scheduled for hepatic US or magnetic resonance imaging (MRI). All participants then underwent both hepatic MRI proton density fat fraction and US. Ultrasound images were then evaluated using ATI with 2 observers who individually determined relative grayscale echogenicity.Analysis showed positive correlation between ATI- and MRI-determined fat percentage in the case group (Spearman correlation: 0.50; P = 0.015). Furthermore, participants with NAFLD tended to have a higher ATI than controls (median: 0.70 vs 0.54 dB/cm/MHz; P < 0.001).This study demonstrates that US ATI combined with grayscale imaging is an effective way of assessing the degree of steatosis in patients with moderate to severe NAFLD.
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15
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Lu CW, Yang KC, Chi YC, Wu TY, Chiang CH, Chang HH, Huang KC, Yang WS. Adiponectin-leptin ratio for the early detection of lean non-alcoholic fatty liver disease independent of insulin resistance. Ann Med 2023; 55:634-642. [PMID: 36790383 PMCID: PMC9937001 DOI: 10.1080/07853890.2023.2179106] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/16/2023] Open
Abstract
BACKGROUND Lean Non-alcoholic Fatty Liver Disease (NAFLD) shares a similar disease burden to those of their overweight counterparts and should be detected early. We hypothesized that the adiponectin-leptin ratio (AL ratio) could be a good marker for early detection of lean NAFLD independent of insulin resistance. MATERIALS AND METHODS A total of 575 adults without diabetes were enrolled in a community-based study. The subjects were stratified into the lean controls, lean NAFLD, simple overweight/obesity and overweight/obesity NAFLD groups according to body mass index (BMI) and ultrasonographic fatty liver indicators. Serum adiponectin and leptin levels were measured by enzyme-linked immunosorbent assay. Multivariate logistic regression analyses were performed to estimate the odds ratio of having NAFLD in relation to the tertiles of serum AL concentration after adjustment. Receiver operating characteristic (ROC) analyses were applied to evaluate the diagnostic performance of the AL ratio for NAFLD. RESULTS The mean age of the participants was 42.8 ± 11.5 years. Comparing with the lean controls, the odds of having lean NAFLD for the highest versus the lowest tertile of AL ratio was 0.28(95%CI: 0.12-0.69) after adjustment. Putting AL ratio, BMI, triglyceride, AST/ALT ratio to the diagnosis performance of NAFLD, the ROC was 0.85 (95% CI: 0.82-0.88), 0.83 (95% CI 0.78-0.87) and 0.86 (95% CI 081-0.91) for all NAFLD, NAFLD in women and NAFLD in men, respectively. (p < .001). CONCLUSIONS The study revealed that the AL ratio could be a good biomarker to early distinguish lean NAFLD patients from lean controls independent of insulin resistance. [AQ3]Key messagesThe prevalence of non-alcoholic fatty liver disease (NAFLD) increases globally and is related to liver diseases and metabolic dysfunctions. Lean subset of NAFLD shares a similar disease burden to those of their overweight counterparts and should be detected early.Adiponectin-leptin ratio were associated with the severity of steatosis and was a predictor of obese NAFLD better than each single adipokine. To date, there is no investigation that explores specifically for the relationship between lean NAFLD and AL ratio.Our study found that adiponectin-leptin ratio is a sole independent marker regardless of insulin resistance in lean NAFLD. Having lean NAFLD for the highest versus the lowest tertile of adiponectin-leptin ratio was 0.28(95%CI: 0.12-0.69) after adjustment of age, sex, current smoking, exercise habits, HOMA-IR and AST/ALT. ROC for the NAFLD performance is good for the early detection (0.85; 95% CI: 0.82-0.88). Further rigorous investigation is necessary and should be promptly performed.
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Affiliation(s)
- Chia-Wen Lu
- Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.,Department of Family Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Kuen-Cheh Yang
- Department of Family Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Yu-Chiao Chi
- Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.,Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Tsan-Yu Wu
- Department of Family Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Chien-Hsieh Chiang
- Department of Family Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Department of Family Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Hao-Hsiang Chang
- Department of Family Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Department of Family Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Kuo-Chin Huang
- Department of Family Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Department of Family Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.,Department of Family Medicine, National Taiwan University Hospital, Hsin-Chu, Taiwan
| | - Wei-Shiung Yang
- Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.,Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
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16
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Polti G, Frigerio F, Del Gaudio G, Pacini P, Dolcetti V, Renda M, Angeletti S, Di Martino M, Iannetti G, Perla FM, Poggiogalle E, Cantisani V. Quantitative ultrasound fatty liver evaluation in a pediatric population: comparison with magnetic resonance imaging of liver proton density fat fraction. Pediatr Radiol 2023; 53:2458-2465. [PMID: 37698614 PMCID: PMC10635941 DOI: 10.1007/s00247-023-05749-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Revised: 08/11/2023] [Accepted: 08/14/2023] [Indexed: 09/13/2023]
Abstract
BACKGROUND Biopsy remains the gold standard for the diagnosis of hepatic steatosis, the leading cause of pediatric chronic liver disease; however, its costs call for less invasive methods. OBJECTIVE This study examined the diagnostic accuracy and reliability of quantitative ultrasound (QUS) for the assessment of liver fat content in a pediatric population, using magnetic resonance imaging proton density fat fraction (MRI-PDFF) as the reference standard. MATERIALS AND METHODS We enrolled 36 patients. MRI-PDFF involved a 3-dimensional T2*-weighted with Dixon pulse multiple-echo sequence using iterative decomposition of water and fat with echo asymmetry and least squares estimation (IDEAL IQ). QUS imaging relied on the ultrasound system "RS85 A" (Samsung Medison, Seoul, South Korea) and the following software: Hepato-Renal Index with automated region of interest recommendation (EzHRI), Tissue Attenuation Imaging (TAI), and Tissue Scatter Distribution Imaging (TSI). For each QUS index, receiver operating characteristic (ROC) curve analysis against MRI-PDFF was used to identify the associated cut-off value and the area under the ROC curve (AUROC). Concordance between two radiologists was assessed by intraclass correlation coefficients (ICCs) and Bland-Altman analysis. RESULTS A total of 61.1% of the sample (n=22) displayed a MRI-PDFF ≥ 5.6%; QUS cut-off values were TAI=0.625 (AUROC 0.90, confidence interval [CI] 0.77-1.00), TSI=91.95 (AUROC 0.99, CI 0.98-1.00) and EzHRI=1.215 (AUROC 0.98, CI 0.94-1.00). Inter-rater reliability was good-to-excellent for EzHRI (ICC 0.91, 95% C.I. 0.82-0.95) and TAI (ICC 0.94, 95% C.I. 0.88-0.97) and moderate to good for TSI (ICC 0.73; 95% C.I. 0.53-0.85). CONCLUSION Our results suggest that QUS can be used to reliably assess the presence and degree of pediatric hepatic steatosis.
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Affiliation(s)
- Giorgia Polti
- Department of Radiological Sciences, Oncology and Pathology, Sapienza University of Rome, Rome, Italy
| | - Francesco Frigerio
- Department of Experimental Medicine, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185, Rome, Italy
| | - Giovanni Del Gaudio
- Department of Radiological Sciences, Oncology and Pathology, Sapienza University of Rome, Rome, Italy
| | - Patrizia Pacini
- Department of Radiological Sciences, Oncology and Pathology, Sapienza University of Rome, Rome, Italy
| | - Vincenzo Dolcetti
- Department of Radiological Sciences, Oncology and Pathology, Sapienza University of Rome, Rome, Italy
| | - Maurizio Renda
- Department of Radiological Sciences, Oncology and Pathology, Sapienza University of Rome, Rome, Italy
| | - Sergio Angeletti
- Department of Radiological Sciences, Oncology and Pathology, Sapienza University of Rome, Rome, Italy
| | - Michele Di Martino
- Department of Radiological Sciences, Oncology and Pathology, Sapienza University of Rome, Rome, Italy
| | - Giovanni Iannetti
- Department of Radiological Sciences, Oncology and Pathology, Sapienza University of Rome, Rome, Italy
| | | | - Eleonora Poggiogalle
- Department of Experimental Medicine, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185, Rome, Italy.
| | - Vito Cantisani
- Department of Radiological Sciences, Oncology and Pathology, Sapienza University of Rome, Rome, Italy
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Ballestri S, Lonardo A. Ultrasonographic fatty liver indicator (US-FLI): a reliable biomarker for non-invasive NAFLD stratification. METABOLISM AND TARGET ORGAN DAMAGE 2023; 3. [DOI: 10.20517/mtod.2023.21] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Here, we comment on a recent article supporting the use of the ultrasonographic fatty liver indicator (US-FLI) as a point-of-care biomarker to be used in the community to rule out nonalcoholic steatohepatitis (NASH). To this end, we discuss definitions and characteristics of US-FLI, and we critically summarize the principal studies published from 2012 to 2023. We conclude that US-FLI exhibits high reproducibility. It finds utility across both the pediatric population and the point-of-care settings. Furthermore, it demonstrates a robust correlation with metabolic derangements, and also serves as a predictive tool for varying grades of hepatic steatosis and important liver histology endpoints. Notably, it excels in its capacity to differentiate between bland steatosis and true NASH. However, US-FLI reportedly exhibits limited accuracy among patient populations with obesity. Finally, we propose a detailed agenda to advance research on US-FLI.
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Yoon JS, Lim KJ, Hwang IT. Usefulness of two-dimensional shear wave elastography in the assessment of non-alcoholic fatty liver disease in children and adolescents. Sci Rep 2023; 13:10062. [PMID: 37344574 DOI: 10.1038/s41598-023-37281-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Accepted: 06/19/2023] [Indexed: 06/23/2023] Open
Abstract
Two-dimensional shear wave elastography (2D-SWE) evaluates liver stiffness using a non-invasive method, but studies in the paediatric population are rare. This study evaluated the role of 2D-SWE in the diagnosis and severity of paediatric non-alcoholic fatty liver disease (NAFLD). In total, 131 patients with NAFLD and 25 healthy controls were enrolled in this study. The diagnosis and severity of NAFLD were initially assessed using the ultrasound fatty liver index (US-FLI), and all participants underwent 2D-SWE. US-FLI semi-quantitatively measures the severity of NAFLD on a scale of 2-8. The assessment of liver stiffness measurement (LSM) by 2D-SWE is presented in kilopascals (kPa). The NAFLD group was characterised by significantly higher LSM (4.40 ± 0.90 kPa) than the control group (3.76 ± 0.28 kPa) (P < 0.001). 2D-SWE significantly correlated with age, height, weight, body mass index, glucose, aspartate aminotransferase, alanine aminotransferase, high-density lipoprotein cholesterol, US-FLI, and triglyceride-glucose index (P < 0.001). In the receiver operating characteristic curve analysis, the area under the curve of LSM for predicting US-FLI ≥ 2 and ≥ 6 was 0.784 (P < 0.001) and 0.819 (P < 0.001), respectively. In conclusion, we suggest that 2D-SWE can be used as a non-invasive diagnostic tool for diagnosing and assessing the severity of paediatric NAFLD.
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Affiliation(s)
- Jong Seo Yoon
- Department of Paediatrics, Hallym University Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, South Korea
| | - Kyoung Ja Lim
- Department of Radiology, Hallym University Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, 05355, South Korea.
| | - Il Tae Hwang
- Department of Paediatrics, Hallym University Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, South Korea
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Collin R, Magnin B, Gaillard C, Nicolas C, Abergel A, Buchard B. Prospective study comparing hepatic steatosis assessment by magnetic resonance imaging and four ultrasound methods in 105 successive patients. World J Gastroenterol 2023; 29:3548-3560. [PMID: 37389233 PMCID: PMC10303516 DOI: 10.3748/wjg.v29.i22.3548] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Revised: 04/04/2023] [Accepted: 05/12/2023] [Indexed: 06/06/2023] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is becoming a major health problem, resulting in hepatic, metabolic and cardio-vascular morbidity.
