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Kraus EM, Pierce SL, Porter R, Kompaniyets L, Vos MB, Blanck HM, King RJ, Goodman AB. Using Real-World Electronic Health Record Data to Assess Chronic Disease Screening in Children: A Case Study of Non-Alcoholic Fatty Liver Disease. Child Obes 2024; 20:41-47. [PMID: 36862137 PMCID: PMC10790548 DOI: 10.1089/chi.2022.0208] [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] [Indexed: 03/03/2023]
Abstract
Background: Data sources for assessing pediatric chronic diseases and associated screening practices are rare. One example is non-alcoholic fatty liver disease (NAFLD), a common chronic liver disease prevalent among children with overweight and obesity. If undetected, NAFLD can cause liver damage. Guidelines recommend screening for NAFLD using alanine aminotransferase (ALT) tests in children ≥9 years with obesity or those with overweight and cardiometabolic risk factors. This study explores how real-world data from electronic health records (EHRs) can be used to study NAFLD screening and ALT elevation. Research Design: Using IQVIA's Ambulatory Electronic Medical Record database, we studied patients 2-19 years of age with body mass index ≥85th percentile. Using a 3-year observation period (January 1, 2019 to December 31, 2021), ALT results were extracted and assessed for elevation (≥1 ALT result ≥22.1 U/L for females and ≥25.8 U/L for males). Patients with liver disease (including NAFLD) or receiving hepatotoxic medications during 2017-2018 were excluded. Results: Among 919,203 patients 9-19 years of age, only 13% had ≥1 ALT result, including 14% of patients with obesity and 17% of patients with severe obesity. ALT results were identified for 5% of patients 2-8 years of age. Of patients with ALT results, 34% of patients 2-8 years of age and 38% of patients 9-19 years of age had ALT elevation. Males 9-19 years of age had a higher prevalence of ALT elevation than females (49% vs. 29%). Conclusions: EHR data offered novel insights into NAFLD screening: despite screening recommendations, ALT results among children with excess weight were infrequent. Among those with ALT results, ALT elevation was common, underscoring the importance of screening for early disease detection.
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Affiliation(s)
- Emily M. Kraus
- Division of Nutrition, Physical Activity, and Obesity, Centers for Disease Control and Prevention, Atlanta, GA, USA
- Public Health Informatics Institute, Taskforce for Global Health, Atlanta, GA, USA
| | - Samantha Lange Pierce
- Division of Nutrition, Physical Activity, and Obesity, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Renee Porter
- Division of Nutrition, Physical Activity, and Obesity, Centers for Disease Control and Prevention, Atlanta, GA, USA
- McKing Consulting Corporation, Atlanta, GA, USA
| | - Lyudmyla Kompaniyets
- Division of Nutrition, Physical Activity, and Obesity, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Miriam B. Vos
- Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA
- Children's Healthcare of Atlanta, Atlanta, GA, USA
| | - Heidi M. Blanck
- Division of Nutrition, Physical Activity, and Obesity, Centers for Disease Control and Prevention, Atlanta, GA, USA
- United States Public Health Service, Washington, DC, USA
| | - Raymond J. King
- Division of Nutrition, Physical Activity, and Obesity, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Alyson B. Goodman
- Division of Nutrition, Physical Activity, and Obesity, Centers for Disease Control and Prevention, Atlanta, GA, USA
- United States Public Health Service, Washington, DC, USA
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Guo X, Huang Z, Chen J, He K, Lin J, Zhang H, Zeng Y. Synergistic delivery of resveratrol and ultrasmall copper-based nanoparticles by aptamer-functionalized ultrasound nanobubbles for the treatment of nonalcoholic fatty liver disease. Front Physiol 2022; 13:950141. [PMID: 36160874 PMCID: PMC9502034 DOI: 10.3389/fphys.2022.950141] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Accepted: 08/15/2022] [Indexed: 11/18/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is related to the production of reactive oxygen species (ROS) and oxidative stress, so antioxidant treatment can prevent its further development. Ultrasmall copper-based nanoparticles (CuNPs) have shown multiple enzyme-like activities for scavenging oxygen species, providing a new strategy for the treatment of inflammatory diseases. Resveratrol (Res), a natural polyphenol compound, has attracted much attention due to its ability to inhibit oxidative stress. We therefore aimed to first combine these two agents for the treatment of NAFLD. However, due to the poor water solubility and stability of Res, which is easily metabolized in the intestine, the development of a stable and effective carrier became the key to achieving a synergistic effect. Liver-targeted nanocarriers loaded with bioactive compounds may provide a more effective approach for the treatment of NAFLD. Therefore, we developed a novel ultrasonic nanobubble carrying nucleic acid aptamers with liver targeting properties, which has the advantages of a small molecular weight, no immunogenicity, a low cost of synthesis, and high stability through chemical modification. Res and the ultrasmall CuNPs were specifically delivered to liver tissue to maximize therapeutic efficiency. This study found that the combination of these two components can effectively treat inflammation in NAFLD and suggested that liver-targeted NAFLD-specific aptamer-mediated targeted ultrasound nanobubbles that can simultaneously deliver Res and CuNPs may be a safe and effective new platform for NAFLD and other liver diseases.
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Affiliation(s)
- Xinmin Guo
- Department of Ultrasound, Guangzhou Red Cross Hospital of Jinan University, Guangzhou, China
- *Correspondence: Xinmin Guo,
| | - Zhihui Huang
- Department of Nuclear Medicine, Guangzhou Red Cross Hospital of Jinan University, Guangzhou, China
| | - Jialin Chen
- Department of Ultrasound, Guangzhou Red Cross Hospital of Jinan University, Guangzhou, China
| | - Kun He
- Department of Ultrasound, Guangzhou Red Cross Hospital of Jinan University, Guangzhou, China
| | - Jianru Lin
- Department of Ultrasound, Guangzhou Red Cross Hospital of Jinan University, Guangzhou, China
| | - Hui Zhang
- Department of Ultrasound, Guangzhou Red Cross Hospital of Jinan University, Guangzhou, China
| | - Yanying Zeng
- Department of Ultrasound, Guangzhou Red Cross Hospital of Jinan University, Guangzhou, China
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Cao D, Li M, Liu Y, Jin H, Yang D, Xu H, Lv H, Liu JI, Zhang P, Zhang Z, Yang Z. Comparison of reader agreement, correlation with liver biopsy, and time-burden sampling strategies for liver proton density fat fraction measured using magnetic resonance imaging in patients with obesity: a secondary cross-sectional study. BMC Med Imaging 2022; 22:92. [PMID: 35581577 PMCID: PMC9112589 DOI: 10.1186/s12880-022-00821-6] [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: 12/30/2021] [Accepted: 05/10/2022] [Indexed: 11/29/2022] Open
Abstract
Background The magnetic resonance imaging (MRI)-based proton density fat fraction (PDFF) has become popular for quantifying liver fat content. However, the variability of the region-of-interest (ROI) sampling strategy may result in a lack of standardisation of this technology. In an effort to establish an accurate and effective PDFF measurement scheme, this study assessed the pathological correlation, the reader agreement, and time-burden of different sampling strategies with variable ROI size, location, and number. Methods Six-echo spoiled gradient-recalled-echo magnitude-based fat quantification was performed for 50 patients with obesity, using a 3.0-T MRI scanner. Two readers used different ROI sampling strategies to measure liver PDFF, three times. Intra-reader and inter-reader agreement was evaluated using intra-class correlation coefficients and Bland‒Altman analysis. Pearson correlations were used to assess the correlation between PDFFs and liver biopsy. Time-burden was recorded. Results For pathological correlations, the correlations for the strategy of using three large ROIs in Couinaud segment 3 (S3 3L-ROI) were significantly greater than those for all sampling strategies at the whole-liver level (P < 0.05). For inter-reader agreement, the sampling strategies at the segmental level for S3 3L-ROI and using three large ROIs in Couinaud segment 6 (S6 3L-ROI) and the sampling strategies at the whole-liver level for three small ROIs per Couinaud segment (27S-ROI), one large ROI per Couinaud segment (9L-ROI), and three large ROIs per Couinaud segment (27S-ROI) had limits of agreement (LOA) < 1.5%. For intra-reader agreement, the sampling strategies at the whole-liver level for 27S-ROI, 9L-ROI, and 27L-ROI had both intraclass coefficients > 0.995 and LOAs < 1.5%. The change in the time-burden was the largest (100.80 s) when 9L-ROI was changed to 27L-ROI. Conclusions For hepatic PDFF measurement without liver puncture biopsy as the gold standard, and for general hepatic PDFF assessment, 9L-ROI sampling strategy at the whole-liver level should be used preferentially. For hepatic PDFF with liver puncture biopsy as the gold standard, 3L-ROI sampling strategy at the puncture site segment is recommended.
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Affiliation(s)
- Di Cao
- Department of Radiology, Beijing Friendship Hospital, Capital Medical University, No. 95 Yong-an Road, Xi-Cheng District, Beijing, 100050, China
| | - Mengyi Li
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University and National Clinical Research Center for Digestive Diseases, No. 95 Yong-an Road, Xi-Cheng District, Beijing, 100050, China
| | - Yang Liu
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University and National Clinical Research Center for Digestive Diseases, No. 95 Yong-an Road, Xi-Cheng District, Beijing, 100050, China
| | - He Jin
- Department of Radiology, Beijing Friendship Hospital, Capital Medical University, No. 95 Yong-an Road, Xi-Cheng District, Beijing, 100050, China
| | - Dawei Yang
- Department of Radiology, Beijing Friendship Hospital, Capital Medical University, No. 95 Yong-an Road, Xi-Cheng District, Beijing, 100050, China
| | - Hui Xu
- Department of Radiology, Beijing Friendship Hospital, Capital Medical University, No. 95 Yong-an Road, Xi-Cheng District, Beijing, 100050, China
| | - Han Lv
- Department of Radiology, Beijing Friendship Hospital, Capital Medical University, No. 95 Yong-an Road, Xi-Cheng District, Beijing, 100050, China
| | - JIa Liu
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University and National Clinical Research Center for Digestive Diseases, No. 95 Yong-an Road, Xi-Cheng District, Beijing, 100050, China
| | - Peng Zhang
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University and National Clinical Research Center for Digestive Diseases, No. 95 Yong-an Road, Xi-Cheng District, Beijing, 100050, China
| | - Zhongtao Zhang
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University and National Clinical Research Center for Digestive Diseases, No. 95 Yong-an Road, Xi-Cheng District, Beijing, 100050, China.
| | - Zhenghan Yang
- Department of Radiology, Beijing Friendship Hospital, Capital Medical University, No. 95 Yong-an Road, Xi-Cheng District, Beijing, 100050, China.
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The Interplay between Insulin Resistance, Inflammation, Oxidative Stress, Base Excision Repair and Metabolic Syndrome in Nonalcoholic Fatty Liver Disease. Int J Mol Sci 2021; 22:ijms222011128. [PMID: 34681787 PMCID: PMC8537238 DOI: 10.3390/ijms222011128] [Citation(s) in RCA: 85] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Revised: 10/11/2021] [Accepted: 10/12/2021] [Indexed: 02/06/2023] Open
Abstract
One of the most common chronic liver disorders, affecting mainly people in Western countries, is nonalcoholic fatty liver disease (NAFLD). Unfortunately, its pathophysiological mechanism is not fully understood, and no dedicated treatment is available. Simple steatosis can lead to nonalcoholic steatohepatitis and even to fibrosis, cancer, and cirrhosis of the liver. NAFLD very often occurs in parallel with type 2 diabetes mellitus and in obese people. Furthermore, it is much more likely to develop in patients with metabolic syndrome (MS), whose criteria include abdominal obesity, elevated blood triacylglycerol level, reduced high-density lipoprotein cholesterol level, increased blood pressure, and high fasting glucose. An important phenomenon in MS is also insulin resistance (IR), which is very common in NAFLD. Liver IR and NAFLD development are linked through an interaction between the accumulation of free fatty acids, hepatic inflammation, and increased oxidative stress. The liver is particularly exposed to elevated levels of reactive oxygen species due to a large number of mitochondria in hepatocytes. In these organelles, the main DNA repair pathway is base excision repair (BER). The present article will illustrate how impairment of BER may be related to the development of NAFLD.
