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Huang J, Lin H, Liu AN, Wu W, Alisi A, Loomba R, Xu C, Xiang W, Shao J, Dong G, Zheng MH, Fu J, Ni Y. Dynamic pattern of postprandial bile acids in paediatric non-alcoholic fatty liver disease. Liver Int 2024; 44:2793-2806. [PMID: 39082260 DOI: 10.1111/liv.16054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Revised: 07/04/2024] [Accepted: 07/15/2024] [Indexed: 10/10/2024]
Abstract
BACKGROUND Dysregulation of bile acids (BAs), as important signalling molecules in regulating lipid and glucose metabolism, contributes to the development of non-alcoholic fatty liver disease (NAFLD). However, static BA profiles during fasting may obscure certain pathogenetic aspects. In this study, we investigate the dynamic alterations of BAs in response to an oral glucose tolerance test (OGTT) among children with NAFLD. METHODS We recruited 230 subjects, including children with overweight/obesity, or complicated with NAFLD, and healthy controls. Serum BAs, 7-hydroxy-4-cholesten-3-one (C4) and fibroblast growth factor 19 (FGF19) were quantified during OGTT. Clinical markers related to liver function, lipid metabolism and glucose metabolism were assessed at baseline or during OGTT. FINDINGS Conjugated BAs increased while unconjugated ones decreased after glucose uptake. Most BAs were blunted in response to glucose in NAFLD (p > .05); only glycine and taurine-conjugated chenodeoxycholic acid (CDCA) and cholic acid (CA) were responsive (p < .05). Primary BAs were significantly increased while secondary BAs were decreased in NAFLD. C4 and FGF19 were significantly increased while their ratio FGF19/C4 ratio was decreased in NAFLD. The dynamic pattern of CDCA and taurine-conjugated hyocholic acid (THCA) species was closely correlated with glucose (correlation coefficient r = .175 and -.233, p < .05), insulin (r = .327 and -.236, p < .05) and c-peptide (r = .318 and -.238, p < .05). Among which, CDCA was positively associated with liver fat content in NAFLD (r = .438, p < .05). Additionally, glycochenodeoxycholic acid (GCDCA), CDCA and THCA were potential biomarkers to discriminate paediatric NAFLD from healthy controls and children with obesity. INTERPRETATION This study provides novel insights into the dynamics of BAs during OGTT in paediatric NAFLD. The observed variations in CDCA and HCA species were associated with liver dysfunction, dyslipidaemia and dysglycaemia, highlighting their potential roles as promising diagnostic and therapeutic targets in NAFLD.
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Affiliation(s)
- Jiating Huang
- Department of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
| | - Hu Lin
- Department of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
| | - A-Na Liu
- Department of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
| | - Wei Wu
- Department of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
| | - Anna Alisi
- Research Unit of Genetics of Complex Phenotypes, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Rohit Loomba
- NAFLD Research Center, Division of Gastroenterology, University of California, San Diego, La Jolla, California, USA
| | - Cuifang Xu
- Department of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
| | - Wenqin Xiang
- Department of Clinical Laboratory, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
| | - Jie Shao
- Department of Child Healthcare, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
| | - Guanping Dong
- Department of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
| | - Ming-Hua Zheng
- MAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Junfen Fu
- Department of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
| | - Yan Ni
- Department of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
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Radulescu A, Dugan AJ, Killian M, Attia SL, Mouzaki M, Fuchs GJ, Kohli R, Bada H, Kern PA, Softic S. Stratification by obesity class, rather than age, can identify a higher percent of children at risk for non-alcoholic fatty liver disease and metabolic dysfunction. Pediatr Obes 2022; 17:e12862. [PMID: 34662928 PMCID: PMC11167530 DOI: 10.1111/ijpo.12862] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Revised: 09/04/2021] [Accepted: 09/20/2021] [Indexed: 01/19/2023]
Abstract
BACKGROUND An increasing number of clinical practice guidelines recommend screening children with obesity for non-alcoholic fatty liver disease (NAFLD). However, there is limited evidence regarding what parameters should be used to initiate the screening. OBJECTIVE The objective of this study was to determine whether obesity class rather than age group can identify a higher percent of children at risk of NAFLD as assessed by abnormal alanine aminotransferase (ALT). METHODS This is a cross-sectional study in a regional referral clinic for evaluation of obesity. Children were stratified by age group or by obesity class, and data obtained at first visit were analysed. RESULTS Of the 784 children, 482 were ≥10, 209 were 6 to 9 and 93 were 2 to 5 years of age. Abnormal ALT was observed in 32.1%, 46.9% and 61.0% of children with class I, II or III obesity, respectively (p < 0.001), while the risk of abnormal ALT did not differ in very young (2-5), young (6-9), or children older than 10 years. A multivariable analysis showed that class II and class III obesity were associated with 2.1-fold (1.27-3.72) and 4-fold (2.41-6.96) greater odds of abnormal ALT compared with class I obesity. African-American children had lower risk of abnormal ALT (0.27), whereas Hispanic children had higher risk (2.37). Obesity class was a better predictor of abnormal ALT than age, especially in girls. Furthermore, 66.7% of boys (p = 0.009) and 69% of girls (p < 0.001) with abnormal ALT exhibited additional signs of metabolic dysfunction. CONCLUSION Obesity class is more strongly associated with abnormal ALT than age.