AIM To evaluate new ultrasonographic tools to detect and measure hepatic steatosis.
METHODS We prospectively included 105 patients referred to our liver unit for NAFLD suspicion or follow-up. They underwent ultrasonographic measurement of liver sound speed estimation (SSE) and attenuation coefficient (AC) using Aixplorer MACH 30 (Supersonic Imagine, France), continuous controlled attenuation parameter (cCAP) using Fibroscan (Echosens, France) and standard liver ultrasound with hepato-renal index (HRI) calculation. Hepatic steatosis was then classified according to magnetic resonance imaging proton density fat fraction (PDFF). Receiver operating curve (ROC) analysis was performed to evaluate the diagnostic performance in the diagnosis of steatosis.
RESULTS Most patients were overweight or obese (90%) and had metabolic syndrome (70%). One third suffered from diabetes. Steatosis was identified in 85 patients (81%) according to PDFF. Twenty-one patients (20%) had advanced liver disease. SSE, AC, cCAP and HRI correlated with PDFF, with respective Spearman correlation coefficient of -0.39, 0.42, 0.54 and 0.59 (P < 0.01). Area under the receiver operating characteristic curve (AUROC) for detection of steatosis with HRI was 0.91 (0.83-0.99), with the best cut-off value being 1.3 (Se = 83%, Sp = 98%). The optimal cCAP threshold of 275 dB/m, corresponding to the recent EASL-suggested threshold, had a sensitivity of 72% and a specificity of 80%. Corresponding AUROC was 0.79 (0.66-0.92). The diagnostic accuracy of cCAP was more reliable when standard deviation was < 15 dB/m with an AUC of 0.91 (0.83-0.98). An AC threshold of 0.42 dB/cm/MHz had an AUROC was 0.82 (0.70-0.93). SSE performed moderately with an AUROC of 0.73 (0.62-0.84).
CONCLUSION Among all ultrasonographic tools evaluated in this study, including new-generation tools such as cCAP and SSE, HRI had the best performance. It is also the simplest and most available method as most ultrasound scans are equipped with this module.
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Affiliation(s)
- Remi Collin
- Gastroenterology and Endoscopy Unit, Dupuytren University Hospital, Limoges 87000, France
- Department of Hepatology and Gastroenterology, Clermont-Ferrand University Hospital, Clermont-Ferrand 63000, France
| | - Benoit Magnin
- Department of Radiology, Clermont-Ferrand University Hospital, Clermont-Ferrand 63000, France
| | - Constance Gaillard
- Department of Radiology, Clermont-Ferrand University Hospital, Clermont-Ferrand 63000, France
| | - Carine Nicolas
- Department of Hepatology and Gastroenterology, Clermont-Ferrand University Hospital, Clermont-Ferrand 63000, France
| | - Armand Abergel
- Department of Hepatology and Gastroenterology, Clermont-Ferrand University Hospital, Clermont-Ferrand 63000, France
| | - Benjamin Buchard
- Department of Hepatology and Gastroenterology, Clermont-Ferrand University Hospital, Clermont-Ferrand 63000, France
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Atzori S, Pasha Y, Maurice JB, Taylor-Robinson SD, Campbell L, Lim AKP. The Accuracy of Ultrasound Controlled Attenuation Parameter in Diagnosing Hepatic Fat Content. Hepat Med 2023; 15:51-61. [PMID: 37325088 PMCID: PMC10263157 DOI: 10.2147/hmer.s411619] [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: 03/23/2023] [Accepted: 06/02/2023] [Indexed: 06/17/2023] Open
Abstract
Purpose The Controlled Attenuation Parameter (CAP score) is based on ultrasonic properties of retropropagated radiofrequency signals acquired by FibroscanTM (Echosens, Paris, France). Since ultrasound propagation is influenced by the presence of fat, CAP score was developed to quantify steatosis. The aim of this study was to delineate the accuracy of CAP in diagnosing hepatic steatosis, compared to the gold standard of liver biopsy. Patients and Methods A total of 150 patients underwent same-day liver biopsy and measurement of hepatic steatosis with Fibroscan. Only examinations with 10 satisfactory measurements, and an inter-quartile range of less than 30% of the median liver stiffness values were included for data analysis. Histological staging was then correlated with median values and Spearman correlation calculated. P values of <0.05 were considered statistically significant. Results For diagnosis of hepatic steatosis (HS), CAP could predict the steatosis S2 with AUROC 0.815 (95% CI 0.741-0.889), sensitivity (0.81) and specificity (0.73) when the optimal cut-off value was set at 288 dB/m. CAP detected histological grade S3 with AUROC 0.735 (95% CI 0.618-0.851), sensitivity (0.71) and specificity (0.74), with a cut-off value of 330 dB/m. The AUROC for steatosis grade S1 was 0.741 (95% CI 0.650-0.824), with a cut-off value of 263 dB/m with sensitivity 0.75 and specificity 0.70. Univariate analysis showed a correlation between CAP and diabetes (p 0.048). Conclusion The performance of CAP to diagnose steatosis severity decreases as steatosis progresses. CAP is associated with diabetes but not other clinical factors and parameters of the metabolic syndrome.
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Affiliation(s)
- Sebastiana Atzori
- Department of Surgery and Cancer, Imperial College London, London, W1 1NY, UK
- Department of Medicine, Sassari University Hospital, Sassari, 07100, Italy
| | - Yasmin Pasha
- Department of Surgery and Cancer, Imperial College London, London, W1 1NY, UK
| | - James B Maurice
- Department of Surgery and Cancer, Imperial College London, London, W1 1NY, UK
- UCL Institute for Liver and Digestive Health, Royal Free Hospital Campus, London, NW3 2QG, UK
| | | | - Louise Campbell
- Department of Surgery and Cancer, Imperial College London, London, W1 1NY, UK
- Office of the Clinical Director, Tawazun Health, London, W1G 9QN, UK
| | - Adrian K P Lim
- Department of Surgery and Cancer, Imperial College London, London, W1 1NY, UK
- Department of Imaging, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, W6 8RF, UK
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Sourianarayanane A, McCullough AJ. Accuracy of ultrasonographic fatty liver index using point-of-care ultrasound in stratifying non-alcoholic fatty liver disease patients. Eur J Gastroenterol Hepatol 2023; 35:654-661. [PMID: 37115988 DOI: 10.1097/meg.0000000000002544] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/30/2023]
Abstract
BACKGROUND The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing in the USA. Some of these patients develop non-alcoholic steatohepatitis (NASH), which can progress to cirrhosis. Ultrasound imaging is one of the most used modalities for diagnosing hepatic steatosis. Primary care providers are increasingly using point-of-care ultrasound (POCUS), which could increase the number of subjects diagnosed with NAFLD. This study evaluates the accuracy of POCUS in identifying patients with NASH. METHODS Patients with hepatic steatosis without excess alcohol intake or other liver diseases undergoing liver biopsy were included in this study. These patients underwent POCUS and vibration-controlled transient elastography (VCTE) evaluations within 3 months of a liver biopsy. A comparison of POCUS data with liver histology and VCTE were made to assess the validity of POCUS evaluation in diagnosing NAFLD and NASH. RESULTS The steatosis score from the liver histology had a low correlation with the controlled attenuation parameter score from VCTE ( r = 0.27) and a moderate correlation with the grade of steatosis detected by the POCUS exam ( r = 0.57). The NAFLD activity score on histology was found to correlate with the ultrasonographic fatty liver index (USFLI) from the POCUS exam ( r = 0.59). A USFLI ≥ 6 diagnosed NASH with a sensitivity of 81%, and a value of ≤3 ruled out the diagnosis of NASH with a sensitivity of 100%. CONCLUSION The provider can use the POCUS exam in clinical practice to diagnose NAFLD and reliably stratify patients who have NASH.
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Affiliation(s)
| | - Arthur J McCullough
- Department of Medicine, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA
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Osman HE, Osama H, Yousef M, Alsalamah A, Bushara L, Abdalaziz I. Correlation Between Clinical Features of Type 2 Diabetes Mellitus with CT Findings of Fatty Liver Patients. PERTANIKA JOURNAL OF SCIENCE AND TECHNOLOGY 2023; 31:1313-1324. [DOI: 10.47836/pjst.31.3.11] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
People with fatty liver disease are at major risk of liver cirrhosis and malignancies. This study aims to evaluate the correlation between fatty liver and diabetes features on computed tomography (CT) using Hounsfield units for the liver and spleen. The research was conducted in Jeddah Hospital’s Medical Imaging Department and CT scan department from March 2018 until March 2020. A total of 50 patients with diabetes were chosen randomly, with males (26) and females (24) ranging in age from 31 to 80 years old. Descriptive statistics of body mass index were recorded for the liver and the spleen; the main liver enzymes were Alanine aminotransferase (ALT), Gamma-glutamyltransferase (GGT), albumin, total bilirubin, and direct bilirubin, which were measured and analyzed using the Statistical Package for the Social Sciences program, version 23. We found a significant correlation of ALT and direct bilirubin with liver and spleen HU at p value < 0.017 and < 0.073, respectively; the mean and standard deviation for the other liver enzymes GGT, albumin, and total bilirubin in segment 3 of the left liver were 45.48 ± 7.077 HU, 45.00 ± 7.797 HU, 36.67 ± 5.776 HU, and 37.23 ± 4.885 HU, respectively. We concluded that fatty liver is associated with type 2 diabetes mellitus symptoms such as high ALT and direct bilirubin, with no significant association between GGT, albumin, total bilirubin, and liver and spleen HU.
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23
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Ultrasound-based hepatic fat quantification: current status and future directions. Clin Radiol 2023; 78:187-200. [PMID: 36411088 DOI: 10.1016/j.crad.2022.10.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Revised: 09/22/2022] [Accepted: 10/06/2022] [Indexed: 11/19/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a spectrum of disease from fatty accumulation (steatosis), necro-inflammation though to fibrosis. It is of increasing global prevalence as a hepatic manifestation of the metabolic syndrome. Although accurate histopathology and magnetic resonance imaging techniques for hepatic fat quantification exist, these are limited by invasiveness and availability, respectively. Ultrasonography is potentially ideal for assessing and monitoring hepatic steatosis given the examination is rapid and readily available. Traditional ultrasound methods include qualitative B-mode for imaging markers, such as increased hepatic parenchymal echogenicity compared to adjacent renal cortex are commonplace; however, there is acknowledged significant interobserver variability and they are suboptimal for detecting mild steatosis. Recently quantitative ultrasound metrics have been investigated as biomarkers for hepatic steatosis. These methods rely on changes in backscatter, attenuation, and speed of sound differences encountered in a steatotic liver. Prospective studies using quantitative ultrasound parameters show good diagnostic performance even at low steatosis grades and in NAFLD. This review aims to define the clinical need for ultrasound-based assessments of liver steatosis, to describe briefly the physics that underpins the various techniques available, and to assess the evidence base for the effectiveness of the techniques that are available commercially from various ultrasound vendors.