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Zhang P, Wang W, Mao M, Gao R, Shi W, Li D, Calderone R, Sui B, Tian X, Meng X. Similarities and Differences: A Comparative Review of the Molecular Mechanisms and Effectors of NAFLD and AFLD. Front Physiol 2021; 12:710285. [PMID: 34393826 PMCID: PMC8362097 DOI: 10.3389/fphys.2021.710285] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2021] [Accepted: 06/29/2021] [Indexed: 12/12/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD) are the most prevalent metabolic liver diseases globally. Due to the complex pathogenic mechanisms of NAFLD and AFLD, no specific drugs were approved at present. Lipid accumulation, oxidative stress, insulin resistance, inflammation, and dietary habits are all closely related to the pathogenesis of NAFLD and AFLD. However, the mechanism that promotes disease progression has not been fully elucidated. Meanwhile, the gut microbiota and their metabolites also play an important role in the pathogenesis and development of NAFLD and AFLD. This article comparatively reviewed the shared and specific signaling pathways, clinical trials, and potential intervention effectors of NAFLD and AFLD, revealing their similarities and differences. By comparing the shared and specific molecular regulatory mechanisms, this paper provides mutual reference strategies for preventing and treating NAFLD, AFLD, and related metabolic diseases. Furthermore, it provides enlightenment for discovering novel therapies of safe and effective drugs targeting the metabolic liver disease.
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Affiliation(s)
- Pengyi Zhang
- School of Sports and Health, Shandong Sport University, Jinan, China
| | - Weiya Wang
- School of Sports and Health, Shandong Sport University, Jinan, China.,Shandong Academy of Pharmaceutical Science, Jinan, China
| | - Min Mao
- Department of Allied Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
| | - Ruolin Gao
- School of Sports and Health, Shandong Sport University, Jinan, China
| | - Wenting Shi
- School of Sports and Health, Shandong Sport University, Jinan, China
| | - Dongmei Li
- Department of Microbiology and Immunology, Georgetown University Medical Center, Washington, DC, United States
| | - Richard Calderone
- Department of Microbiology and Immunology, Georgetown University Medical Center, Washington, DC, United States
| | - Bo Sui
- School of Sports and Health, Shandong Sport University, Jinan, China
| | - Xuewen Tian
- School of Sports and Health, Shandong Sport University, Jinan, China
| | - Xiangjing Meng
- Shandong Academy of Pharmaceutical Science, Jinan, China
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Farzanegi P, Dana A, Ebrahimpoor Z, Asadi M, Azarbayjani MA. Mechanisms of beneficial effects of exercise training on non-alcoholic fatty liver disease (NAFLD): Roles of oxidative stress and inflammation. Eur J Sport Sci 2019; 19:994-1003. [PMID: 30732555 DOI: 10.1080/17461391.2019.1571114] [Citation(s) in RCA: 238] [Impact Index Per Article: 39.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disorder which is associated with accumulation of fats in the liver. It causes a wide variety of pathological effects such as non-alcoholic steatohepatitis (NASH) and cirrhosis, insulin resistance, obesity, hypertension, dyslipidaemia, diabetes and cardiovascular disease. The molecular mechanisms that cause the initiation and progression of NAFLD are not fully understood. Oxidative stress (OS) induced by reactive oxygen species (ROS) and inflammation are likely a significant mechanism which can lead to hepatic cell death and tissue injury. Mitochondrial abnormalities, down-regulation of several antioxidant enzymes, glutathione (GSH) depletion and decreased activity of GSH-dependent antioxidants, accumulation of leukocytes and hepatic inflammation are the major sources of ROS overproduction in NAFLD. Excessive production of ROS suppresses the capacity of other antioxidant defence systems in NAFLD and causes further oxidative damage. Regular exercise can be considered as an effective strategy for treatment of NAFLD. It improves NAFLD by reducing intrahepatic fat content, increasing β-oxidation of fatty acids, inducing hepato-protective autophagy, overexpressing peroxisome proliferator-activated receptor- γ (PPAR-γ), as well as attenuating hepatocyte apoptosis and increasing insulin sensitivity. Exercise training also suppresses ROS overproduction and OS in NAFLD via up-regulation of several antioxidant enzymes and anti-inflammatory mediators. Therefore, an understanding of these molecules and signalling pathways gives us valuable information about NAFLD progression and a method for developing a suitable clinical treatment. This review aimed to evaluate sources of ROS and OS in NAFLD and the molecular mechanisms involved in the beneficial effects of exercises on NAFLD.
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Affiliation(s)
- Parvin Farzanegi
- a Department of Exercise Physiology, Sari Branch , Islamic Azad University , Sari , Iran
| | - Amir Dana
- b Department of Physical Education, Tabriz Branch , Islamic Azad University , Tabriz , Iran
| | - Zeynab Ebrahimpoor
- c Department of Exercise Physiology, Qaemshahr Branch , Islamic Azad University , Qaemshahr , Iran
| | - Mahdieh Asadi
- a Department of Exercise Physiology, Sari Branch , Islamic Azad University , Sari , Iran
| | - Mohammad Ali Azarbayjani
- d Department of Exercise Physiology , Islamic Azad University, Central Tehran Branch , Tehran , Iran
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Mohammadzadeh A, Shahkarami V, Shakiba M, Sabetrasekh P, Mohammadzadeh M. Association of Non-Alcoholic Fatty Liver Disease with Increased Carotid Intima-Media Thickness Considering Other Cardiovascular Risk Factors. IRANIAN JOURNAL OF RADIOLOGY 2019; 16. [DOI: 10.5812/iranjradiol.14260] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Hajighasem A, Farzanegi P, Mazaheri Z. Effects of combined therapy with resveratrol, continuous and interval exercises on apoptosis, oxidative stress, and inflammatory biomarkers in the liver of old rats with non-alcoholic fatty liver disease. Arch Physiol Biochem 2019; 125:142-149. [PMID: 29463133 DOI: 10.1080/13813455.2018.1441872] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
CONTEXT Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder. OBJECTIVE Effects of combined therapy with resveratrol, interval and continuous exercises on oxidative stress, inflammation, and apoptosis in the liver of rats with NAFLD. METHODS NAFLD rats were organised in patient, saline, resveratrol (RSV), continuous exercise, interval exercise, continuous exercise + RSV, and interval exercise + RSV groups. RESULTS Resveratrol supplementation alone or in combination with interval and continuous training significantly decreased malondialdehyde and TNF-α level (p < .05), while the levels of catalase; superoxide dismutase and IL-10 were significantly increased (p < .05). Although RSV alone significantly decreased the percentage of apoptotic cells (17.12%), its combination with interval (10.74%), and continuous (14.85%) exercise training demonstrated higher anti-apoptotic activity (p < .05). CONCLUSIONS Although resveratrol alone has an antioxidant, anti-apoptotic and anti-inflammatory properties, combined therapy with interval, and continuous training can be more effective to mitigate these abnormalities in NAFLD patients.
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Affiliation(s)
- Amir Hajighasem
- a Department of Exercise Physiology, Sari Branch , Islamic Azad University , Sari , Iran
| | - Parvin Farzanegi
- a Department of Exercise Physiology, Sari Branch , Islamic Azad University , Sari , Iran
| | - Zohreh Mazaheri
- b Department of Anatomical Sciences, Faculty of Medical Sciences , Tarbiat Modares University , Tehran , Iran
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Noncontrast Chest Computed Tomographic Imaging of Obesity and the Metabolic Syndrome. J Thorac Imaging 2019; 34:116-125. [DOI: 10.1097/rti.0000000000000391] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
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10
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Noncontrast Chest Computed Tomographic Imaging of Obesity and the Metabolic Syndrome. J Thorac Imaging 2019; 34:126-135. [DOI: 10.1097/rti.0000000000000393] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
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Hajighasem A, Farzanegi P, Mazaheri Z, Naghizadeh M, Salehi G. Effects of resveratrol, exercises and their combination on Farnesoid X receptor, Liver X receptor and Sirtuin 1 gene expression and apoptosis in the liver of elderly rats with nonalcoholic fatty liver. PeerJ 2018; 6:e5522. [PMID: 30221089 PMCID: PMC6136396 DOI: 10.7717/peerj.5522] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2018] [Accepted: 08/04/2018] [Indexed: 12/17/2022] Open
Abstract
Background Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder. This study aims to consider effects of resveratrol, exercise and their combination on Farnesoid X receptor (Fxr), the liver X receptor (Lxr) and Sirtuin 1 (Sirt 1) genes expression in the liver of elderly rats with NAFLD. Methods Rats with NAFLD were randomly divided into seven groups including patient, saline, resveratrol (RSV), interval exercise, continuous exercise, interval exercise + RSV and continuous exercise + RSV. Levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) in the liver tissue were measured using specific ELISA kits. A TUNEL assay kit was used for the assessment of hepatic cells apoptosis. Lipid profiles were considered by measuring the serum triglyceride, cholesterol, LDL, and HDL. Expression of Sirt1, Lxr and Fxr genes was considered using RT-PCR. Results Resveratrol administration alone or combined with exercise training significantly improved the expression of Sirt1, Lxr and Fxr genes (p < 0.05) in the hepatic tissue of rats with NAFLD, while levels of AST, ALT, ALP enzymes, as well as apoptotic cells were significantly decreased (p < 0.05). Discussion Although resveratrol alone improves the expression of Sirt1, Lxr and Fxr, as well as liver function, combined therapy with exercise training is more effective to improve NAFLD.
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Affiliation(s)
- Amir Hajighasem
- Department of Exercise Physiology, Sari Branch, Islamic Azad University, Sari, Iran
| | - Parvin Farzanegi
- Department of Exercise Physiology, Sari Branch, Islamic Azad University, Sari, Iran
| | - Zohreh Mazaheri
- Department of Anatomical Sciences, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Marjan Naghizadeh
- Department of Exercise Physiology, Sari Branch, Islamic Azad University, Sari, Iran
| | - Ghoncheh Salehi
- Department of Exercise Physiology, Sari Branch, Islamic Azad University, Sari, Iran
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Guillen Sacoto MJ, Martinez AF, Abe Y, Kruszka P, Weiss K, Everson JL, Bataller R, Kleiner DE, Ward JM, Sulik KK, Lipinski RJ, Solomon BD, Muenke M. Human germline hedgehog pathway mutations predispose to fatty liver. J Hepatol 2017; 67. [PMID: 28645738 PMCID: PMC5613974 DOI: 10.1016/j.jhep.2017.06.008] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND & AIMS Non-alcoholic fatty liver disease (NAFLD) is the most common form of liver disease. Activation of hedgehog (Hh) signaling has been implicated in the progression of NAFLD and proposed as a therapeutic target; however, the effects of Hh signaling inhibition have not been studied in humans with germline mutations that affect this pathway. METHODS Patients with holoprosencephaly (HPE), a disorder associated with germline mutations disrupting Sonic hedgehog (SHH) signaling, were clinically evaluated for NAFLD. A combined mouse model of Hh signaling attenuation (Gli2 heterozygous null: Gli2+/-) and diet-induced NAFLD was used to examine aspects of NAFLD and hepatic gene expression profiles, including molecular markers of hepatic fibrosis and inflammation. RESULTS Patients with HPE had a higher prevalence of liver steatosis compared to the general population, independent of obesity. Exposure of Gli2+/- mice to fatty liver-inducing diets resulted in increased liver steatosis compared to wild-type mice. Similar to humans, this effect was independent of obesity in the mutant mice and was associated with decreased expression of pro-fibrotic and pro-inflammatory genes, and increased expression of PPARγ, a potent anti-fibrogenic and anti-inflammatory regulator. Interestingly, tumor suppressors p53 and p16INK4 were found to be downregulated in the Gli2+/- mice exposed to a high-fat diet. CONCLUSIONS Our results indicate that germline mutations disrupting Hh signaling promotes liver steatosis, independent of obesity, with reduced fibrosis. While Hh signaling inhibition has been associated with a better NAFLD prognosis, further studies are required to evaluate the long-term effects of mutations affecting this pathway. Lay summary: Non-alcoholic fatty liver disease (NAFLD) is characterized by excess fat deposition in the liver predominantly due to high calorie intake and a sedentary lifestyle. NAFLD progression is usually accompanied by activation of the Sonic hedgehog (SHH) pathway leading to fibrous buildup (scar tissue) and inflammation of the liver tissue. For the first time patients with holoprosencephaly, a disease caused by SHH signaling mutations, are shown to have increased liver steatosis independent of obesity. This observation was recapitulated in a mouse model of attenuated SHH signaling that also showed increased liver steatosis but with decreased fibrosis and inflammation. While SHH inhibition is associated with a good NAFLD prognosis, this increase in liver fat accumulation in the context of SHH signaling inhibition must be studied prospectively to evaluate its long-term effects, especially in individuals with Western-type dietary habits.
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Affiliation(s)
| | - Ariel F. Martinez
- National Human Genome Research Institute, National Institutes of Health, Bethesda, MD
| | - Yu Abe
- National Human Genome Research Institute, National Institutes of Health, Bethesda, MD
| | - Paul Kruszka
- National Human Genome Research Institute, National Institutes of Health, Bethesda, MD
| | - Karin Weiss
- National Human Genome Research Institute, National Institutes of Health, Bethesda, MD
| | - Joshua L. Everson
- Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI
| | - Ramon Bataller
- Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina at Chapel Hill, NC
| | - David E. Kleiner
- Laboratory of Pathology, National Cancer Institute, Bethesda, MD
| | | | - Kathleen K. Sulik
- Carolina Institute for Developmental Disabilities, University of North Carolina, Chapel Hill, NC; Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC,Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, NC
| | - Robert J. Lipinski
- Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI
| | - Benjamin D. Solomon
- National Human Genome Research Institute, National Institutes of Health, Bethesda, MD,Division of Medical Genomics, Inova Translational Medicine Institute, Falls Church, VA; Department of Pediatrics, Inova Children’s Hospital and Virginia Commonwealth University School of Medicine, Falls Church, VA,GeneDx, Gaithersburg, MD
| | - Maximilian Muenke
- National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United States.
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Accuracy of Liver Fat Quantification With Advanced CT, MRI, and Ultrasound Techniques: Prospective Comparison With MR Spectroscopy. AJR Am J Roentgenol 2016; 208:92-100. [PMID: 27726414 DOI: 10.2214/ajr.16.16565] [Citation(s) in RCA: 163] [Impact Index Per Article: 18.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVE The purpose of this study was to prospectively evaluate the accuracy of proton-density fat-fraction, single- and dual-energy CT (SECT and DECT), gray-scale ultrasound (US), and US shear-wave elastography (US-SWE) in the quantification of hepatic steatosis with MR spectroscopy (MRS) as the reference standard. SUBJECTS AND METHODS Fifty adults who did not have symptoms (23 men, 27 women; mean age, 57 ± 5 years; body mass index, 27 ± 5) underwent liver imaging with un-enhanced SECT, DECT, gray-scale US, US-SWE, proton-density fat-fraction MRI, and MRS for this prospective trial. MRS voxels for the reference standard were colocalized with all other modalities under investigation. For SECT (120 kVp), attenuation values were recorded. For rapid-switching DECT (80/140 kVp), monochromatic images (70-140 keV) and fat density-derived material decomposition images were reconstructed. For proton-density fat fraction MRI, a quantitative chemical shift-encoded method was used. For US, echogenicity was evaluated on a qualitative 0-3 scale. Quantitative US shear-wave velocities were also recorded. Data were analyzed by linear regression for each technique compared with MRS. RESULTS There was excellent correlation between MRS and both proton-density fat-fraction MRI (r2 = 0.992; slope, 0.974; intercept, -0.943) and SECT (r2 = 0.856; slope, -0.559; intercept, 35.418). DECT fat attenuation had moderate correlation with MRS measurements (r2 = 0.423; slope, 0.034; intercept, 8.459). There was good correlation between qualitative US echogenicity and MRS measurements with a weighted kappa value of 0.82. US-SWE velocity did not have reliable correlation with MRS measurements (r2 = 0.004; slope, 0.069; intercept, 6.168). CONCLUSION Quantitative MRI proton-density fat fraction and SECT fat attenuation have excellent linear correlation with MRS measurements and can serve as accurate noninvasive biomarkers for quantifying steatosis. Material decomposition with DECT does not improve the accuracy of fat quantification over conventional SECT attenuation. US-SWE has poor accuracy for liver fat quantification.
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Kwon KA, Chun P, Park JH. Clinical significance of serum alanine aminotransferase and lifestyle intervention in children with nonalcoholic fatty liver disease. KOREAN JOURNAL OF PEDIATRICS 2016; 59:362-367. [PMID: 27721840 PMCID: PMC5052134 DOI: 10.3345/kjp.2016.59.9.362] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/25/2012] [Revised: 02/07/2016] [Accepted: 04/06/2016] [Indexed: 12/19/2022]
Abstract
Purpose This study aimed to investigate the clinical significance of serum alanine aminotransferase (ALT) levels in children with nonalcoholic fatty liver disease (NAFLD) and the effect of lifestyle intervention on NAFLD. Methods The clinical data of 86 children diagnosed with NAFLD were reviewed retrospectively. Forty-six patients belonged to the elevated ALT group and 40 to the normal ALT group. The clinical parameters of patients with NAFLD were also compared based on the status of ALT levels after lifestyle intervention. Results Patients with elevated ALT had significantly higher body mass index (BMI) scores than those with normal ALT (P<0.05). Of all the patients with elevated ALT, 89% exhibited moderate or severe degree of fatty change in the liver on ultrasonographic examination, whereas most patients with normal ALT exhibited mild or moderate degree changes. Liver biopsy was performed in 15 children with elevated ALT and all showed mild histological changes. Of all patients with elevated ALT, 49% achieved normal ALT levels after lifestyle intervention. Those with more severe histological changes tended to have continuously increasing ALT levels. There was no correlation between the normalization of posttreatment ALT level and BMI, as well as ultrasonographic findings at diagnosis. Conclusion ALT elevation in NAFLD is highly associated with higher BMI scores and more severe degree of fatty changes on ultrasonographic examination. Lifestyle intervention can significantly improve ALT in children with NAFLD. The degree of histologic changes appears to be a predictor of the treatment response to NAFLD.
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Affiliation(s)
- Kyoung Ah Kwon
- Department of Pediatrics, Pusan National University School of Medicine, Busan, Korea
| | - Peter Chun
- Department of Pediatrics, Pusan National University School of Medicine, Busan, Korea
| | - Jae Hong Park
- Department of Pediatrics, Pusan National University School of Medicine, Busan, Korea
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15
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Achmad E, Yokoo T, Hamilton G, Heba ER, Hooker JC, Changchien C, Schroeder M, Wolfson T, Gamst A, Schwimmer JB, Lavine JE, Sirlin CB, Middleton MS. Feasibility of and agreement between MR imaging and spectroscopic estimation of hepatic proton density fat fraction in children with known or suspected nonalcoholic fatty liver disease. ACTA ACUST UNITED AC 2016. [PMID: 26205992 DOI: 10.1007/s00261-015-0506-9] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
PURPOSE To assess feasibility of and agreement between magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) for estimating hepatic proton density fat fraction (PDFF) in children with known or suspected nonalcoholic fatty liver disease (NAFLD). MATERIALS AND METHODS Children were included in this study from two previous research studies in each of which three MRI and three MRS acquisitions were obtained. Sequence acceptability, and MRI- and MRS-estimated PDFF were evaluated. Agreement of MRI- with MRS-estimated hepatic PDFF was assessed by linear regression and Bland-Altman analysis. Age, sex, BMI-Z score, acquisition time, and artifact score effects on MRI- and MRS-estimated PDFF agreement were assessed by multiple linear regression. RESULTS Eighty-six children (61 boys and 25 girls) were included in this study. Slope and intercept from regressing MRS-PDFF on MRI-PDFF were 0.969 and 1.591%, respectively, and the Bland-Altman bias and 95% limits of agreement were 1.17% ± 2.61%. MRI motion artifact score was higher in boys than girls (by 0.21, p = 0.021). Higher BMI-Z score was associated with lower agreement between MRS and MRI (p = 0.045). CONCLUSION Hepatic PDFF estimation by both MRI and MRS is feasible, and MRI- and MRS-estimated PDFF agree closely in children with known or suspected NAFLD.
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Affiliation(s)
- Emil Achmad
- Liver Imaging Group, Department of Radiology, School of Medicine, University of California, San Diego, San Diego, CA, USA
| | - Takeshi Yokoo
- Liver Imaging Group, Department of Radiology, School of Medicine, University of California, San Diego, San Diego, CA, USA
- Department of Radiology and Advanced Imaging Research Center, UT Southwestern School of Medicine, Dallas, TX, USA
| | - Gavin Hamilton
- Liver Imaging Group, Department of Radiology, School of Medicine, University of California, San Diego, San Diego, CA, USA
| | - Elhamy R Heba
- Liver Imaging Group, Department of Radiology, School of Medicine, University of California, San Diego, San Diego, CA, USA
| | - Jonathan C Hooker
- Liver Imaging Group, Department of Radiology, School of Medicine, University of California, San Diego, San Diego, CA, USA
| | - Christopher Changchien
- Liver Imaging Group, Department of Radiology, School of Medicine, University of California, San Diego, San Diego, CA, USA
| | - Michael Schroeder
- Liver Imaging Group, Department of Radiology, School of Medicine, University of California, San Diego, San Diego, CA, USA
| | - Tanya Wolfson
- Computational and Applied Statistics Laboratory (CASL), San Diego Supercomputing Center (SDSC), University of California, San Diego, San Diego, CA, USA
| | - Anthony Gamst
- Computational and Applied Statistics Laboratory (CASL), San Diego Supercomputing Center (SDSC), University of California, San Diego, San Diego, CA, USA
| | - Jeffrey B Schwimmer
- Liver Imaging Group, Department of Radiology, School of Medicine, University of California, San Diego, San Diego, CA, USA
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, School of Medicine, University of California, San Diego, San Diego, CA, USA
- Department of Gastroenterology, Rady Children's Hospital San Diego, San Diego, CA, USA
| | - Joel E Lavine
- Department of Pediatrics, Columbia University, New York, NY, USA
| | - Claude B Sirlin
- Liver Imaging Group, Department of Radiology, School of Medicine, University of California, San Diego, San Diego, CA, USA
| | - Michael S Middleton
- Liver Imaging Group, Department of Radiology, School of Medicine, University of California, San Diego, San Diego, CA, USA.
- UCSD Department of Radiology, UCSD MRI Institute, 410 West Dickinson Street, San Diego, CA, 92103-8749, USA.