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Evaluation of Artificial Intelligence-Calculated Hepatorenal Index for Diagnosing Mild and Moderate Hepatic Steatosis in Non-Alcoholic Fatty Liver Disease. Medicina (B Aires) 2023; 59:medicina59030469. [PMID: 36984470 PMCID: PMC10058464 DOI: 10.3390/medicina59030469] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Revised: 02/12/2023] [Accepted: 02/23/2023] [Indexed: 03/03/2023] Open
Abstract
Background and Objectives: This study aims to evaluate artificial intelligence-calculated hepatorenal index (AI-HRI) as a diagnostic method for hepatic steatosis. Materials and Methods: We prospectively enrolled 102 patients with clinically suspected non-alcoholic fatty liver disease (NAFLD). All patients had a quantitative ultrasound (QUS), including AI-HRI, ultrasound attenuation coefficient (AC,) and ultrasound backscatter-distribution coefficient (SC) measurements. The ultrasonographic fatty liver indicator (US-FLI) score was also calculated. The magnetic resonance imaging fat fraction (MRI-PDFF) was the reference to classify patients into four grades of steatosis: none < 5%, mild 5–10%, moderate 10–20%, and severe ≥ 20%. We compared AI-HRI between steatosis grades and calculated Spearman’s correlation (rs) between the methods. We determined the agreement between AI-HRI by two examiners using the intraclass correlation coefficient (ICC) of 68 cases. We performed a receiver operating characteristics (ROC) analysis to estimate the area under the curve (AUC) for AI-HRI. Results: The mean AI-HRI was 2.27 (standard deviation, ±0.96) in the patient cohort. The AI-HRI was significantly different between groups without (1.480 ± 0.607, p < 0.003) and with mild steatosis (2.155 ± 0.776), as well as between mild and moderate steatosis (2.777 ± 0.923, p < 0.018). AI-HRI showed moderate correlation with AC (rs = 0.597), SC (rs = 0.473), US-FLI (rs = 0.5), and MRI-PDFF (rs = 0.528). The agreement in AI-HRI was good between the two examiners (ICC = 0.635, 95% confidence interval (CI) = 0.411–0.774, p < 0.001). The AI-HRI could detect mild steatosis (AUC = 0.758, 95% CI = 0.621–0.894) with fair and moderate/severe steatosis (AUC = 0.803, 95% CI = 0.721–0.885) with good accuracy. However, the performance of AI-HRI was not significantly different (p < 0.578) between the two diagnostic tasks. Conclusions: AI-HRI is an easy-to-use, reproducible, and accurate QUS method for diagnosing mild and moderate hepatic steatosis.
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Kjaergaard M, Lindvig KP, Hansen CD, Detlefsen S, Krag A, Thiele M. Hepatorenal Index by B-Mode Ratio Versus Imaging and Fatty Liver Index to Diagnose Steatosis in Alcohol-Related and Nonalcoholic Fatty Liver Disease. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2023; 42:487-496. [PMID: 35475550 PMCID: PMC10084348 DOI: 10.1002/jum.15991] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/05/2022] [Revised: 03/26/2022] [Accepted: 03/28/2022] [Indexed: 05/12/2023]
Abstract
OBJECTIVES We aimed to evaluate the accuracy of the hepatorenal index by B-mode ratio to diagnose hepatic steatosis, compared to ultrasound steatosis score, controlled attenuation parameter, and the fatty liver index using histology as the gold standard. METHODS We prospectively included participants with alcohol-related or nonalcoholic fatty liver disease for same-day noninvasive investigations and liver biopsy. RESULTS We included 137 participants, 72% male, median age 60 years (53-65) and body mass index 32 kg/m2 (28-38). Eighty percent had steatosis (S0/S1/S2/S3 = 20/37/24/19%). B-mode ratio had moderate diagnostic accuracy for any steatosis (≥S1, area under the receiver operating characteristics curve [AUROC] = 0.79; 95% confidence interval 0.70-0.88), significant steatosis (≥S2, AUROC = 0.76; 0.66-0.85), and severe steatosis (=S3, AUROC = 0.74; 0.62-0.86), independent of disease etiology. The cutoff values to rule-out and rule-in any steatosis were 1.09 and 1.45. While B-mode ratio and controlled attenuation parameter correlated poorly, their diagnostic accuracies were comparable to each other and to ultrasound steatosis scoring. Fatty liver index did not differ from B-mode ratio in detecting any steatosis but had poor accuracy to detect higher steatosis grades. B-mode ratio measurements failed in 12% of patients, compared to 1% for ultrasound steatosis scoring and 2% for controlled attenuation parameter. CONCLUSION The hepatorenal index by B-mode ratio diagnose steatosis with moderate accuracy in patients with alcohol-related or nonalcoholic fatty liver disease, comparable to B-mode ultrasound steatosis scoring and controlled attenuation parameter. However, its clinical use is limited by a high failure rate.
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Affiliation(s)
- Maria Kjaergaard
- Department of Gastroenterology and HepatologyOdense University HospitalOdenseDenmark
- Institute of Clinical Research, University of Southern DenmarkOdenseDenmark
| | - Katrine Prier Lindvig
- Department of Gastroenterology and HepatologyOdense University HospitalOdenseDenmark
- Institute of Clinical Research, University of Southern DenmarkOdenseDenmark
| | - Camilla Dalby Hansen
- Department of Gastroenterology and HepatologyOdense University HospitalOdenseDenmark
- Institute of Clinical Research, University of Southern DenmarkOdenseDenmark
| | - Sönke Detlefsen
- Institute of Clinical Research, University of Southern DenmarkOdenseDenmark
- Department of PathologyOdense University HospitalOdenseDenmark
| | - Aleksander Krag
- Department of Gastroenterology and HepatologyOdense University HospitalOdenseDenmark
- Institute of Clinical Research, University of Southern DenmarkOdenseDenmark
| | - Maja Thiele
- Department of Gastroenterology and HepatologyOdense University HospitalOdenseDenmark
- Institute of Clinical Research, University of Southern DenmarkOdenseDenmark
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Chee D, Ng CH, Chan KE, Huang DQ, Teng M, Muthiah M. The Past, Present, and Future of Noninvasive Test in Chronic Liver Diseases. Med Clin North Am 2023; 107:397-421. [PMID: 37001944 DOI: 10.1016/j.mcna.2022.12.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/22/2023]
Abstract
Chronic liver disease is a major global health threat and is the 11th leading cause of death globally. A liver biopsy is frequently required in assessing the degree of steatosis and fibrosis, information that is important in diagnosis, management, and prognostication. However, liver biopsies have limitations and carry a considerable risk, leading to the development of various modalities of noninvasive testing tools. These tools have been developed in recent years and have improved markedly in diagnostic accuracy. Moving forward, they may change the practice of hepatology.
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Affiliation(s)
- Douglas Chee
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Tower Block Level 10, 1E Kent Ridge Road, Singapore 119228, Singapore
| | - Cheng Han Ng
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Tower Block Level 10, 1E Kent Ridge Road, Singapore 119228, Singapore
| | - Kai En Chan
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Tower Block Level 10, 1E Kent Ridge Road, Singapore 119228, Singapore
| | - Daniel Q Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Tower Block Level 10, 1E Kent Ridge Road, Singapore 119228, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Tower Block Level 10, 1E Kent Ridge Road, Singapore 119228, Singapore; National University Centre for Organ Transplantation, National University Health System, Tower Block Level 10, 1E Kent Ridge Road, Singapore 119228, Singapore
| | - Margaret Teng
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Tower Block Level 10, 1E Kent Ridge Road, Singapore 119228, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Tower Block Level 10, 1E Kent Ridge Road, Singapore 119228, Singapore; National University Centre for Organ Transplantation, National University Health System, Tower Block Level 10, 1E Kent Ridge Road, Singapore 119228, Singapore
| | - Mark Muthiah
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Tower Block Level 10, 1E Kent Ridge Road, Singapore 119228, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Tower Block Level 10, 1E Kent Ridge Road, Singapore 119228, Singapore; National University Centre for Organ Transplantation, National University Health System, Tower Block Level 10, 1E Kent Ridge Road, Singapore 119228, Singapore.
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27
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Yip TCF, Lyu F, Lin H, Li G, Yuen PC, Wong VWS, Wong GLH. Non-invasive biomarkers for liver inflammation in non-alcoholic fatty liver disease: present and future. Clin Mol Hepatol 2023; 29:S171-S183. [PMID: 36503204 PMCID: PMC10029958 DOI: 10.3350/cmh.2022.0426] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Accepted: 12/06/2022] [Indexed: 12/14/2022] Open
Abstract
Inflammation is the key driver of liver fibrosis progression in non-alcoholic fatty liver disease (NAFLD). Unfortunately, it is often challenging to assess inflammation in NAFLD due to its dynamic nature and poor correlation with liver biochemical markers. Liver histology keeps its role as the standard tool, yet it is well-known for substantial sampling, intraobserver, and interobserver variability. Serum proinflammatory cytokines and apoptotic markers, namely cytokeratin-18, are well-studied with reasonable accuracy, whereas serum metabolomics and lipidomics have been adopted in some commercially available diagnostic models. Ultrasound and computed tomography imaging techniques are attractive due to their wide availability; yet their accuracies may not be comparable with magnetic resonance imaging-based tools. Machine learning and deep learning models, be they supervised or unsupervised learning, are promising tools to identify various subtypes of NAFLD, including those with dominating liver inflammation, contributing to sustainable care pathways for NAFLD.
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Affiliation(s)
- Terry Cheuk-Fung Yip
- Medical Data Analytic Centre, Prince of Wales Hospital and the University is The Chinese University of Hong Kong, Hong Kong, China
- Department of Medicine and Therapeutics, Prince of Wales Hospital and the University is The Chinese University of Hong Kong, Hong Kong, China
- Institute of Digestive Disease, Prince of Wales Hospital and the University is The Chinese University of Hong Kong, Hong Kong, China
| | - Fei Lyu
- Department of Computer Science, Hong Kong Baptist University, Hong Kong, China
| | - Huapeng Lin
- Medical Data Analytic Centre, Prince of Wales Hospital and the University is The Chinese University of Hong Kong, Hong Kong, China
- Department of Medicine and Therapeutics, Prince of Wales Hospital and the University is The Chinese University of Hong Kong, Hong Kong, China
- Institute of Digestive Disease, Prince of Wales Hospital and the University is The Chinese University of Hong Kong, Hong Kong, China
| | - Guanlin Li
- Medical Data Analytic Centre, Prince of Wales Hospital and the University is The Chinese University of Hong Kong, Hong Kong, China
- Department of Medicine and Therapeutics, Prince of Wales Hospital and the University is The Chinese University of Hong Kong, Hong Kong, China
- Institute of Digestive Disease, Prince of Wales Hospital and the University is The Chinese University of Hong Kong, Hong Kong, China
| | - Pong-Chi Yuen
- Department of Computer Science, Hong Kong Baptist University, Hong Kong, China
| | - Vincent Wai-Sun Wong
- Medical Data Analytic Centre, Prince of Wales Hospital and the University is The Chinese University of Hong Kong, Hong Kong, China
- Department of Medicine and Therapeutics, Prince of Wales Hospital and the University is The Chinese University of Hong Kong, Hong Kong, China
- Institute of Digestive Disease, Prince of Wales Hospital and the University is The Chinese University of Hong Kong, Hong Kong, China
| | - Grace Lai-Hung Wong
- Medical Data Analytic Centre, Prince of Wales Hospital and the University is The Chinese University of Hong Kong, Hong Kong, China
- Department of Medicine and Therapeutics, Prince of Wales Hospital and the University is The Chinese University of Hong Kong, Hong Kong, China
- Institute of Digestive Disease, Prince of Wales Hospital and the University is The Chinese University of Hong Kong, Hong Kong, China
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28
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Jesper D, Fiedler S, Klett D, Waldner MJ, Schellhaas B, Zundler S, Neurath MF, Pfeifer L. Shear Wave Dispersion Imaging for the Characterization of Focal Liver Lesions - A Pilot study. ULTRASCHALL IN DER MEDIZIN (STUTTGART, GERMANY : 1980) 2022; 43:507-513. [PMID: 34614516 DOI: 10.1055/a-1610-9171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
PURPOSE Shear wave dispersion imaging is a novel ultrasound-based technique, which analyzes the speed of different shear wave components depending on their frequency. The dispersion of shear wave speed correlates with the viscosity of the liver parenchyma. The aim of this prospective study was to evaluate the use of shear wave dispersion imaging in focal liver lesions in the non-cirrhotic liver. METHODS Patients with unclear focal liver lesions in B-mode ultrasound were prospectively assigned to shear wave dispersion imaging (m/s/kHz). Measurements were conducted within the lesion and in the liver parenchyma of the right liver lobe using an intercostal window. Histology and contrast-enhanced ultrasound served as the reference for the characterization of the lesions. RESULTS Out of 46 patients included in this study, 24 had liver metastases and 22 had benign liver lesions. Benign lesions consisted mostly of hemangiomas (n=12) and focal nodular hyperplasia (n=8). Malignant lesions showed significantly lower shear wave dispersion (13.0±2.45 m/s/kHz) compared to benign tumors (15.2±2.74 m/s/kHz, p<0.01). In further subgroup analysis, the difference was significant for hemangiomas (15.32±2.42 m/s/kHz, p=0.04) but not for FNHs (14.98±3.36 m/s/kHz, p=0.38). The dispersion of reference liver parenchyma did not differ significantly between the groups (p=0.54). CONCLUSION The quantification of viscosity by shear wave dispersion is a new parameter for the characterization of focal liver lesions with higher dispersion values in hemangiomas and lower dispersion values in metastases. However, it cannot differentiate reliably between benign and malignant lesions.