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Africa JA, Newton KP, Schwimmer JB. Lifestyle Interventions Including Nutrition, Exercise, and Supplements for Nonalcoholic Fatty Liver Disease in Children. Dig Dis Sci 2016; 61:1375-86. [PMID: 27041377 PMCID: PMC4848041 DOI: 10.1007/s10620-016-4126-1] [Citation(s) in RCA: 71] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2016] [Accepted: 03/06/2016] [Indexed: 02/07/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease among children. Lifestyle interventions, such as diet and exercise, are frequently recommended. Children with NAFLD have a distinct physiology that is different from obesity alone and has the potential to influence lifestyle treatments. Studies of diet alone in the treatment of pediatric NAFLD have focused on sugar and carbohydrate, but did not indicate any one dietary approach that was superior to another. For children who are obese and have NAFLD, weight loss may have a beneficial effect regardless of the diet used. Exercise is widely believed to improve NAFLD because a sedentary lifestyle, poor aerobic fitness, and low muscle mass are all risk factors for NAFLD. However, there have been no randomized controlled trials of exercise as a treatment for children with NAFLD. Studies of the combination of diet and exercise suggest a potential for improvement in serum alanine aminotransferase activity and/or magnetic resonance imaging liver fat fraction with intervention. There is also enthusiasm for the use of dietary supplements; however, studies in children have shown inconsistent effects of vitamin E, fish oil, and probiotics. This review presents the available data from studies of lifestyle intervention and dietary supplements published to date and highlights challenges that must be addressed in order to advance the evidence base for the treatment of pediatric NAFLD.
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Bannas P, Kramer H, Hernando D, Agni R, Cunningham AM, Mandal R, Motosugi U, Sharma SD, del Rio AM, Fernandez L, Reeder SB. Quantitative magnetic resonance imaging of hepatic steatosis: Validation in ex vivo human livers. Hepatology 2015; 62. [PMID: 26224591 PMCID: PMC4652324 DOI: 10.1002/hep.28012] [Citation(s) in RCA: 118] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
UNLABELLED Emerging magnetic resonance imaging (MRI) biomarkers of hepatic steatosis have demonstrated tremendous promise for accurate quantification of hepatic triglyceride concentration. These methods quantify the proton density fat-fraction (PDFF), which reflects the concentration of triglycerides in tissue. Previous in vivo studies have compared MRI-PDFF with histologic steatosis grading for assessment of hepatic steatosis. However, the correlation of MRI-PDFF with the underlying hepatic triglyceride content remained unknown. The aim of this ex vivo study was to validate the accuracy of MRI-PDFF as an imaging biomarker of hepatic steatosis. Using ex vivo human livers, we compared MRI-PDFF with magnetic resonance spectroscopy-PDFF (MRS-PDFF), biochemical triglyceride extraction, and histology as three independent reference standards. A secondary aim was to compare the precision of MRI-PDFF relative to biopsy for the quantification of hepatic steatosis. MRI-PDFF was prospectively performed at 1.5 Tesla in 13 explanted human livers. We performed colocalized paired evaluation of liver fat content in all nine Couinaud segments using single-voxel MRS-PDFF (n=117) and tissue wedges for biochemical triglyceride extraction (n=117), and five core biopsies performed in each segment for histologic grading (n=585). Accuracy of MRI-PDFF was assessed through linear regression with MRS-PDFF, triglyceride extraction, and histology. Intraobserver agreement, interobserver agreement, and repeatability of MRI-PDFF and histologic grading were assessed through Bland-Altman analyses. MRI-PDFF showed an excellent correlation with MRS-PDFF (r=0.984, confidence interval 0.978-0.989) and strong correlation with histology (r=0.850, confidence interval 0.791-0.894) and triglyceride extraction (r=0.871, confidence interval 0.818-0.909). Intraobserver agreement, interobserver agreement, and repeatability showed a significantly smaller variance for MRI-PDFF than for histologic steatosis grading (all P<0.001). CONCLUSION MRI-PDFF is an accurate, precise, and reader-independent noninvasive imaging biomarker of liver triglyceride content, capable of steatosis quantification over the entire liver.
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Affiliation(s)
- Peter Bannas
- Department of Radiology, University of Wisconsin-Madison, Madison, WI,Department of Radiology, University Hospital Hamburg-Eppendorf, Hamburg, Germany,Contact Information: Scott B. Reeder, M.D., Ph.D., Department of Radiology, University of Wisconsin-Madison, 600 Highland Avenue, Room E1/372, Madison, WI 53792–3252, Phone (608) 698-6121,
| | - Harald Kramer
- Department of Radiology, University of Wisconsin-Madison, Madison, WI,Department of Radiology, Ludwig-Maximilians-University Hospital, Munich, Germany,Contact Information: Scott B. Reeder, M.D., Ph.D., Department of Radiology, University of Wisconsin-Madison, 600 Highland Avenue, Room E1/372, Madison, WI 53792–3252, Phone (608) 698-6121,
| | - Diego Hernando
- Department of Radiology, University of Wisconsin-Madison, Madison, WI
| | - Rashmi Agni
- Department of Pathology, University of Wisconsin-Madison, Madison, WI
| | | | - Rakesh Mandal
- Department of Pathology, University of Wisconsin-Madison, Madison, WI
| | - Utaroh Motosugi
- Department of Radiology, University of Wisconsin-Madison, Madison, WI
| | - Samir D. Sharma
- Department of Radiology, University of Wisconsin-Madison, Madison, WI
| | | | - Luis Fernandez
- Department of Surgery, University of Wisconsin-Madison, Madison, WI
| | - Scott B. Reeder
- Department of Radiology, University of Wisconsin-Madison, Madison, WI,Department of Medical Physics, University of Wisconsin-Madison, Madison, WI,Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI,Department of Medicine, University of Wisconsin-Madison, Madison, WI,Department of Emergency Medicine, University of Wisconsin-Madison, Madison, WI
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18
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Rehm JL, Wolfgram PM, Hernando D, Eickhoff JC, Allen DB, Reeder SB. Proton density fat-fraction is an accurate biomarker of hepatic steatosis in adolescent girls and young women. Eur Radiol 2015; 25:2921-30. [PMID: 25916386 PMCID: PMC4564339 DOI: 10.1007/s00330-015-3724-1] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2014] [Revised: 03/18/2015] [Accepted: 03/19/2015] [Indexed: 02/07/2023]
Abstract
OBJECTIVES To compare complex quantitative magnetic resonance imaging (MRI) with MR spectroscopy (MRS) for quantification of hepatic steatosis (HS) and determine clinically significant MRI-based thresholds of HS in female youths. METHODS This prospective, cross-sectional study was conducted in 132 healthy females (11-22 years, mean 13.3 ± 2). Proton density fat-fraction (PDFF) was measured using complex quantitative MRI and MRS. Body mass index (BMI), fasting labs [glucose, insulin, alanine aminotransferase (ALT), and other metabolic markers] were obtained. Outcomes were measured using regression analysis, Spearman-rank correlation, and receiver operator characteristics (ROC) analysis. HS was defined as MRI-PDFF >5.6%. RESULTS HS was detected by MRI-PDFF in 15% of all subjects. Linear regression demonstrated excellent correlation and agreement [r(2) = 0.96, slope = 0.97 (95 %CI: 0.94-1.00), intercept = 0.78% (95 %CI: 0.58-0.98%)] between MRI-PDFF and MRS-PDFF. MRI-PDFF had a sensitivity of 100% (95 %CI: 0.79-1.00), specificity of 96.6% (95 %CI: 0.91-0.99), and a kappa index of 87% (95 %CI: 0.75-0.99) for identifying HS. In overweight subjects with HS, MRI-PDFF correlated with ALT (r = 0.84, p < 0.0001) and insulin (r = 0.833, p < 0.001), but not with BMI or WC. ROC analysis ascertained an optimal MRI-PDFF threshold of 3.5% for predicting metabolic syndrome (sensitivity = 76 %, specificity = 83 %). CONCLUSION Complex quantitative MRI demonstrates strong correlation and agreement with MRS to quantify hepatic triglyceride content in adolescent girls and young women. A low PDFF threshold is predictive of metabolic syndrome in this population. KEY POINTS • Confounder-corrected quantitative MRI (ccqMRI) effectively measures hepatic triglyceride content in adolescent girls. • MRS and ccqMRI strongly correlate in liver proton density fat-fraction (PDFF) detection. • A PDFF threshold of 3.5% may be predictive of paediatric metabolic syndrome.
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Affiliation(s)
- Jennifer L Rehm
- Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Madison, WI, 53715-4108, USA,
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Schwimmer JB, Middleton MS, Behling C, Newton KP, Awai HI, Paiz MN, Lam J, Hooker JC, Hamilton G, Fontanesi J, Sirlin CB. Magnetic resonance imaging and liver histology as biomarkers of hepatic steatosis in children with nonalcoholic fatty liver disease. Hepatology 2015; 61:1887-95. [PMID: 25529941 PMCID: PMC4670559 DOI: 10.1002/hep.27666] [Citation(s) in RCA: 136] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2014] [Accepted: 12/13/2014] [Indexed: 12/12/2022]
Abstract
UNLABELLED Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children. In order to advance the field of NAFLD, noninvasive imaging methods for measuring liver fat are needed. Advanced magnetic resonance imaging (MRI) has shown great promise for the quantitative assessment of hepatic steatosis but has not been validated in children. Therefore, this study was designed to evaluate the correlation and diagnostic accuracy of MRI-estimated liver proton density fat fraction (PDFF), a biomarker for hepatic steatosis, compared to histologic steatosis grade in children. The study included 174 children with a mean age of 14.0 years. Liver PDFF estimated by MRI was significantly (P < 0.01) correlated (0.725) with steatosis grade. The correlation of MRI-estimated liver PDFF and steatosis grade was influenced by both sex and fibrosis stage. The correlation was significantly (P < 0.01) stronger in girls (0.86) than in boys (0.70). The correlation was significantly (P < 0.01) weaker in children with stage 2-4 fibrosis (0.61) than children with no fibrosis (0.76) or stage 1 fibrosis (0.78). The diagnostic accuracy of commonly used threshold values to distinguish between no steatosis and mild steatosis ranged from 0.69 to 0.82. The overall accuracy of predicting the histologic steatosis grade from MRI-estimated liver PDFF was 56%. No single threshold had sufficient sensitivity and specificity to be considered diagnostic for an individual child. CONCLUSIONS Advanced magnitude-based MRI can be used to estimate liver PDFF in children, and those PDFF values correlate well with steatosis grade by liver histology. Thus, magnitude-based MRI has the potential for clinical utility in the evaluation of NAFLD, but at this time no single threshold value has sufficient accuracy to be considered diagnostic for an individual child.
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Affiliation(s)
- Jeffrey B. Schwimmer
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Diego School of Medicine, San Diego, California,Department of Gastroenterology, Rady Children’s Hospital San Diego, San Diego, California,Liver Imaging Group, Department of Radiology, University of California, San Diego School of Medicine, San Diego, California
| | - Michael S. Middleton
- Liver Imaging Group, Department of Radiology, University of California, San Diego School of Medicine, San Diego, California
| | - Cynthia Behling
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Diego School of Medicine, San Diego, California,Department of Pathology, Sharp Medical Center, San Diego, California
| | - Kimberly P. Newton
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Diego School of Medicine, San Diego, California,Department of Gastroenterology, Rady Children’s Hospital San Diego, San Diego, California
| | - Hannah I. Awai
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Diego School of Medicine, San Diego, California,Department of Gastroenterology, Rady Children’s Hospital San Diego, San Diego, California,Liver Imaging Group, Department of Radiology, University of California, San Diego School of Medicine, San Diego, California
| | - Melissa N. Paiz
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Diego School of Medicine, San Diego, California
| | - Jessica Lam
- Liver Imaging Group, Department of Radiology, University of California, San Diego School of Medicine, San Diego, California,School of Medicine, Loma Linda University, Loma Linda, California
| | - Jonathan C. Hooker
- Liver Imaging Group, Department of Radiology, University of California, San Diego School of Medicine, San Diego, California
| | - Gavin Hamilton
- Liver Imaging Group, Department of Radiology, University of California, San Diego School of Medicine, San Diego, California
| | - John Fontanesi
- Center for Management Science in Health, Division of General Internal Medicine, Department of Medicine, University of California, San Diego School of Medicine, La Jolla, California,Department of Family and Preventive Medicine, University of California, San Diego School of Medicine, La Jolla, California,Department of Pediatrics, University of California, San Diego School of Medicine, La Jolla, California
| | - Claude B. Sirlin
- Liver Imaging Group, Department of Radiology, University of California, San Diego School of Medicine, San Diego, California
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Abd El-Kader SM, El-Den Ashmawy EMS. Non-alcoholic fatty liver disease: The diagnosis and management. World J Hepatol 2015; 7:846-858. [PMID: 25937862 PMCID: PMC4411527 DOI: 10.4254/wjh.v7.i6.846] [Citation(s) in RCA: 259] [Impact Index Per Article: 25.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2014] [Revised: 11/26/2014] [Accepted: 01/19/2015] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is now the most frequent chronic liver disease that occurs across all age groups and is recognized to occur in 14%-30% of the general population, representing a serious and growing clinical problem due to the growing prevalence of obesity and overweight. Histologically, it resembles alcoholic liver injury but occurs in patients who deny significant alcohol consumption. NAFLD encompasses a spectrum of conditions, ranging from benign hepatocellular steatosis to inflammatory nonalcoholic steatohepatitis, fibrosis, and cirrhosis. The majority of hepatocellular lipids are stored as triglycerides, but other lipid metabolites, such as free fatty acids, cholesterol, and phospholipids, may also be present and play a role in disease progression. NAFLD is associated with obesity and insulin resistance and is considered the hepatic manifestation of the metabolic syndrome, a combination of medical conditions including type 2 diabetes mellitus, hypertension, hyperlipidemia, and visceral adiposity. Confirmation of the diagnosis of NAFLD can usually be achieved by imaging studies; however, staging the disease requires a liver biopsy. Current treatment relies on weight loss and exercise, although various insulin-sensitizing agents, antioxidants and medications appear promising. The aim of this review is to highlight the current information regarding epidemiology, diagnosis, and management of NAFLD as well as new information about pathogenesis, diagnosis and management of this disease.
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Guijarro de Armas MG, Monereo Megías S, Navea Aguilera C, Viveros MM, Vega Piñero MB. Non-alcoholic fatty liver in children and adolescents with excess weight and obesity. ACTA ACUST UNITED AC 2015. [DOI: 10.1016/j.medcle.2014.02.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
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[Non-alcoholic fatty liver in children and adolescents with excess weight and obesity]. Med Clin (Barc) 2014; 144:55-8. [PMID: 24768200 DOI: 10.1016/j.medcli.2014.02.018] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2013] [Revised: 02/13/2014] [Accepted: 02/20/2014] [Indexed: 11/21/2022]
Abstract
BASIS AND OBJECTIVE Hepatic steatosis, also known as non-alcoholic fatty liver (NAFL), is the most frequent liver disease in obese children. Due to an increase in infantile obesity, it is experiencing a significant increment in incidence. Our objetives are: Estimate the prevalence of NAFL in children with excess weight and obesity using the glutamate pyruvate transaminase (GPT) value as a biochemical test and an abdominal ultrasound, and correlate the presence of hepatic steatosis with various anthropometric and biochemical parameters. PATIENTS AND METHOD Cross-sectional prevalence study which includes children with excess weight and obesity between the ages of 5 and 15 years, between the years 2004-2012. The independent variables included were: age, sex, weight, size, body mass index (BMI), waist circumference (WC), waist size index (WSI), insulinemia, Homeostasis model assessment-insulin resistance (HOMA-R), total cholesterol, triglycerides (TG), high density lipoproteins (HDL), low density lipoproteins (LDL), glutamic-oxaloacetic transaminase (GOT), GPT and gamma-glutamyl transpeptidase (GGT). RESULTS One hundred and twenty-six patients, with an average age of 11.94 (3.12) years were recruited. A percentage of 19.66 of the patients presented elevated GPT pathology. Of the 126 abdominal ultrasounds performed, 38 patients presented hepatic steatosis (30.15%). The levels of insulinemia, HOMA-R and LDL were significantly higher in patients with altered GPT, compared to those with normal GPT values (P=.015, P=.008 and P=.002, respectively). The patients with an objective HGNA in ultrasound, also showed greater levels of insulinemia, WC, WSI, total cholesterol, TG, LDL, GLT, GPT and GGT than the patients with normal ultrasounds, thereby achieving statistical significance in insulinemia, HOMA-R, LDL and GPT values. CONCLUSIONS NAFL is a relatively frequent disorder in obese children and adolescents. In our study, 2 of 10 children -using GPT- and 3 of every 10 -using abdominal ultrasound- present the same. The biochemical marker which best defines it is an elevation in GPT. A modification in lifestyle which includes weight loss as a principal means of avoiding complications in adult life, is essential and necessary.
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Sundaram SS, Sokol RJ, Capocelli KE, Pan Z, Sullivan JS, Robbins K, Halbower AC. Obstructive sleep apnea and hypoxemia are associated with advanced liver histology in pediatric nonalcoholic fatty liver disease. J Pediatr 2014; 164:699-706.e1. [PMID: 24321532 PMCID: PMC4014349 DOI: 10.1016/j.jpeds.2013.10.072] [Citation(s) in RCA: 72] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2013] [Revised: 09/25/2013] [Accepted: 10/24/2013] [Indexed: 12/14/2022]
Abstract
OBJECTIVE To determine whether obstructive sleep apnea (OSA) and/or nocturnal hypoxemia are associated with the severity of liver injury in patients with pediatric nonalcoholic fatty liver disease (NAFLD). STUDY DESIGN Obese children aged 10-18 years with liver biopsy-proven NAFLD were enrolled. Demographic, clinical, and laboratory data were collected, polysomnography was performed, and liver histology was scored. Subjects were divided into those with OSA/hypoxemia and those without OSA/hypoxemia for analysis. RESULTS Of 25 subjects with NAFLD, OSA/hypoxemia was present in 15 (60%) (mean age, 12.8 ± 1.9 years; 68% male; 88% Hispanic; mean body mass index z-score, 2.3 ± 0.3). Subjects with and without OSA/hypoxemia had similar levels of serum aminotransferases, serum lipids, and inflammatory and insulin resistance markers. Although there were no differences between groups in the histological severity of steatosis, inflammation, ballooning degeneration, NAFLD activity score, or histological grade, subjects with OSA/hypoxemia had significantly more severe hepatic fibrosis. Moreover, oxygen saturation nadir during polysomnography was related to hepatic fibrosis stage (r = -0.49; P = .01) and aspartate aminotransferase level (r = 0.42; P < .05). Increasing percentage of time with oxygen saturation ≤90% was related to NAFLD inflammation grade (r = 0.44; P = .03), degree of hepatic steatosis (r = -0.50; P = .01), NAFLD activity score (r = 0.42; P = .04), aspartate aminotransferase level (r = 0.56; P = .004), and alanine aminotransferase level (r = 0.44; P = .03). CONCLUSION Moderate OSA/hypoxemia is common in pediatric patients with biopsy-proven NAFLD. OSA and the severity/duration of hypoxemia are associated with biochemical and histological measures of NAFLD severity.
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Affiliation(s)
- Shikha S. Sundaram
- Section of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics and the Digestive Health Institute, Children’s Hospital Colorado and University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO
| | - Ronald J. Sokol
- Section of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics and the Digestive Health Institute, Children’s Hospital Colorado and University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO
| | | | - Zhaoxing Pan
- Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, CO
| | - Jillian S. Sullivan
- Section of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics and the Digestive Health Institute, Children’s Hospital Colorado and University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO
| | - Kristen Robbins
- Section of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics and the Digestive Health Institute, Children’s Hospital Colorado and University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO
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Kühn JP, Hernando D, Mensel B, Krüger PC, Ittermann T, Mayerle J, Hosten N, Reeder SB. Quantitative chemical shift-encoded MRI is an accurate method to quantify hepatic steatosis. J Magn Reson Imaging 2013; 39:1494-501. [PMID: 24123655 DOI: 10.1002/jmri.24289] [Citation(s) in RCA: 72] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2013] [Accepted: 05/24/2013] [Indexed: 12/13/2022] Open
Abstract
PURPOSE To compare the accuracy of liver fat quantification using a three-echo chemical shift-encoded magnetic resonance imaging (MRI) technique without and with correction for confounders with spectroscopy (MRS) as the reference standard. MATERIALS AND METHODS Fifty patients (23 women, mean age 56.6 ± 13.2 years) with fatty liver disease were enrolled. Patients underwent T2-corrected single-voxel MRS and a three-echo chemical shift-encoded gradient echo (GRE) sequence at 3.0T. MRI fat fraction (FF) was calculated without and with T2* and T1 correction and multispectral modeling of fat and compared with MRS-FF using linear regression. RESULTS The spectroscopic range of liver fat was 0.11%-38.7%. Excellent correlation between MRS-FF and MRI-FF was observed when using T2* correction (R(2) = 0.96). With use of T2* correction alone, the slope was significantly different from 1 (1.16 ± 0.03, P < 0.001) and the intercept was different from 0 (1.14% ± 0.50%, P < 0.023). This slope was significantly different than 1.0 when no T1 correction was used (P = 0.001). When T2*, T1, and spectral complexity of fat were addressed, the results showed equivalence between fat quantification using MRI and MRS (slope: 1.02 ± 0.03, P = 0.528; intercept: 0.26% ± 0.46%, P = 0.572). CONCLUSION Complex three-echo chemical shift-encoded MRI is equivalent to MRS for quantifying liver fat, but only with correction for T2* decay and T1 recovery and use of spectral modeling of fat. This is necessary because T2* decay, T1 recovery, and multispectral complexity of fat are processes which may otherwise bias the measurements.
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Affiliation(s)
- Jens-Peter Kühn
- Department of Radiology and Neuroradiology, Ernst Moritz Arndt University, Greifswald, Germany
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Akın L, Kurtoglu S, Yikilmaz A, Kendirci M, Elmalı F, Mazicioglu M. Fatty liver is a good indicator of subclinical atherosclerosis risk in obese children and adolescents regardless of liver enzyme elevation. Acta Paediatr 2013. [PMID: 23190373 DOI: 10.1111/apa.12099] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
AIM To investigate the presence of association between nonalcoholic fatty liver disease (NAFLD) and subclinical atherosclerosis using carotid intima media thickness (c-IMT) in obese children and adolescents. Additionally, we wished to investigate the relationship between fatty liver and elevated liver enzymes. METHODS A total of 157 obese patients (78 boys and 79 girls, mean age: 11.3 ± 2.6 years, age range: 6-16 years) were enrolled in the study. Aminotransferase, fasting glucose and lipid levels were determined. An oral glucose tolerance test was performed. The c-IMT was measured. Infectious and metabolic causes of elevated liver enzymes were excluded. The diagnosis of NAFLD was based on ultrasound scan. RESULTS Obese patients with NAFLD had markedly increased carotid IMT (mean: 0.48 mm, 95% CI: 0.47-0.49) than those without NAFLD (mean: 0.45 mm 95% CI: 0.44-0.45, p < 0.001). The presence of NAFLD significantly increased c-IMT whether the patient had elevated liver enzyme or not (ANOVA, p < 0.001). In a multiple-regression model, only the presence of NAFLD was associated with increased c-IMT (β = 0.031, SE (β) = 0.008, p < 0.001). CONCLUSION Obese children and adolescents with NAFLD are at risk of early atherosclerotic changes. As liver function tests are not sufficient to identify patients with fatty liver, ultrasonographic evaluation of NAFLD might be considered in all obese children and adolescents.