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Affiliation(s)
- Daniel Jesper
- Department of Internal Medicine 1, Erlangen University Hospital Department of Medicine 1 Gastroenterology Endocrinology and Pneumology, Erlangen, Germany
| | - Steffen Fiedler
- Department of Anaesthesiology, Erlangen University Hospital Department of Anaesthesiology, Erlangen, Germany
| | - Daniel Klett
- Department of Internal Medicine 1, Erlangen University Hospital Department of Medicine 1 Gastroenterology Endocrinology and Pneumology, Erlangen, Germany
| | - Maximilian J Waldner
- Department of Internal Medicine 1, Erlangen University Hospital Department of Medicine 1 Gastroenterology Endocrinology and Pneumology, Erlangen, Germany
| | - Barbara Schellhaas
- Department of Internal Medicine 1, Erlangen University Hospital Department of Medicine 1 Gastroenterology Endocrinology and Pneumology, Erlangen, Germany
| | - Sebastian Zundler
- Department of Internal Medicine 1, Erlangen University Hospital Department of Medicine 1 Gastroenterology Endocrinology and Pneumology, Erlangen, Germany
| | - Markus F Neurath
- Department of Internal Medicine 1, Erlangen University Hospital Department of Medicine 1 Gastroenterology Endocrinology and Pneumology, Erlangen, Germany
| | - Lukas Pfeifer
- Department of Internal Medicine 1, Erlangen University Hospital Department of Medicine 1 Gastroenterology Endocrinology and Pneumology, Erlangen, Germany
- Department of Gastroenterology and Interventional Endoscopy, Barmherzige Bruder gemeinnutzige Krankenhaus GmbH, Regensburg, Germany
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Bozic D, Podrug K, Mikolasevic I, Grgurevic I. Ultrasound Methods for the Assessment of Liver Steatosis: A Critical Appraisal. Diagnostics (Basel) 2022; 12:2287. [PMID: 36291976 PMCID: PMC9600709 DOI: 10.3390/diagnostics12102287] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Revised: 09/14/2022] [Accepted: 09/17/2022] [Indexed: 08/10/2023] Open
Abstract
The prevalence of the non-alcoholic fatty liver disease has reached major proportions, being estimated to affect one-quarter of the global population. The reference techniques, which include liver biopsy and the magnetic resonance imaging proton density fat fraction, have objective practical and financial limitations to their routine use in the detection and quantification of liver steatosis. Therefore, there has been a rising necessity for the development of new inexpensive, widely applicable and reliable non-invasive diagnostic tools. The controlled attenuation parameter has been considered the point-of-care technique for the assessment of liver steatosis for a long period of time. Recently, many ultrasound (US) system manufacturers have developed proprietary software solutions for the quantification of liver steatosis. Some of these methods have already been extensively tested with very good performance results reported, while others are still under evaluation. This manuscript reviews the currently available US-based methods for diagnosing and grading liver steatosis, including their classification and performance results, with an appraisal of the importance of this armamentarium in daily clinical practice.
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Affiliation(s)
- Dorotea Bozic
- Department of Gastroenterology and Hepatology, University Hospital Center Split, Spinčićeva 1, 21 000 Split, Croatia
| | - Kristian Podrug
- Department of Gastroenterology and Hepatology, University Hospital Center Split, Spinčićeva 1, 21 000 Split, Croatia
| | - Ivana Mikolasevic
- Department of Gastroenterology and Hepatology, University Hospital Center Rijeka, Krešimirova 42, 51 000 Rijeka, Croatia
| | - Ivica Grgurevic
- Department of Gastroenterology, Hepatology and Clinical Nutrition, University Hospital Dubrava, Avenija Gojka Šuška 6, 10 000 Zagreb, Croatia
- School of Medicine, University of Zagreb, Šalata 2, 10 000 Zagreb, Croatia
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30
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Guan X, Chen YC, Xu HX. New horizon of ultrasound for screening and surveillance of non-alcoholic fatty liver disease spectrum. Eur J Radiol 2022; 154:110450. [PMID: 35917757 DOI: 10.1016/j.ejrad.2022.110450] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2022] [Revised: 07/01/2022] [Accepted: 07/19/2022] [Indexed: 12/07/2022]
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Luo L, Ye J, Shao C, Lin Y, Sun Y, Feng S, Wang W, Zhong B. Vitamin D Status Presents Different Relationships with Severity in Metabolic-Associated Fatty Liver Disease Patients with or without Hepatitis B Infection. Nutrients 2022; 14:nu14102114. [PMID: 35631255 PMCID: PMC9147199 DOI: 10.3390/nu14102114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2022] [Revised: 05/10/2022] [Accepted: 05/13/2022] [Indexed: 11/16/2022] Open
Abstract
Whether the associations between serum vitamin D (VitD) and metabolic-associated fatty liver disease (MAFLD) vary with chronic hepatitis B (CHB) infection has not been well established. This study aims to investigate the relationships between serum VitD and metabolism, liver fat content (LFC) and fibrosis among MAFLD patients with and without CHB. Consecutive subjects (healthy controls: 360, CHB: 684, MAFLD: 521, CHB with MAFLD: 206) were prospectively enrolled between January 2015 and December 2021. Anthropometric, laboratory, imaging, and histological evaluations were conducted, with LFC measured via magnetic resonance imaging-based proton density fat fraction (MRI-PDFF). Serum VitD levels were lower in MAFLD patients than in healthy controls and patients with CHB alone or overlapping with MAFLD (24.4 ± 8.1 vs. 29.0 ± 9.5 vs. 27.4 ± 9.6 vs. 26.8 ± 8.4 ng/mL respectively; p < 0.001 in one-way ANOVA test). After adjusting for confounding factors, including season, hypersensitive C-reactive protein, insulin resistance, liver stiffness measurements, sun exposure, exercise and dietary intake, multivariate linear regression analysis revealed that VitD remained significantly negatively correlated with LFC in MAFLD patients (β = −0.38, p < 0.001), but not in CHB with MAFLD patients. Moreover, quantile regression models also demonstrated that lower VitD tertiles were inversely associated with the risk of insulin resistance and moderate−severe steatosis in the MAFLD group (p for trend <0.05) but not in the MAFLD with CHB group. VitD deficiency was associated with the severity of metabolic abnormalities and steatosis independent of lifestyle factors in MAFLD-alone subjects but not in MAFLD with CHB subjects.
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Affiliation(s)
- Ling Luo
- Department of Gastroenterology of the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; (L.L.); (J.Y.); (C.S.); (Y.L.)
| | - Junzhao Ye
- Department of Gastroenterology of the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; (L.L.); (J.Y.); (C.S.); (Y.L.)
| | - Congxiang Shao
- Department of Gastroenterology of the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; (L.L.); (J.Y.); (C.S.); (Y.L.)
| | - Yansong Lin
- Department of Gastroenterology of the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; (L.L.); (J.Y.); (C.S.); (Y.L.)
| | - Yanhong Sun
- Department of Clinical Laboratory, The East Division of the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China;
| | - Shiting Feng
- Department of Radiology of the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China;
| | - Wei Wang
- Department of Medical Ultrasonics of the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China;
| | - Bihui Zhong
- Department of Gastroenterology of the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; (L.L.); (J.Y.); (C.S.); (Y.L.)
- Correspondence: ; Tel.: +86-20-8776-6335
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Vilalta A, Gutiérrez JA, Chaves S, Hernández M, Urbina S, Hompesch M. Adipose tissue measurement in clinical research for obesity, type 2 diabetes and NAFLD/NASH. Endocrinol Diabetes Metab 2022; 5:e00335. [PMID: 35388643 PMCID: PMC9094496 DOI: 10.1002/edm2.335] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 03/04/2022] [Accepted: 03/09/2022] [Indexed: 01/25/2023] Open
Affiliation(s)
| | - Julio A. Gutiérrez
- ProSciento San Diego California USA
- Scripps Center for Organ Transplantation La Jolla California USA
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Cioni D, Gabelloni M, Sanguinetti A, De Rosa L, Aringhieri G, Tintori R, Candita G, Febi M, Faita F, Lencioni R, Neri E. A New SteatoScore in the Evaluation of Non-Alcoholic Liver Disease in Oncologic Patients. Front Oncol 2022; 12:873524. [PMID: 35574336 PMCID: PMC9093140 DOI: 10.3389/fonc.2022.873524] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Accepted: 03/28/2022] [Indexed: 11/13/2022] Open
Abstract
Purpose The aims of this study were to evaluate the reproducibility of a new multi-parametric steatoscore (new SteatoScore) in oncologic patients with non-alcoholic fatty liver disease (NAFLD) and to compare it with computed tomography (CT). Materials and Methods Fifty-one (31 men, 20 women) oncologic patients, with a mean age and weight of 63.9 years and 78.33 kg, respectively, were retrospectively enrolled in the study. Patients underwent ultrasound (US) and computed tomography (CT) examinations as part of their oncologic follow-up protocol. US examinations were performed by using a 3.5-MHz convex probe. During the US examination, three standardized clips were obtained in each patient. Two operators performed all measurements, one of whom repeated the processing twice in 1 year. Hepatic/renal ratio (HR), attenuation rate (AR), diaphragm visualization (DV), hepatic/portal vein ratio (HPV), and portal vein wall visualization (PVW) were acquired and calculated by using Matlab and inserted in a multi-parametric algorithm called new SteatoScore. On unenhanced CT scan, hepatic attenuation (HA), liver-spleen difference (L-S), and liver/spleen ratio (L/S) were measured by placement of a region of interest (ROI) within liver and spleen parenchyma, avoiding areas with vessels and biliary ducts. Results The intra-observer variability was greater than the inter-observer one, with intraclass correlation coefficient (ICC) values of 0.94 and 0.97, respectively. Correlation between single US and CT parameters provided an agreement in no case exceeding 50%. New SteatoScore showed high reproducibility, and high coefficient of correlation with L-S (R = -0.64; p < 0.0001) and L/S (R = -0.62; p < 0.0001) at CT. Conclusion New SteatoScore has a high reproducibility and shows a good correlation with unenhanced CT in evaluation of oncologic patients with NAFLD.
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Affiliation(s)
- Dania Cioni
- Department of Surgical, Medical, Molecular Pathology and Emergency Medicine, University of Pisa, Pisa, Italy
| | - Michela Gabelloni
- Academic Radiology, Department of Translational Research, University of Pisa, Pisa, Italy
| | - Andrea Sanguinetti
- Academic Radiology, Department of Translational Research, University of Pisa, Pisa, Italy
| | - Laura De Rosa
- Hepatology Unit, Pisa University Hospital, Pisa, Italy
| | - Giacomo Aringhieri
- Academic Radiology, Department of Translational Research, University of Pisa, Pisa, Italy
| | - Rachele Tintori
- Academic Radiology, Department of Translational Research, University of Pisa, Pisa, Italy
| | - Gianvito Candita
- Academic Radiology, Department of Translational Research, University of Pisa, Pisa, Italy
| | - Maria Febi
- Academic Radiology, Department of Translational Research, University of Pisa, Pisa, Italy
| | - Francesco Faita
- Institute of Clinical Physiology, National Research Council, Pisa, Italy
| | - Riccardo Lencioni
- Department of Surgical, Medical, Molecular Pathology and Emergency Medicine, University of Pisa, Pisa, Italy
| | - Emanuele Neri
- Academic Radiology, Department of Translational Research, University of Pisa, Pisa, Italy
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Zhou H, Zhou Y, Ding J, Chen Y, Wen J, Zhao L, Zhang Q, Jing X. Clinical evaluation of grayscale and linear scale hepatorenal indices for fatty liver quantification: a prospective study of a native Chinese population. Abdom Radiol (NY) 2022; 47:1321-1332. [PMID: 35150314 DOI: 10.1007/s00261-022-03434-3] [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: 10/10/2021] [Revised: 01/26/2022] [Accepted: 01/28/2022] [Indexed: 11/29/2022]
Abstract
BACKGROUND AND AIMS Hepato-renal index (HRI) has been investigated extensively in various clinical studies. New linear scale HRI (LS-HRI) is proposed as an alternative to conventional grayscale HRI (GS-HRI) that suffers from lack of a widely accepted cut-off value for differentiation of fatty from normal livers. To investigate the diagnostic performance of conventional GS-HRI and new LS-HRI for a relatively large Chinese population with NAFLD using a well-established ultrasonographic fatty liver indicator (US-FLI) as the reference standard for steatosis grades. MATERIALS AND METHODS A total of 106 patients with various stages of NAFLD were prospectively enrolled. All ultrasound images for these patients were first acquired by a highly experienced ultrasound doctor and their US-FLI scores then obtained by the same doctor. Both GS-HRI and LS-HRI values were measured off-line by two additional ultrasound doctors. Four steatosis grades were determined from US-FLI scores for steatosis detection and staging. RESULTS Inter-observer agreements for both GS-HRI and LS-HRI were excellent with the respective concordance correlation coefficient (CCC) of 0.900 for GS-HRI and 0.822 for LS-HRI. A linear correlation to US-FLI for LS-HRI (R = 0.74) was substantially superior to that for GS-HRI (R = 0.46). LS-HRI had a sensitivity of 85.9% and a specificity of 96.3% to differentiate steatosis from the normal liver (AUROC: 95.5%) while GS-HRI had a sensitivity of 85.9% and a specificity of 92.6% to distinguish steatosis from the normal liver (AUROC: 94.7%). CONCLUSIONS Both GS-HRI and LS-HRI measurements are reproducible between two ultrasonographic clinicians and are evidently effective for steatosis detection.
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Affiliation(s)
- Hongyu Zhou
- Department of Ultrasound, The Third Central Hospital of Tianjin/Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases/Artificial Cell Engineering Technology Research Center, Tianjin, China/Tianjin Institute of Hepatobiliary Disease, Tianjin, China, 83 Jintang Road, Hedong District, Tianjin, 300170, China
| | - Yan Zhou
- Department of Ultrasound, The Third Central Hospital of Tianjin/Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases/Artificial Cell Engineering Technology Research Center, Tianjin, China/Tianjin Institute of Hepatobiliary Disease, Tianjin, China, 83 Jintang Road, Hedong District, Tianjin, 300170, China
| | - Jianmin Ding
- Department of Ultrasound, The Third Central Hospital of Tianjin/Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases/Artificial Cell Engineering Technology Research Center, Tianjin, China/Tianjin Institute of Hepatobiliary Disease, Tianjin, China, 83 Jintang Road, Hedong District, Tianjin, 300170, China
| | - Ying Chen
- Department of Ultrasound, The Third Central Hospital of Tianjin/Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases/Artificial Cell Engineering Technology Research Center, Tianjin, China/Tianjin Institute of Hepatobiliary Disease, Tianjin, China, 83 Jintang Road, Hedong District, Tianjin, 300170, China
| | - Jing Wen
- Department of Ultrasound, The Third Central Hospital of Tianjin/Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases/Artificial Cell Engineering Technology Research Center, Tianjin, China/Tianjin Institute of Hepatobiliary Disease, Tianjin, China, 83 Jintang Road, Hedong District, Tianjin, 300170, China
| | - Lei Zhao
- Department of Ultrasound, The Third Central Hospital of Tianjin/Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases/Artificial Cell Engineering Technology Research Center, Tianjin, China/Tianjin Institute of Hepatobiliary Disease, Tianjin, China, 83 Jintang Road, Hedong District, Tianjin, 300170, China
| | - Qian Zhang
- The Third Central Clinical College of Tianjin Medical University, Tianjin, 300170, China
| | - Xiang Jing
- Department of Ultrasound, The Third Central Hospital of Tianjin/Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases/Artificial Cell Engineering Technology Research Center, Tianjin, China/Tianjin Institute of Hepatobiliary Disease, Tianjin, China, 83 Jintang Road, Hedong District, Tianjin, 300170, China.
- Department of Ultrasound, The Third Central Hospital of Tianjin, Tianjin, China, 83 Jintang Road, Hedong District, Tianjin, 300170, China.
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Effects of Different Scan Projections on the Quantitative Ultrasound-Based Evaluation of Hepatic Steatosis. Healthcare (Basel) 2022; 10:healthcare10020374. [PMID: 35206988 PMCID: PMC8872438 DOI: 10.3390/healthcare10020374] [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: 12/22/2021] [Revised: 01/28/2022] [Accepted: 02/11/2022] [Indexed: 02/04/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is becoming a global public health issue and the identification of the steatosis severity is very important for the patients’ health. Ultrasound (US) images of 214 patients were acquired in two different scan views (subcostal and intercostal). A classification of the level of steatosis was made by a qualitative evaluation of the liver ultrasound images. Furthermore, an US image processing algorithm provided quantitative parameters (hepatic–renal ratio (HR) and Steato-score) designed to quantifying the fatty liver content. The aim of the study is to evaluate the differences in the assessment of hepatic steatosis acquiring and processing different US scan views. No significant differences were obtained calculating the HR and the Steato-score parameters, not even with the classification of patients on the basis of body mass index (BMI) and of different classes of steatosis severity. Significant differences between the two parameters were found only for patients with absence or mild level of steatosis. These results show that the two different scan projections do not greatly affect HR and the Steato-score assessment. Accordingly, the US-based steatosis assessment is independent from the view of the acquisitions, thus making the subcostal and intercostal scans interchangeable, especially for patients with moderate and severe steatosis.
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Diagnostic Modalities of Non-Alcoholic Fatty Liver Disease: From Biochemical Biomarkers to Multi-Omics Non-Invasive Approaches. Diagnostics (Basel) 2022; 12:diagnostics12020407. [PMID: 35204498 PMCID: PMC8871470 DOI: 10.3390/diagnostics12020407] [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: 12/22/2021] [Revised: 01/31/2022] [Accepted: 02/02/2022] [Indexed: 02/05/2023] Open
Abstract
Non-Alcoholic Fatty Liver Disease (NAFLD) is currently the most common cause of chronic liver disease worldwide, and its prevalence is increasing globally. NAFLD is a multifaceted disorder, and its spectrum includes steatosis to steatohepatitis, which may evolve to advanced fibrosis and cirrhosis. In addition, the presence of NAFLD is independently associated with a higher cardiometabolic risk and increased mortality rates. Considering that the vast majority of individuals with NAFLD are mainly asymptomatic, early diagnosis of non-alcoholic steatohepatitis (NASH) and accurate staging of fibrosis risk is crucial for better stratification, monitoring and targeted management of patients at risk. To date, liver biopsy remains the gold standard procedure for the diagnosis of NASH and staging of NAFLD. However, due to its invasive nature, research on non-invasive tests is rapidly increasing with significant advances having been achieved during the last decades in the diagnostic field. New promising non-invasive biomarkers and techniques have been developed, evaluated and assessed, including biochemical markers, imaging modalities and the most recent multi-omics approaches. Our article provides a comprehensive review of the currently available and emerging non-invasive diagnostic tools used in assessing NAFLD, also highlighting the importance of accurate and validated diagnostic tools.
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Tamaki N, Ajmera V, Loomba R. Non-invasive methods for imaging hepatic steatosis and their clinical importance in NAFLD. Nat Rev Endocrinol 2022; 18:55-66. [PMID: 34815553 PMCID: PMC9012520 DOI: 10.1038/s41574-021-00584-0] [Citation(s) in RCA: 125] [Impact Index Per Article: 41.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/11/2021] [Indexed: 01/27/2023]
Abstract
Hepatic steatosis is a key histological feature of nonalcoholic fatty liver disease (NAFLD). The non-invasive quantification of liver fat is now possible due to advances in imaging modalities. Emerging data suggest that high levels of liver fat and its temporal change, as measured by quantitative non-invasive methods, might be associated with NAFLD progression. Ultrasound-based modalities have moderate diagnostic accuracy for liver fat content and are suitable for screening. However, of the non-invasive imaging modalities, MRI-derived proton density fat fraction (MRI-PDFF) has the highest diagnostic accuracy and is used for trial enrolment and to evaluate therapeutic effects in early-phase clinical trials in nonalcoholic steatohepatitis (NASH). In patients with NAFLD without advanced fibrosis, high levels of liver fat are associated with rapid disease progression. Furthermore, changes on MRI-PDFF (≥30% decline relative to baseline) are associated with NAFLD activity score improvement and fibrosis regression. However, an inverse association exists between liver fat and complications of cirrhosis. Liver fat decreases as liver fibrosis progresses towards cirrhosis, and the clinical importance of quantitative measurements of liver fat differs by NAFLD status. As such, patients with NAFLD should be stratified by fibrosis severity to investigate the utility of quantitative measurements of liver fat for assessing NAFLD progression and prognosis.
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Affiliation(s)
- Nobuharu Tamaki
- NAFLD Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, CA, USA
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Veeral Ajmera
- NAFLD Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, CA, USA
| | - Rohit Loomba
- NAFLD Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, CA, USA.
- The Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA, USA.