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Affiliation(s)
- Leyla Akın
- Department of Pediatric Endocrinology; Faculty of Medicine; Erciyes University; Kayseri; Turkey
| | - Selim Kurtoglu
- Department of Pediatric Endocrinology; Faculty of Medicine; Erciyes University; Kayseri; Turkey
| | - Ali Yikilmaz
- Department of Pediatric Radiology; Faculty of Medicine; Erciyes University; Kayseri; Turkey
| | - Mustafa Kendirci
- Department of Pediatric Endocrinology; Faculty of Medicine; Erciyes University; Kayseri; Turkey
| | - Ferhan Elmalı
- Department of Biostatistics; Faculty of Medicine; Erciyes University; Kayseri; Turkey
| | - Mümtaz Mazicioglu
- Department of Family Medicine; Faculty of Medicine; Erciyes University; Kayseri; Turkey
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26
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Hudson OD, Nunez M, Shaibi GQ. Ethnicity and elevated liver transaminases among newly diagnosed children with type 2 diabetes. BMC Pediatr 2012; 12:174. [PMID: 23134937 PMCID: PMC3534506 DOI: 10.1186/1471-2431-12-174] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2012] [Accepted: 10/25/2012] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND To examine the influence of ethnicity on liver transaminases among adolescents with type 2 diabetes mellitus (T2DM). METHODS A retrospective medical chart review of 57 (30 males and 27 females) newly diagnosed patients with T2DM. Ethnicity was determined by self-report and height, weight, body mass index (BMI) and glycosylated hemoglobin (HbA1c) were obtained using standard clinical procedures. Fasting levels of alanine aminotransaminase (ALT) and aspartate aminotransferase (AST) were collected prior to the initiation of any therapy. RESULTS Age, gender, height, weight, BMI, and HbA1c did not differ between ethnic groups. Compared to African-Americans, Hispanics had significantly higher ALT (23.9 ± 3.4 vs. 107.8 ± 20.3, p=0.002) and AST (17.7 ± 2.5 vs. 71.1 ± 15.7, p<0.001) and were significantly more likely to have ALT values above the upper limit of normal (20% vs. 71%, p=0.005) and twice the upper limit of normal (0% vs. 39%, p=0.05) as well as AST values above the upper limit of normal (0% vs. 53%, p=0.002). No differences in ALT or AST were found between Hispanics and non-Hispanic whites or between African-Americans and non-Hispanic whites. CONCLUSIONS These preliminary findings suggest that Hispanic children with T2DM may be at higher risk for developing non-alcoholic fatty liver disease and indicate that a comprehensive hepatic evaluation is warranted in this population. Future studies that incorporate more precise and proximal measures of liver health are warranted in this population.
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Affiliation(s)
- Omar D Hudson
- Division of Pediatric Endocrinology and Diabetes, Phoenix Children's Hospital, Phoenix, AZ, USA
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Blomme B, Fitzpatrick E, Quaglia A, De Bruyne R, Dhawan A, Van Vlierberghe H. Serum protein N-glycosylation in paediatric non-alcoholic fatty liver disease. Pediatr Obes 2012; 7:165-73. [PMID: 22434757 DOI: 10.1111/j.2047-6310.2011.00024.x] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2011] [Revised: 11/11/2011] [Accepted: 11/24/2011] [Indexed: 12/23/2022]
Abstract
OBJECTIVE We have previously shown the potential of glycomics to distinguish patients with steatosis from patients with non-alcoholic steatohepatitis (NASH) in an adult population. The pattern of disease in paediatric patients is distinct from adults. The objective of this study was to characterize the N -glycomic profile of children with varying degrees of non-alcoholic fatty liver disease (NAFLD) and identify potential biomarker profiles of disease. METHODS Serum protein N-glycosylation patterns of 51 paediatric NAFLD patients were assessed with deoxyribonucleic acid sequencer-assisted fluorophore-assisted capillary electrophoresis and compared with histology. RESULTS Peak 1 (NGA2F) is the most significantly elevated N-glycan in paediatric NASH patients with peak 5 (NA2) demonstrating the largest decrease. The logarithmically transformed ratio of peak 1 to peak 5 was -0.85 (standard deviation [SD] 0.22) in patients with steatosis and borderline NASH and -0.73 (SD 0.12) in NASH (P = 0.02). The biomarker correlated well with the amount of lobular inflammation with a consistent increase of marker score in ascending stage of lobular inflammation. There was also a trend in differentiating patients with significant fibrosis ≥F2; -0.74 (SD 0.13) from patients with no/minimal fibrosis <F2; -0.86 (SD 0.24), P = 0.06. Analysis of the N-glycans on immunoglobulin G confirmed the undergalactosylation status typical for chronic inflammatory conditions. CONCLUSIONS This study is the first glycomic analysis performed in a paediatric NAFLD population. In agreement with the results obtained in adults, B cells play a dominant role in the N-glycan alterations of paediatric NASH patients.
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Affiliation(s)
- B Blomme
- Department of Hepatology and Gastroenterology, Ghent University Hospital, Ghent, Belgium.
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Kim JK, Chon NR, Lim HC, Lee KS, Han KH, Chon CY, Park YN, Paik YH. Transitional features of histologic type of non-alcoholic fatty liver disease in Korean young men. J Gastroenterol Hepatol 2012; 27:142-8. [PMID: 21883454 DOI: 10.1111/j.1440-1746.2011.06895.x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND AND AIM The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing in Korea as the dietary pattern and lifestyle become more Westernized and the obese population increases. The spectrum of NAFLD ranges from asymptomatic steatosis to non-alcoholic steatohepatitis (NASH) and cirrhosis. Schwimmer et al. divided NASH into three types according to the histological characteristics, such as adult type, pediatric type and overlap type. We investigated clinical and histologic features of NAFLD patients in Korean young men. METHODS A total of 64 male patients under age 30 years, diagnosed as NAFLD by a liver biopsy, were reviewed retrospectively. NASH was diagnosed by NAFLD activity score (NAS), and NASH patients were classified with Schwimmer's histological classification. RESULTS Pathological features of liver biopsy revealed NASH in most cases (59 cases, 92.2%) including 29 cases (45.3%) of borderline NASH and 30 cases (46.9%) of definite NASH. The definite NASH group showed significantly high aspartate aminotransferase/alanine aminotransferase levels compared to the borderline NASH group. There were four cases (6.8%) of pediatric type, 17 cases (28.8%) of adult type, and 38 cases (64.4%) of overlap type in the NASH group. NAS was 3.75 ± 0.05 in the pediatric type, 4.29 ± 1.16 in the adult type and 4.87 ± 1.21 in the overlap type, and the overlap type showed a higher NAS than the pediatric type. The fibrosis stage was significantly higher in the overlap type than the other types. CONCLUSION Most Korean young men with NAFLD turned out to have borderline or definite NASH. More than half of the NASH cases showed overlap type in Korean young men.
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Affiliation(s)
- Ja Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
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29
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Sanada Y, Urahashi T, Wakiya T, Okada N, Hishikawa S, Kawano Y, Ushijima K, Otomo S, Sakamoto K, Mizuta K. Non-alcoholic steatohepatitis caused by malnutrition after pediatric liver transplantation. Pediatr Int 2011; 53:1077-81. [PMID: 22181567 DOI: 10.1111/j.1442-200x.2011.03447.x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Affiliation(s)
- Yukihiro Sanada
- Department of Transplant Surgery, Jichi Medical University, Tochigi, Japan.
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Tannapfel A, Denk H, Dienes HP, Langner C, Schirmacher P, Trauner M, Flott-Rahmel B. Histopathological diagnosis of non-alcoholic and alcoholic fatty liver disease. VIRCHOWS ARCHIV : AN INTERNATIONAL JOURNAL OF PATHOLOGY 2011. [PMID: 21442288 DOI: 10.1007/s00428-011-1066-1]] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The diagnostic procedures in patients with suspected fatty liver disease-with or without known alcohol consumption-should be standardized and generally accepted. We therefore present a guideline, summarizing the current concepts of etiology, diagnostic as well as differential diagnostic of patients with fatty liver disease. Alcoholic as well as and non-alcoholic fatty liver are characterised by lipid deposition in hepatocytes. The diagnosis of steatosis is made when lipid deposition exceeds 5% of hepatocytes, while involvement of more than 50% is called "fatty liver". An additional inflammatory reaction leads to alcoholic (ASH) or non-alcoholic steatohepatitis (NASH). Steatohepatitis is present when both inflammatory infiltrates of mixed cells in the small liver lobules as well as liver cell injury in terms of ballooning can be detected. Liver biopsy represents the "golden standard" for confirming diagnosis and determining inflammatory activity and potential fibrosis of fatty liver disease. The differential diagnosis of ASH vs. NASH cannot be made on the basis of histological criteria alone. Steatosis, inflammatory changes and hepatocytic injury can be semiquantified as a "Brunt Score" or "NAS" (NAFLD activity score), providing the basis on which to decide whether or not steatohepatitis is present. People at increased risk of developing a fatty liver possess an increased risk of developing chemotherapy-associated steatohepatitis. Histologically, pediatric NASH differs from adult NASH and is often only clinically manifest through a mild if persistent elevation in transaminases.
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Affiliation(s)
- Andrea Tannapfel
- Institut für Pathologie, Ruhr-Universität Bochum, Bürkle-de-la-Camp Platz 1, Bochum, Germany.
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31
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Abstract
The diagnostic procedures in patients with suspected fatty liver disease-with or without known alcohol consumption-should be standardized and generally accepted. We therefore present a guideline, summarizing the current concepts of etiology, diagnostic as well as differential diagnostic of patients with fatty liver disease. Alcoholic as well as and non-alcoholic fatty liver are characterised by lipid deposition in hepatocytes. The diagnosis of steatosis is made when lipid deposition exceeds 5% of hepatocytes, while involvement of more than 50% is called "fatty liver". An additional inflammatory reaction leads to alcoholic (ASH) or non-alcoholic steatohepatitis (NASH). Steatohepatitis is present when both inflammatory infiltrates of mixed cells in the small liver lobules as well as liver cell injury in terms of ballooning can be detected. Liver biopsy represents the "golden standard" for confirming diagnosis and determining inflammatory activity and potential fibrosis of fatty liver disease. The differential diagnosis of ASH vs. NASH cannot be made on the basis of histological criteria alone. Steatosis, inflammatory changes and hepatocytic injury can be semiquantified as a "Brunt Score" or "NAS" (NAFLD activity score), providing the basis on which to decide whether or not steatohepatitis is present. People at increased risk of developing a fatty liver possess an increased risk of developing chemotherapy-associated steatohepatitis. Histologically, pediatric NASH differs from adult NASH and is often only clinically manifest through a mild if persistent elevation in transaminases.
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32
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Histopathological diagnosis of non-alcoholic and alcoholic fatty liver disease. Virchows Arch 2011; 458:511-23. [PMID: 21442288 DOI: 10.1007/s00428-011-1066-1] [Citation(s) in RCA: 91] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2010] [Revised: 03/02/2011] [Accepted: 03/08/2011] [Indexed: 02/07/2023]
Abstract
The diagnostic procedures in patients with suspected fatty liver disease-with or without known alcohol consumption-should be standardized and generally accepted. We therefore present a guideline, summarizing the current concepts of etiology, diagnostic as well as differential diagnostic of patients with fatty liver disease. Alcoholic as well as and non-alcoholic fatty liver are characterised by lipid deposition in hepatocytes. The diagnosis of steatosis is made when lipid deposition exceeds 5% of hepatocytes, while involvement of more than 50% is called "fatty liver". An additional inflammatory reaction leads to alcoholic (ASH) or non-alcoholic steatohepatitis (NASH). Steatohepatitis is present when both inflammatory infiltrates of mixed cells in the small liver lobules as well as liver cell injury in terms of ballooning can be detected. Liver biopsy represents the "golden standard" for confirming diagnosis and determining inflammatory activity and potential fibrosis of fatty liver disease. The differential diagnosis of ASH vs. NASH cannot be made on the basis of histological criteria alone. Steatosis, inflammatory changes and hepatocytic injury can be semiquantified as a "Brunt Score" or "NAS" (NAFLD activity score), providing the basis on which to decide whether or not steatohepatitis is present. People at increased risk of developing a fatty liver possess an increased risk of developing chemotherapy-associated steatohepatitis. Histologically, pediatric NASH differs from adult NASH and is often only clinically manifest through a mild if persistent elevation in transaminases.