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Wang J, Su Z, Feng Y, Xi R, Liu J, Wang P. Comparison of several blood lipid-related indexes in the screening of non-alcoholic fatty liver disease in women: a cross-sectional study in the Pearl River Delta region of southern China. BMC Gastroenterol 2021; 21:482. [PMID: 34923965 PMCID: PMC8684623 DOI: 10.1186/s12876-021-02072-1] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Accepted: 12/15/2021] [Indexed: 12/22/2022] Open
Abstract
Background Lipid metabolism disorders play a critical role in the progression of non-alcoholic fatty liver disease (NAFLD). However, the number of studies on the relationships among blood lipid-related indexes and NAFLD is limited, and few studies have emphasized the comparison of blood lipid-related indexes in the same population to identify the optimal index for NAFLD screening. This study aimed to investigate the relationships among several blood lipid-related indexes and NAFLD, and to find the index with the best screening value for NAFLD. Methods Based on a general health examination at community health service agencies in the Pearl River Delta region of China in 2015, 3239 women were recruited in this cross-sectional study. The relationships among blood lipid-related indexes and NAFLD were assessed separately by constructing multivariate logistic regression models. Receiver operating characteristic analysis was used to evaluate and compare the screening abilities of the indexes for NAFLD. All data analyses were conducted in SPSS and MedCalc software. Results Whether in the crude model or each model adjusted for possible confounding factors, the risk of NAFLD significantly rose with increasing cardiometabolic index (CMI), triglyceride glucose index (TyG), triglycerides (TG) to high-density lipoprotein cholesterol (HDL-C) ratio (TG/HDL-C), total cholesterol (TC) to HDL-C ratio (TC/HDL-C) and low-density lipoprotein (LDL-C) to HDL-C ratio (LDL-C/HDL-C). Moreover, the area under the curve (AUC) of CMI was 0.744, which was better than that of TyG (0.725), TG/HDL-C (0.715), TC/HDL-C (0.650), and LDL-C/HDL-C (0.644) (P < 0.001). In addition, the optimal cut-off points were 0.62 for CMI, 8.55 for TyG, 1.15 for TG/HDL-C, 4.17 for TC/HDL-C, and 2.22 for LDL-C/HDL-C. Conclusions CMI is easy to obtain, is a recommended index in the screening of NAFLD in women and may be useful for detecting populations that are at high risk of NAFLD.
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Affiliation(s)
- Jingrui Wang
- Institute of Chronic Disease Risks Assessment, School of Nursing and Health, Henan University, Kaifeng, 475004, China
| | - Zhenzhen Su
- Institute of Chronic Disease Risks Assessment, School of Nursing and Health, Henan University, Kaifeng, 475004, China
| | - Yijin Feng
- Institute of Chronic Disease Risks Assessment, School of Nursing and Health, Henan University, Kaifeng, 475004, China
| | - Ruihan Xi
- Institute of Chronic Disease Risks Assessment, School of Nursing and Health, Henan University, Kaifeng, 475004, China
| | - Jiamin Liu
- Institute of Chronic Disease Risks Assessment, School of Nursing and Health, Henan University, Kaifeng, 475004, China
| | - Peixi Wang
- Institute of Chronic Disease Risks Assessment, School of Nursing and Health, Henan University, Kaifeng, 475004, China. .,General Practice Center, The Seventh Affiliated Hospital of Southern Medical University, Foshan, 528244, China.
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Elevated serum S14 levels are associated with more severe liver steatosis by ultrasonography. Sci Rep 2021; 11:24181. [PMID: 34921174 PMCID: PMC8683400 DOI: 10.1038/s41598-021-03279-8] [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: 08/11/2021] [Accepted: 11/17/2021] [Indexed: 11/23/2022] Open
Abstract
S14 has been identified as a potent stimulator of de novo hepatic lipogenesis (DNL) in rodents. However, it is unclear how S14 is regulated in humans with non-alcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the relationship between serum S14 and liver steatosis in humans with NAFLD. A total of 614 participants were recruited from community. Liver steatosis were evaluated according to the Ultrasonographic Fatty Liver Indicator (US-FLI), which is a semi-quantitative liver ultrasound score. Anthropometric and biochemical indices were collected for further analysis. The risk of liver steatosis severity was estimated by a cumulative logistic regression model. NAFLD was found in 52.2% of the participants. The subjects with NAFLD showed higher levels of waist circumference, body mass index, insulin resistance, aspartate aminotransferase, dyslipidemia, visceral fat, serum S14 and risk of metabolic syndrome (MetS) than those of controls. Compared with the first tertile of serum S14, the odds ratios for the risk of more severe liver steatosis were 1.22 (95% confidence interval [CI]: 0.78–1.92) for those of the second tertile and 2.08 (95% CI: 1.28–3.39) for the third tertile (P for trend < 0.05) after adjusting for confounding factors. Higher serum S14 level was not only found in NAFLD subjects but also was positively correlated with the severity of liver steatosis. S14 may play an important role in the mechanism of DNL for NAFLD in humans.
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Targher G, Mantovani A, Grander C, Foco L, Motta B, Byrne CD, Pramstaller PP, Tilg H. Association between non-alcoholic fatty liver disease and impaired cardiac sympathetic/parasympathetic balance in subjects with and without type 2 diabetes-The Cooperative Health Research in South Tyrol (CHRIS)-NAFLD sub-study. Nutr Metab Cardiovasc Dis 2021; 31:3464-3473. [PMID: 34627696 DOI: 10.1016/j.numecd.2021.08.037] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Revised: 07/27/2021] [Accepted: 08/16/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Cardiovascular disease (CVD) is the leading cause of death in patients with non-alcoholic fatty liver disease (NAFLD), both with and without type 2 diabetes mellitus (T2DM). Cardiac autonomic dysfunction is a risk factor for CVD morbidity and mortality. The aim of this pilot study was to assess whether there is an association between NAFLD and impaired cardiac autonomic function. METHODS AND RESULTS Among the first 4979 participants from the Cooperative Health Research in South Tyrol (CHRIS) study, we randomly recruited 173 individuals with T2DM and 183 age- and sex-matched nondiabetic controls. Participants underwent ultrasonography and vibration-controlled transient elastography (Fibroscan®, Echosens) to assess hepatic steatosis and liver stiffness. The low-to-high-frequency (LF/HF) power ratio and other heart rate variability (HRV) measures were calculated from a 20-min resting electrocardiogram (ECG) to derive a measure of cardiac sympathetic/parasympathetic imbalance. Among the 356 individuals recruited for the study, 117 had NAFLD and T2DM, 56 had T2DM alone, 68 had NAFLD alone, and 115 subjects had neither condition. Individuals with T2DM and NAFLD (adjusted odds ratio [OR] 4.29, 95% confidence intervals [CI] 1.90-10.6) and individuals with NAFLD alone (adjusted OR 3.41, 95% CI 1.59-7.29), but not those with T2DM alone, had a substantially increased risk of having cardiac sympathetic/parasympathetic imbalance, compared with those without NAFLD and T2DM. Logistic regression models were adjusted for age, sex, body mass index (BMI), hypertension, dyslipidemia, insulin resistance, hemoglobin A1c (HbA1c), C-reactive protein (CRP), and Fibroscan®-measured liver stiffness. CONCLUSIONS NAFLD was associated with cardiac sympathetic/parasympathetic imbalance, regardless of the presence or absence of T2DM, liver stiffness, and other potential confounding factors.
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Affiliation(s)
- Giovanni Targher
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy.
| | - Alessandro Mantovani
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Christoph Grander
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University Innsbruck, Innsbruck, Austria
| | - Luisa Foco
- Institute for Biomedicine, Eurac Research (Affiliated to the University of Lübeck), Bolzano, Italy
| | - Benedetta Motta
- Institute for Biomedicine, Eurac Research (Affiliated to the University of Lübeck), Bolzano, Italy; Department of Medicine and Surgery, University of Salerno, Salerno, Italy
| | - Christopher D Byrne
- Nutrition and Metabolism, Faculty of Medicine, University of Southampton, Southampton, UK; Southampton National Institute for Health Research Biomedical Research Centre, University Hospital Southampton, UK
| | - Peter P Pramstaller
- Institute for Biomedicine, Eurac Research (Affiliated to the University of Lübeck), Bolzano, Italy
| | - Herbert Tilg
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University Innsbruck, Innsbruck, Austria
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Małecki P, Mania A, Tracz J, Łuczak M, Mazur-Melewska K, Figlerowicz M. Adipocytokines as Risk Factors for Development of Nonalcoholic Fatty Liver Disease in Children. J Clin Exp Hepatol 2021; 11:646-653. [PMID: 34866842 PMCID: PMC8617538 DOI: 10.1016/j.jceh.2021.03.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2020] [Accepted: 03/03/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Noninvasive diagnostics of nonalcoholic fatty liver disease (NAFLD), the most common cause of liver dysfunction in children, are based on imaging, biochemical tests and their compilation. The study aimed to evaluate the serological biomarkers of steatosis, inflammation and liver fibrosis to assess the risk of NAFLD in children. METHODS A total of 73 children were included in the prospective study; 50 of them were diagnosed with NAFLD based on ultrasound, and 23 formed a control group. Basic anthropometric parameters were measured, blood samples were taken for laboratory tests and evaluated proteins were assessed by enzyme-linked immunosorbent assay-adiponectin, tumour necrosis factor alpha, fibroblast growth factor 21, liver fatty acid-binding protein (L-FABP) and interleukin 6. RESULTS Statistically significant differences between the levels of two proteins were found: the adiponectin level was lower in the NAFLD group (12.24 ± 7.01 vs 16.88 ± 9.21 μg/mL, P = 0.024), and L-FABP levels were higher (21.48 ± 20.61 vs 11.74 ± 8.39 ng/mL, P = 0.031). In the group of children with body mass index (BMI)-for-age >1 standard deviation (SD), adiponectin concentration was also significantly lower (12.18 ± 6.43 μg/mL) than in the group with BMI ≤1 SD (17.29 ± 9.42 μg/mL, P = 0.015). The odds ratios and 95% confidence interval for the relation between adiponectin and NAFLD and obesity were 0.868 (0.767-0.982) and 0.838 (0.719-0.977), respectively. CONCLUSION Adiponectin may be useful in evaluating the risk of NAFLD and obesity in children.
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Key Words
- ALF, acute liver failure
- ALT, alanine aminotransferase
- AMPK, adenosine monophosphate–activated protein kinase
- APRI, AST to Platelet Ratio Index
- AST, aspartate aminotransferase
- BMI, body mass index
- ER, endoplasmic reticulum
- FFA, free fatty acid
- FGF-21, fibroblast growth factor 21
- HMW, high-molecular-weight
- IR, insulin resistance
- L-FABP, liver fatty acid-binding protein
- LPS, lipopolysaccharide
- NAFLD, nonalcoholic fatty liver disease
- NASH, nonalcoholic steatohepatitis
- OR, odds ratio
- PNFS, Paediatric NAFLD Fibrosis Scale
- PPAR-α, peroxisome proliferator–activated receptor-α
- SD, standard deviation
- SOCS3, suppressor of cytokine signalling 3
- TNF-α, tumour necrosis factor α
- US-FLI, ultrasound fatty liver indicator
- WHO, World Health Organization
- adipokines
- children
- nonalcoholic fatty liver disease
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Affiliation(s)
- Paweł Małecki
- Department of Infectious Diseases and Child Neurology, Poznan University of Medical Sciences, Poznan, Poland
| | - Anna Mania
- Department of Infectious Diseases and Child Neurology, Poznan University of Medical Sciences, Poznan, Poland
| | - Joanna Tracz
- Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland
| | - Magdalena Łuczak
- Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland
| | - Katarzyna Mazur-Melewska
- Department of Infectious Diseases and Child Neurology, Poznan University of Medical Sciences, Poznan, Poland
| | - Magdalena Figlerowicz
- Department of Infectious Diseases and Child Neurology, Poznan University of Medical Sciences, Poznan, Poland
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Chen TP, Lin WY, Chiang CH, Shen TH, Huang KC, Yang KC. Metabolically healthy obesity and risk of non-alcoholic fatty liver disease severity independent of visceral fat. J Gastroenterol Hepatol 2021; 36:2903-2910. [PMID: 33973273 DOI: 10.1111/jgh.15544] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Revised: 05/01/2021] [Accepted: 05/07/2021] [Indexed: 12/20/2022]
Abstract
BACKGROUND AND AIM Obesity and metabolic conditions may be related to non-alcoholic fatty liver disease (NAFLD). The study assesses the risk of NAFLD according to obesity and metabolic health status in a community-based population. METHODS A total of 1651 subjects were recruited from the community. Individuals were categorized into four groups according to obesity status (defined as a body mass index ≥ 25 kg/m2 ) and metabolically healthy status: metabolically healthy nonobesity (MHNO), metabolically healthy obesity (MHO), metabolically unhealthy nonobesity (MUHNO), and metabolically unhealthy obesity (MUHO). NAFLD was diagnosed based on a semiquantitative ultrasonography measurement. Visceral fat was assessed through bioelectrical impedance analysis and is shown by tertile (T1, T2, and T3). A proportional odds model was used to assess the cumulative risk of NAFLD. RESULTS The NAFLD prevalence was 26.7%, 62.8%, 47.0%, and 76.7% in subjects with MHNO, MHO, MUHNO, and MUHO, respectively (P < 0.0001). After adjustment for age, sex, exercise habits, alcohol consumption, cigarette smoking, and visceral fat, the odds ratios for more severe NAFLD were 2.44 (95% confidence interval [CI]: 1.64-3.65), 2.75 (95% CI: 1.91-3.94), and 7.41 (95% CI: 4.94-11.12) in the MHO, MUHNO, and MUHO groups, respectively, compared with the MHNO group. In addition, the odds ratios for more severe NAFLD significantly increased with the increase in visceral fat level (T2 vs T1: 3.83, 95% CI: 2.65-5.53; T3 vs T1: 9.17, 95% CI: 5.33-15.79). CONCLUSION Both obesity and metabolically unhealthy status were associated with a higher risk of NAFLD independent of visceral fat level.
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Affiliation(s)
- Tsung-Po Chen
- Department of Community and Family Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Wen-Yuan Lin
- Department of Community and Family Medicine, China Medical University Hospital, Taichung, Taiwan.,Department of Social Medicine, College of Medicine, China Medical University, Taichung, Taiwan
| | - Chien-Hsieh Chiang
- Department of Family Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Ting-Hsin Shen
- Department of Community and Family Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Kuo-Chin Huang
- Department of Family Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Department of Family Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Kuen-Cheh Yang
- Department of Family Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
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43
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Chou TH, Yeh HJ, Chang CC, Tang JH, Kao WY, Su IC, Li CH, Chang WH, Huang CK, Sufriyana H, Su ECY. Deep learning for abdominal ultrasound: A computer-aided diagnostic system for the severity of fatty liver. J Chin Med Assoc 2021; 84:842-850. [PMID: 34282076 DOI: 10.1097/jcma.0000000000000585] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND The prevalence of nonalcoholic fatty liver disease is increasing over time worldwide, with similar trends to those of diabetes and obesity. A liver biopsy, the gold standard of diagnosis, is not favored due to its invasiveness. Meanwhile, noninvasive evaluation methods of fatty liver are still either very expensive or demonstrate poor diagnostic performances, thus, limiting their applications. We developed neural network-based models to assess fatty liver and classify the severity using B-mode ultrasound (US) images. METHODS We followed standards for reporting of diagnostic accuracy guidelines to report this study. In this retrospective study, we utilized B-mode US images from a consecutive series of patients to develop four-class, two-class, and three-class diagnostic prediction models. The images were eligible if confirmed by at least two gastroenterologists. We compared pretrained convolutional neural network models, consisting of visual geometry group (VGG)19, ResNet-50 v2, MobileNet v2, Xception, and Inception v2. For validation, we utilized 20% of the dataset resulting in >100 images for each severity category. RESULTS There were 21,855 images from 2,070 patients classified as normal (N = 11,307), mild (N = 4,467), moderate (N = 3,155), or severe steatosis (N = 2,926). We used ResNet-50 v2 for the final model as the best ones. The areas under the receiver operating characteristic curves were 0.974 (mild steatosis vs others), 0.971 (moderate steatosis vs others), 0.981 (severe steatosis vs others), 0.985 (any severity vs normal), and 0.996 (moderate-to-severe steatosis/clinically abnormal vs normal-to-mild steatosis/clinically normal). CONCLUSION Our deep learning models achieved comparable predictive performances to the most accurate, yet expensive, noninvasive diagnostic methods for fatty liver. Because of the discriminative ability, including for mild steatosis, significant impacts on clinical applications for fatty liver are expected. However, we need to overcome machine-dependent variation, motion artifacts, lacking of second confirmation from any other tools, and hospital-dependent regional bias.
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Affiliation(s)
- Tsung-Hsien Chou
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan, ROC
| | - Hsing-Jung Yeh
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan, ROC
| | - Chun-Chao Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan, ROC
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC
| | - Jui-Hsiang Tang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan, ROC
| | - Wei-Yu Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan, ROC
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC
| | - I-Chia Su
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan, ROC
| | - Chien-Hung Li
- Acer Value Lab Advanced Tech Business Unit, Acer Incorporated, New Taipei City, Taiwan, ROC
| | - Wei-Hao Chang
- Acer Value Lab Advanced Tech Business Unit, Acer Incorporated, New Taipei City, Taiwan, ROC
| | - Chun-Kai Huang
- Acer Value Lab Advanced Tech Business Unit, Acer Incorporated, New Taipei City, Taiwan, ROC
| | - Herdiantri Sufriyana
- Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan, ROC
- Department of Medical Physiology, College of Medicine, University of Nahdlatul Ulama Surabaya, Surabaya, Indonesia
| | - Emily Chia-Yu Su
- Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan, ROC
- Clinical Big Data Research Center, Taipei Medical University Hospital, Taipei, Taiwan, ROC
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Independent Dose-Response Associations between Fetuin-A and Lean Nonalcoholic Fatty Liver Disease. Nutrients 2021; 13:nu13092928. [PMID: 34578806 PMCID: PMC8468081 DOI: 10.3390/nu13092928] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2021] [Revised: 08/23/2021] [Accepted: 08/23/2021] [Indexed: 12/13/2022] Open
Abstract
Patients with lean NAFLD make up an increasing subset of liver disease patients. The association between lean NAFLD and feutin-A, which serves as a hepatokine and adipokine, has never been examined. Our study aimed to explore the association of serum fetuin-A among lean and non-lean patients. The study comprised 606 adults from the community, stratified into lean or non-lean (BMI </≥ 24 kg/m2) and NAFLD or non-NAFLD (scoring of ultrasonographic fatty liver indicator, US-FLI ≥ 2/< 2). Multivariate logistic regression analyses were performed to estimate the odds ratio of having NAFLD among the tertiles of fetuin-A after adjustment. The least square means were computed by general linear models to estimate marginal means of the serum fetuin-A concentrations in relation to the NAFLD groups. The odds ratio (OR) of having NAFLD for the highest versus the lowest tertile of fetuin-A was 2.62 (95% CI: 1.72–3.98; p for trend < 0.001). Stratifying by BMI, the OR of having lean NAFLD for the highest versus the lowest tertile of fetuin-A was 2.09 (95% CI: 1.09–3.98; p for trend 0.026), while non-lean NAFLD had no significant association with the fetuin-A gradient after adjustments. Fetuin-A was positively associated with lean NAFLD after adjusting for central obesity and insulin resistance.
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45
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Alqahtani SA, Schattenberg JM. Nonalcoholic fatty liver disease: use of diagnostic biomarkers and modalities in clinical practice. Expert Rev Mol Diagn 2021; 21:1065-1078. [PMID: 34346799 DOI: 10.1080/14737159.2021.1964958] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
INTRODUCTION The global burden of liver disease is increasing, and nonalcoholic fatty liver disease (NAFLD) is among the most common chronic liver diseases in Asia, Europe, North and South America. The field of noninvasive diagnostic and their role in staging, but also predicting outcome is evolving rapidly. There is a high-unmet need to stage patients with NAFLD and to identify the subset of patients at risk of progression to end-stage liver disease. AREAS COVERED The review covers all established diagnostic blood-based and imaging biomarkers to stage and grade NAFLD. Noninvasive surrogate scores are put into perspective of the available evidence and recommended use. The outlook includes genetics, combined algorithms, and artificial intelligence that will allow clinicians to guide and support the management in both early and later disease stages. EXPERT OPINION In the future, these diagnostics tests will help clinicians to establish patient care pathways and support the identification of relevant subgroups for monitoring and pharmacotherapy. In addition, researchers will be guided to better understand available scores and support the development of future prediction systems. These will likely include multiparametric aspects of the disease and machine learning algorithms will refine their use and integration with large datasets.
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Affiliation(s)
- Saleh A Alqahtani
- Liver Transplantation Unit, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia.,Division Of Gastroenterology And Hepatology, Johns Hopkins University, Baltimore, USA
| | - Jörn M Schattenberg
- Metabolic Liver Research Program, I. Department Of Medicine, University Medical Center, Mainz, Germany
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Association between the Severity of Nonalcoholic Fatty Liver Disease and the Risk of Coronary Artery Calcification. MEDICINA (KAUNAS, LITHUANIA) 2021; 57:medicina57080807. [PMID: 34441013 PMCID: PMC8400018 DOI: 10.3390/medicina57080807] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Revised: 07/28/2021] [Accepted: 08/04/2021] [Indexed: 12/13/2022]
Abstract
Background and Objectives: There are limited data on the association between severity of non-alcoholic fatty liver disease (NAFLD) and coronary artery calcification. This study investigated sonographic diagnosed NAFLD and coronary artery calcium score (CAC) as detected by cardiac multidetector computed tomography in general populations. Materials and Methods: A total of 545 patients were enrolled in this study. NAFLD was diagnosed by ultrasonography examination and CAC score were evaluated by cardiac multidetector computed tomography. The association between NAFLD and artery calcium score stage was determined by logistic regression analysis and Spearman correlation coefficient analysis. Results: Of all the participants, 437 (80.2%) had ultrasonography-diagnosed NAFLD and 242 (44%) had coronary artery calcification (CAC > 0). After adjustment for cardiovascular risk factors, the risk of developing coronary artery calcification was 1.36-fold greater in the patients with different severity of NAFLD compared to those without NAFLD (OR = 1.36, 95% CI = 1.07-1.77, p = 0.016). The highest OR for separate coronary artery calcification was 1.98 (OR = 1.98, 95% CI = 1.37-2.87, p < 0.001) in the left main artery, and the risk was still 1.71-fold greater after adjustments (OR = 1.71, 95% CI = 1.16-2.54, p = 0.007). Conclusions: This cross-sectional study demonstrated that the severity of NAFLD was associated with the presence of significant coronary artery calcification, especially in the left main coronary artery, suggesting increasing the cardiovascular risk.