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33
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Marecki JC, Ronis MJ, Shankar K, Badger TM. Hyperinsulinemia and ectopic fat deposition can develop in the face of hyperadiponectinemia in young obese rats. J Nutr Biochem 2011; 22:142-52. [DOI: 10.1016/j.jnutbio.2010.01.001] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2009] [Revised: 12/22/2009] [Accepted: 01/04/2010] [Indexed: 12/26/2022]
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Abstract
Fatty liver disease (FLD) represents a common form of hepatic dysfunction among adults and children. Recognition of steatosis is usually straightforward but the differential diagnosis is broad. Macrovesicular steatosis may occur due to alcohol use or metabolic factors including obesity and hyperinsulinemia. Steatosis is, in some patients, accompanied by varying degrees of inflammation, ballooning hepatocyte degeneration or fibrosis, or both. The pathologist's recognition and interpretation of these features, when present, is critical for the classification and prognostication of the disease. Recent advances in the study of FLD have yielded new information for the surgical pathologist to guide the interpretation of steatosis in children and adults, and in patients with other forms of liver disease such as chronic viral hepatitis. This article details the current terminology for various forms of FLD, highlights the key histological features and reviews recent advances in the field.
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Affiliation(s)
- Lisa Yerian
- Department of Anatomic Pathology, Cleveland Clinic, Cleveland, Ohio 44195, USA.
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35
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Meisamy S, Hines CDG, Hamilton G, Sirlin CB, McKenzie CA, Yu H, Brittain JH, Reeder SB. Quantification of hepatic steatosis with T1-independent, T2-corrected MR imaging with spectral modeling of fat: blinded comparison with MR spectroscopy. Radiology 2011; 258:767-75. [PMID: 21248233 DOI: 10.1148/radiol.10100708] [Citation(s) in RCA: 314] [Impact Index Per Article: 22.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
PURPOSE To prospectively compare an investigational version of a complex-based chemical shift-based fat fraction magnetic resonance (MR) imaging method with MR spectroscopy for the quantification of hepatic steatosis. MATERIALS AND METHODS This study was approved by the institutional review board and was HIPAA compliant. Written informed consent was obtained before all studies. Fifty-five patients (31 women, 24 men; age range, 24-71 years) were prospectively imaged at 1.5 T with quantitative MR imaging and single-voxel MR spectroscopy, each within a single breath hold. The effects of T2 correction, spectral modeling of fat, and magnitude fitting for eddy current correction on fat quantification with MR imaging were investigated by reconstructing fat fraction images from the same source data with different combinations of error correction. Single-voxel T2-corrected MR spectroscopy was used to measure fat fraction and served as the reference standard. All MR spectroscopy data were postprocessed at a separate institution by an MR physicist who was blinded to MR imaging results. Fat fractions measured with MR imaging and MR spectroscopy were compared statistically to determine the correlation (r(2)), and the slope and intercept as measures of agreement between MR imaging and MR spectroscopy fat fraction measurements, to determine whether MR imaging can help quantify fat, and examine the importance of T2 correction, spectral modeling of fat, and eddy current correction. Two-sided t tests (significance level, P = .05) were used to determine whether estimated slopes and intercepts were significantly different from 1.0 and 0.0, respectively. Sensitivity and specificity for the classification of clinically significant steatosis were evaluated. RESULTS Overall, there was excellent correlation between MR imaging and MR spectroscopy for all reconstruction combinations. However, agreement was only achieved when T2 correction, spectral modeling of fat, and magnitude fitting for eddy current correction were used (r(2) = 0.99; slope ± standard deviation = 1.00 ± 0.01, P = .77; intercept ± standard deviation = 0.2% ± 0.1, P = .19). CONCLUSION T1-independent chemical shift-based water-fat separation MR imaging methods can accurately quantify fat over the entire liver, by using MR spectroscopy as the reference standard, when T2 correction, spectral modeling of fat, and eddy current correction methods are used.
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Affiliation(s)
- Sina Meisamy
- Liver Imaging Research Program, Department of Radiology, University of Wisconsin, 600 Highland Ave, E3/311 CSC, Madison, WI 53792-3252, USA.
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Padilha PDC, Rocha HFD, Alves N, Peres WAF. Prevalência de doença hepática não-alcoólica em crianças e adolescentes obesos: uma revisão sistemática. REVISTA PAULISTA DE PEDIATRIA 2010. [DOI: 10.1590/s0103-05822010000400016] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
OBJETIVO: Revisar publicações que investigaram a prevalência de doença hepática gordurosa não-alcoólica (DHGNA) em crianças. FONTES DE DADOS: Bancos de dados Medline (versão PubMed) e Latin American and Caribbean Centre on Health Sciences Information (LILACS), considerando-se o período de 1997 a 2008. Aplicou-se a combinação dos seguintes descritores: "nonalcoholic fatty liver disease", "hepatic steatosis", "nonalcoholic steatohepatitis", "overweight children", "overweight adolescent", "pediatric obesity", "children obesity", "childhood obesity". SÍNTESE DOS DADOS: Foram selecionados 14 artigos: cinco transversais, um caso-controle e oito de coorte. A concordância entre os avaliadores na classificação da qualidade dos artigos foi considerada ótima (k=0,81), com intervalo de confiança de 95% (0,52-1,00; p<0,001); porém, apenas um estudo foi considerado de excelente qualidade. Todos os estudos demonstraram associação entre obesidade e DHGNA, com prevalências variando de 3,0 a 60,3%. Os artigos analisados indicam que as alterações bioquímicas e de imagem são rapidamente normalizadas com a programação da perda ponderal por meio de dieta e exercício físico. Observam-se prevalências maiores em meninos, com o aumento da idade. Uma associação relatada com frequência foi a da resistência insulínica com a progressão da DHGNA. CONCLUSÕES: São necessários estudos cuidadosamente desenhados para esclarecer a relação entre obesidade e DHGNA na infância. Recomenda-se que todas as crianças obesas sejam rastreadas, já que a DHGNA representa a maior causa de agravo hepático na infância.
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Abstract
Histological analysis of liver biopsies remains a standard against which other methods of assessment for the presence and amount of hepatic injury due to nonalcoholic fatty liver disease (NAFLD) are measured. Histological evaluation remains the sole method of distinguishing steatosis from advanced forms of NAFLD, i.e. nonalcoholic steatohepatitis (NASH) and fibrosis. Included in the lesions of NAFLD are steatosis, lobular and portal inflammation, hepatocyte injury in the forms of ballooning and apoptosis, and fibrosis. However, patterns of these lesions are as distinguishing as the lesions themselves. Liver injury in adults and children due to NAFLD may have different histological patterns. In this review, the rationale for liver biopsy, as well as the histopathological lesions, the microscopically observable patterns of injury, and the differential diagnoses of NAFLD and NASH are discussed.
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Tannapfel A, Denk H, Dienes HP, Langner C, Schirmacher P, Trauner M, Flott-Rahmel B. [Histopathological diagnosis of non-alcoholic and alcoholic fatty liver disease. Grade 2 consensus-based guidelines]. DER PATHOLOGE 2010; 31 Suppl 2:225-8. [PMID: 20221762 DOI: 10.1007/s00292-010-1298-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Both alcoholic (AFL) and non-alcoholic fatty liver (NAFL) are characterized by lipid deposition in hepatocytes. The diagnosis of steatosis is made when lipid deposition exceeds 5% of hepatocytes, while involvement of more than 50% is called "fatty liver ". An additional inflammatory reaction leads to alcoholic (ASH) or non-alcoholic steatohepatitis (NASH). Steatohepatitis is present when both inflammatory infiltrates of mixed cells in the small liver lobules as well as liver cell injury in terms of ballooning can be detected.Liver biopsy represents the "gold standard" for confirming diagnosis and determining inflammatory activity and potential fibrosis of fatty liver disease.The differential diagnosis of ASH-NASH cannot be made on the basis of histological criteria alone. Steatosis, inflammatory changes and hepatocytic injury can be semiquantified as a "Brunt Score" or "NAS" (NAFLD activity score), providing the basis on which to decide whether or not steatohepatitis is present.People at increased risk of developing a fatty liver possess an increased risk of developing chemotherapy-associated steatohepatitis (CASH).Histologically, pediatric NASH differs from adult NASH and is often only clinically manifest through a mild if persistent elevation in transaminases.
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Affiliation(s)
- A Tannapfel
- Institut für Pathologie, Ruhr-Universität Bochum, Bürkle-de-la-Camp Platz 1, 44789 Bochum.
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Fernandes MTB, Ferraro AA, de Azevedo RA, Fagundes Neto U. Metabolic differences between male and female adolescents with non-alcoholic fatty liver disease, as detected by ultrasound. Acta Paediatr 2010; 99:1218-23. [PMID: 20298493 DOI: 10.1111/j.1651-2227.2010.01774.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
BACKGROUND Age, developmental stage and gender are risk factors for paediatric non-alcoholic fatty liver disease (NAFLD). AIMS The aim of this study was to identify differences in clinical or laboratory variables between sexes in adolescents with NAFLD. METHODOLOGY Ninety obese adolescents including 36 males and 54 females were evaluated. Inclusion criteria for this study were a Body Mass Index above the 95th percentile, as set forth by the National Center for Health Statistics, and an age of 10-19 years. A clinical and laboratory evaluation was conducted for all adolescents. RESULTS The variables that were found to be predictive of NAFLD in adolescence were visceral fat, Aminotransferase, Gamma-Glutamyl Transferase, triglyderides, cholesterol and LDL-cholesterol. We also observed that cholesterol and LDL-cholesterol variables were influenced by gender, i.e. there was a significant statistical difference in the values of these variables between male and female adolescents. With regard to cholesterol serum concentrations, the risk was 6.99 times greater for females, compared with 1.2 times for males; and for LDL-cholesterol serum concentrations the risk was 8.15 times greater for females, compared with and 1.26 times for males. CONCLUSION Female adolescents with NAFLD showed a significantly different metabolic behaviour than males.
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Affiliation(s)
- M T B Fernandes
- Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
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40
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Abstract
PURPOSE OF REVIEW The intent of this review is to provide a concise overview of all recent acquisitions in terms of therapies and early noninvasive diagnostic approaches for nonalcoholic fatty liver disease (NAFLD) in children. RECENT FINDINGS NAFLD is increasingly being diagnosed in children. If undiscovered and if certain risks are present (i.e. obesity), nonalcoholic steatohepatitis, the most severe form of NAFLD, may silently progress to cirrhosis, hepatocarcinoma and liver-related death in adulthood. Current therapies include approaches for reducing the incidence of risk factors (i.e. weight reduction), drugs targeting the major molecular mechanisms thought essential in the pathogenesis of the disease (insulin resistance and oxidative stress) or both, but other novel treatments are under investigation. SUMMARY Although weight reduction, achieved through a combination of diet and exercise, makes it possible to modify the natural course of simple steatosis, the addition of adequate drugs might also provide a therapeutic action on nonalcoholic steatohepatitis. Moreover, preventive strategies and the design and translation into clinical practice of indices that integrate noninvasive diagnostic tools and serum biomarkers might be a winning approach for improving management of paediatric NAFLD/nonalcoholic steatohepatitis in the coming years.
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Affiliation(s)
- Anna Alisi
- Unit of Metabolic and Autoimmune Liver Diseases, Pediatric Hospital IRCCS Bambino Gesù, Rome, Italy
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41
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Abstract
Liver biopsy (LB) is the gold standard method for assessment of liver histology. It provides valuable, otherwise unobtainable information, regarding the degree of fibrosis, parenchymal integrity, degree and pattern of inflammation, bile duct status and deposition of materials and minerals in the liver. This information provides immense help in the diagnosis and prognostication of a variety of liver diseases. With careful selection of patients, and performance of the procedure appropriately, the complications become exceptionally rare in current clinical practice. Furthermore, the limitations of sampling error and inter-/intra-observer variability may be avoided by obtaining adequate tissue specimen and having it reviewed by an experienced liver pathologist. Current noninvasive tools are unqualified to replace LB in clinical practice in the face of specific limitations for each tool, compounded by a poorer performance towards the assessment of the degree of liver fibrosis, particularly for intermediate stages.
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Affiliation(s)
- Khalid A. Alswat
- Gastroenterology and Hepatology Division, Department of Medicine, Liver Disease Research Center, King Saud University Liver Research Center, College of Medicine, Saudi Arabia,Address for correspondence: Dr. Khalid A. Alswat, Division of Gastroenterology and Hepatology, Department of Medicine, King Saud University Liver Research Center, College of Medicine, PO Box 7897, Riyadh-11159, Saudi Arabia. E-mail:
| | - Khalid Mumtaz
- Department of Medicine, Section of Gastroenterology, Aga Khan University Hospital, Karachi, Pakistan
| | - Wasim Jafri
- Department of Medicine, Section of Gastroenterology, Aga Khan University Hospital, Karachi, Pakistan
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Tiniakos DG, Vos MB, Brunt EM. Nonalcoholic fatty liver disease: pathology and pathogenesis. ANNUAL REVIEW OF PATHOLOGY-MECHANISMS OF DISEASE 2010; 5:145-71. [PMID: 20078219 DOI: 10.1146/annurev-pathol-121808-102132] [Citation(s) in RCA: 631] [Impact Index Per Article: 42.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is recognized as the leading cause of chronic liver disease in adults and children. NAFLD encompasses a spectrum of liver injuries ranging from steatosis to steatohepatitis with or without fibrosis. Fibrosis may progress to cirrhosis and complications including hepatocellular carcinoma. Histologic findings represent the complexity of pathophysiology. NAFLD is closely associated with obesity and is most closely linked with insulin resistance; the current Western diet, high in saturated fats and fructose, plays a significant role. There are several mechanisms by which excess triglycerides are acquired and accumulate in hepatocytes. Formation of steatotic droplets may be disordered in NAFLD. Visceral adipose tissue dysfunction in obesity and insulin resistance results in aberrant cytokine expression; many cytokines have a role in liver injury in NAFLD. Cellular stress and immune reactions, as well as the endocannabinoid system, have been implicated in animal models and in some human studies.
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Affiliation(s)
- Dina G Tiniakos
- Laboratory of Histology and Embryology, Medical School, National and Kapodistrian University of Athens, Athens 11527, Greece.
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43
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Histopathologische Diagnose der nichtalkoholischen und alkoholischen Fettlebererkrankung. DER PATHOLOGE 2010; 31:225-37. [DOI: 10.1007/s00292-010-1274-5] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Kistler KD, Molleston J, Unalp A, Abrams SH, Behling C, Schwimmer JB. Symptoms and quality of life in obese children and adolescents with non-alcoholic fatty liver disease. Aliment Pharmacol Ther 2010; 31:396-406. [PMID: 19863497 PMCID: PMC2807909 DOI: 10.1111/j.1365-2036.2009.04181.x] [Citation(s) in RCA: 54] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND Data on the quality of life (QOL) of children with non-alcoholic fatty liver disease (NAFLD) are needed to estimate the true burden of illness in children with NAFLD. AIM To characterize QOL and symptoms of children with NAFLD and to compare QOL in children with NAFLD with that in a sample of healthy children. METHODS Quality of life and symptoms were assessed in children with biopsy-proven NAFLD enrolled in the NASH Clinical Research Network. PedsQL scores were compared with scores from healthy children. For children with NAFLD, between-group comparisons were made to test associations of demography, histological severity, symptoms and QOL. RESULTS A total of 239 children (mean age 12.6 years) were studied. Children with NAFLD had worse total (72.8 vs. 83.8, P < 0.01), physical (77.2 vs. 87.5, P < 0.01) and psychosocial health (70.4 vs. 81.9, P < 0.01) scores compared with healthy children. QOL scores did not significantly differ by histological severity of NAFLD. Fatigue, trouble sleeping and sadness accounted for almost half of the variance in QOL scores. Impaired QOL was present in 39% of children with NAFLD. CONCLUSIONS Children with NAFLD have a decrement in QOL. Symptoms were a major determinant of this impairment. Interventions are needed to restore and optimize QOL in children with NAFLD.
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Affiliation(s)
- K. D. Kistler
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Diego, La Jolla, CA,Joint Doctoral Program in Public Health, San Diego State University and University of California San Diego, La Jolla, CA
| | - J. Molleston
- Pediatric Gastroenterology, Hepatology and Nutrition, James Whitcomb Riley Hospital for Children, Indianapolis, IN
| | - A. Unalp
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
| | - S. H. Abrams
- Texas Children's Hospital, Houston, TX,Baylor College of Medicine, Houston, TX
| | - C. Behling
- Pacific Rim Pathology Group, Sharp Memorial Hospital, San Diego, CA
| | - J. B. Schwimmer
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Diego, La Jolla, CA,Department of Gastroenterology, Rady Children's Hospital, San Diego, CA
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45
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Lindbäck SM, Gabbert C, Johnson BL, Smorodinsky E, Sirlin CB, Garcia N, Pardee PE, Kistler KD, Schwimmer JB. Pediatric nonalcoholic fatty liver disease: a comprehensive review. Adv Pediatr 2010; 57:85-140. [PMID: 21056736 DOI: 10.1016/j.yapd.2010.08.006] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Affiliation(s)
- Sarah M Lindbäck
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Diego School of Medicine, 200 West Arbor Drive, San Diego, CA 92103-8450, USA
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46
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Pardee PE, Lavine JE, Schwimmer JB. Diagnosis and treatment of pediatric nonalcoholic steatohepatitis and the implications for bariatric surgery. Semin Pediatr Surg 2009; 18:144-51. [PMID: 19573756 PMCID: PMC2761012 DOI: 10.1053/j.sempedsurg.2009.04.004] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
This review focuses on the diagnosis, risk factors, prevalence, pathogenesis and treatment of pediatric nonalcoholic steatohepatitis (NASH). NASH is a progressive form of nonalcoholic fatty liver disease (NAFLD), the most common cause of chronic liver disease in children. The factors that account for differences between children with NASH and children with milder forms of NAFLD are unclear. The diagnosis of NASH requires interpretation of liver histology because no noninvasive markers predict the presence or severity of NASH. There is no proven treatment for NASH. Several clinical trials for NAFLD are in progress; however, clinical trials focusing on NASH are needed. Heightened physician awareness of NAFLD, NASH, and associated risk factors is important to identify and treat affected children.
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47
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Reeder SB, Robson PM, Yu H, Shimakawa A, Hines CDG, McKenzie CA, Brittain JH. Quantification of hepatic steatosis with MRI: the effects of accurate fat spectral modeling. J Magn Reson Imaging 2009; 29:1332-9. [PMID: 19472390 DOI: 10.1002/jmri.21751] [Citation(s) in RCA: 197] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
PURPOSE To develop a chemical-shift-based imaging method for fat quantification that accounts for the complex spectrum of fat, and to compare this method with MR spectroscopy (MRS). Quantitative noninvasive biomarkers of hepatic steatosis are urgently needed for the diagnosis and management of nonalcoholic fatty liver disease (NAFLD). MATERIALS AND METHODS Hepatic steatosis was measured with "fat-fraction" images in 31 patients using a multiecho chemical-shift-based water-fat separation method at 1.5T. Fat-fraction images were reconstructed using a conventional signal model that considers fat as a single peak at -210 Hz relative to water ("single peak" reconstruction). Fat-fraction images were also reconstructed from the same source images using two methods that account for the complex spectrum of fat; precalibrated and self-calibrated "multipeak" reconstruction. Single-voxel MRS that was coregistered with imaging was performed for comparison. RESULTS Imaging and MRS demonstrated excellent correlation with single peak reconstruction (r(2) = 0.91), precalibrated multipeak reconstruction (r(2) = 0.94), and self-calibrated multipeak reconstruction (r(2) = 0.91). However, precalibrated multipeak reconstruction demonstrated the best agreement with MRS, with a slope statistically equivalent to 1 (0.96 +/- 0.04; P = 0.4), compared to self-calibrated multipeak reconstruction (0.83 +/- 0.05, P = 0.001) and single-peak reconstruction (0.67 +/- 0.04, P < 0.001). CONCLUSION Accurate spectral modeling is necessary for accurate quantification of hepatic steatosis with MRI.
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Affiliation(s)
- Scott B Reeder
- Department of Radiology, University of Wisconsin, Madison, Wisconsin, USA.
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48
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Abstract
OBJECTIVE With recent advances in technology, advanced MRI methods such as diffusion-weighted and perfusion-weighted MRI, MR elastography, chemical shift-based fat-water separation, and MR spectroscopy can now be applied to liver imaging. We will review the respective roles of these techniques for assessment of chronic liver disease. CONCLUSION MRI plays an increasingly important role in assessment of patients with chronic liver disease because of the lack of ionizing radiation and the possibility of performing multiparametric imaging.
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Affiliation(s)
- Bachir Taouli
- Department of Radiology New York University Medical Center 560 First Avenue New York, NY, 10016
| | - Richard L. Ehman
- Department of Radiology Mayo Clinic 200 First St. SW Rochester, MN, 55905
| | - Scott B. Reeder
- Department of Radiology, Medical Physics and Biomedical Engineering University of Wisconsin 600 Highland Ave, CSC E1/374 Madison, WI 53792-3252
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Kelishadi R, Cook SR, Amra B, Adibi A. Factors associated with insulin resistance and non-alcoholic fatty liver disease among youths. Atherosclerosis 2009; 204:538-43. [DOI: 10.1016/j.atherosclerosis.2008.09.034] [Citation(s) in RCA: 59] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2008] [Revised: 08/19/2008] [Accepted: 09/17/2008] [Indexed: 01/06/2023]
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50
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Abstract
PURPOSE OF REVIEW To increase awareness about the close interrelationship between nonalcoholic fatty liver disease and type 2 diabetes mellitus, and of recent diagnostic and treatment advances in the field. RECENT FINDINGS The perception of nonalcoholic fatty liver disease as an uncommon and benign condition is rapidly changing. Approximately 70% of persons with type 2 diabetes mellitus have a fatty liver and the disease follows a more aggressive course with necroinflammation and fibrosis (i.e. nonalcoholic steatohepatitis) in diabetes. New evidence suggests that it is not steatosis per se but the development of lipotoxicity-induced mitochondrial dysfunction and activation of inflammatory pathways that leads to progressive liver damage. Nonalcoholic steatohepatitis is a leading cause of end-stage liver disease and contributes to cardiovascular disease in patients with type 2 diabetes mellitus. Because nonalcoholic steatohepatitis may develop even in the presence of normal liver transaminases, a liver biopsy is still necessary for a definitive diagnosis. However, new imaging methods and plasma biomarkers are emerging as alternative diagnostic tools. Lifestyle intervention is the gold standard for the management of nonalcoholic steatohepatitis. Recent randomized controlled trials suggest thiazolidiendiones are promising therapeutic agents. SUMMARY Nonalcoholic steatohepatitis is a frequently overlooked and potentially severe complication of type 2 diabetes mellitus. Patients may benefit from its early diagnosis and treatment.
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Affiliation(s)
- Kenneth Cusi
- Diabetes Division, Department of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78284-3900, USA.
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