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Di Ciaula A, Carbone F, Shanmugham H, Molina-Molina E, Bonfrate L, Ministrini S, Montecucco F, Portincasa P. Adiponectin involved in portal flow hepatic extraction of 13C-methacetin in obesity and non-alcoholic fatty liver. Eur J Intern Med 2021; 89:56-64. [PMID: 33867228 DOI: 10.1016/j.ejim.2021.03.036] [Citation(s) in RCA: 10] [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: 12/09/2020] [Revised: 02/23/2021] [Accepted: 03/25/2021] [Indexed: 02/06/2023]
Abstract
Obesity and non-alcoholic fatty liver disease (NAFLD) are high prevalence, inter-related conditions at increased risk for advanced liver diseases and related mortality. Adiponectin and leptin have divergent roles in the pathogenesis of fat accumulation and NAFLD. However, the relationships between body and liver fat accumulation, early modification of liver function and unbalanced adipokine levels are still scarcely explored. We studied by (13C)-methacetin breath test ((13C)-MBT) 67 adults stratified according to body mass index, and to presence/absence of ultrasonographic nonalcoholic fatty liver disease (uNAFLD). uNAFLD was detected in 20%, 73% and 96% of normal weight, overweight and obese subjects, respectively. The delta over baseline after 15 min (DOB15), a marker of hepatic extraction efficiency from portal blood flow, was lower in obese than in normal weight subjects, and in subjects with-, as compared to those without uNAFLD. The cumulative percent dose recovery after 30 min (cPDR30), a marker of liver microsomal function, was lower in uNAFLD patients. DOB15 was positively correlated with adiponectin levels in obese and in uNAFLD patients. uNAFLD patients also showed a positive correlation between cPDR30 values and adiponectin. Our data indicate the existence of early alterations of liver function in obese and in patients with uNAFLD. These dysfunctions are linked to altered leptin/adiponectin balance and can be identified noninvasively by (13C)-MBT.
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Affiliation(s)
- Agostino Di Ciaula
- Clinica Medica "A. Murri", Department of Biomedical Sciences and Human Oncology, University of Bari Aldo Moro, Bari 70124, Italy.
| | - Federico Carbone
- First Clinic of internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy; IRCCS Ospedale Policlinico San Martino, Genoa - Italian Cardiovascular Network, 10 Largo Benzi, 16132 Genoa, Italy..
| | - Harshitha Shanmugham
- Clinica Medica "A. Murri", Department of Biomedical Sciences and Human Oncology, University of Bari Aldo Moro, Bari 70124, Italy
| | - Emilio Molina-Molina
- Clinica Medica "A. Murri", Department of Biomedical Sciences and Human Oncology, University of Bari Aldo Moro, Bari 70124, Italy
| | - Leonilde Bonfrate
- Clinica Medica "A. Murri", Department of Biomedical Sciences and Human Oncology, University of Bari Aldo Moro, Bari 70124, Italy.
| | - Stefano Ministrini
- Internal Medicine, Department of Medicine, Università degli Studi di Perugia, 1 piazzale Gambuli, 06129, Perugia, Italy
| | - Fabrizio Montecucco
- First Clinic of internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy; IRCCS Ospedale Policlinico San Martino, Genoa - Italian Cardiovascular Network, 10 Largo Benzi, 16132 Genoa, Italy..
| | - Piero Portincasa
- Clinica Medica "A. Murri", Department of Biomedical Sciences and Human Oncology, University of Bari Aldo Moro, Bari 70124, Italy.
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Besutti G, Bonilauri L, Manicardi E, Venturelli F, Bonelli E, Monelli F, Manicardi V, Valenti L, Ligabue G, Schianchi S, Massari M, Riva N, Froio E, Tagliavini E, Pattacini P, Giorgi Rossi P. Feasibility and efficiency of European guidelines for NAFLD assessment in patients with type 2 diabetes: A prospective study. Diabetes Res Clin Pract 2021; 177:108882. [PMID: 34082056 DOI: 10.1016/j.diabres.2021.108882] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Revised: 05/21/2021] [Accepted: 05/27/2021] [Indexed: 12/18/2022]
Abstract
AIM We aimed to evaluate the feasibility and efficiency of a guidelines-compliant NAFLD assessment algorithm in patients with newly diagnosed type 2 diabetes (T2D). METHODS Consecutive patients aged < 75 newly diagnosed with T2D without coexisting liver disease or excessive alcohol consumption were enrolled. Patients were stratified based on liver enzymes, fatty liver index, ultrasound, fibrosis scores and liver stiffness measurement. Referral rates and positive predictive values (PPVs) for histological non-alcoholic steatohepatitis (NASH) and significant fibrosis were evaluated. RESULTS Of the 171 enrolled patients (age 59 ± 10.2 years, 42.1% females), 115 (67.3%) were referred to a hepatologist due to abnormal liver enzymes (n = 60) or steatosis plus indeterminate (n = 37) or high NAFLD fibrosis score (n = 18). Liver biopsy was proposed to 30 patients (17.5%), but only 14 accepted, resulting in 12 NASH, one with significant fibrosis. The PPV of hepatological referral was 12/76 (15.8%) for NASH and 1/76 (1.3%) for NASH with significant fibrosis. The PPV of liver biopsy referral was 12/14 (85.7%) for NASH and 1/14 (7.1%) for NASH with significant fibrosis. CONCLUSIONS By applying a guidelines-compliant algorithm, many patients with T2D were referred for hepatological assessment and liver biopsy. Further studies are necessary to refine non-invasive algorithms.
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Affiliation(s)
- Giulia Besutti
- Radiology Unit, Department of Diagnostic Imaging and Laboratory Medicine, AUSL-IRCCS di Reggio Emilia, Reggio Emilia, Italy; Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, Modena, Italy.
| | - Lisa Bonilauri
- Diabetes Clinic, AUSL-IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Elisa Manicardi
- Diabetes Clinic, AUSL-IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | | | - Efrem Bonelli
- Radiology Unit, Department of Diagnostic Imaging and Laboratory Medicine, AUSL-IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Filippo Monelli
- Radiology Unit, Department of Diagnostic Imaging and Laboratory Medicine, AUSL-IRCCS di Reggio Emilia, Reggio Emilia, Italy; Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, Modena, Italy
| | | | - Luca Valenti
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Precision Medicine - Department of Transfusion Medicine and Hematology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Guido Ligabue
- Radiology Unit, Azienda Ospedaliero-Universitaria Policlinico di Modena, University of Modena and Reggio Emilia, Modena, Italy
| | - Susanna Schianchi
- Internal Medicine Unit, AUSL-IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Marco Massari
- Infectious Diseases Unit, AUSL-IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Nicoletta Riva
- Infectious Diseases Unit, AUSL-IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Elisabetta Froio
- Pathology Department, AUSL-IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Elena Tagliavini
- Pathology Department, AUSL-IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Pierpaolo Pattacini
- Radiology Unit, Department of Diagnostic Imaging and Laboratory Medicine, AUSL-IRCCS di Reggio Emilia, Reggio Emilia, Italy
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Papachristodoulou A, Kavvadas D, Karamitsos A, Papamitsou T, Chatzidimitriou M, Sioga A. Diagnosis and Staging of Pediatric Non-Alcoholic Fatty Liver Disease: Is Classical Ultrasound the Answer? Pediatr Rep 2021; 13:312-321. [PMID: 34201230 PMCID: PMC8293345 DOI: 10.3390/pediatric13020039] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Revised: 05/19/2021] [Accepted: 06/01/2021] [Indexed: 12/15/2022] Open
Abstract
The increased prevalence of non-alcoholic fatty liver disease (NAFLD) requires special attention in pediatric patients, as it manifests in them in a more severe and progressive way compared to adults. The implementation of the appropriate therapeutic interventions is determinant of the attempts to treat it. For that purpose, early diagnosis and staging of the disease is essential. The purpose of this review was to find and reveal the most appropriate diagnostic strategies and tools for diagnosis and staging of pediatric NAFLD/NASH based on their accuracy, safety and effectiveness. The methodology followed was that of the literature review. Particular emphasis was put on the recent bibliography. A comparative study of published articles about the diagnosis and management of pediatric NAFLD/NASH was also performed. In terms of diagnosis, the findings converged on the use of classical ultrasound. Ultrasound presented average sensitivity and specificity for diagnosing the disease in children, while in the adult population, sensitivity and specificity were significantly higher. Proton density fat fraction magnetic resonance imaging has been increasingly used for the diagnosis of steatosis in pediatric patients. Elastography is an effective tool for staging liver fibrosis and discriminating NASH from NAFLD in children. Even though liver biopsy is the gold standard, especially for NASH, it should be avoided for pediatric patients. Biochemical tests are less specific and less sensitive for the diagnosis of NAFLD, and some of them are of high cost. It seems that diagnostic imaging should be a first-line tool for the staging and monitoring pediatric NAFLD/NASH in order for appropriate interventions to be implanted in a timely way.
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Affiliation(s)
- Angeliki Papachristodoulou
- Laboratory of Histology and Embryology, School of Medicine, Faculty of Health, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece; (A.P.); (D.K.); (A.S.)
| | - Dimitrios Kavvadas
- Laboratory of Histology and Embryology, School of Medicine, Faculty of Health, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece; (A.P.); (D.K.); (A.S.)
| | - Athanasios Karamitsos
- 2nd Department of Ophthalmology, School of Medicine, Faculty of Health, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece;
| | - Theodora Papamitsou
- Laboratory of Histology and Embryology, School of Medicine, Faculty of Health, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece; (A.P.); (D.K.); (A.S.)
| | - Maria Chatzidimitriou
- Department of Biomedical Sciences, School of Health Sciences, International University of Greece, 574 00 Thessaloniki, Greece;
| | - Antonia Sioga
- Laboratory of Histology and Embryology, School of Medicine, Faculty of Health, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece; (A.P.); (D.K.); (A.S.)
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50
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Li F, Ye J, Sun Y, Lin Y, Wu T, Shao C, Ma Q, Liao X, Feng S, Zhong B. Distinct Dose-Dependent Association of Free Fatty Acids with Diabetes Development in Nonalcoholic Fatty Liver Disease Patients. Diabetes Metab J 2021; 45:417-429. [PMID: 33705650 PMCID: PMC8164943 DOI: 10.4093/dmj.2020.0039] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Accepted: 05/21/2020] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Excessive delivery of free fatty acids (FFAs) to the liver promotes steatosis and insulin resistance (IR), with IR defined as reduced glucose uptake, glycogen synthesis and anti-lipolysis stimulated by normal insulin levels. Whether the associations between FFAs and diabetes development differ between patients with and without nonalcoholic fatty liver disease (NAFLD) remains unclear. METHODS Consecutive subjects (2,220 NAFLD subjects and 1,790 non-NAFLD subjects according to ultrasound imaging) were enrolled from the First Affiliated Hospital of Sun Yat-sen University between 2009 and 2019. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. RESULTS There was an approximate J-shaped relationship between FFA levels and HOMA-IR in the NAFLD group. Higher FFA concentration quartiles were associated with higher risks of IR (odds ratio [OR], 9.24; 95% confidence interval [CI], 6.43 to 13.36), prediabetes (OR, 10.48; 95% CI, 5.66 to 19.39), and type 2 diabetes mellitus (T2DM; OR, 19.43; 95% CI, 12.75 to 29.81) in the NAFLD group but not in the non-NAFLD group. The cut-off points for the FFA levels increased in a stepwise manner in discriminating IR, prediabetes and T2DM (573, 697, and 715 μmol/L) in the NAFLD group but not in non-NAFLD individuals. CONCLUSION A distinct dose-dependent relationship of FFA levels was found with IR, prediabetes and T2DM in NAFLD patients. Screening serum FFA levels in NAFLD patients would be valuable in preventing diabetes development.
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Affiliation(s)
- Fuxi Li
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Junzhao Ye
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yanhong Sun
- Department of Clinical Laboratory, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yansong Lin
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Tingfeng Wu
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Congxiang Shao
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Qianqian Ma
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xianhua Liao
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Shiting Feng
- Department of Radiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Bihui Zhong
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Corresponding author: Bihui Zhong https://orcid.org/0000-0002-4638-7699 Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, NO. 58 Zhongshan II Road, Yuexiu District, Guangzhou 510080, China E-mail:
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