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Affiliation(s)
- Aurelia Radulescu
- Department of Pediatrics, University of Kentucky College of Medicine and Kentucky Children’s Hospital, Lexington, Kentucky, USA
| | - Adam J. Dugan
- Department of Biostatistics, College of Public Health, University of Kentucky, Lexington, Kentucky, USA
| | - Mary Killian
- Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Suzanna L. Attia
- Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, College of Medicine, University of Kentucky, Lexington, Kentucky, USA
| | - Marialena Mouzaki
- Steatohepatitis Center, Cincinnati Children’s Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, USA
| | - George J. Fuchs
- Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, College of Medicine, University of Kentucky, Lexington, Kentucky, USA
| | - Rohit Kohli
- Division of Gastroenterology, Hepatology and Nutrition, Children’s Hospital Los Angeles, Los Angeles, California, USA
| | - Henrietta Bada
- Department of Pediatrics, University of Kentucky College of Medicine and Kentucky Children’s Hospital, Lexington, Kentucky, USA
| | - Philip A. Kern
- Department of Medicine, Division of Endocrinology, University of Kentucky College of Medicine, Lexington, Kentucky, USA
| | - Samir Softic
- Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, College of Medicine, University of Kentucky, Lexington, Kentucky, USA
- Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, Kentucky, USA
- Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, USA
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Khatatbeh M, Momani W, Altaani Z, Al Saad R, Al Bourah AR. Fast Food Consumption, Liver Functions, and Change in Body Weight Among University Students: A Cross-Sectional Study. Int J Prev Med 2021; 12:109. [PMID: 34760120 PMCID: PMC8551780 DOI: 10.4103/ijpvm.ijpvm_194_19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2019] [Accepted: 03/17/2021] [Indexed: 11/14/2022] Open
Abstract
Background: Over the past decades, the consumption of fast foods has increased worldwide and became favored by people of most age groups. The objective of this research was to assess the impact of fast foods on liver enzyme levels and body weight. Methods: A cross-sectional study was conducted at Yarmouk University/Jordan using survey questionnaire and enquired university students about their dietary habits, in addition to laboratory investigations of liver enzymes. Results: In the cross-tabulation analysis, only age and body mass index (BMI) were significantly associated with alanine aminotransferase (ALT) enzyme level. However, all differences between aspartate aminotransferase (AST) level and other variables were statistically insignificant. The AST/ALT ratio was calculated and revealed significant statistical association with BMI of participants (P = 0.001). Change in body weight during one year was significantly associated with eating fast food (P = 0.031), drinking beverages with fast food meals (P = 0.001), and ALT level (P = 0.026). However, this association was statistically insignificant with AST level. Conclusions: Fast food consumption among university students in Jordan was not significantly associated with increasing levels of ALT and AST liver enzymes. However, eating fast food and drinking soft drinks were associated with increasing body weight, which is expected to have adverse effect on liver functions in the long term.
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Affiliation(s)
- Moawiah Khatatbeh
- Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid, Jordan
| | - Waleed Momani
- Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid, Jordan
| | - Zaid Altaani
- Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid, Jordan
| | - Reem Al Saad
- Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid, Jordan
| | - Abdul Rahman Al Bourah
- Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid, Jordan
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Lu Y, Wang Q, Yu L, Yin X, Yang H, Xu X, Xia Y, Luo Y, Peng Y, Yu Q, Chen Z, Yu J, Lai M, Wu N, Pan XB, Zheng X. Revision of serum ALT upper limits of normal facilitates assessment of mild liver injury in obese children with non-alcoholic fatty liver disease. J Clin Lab Anal 2020; 34:e23285. [PMID: 32267017 PMCID: PMC7370732 DOI: 10.1002/jcla.23285] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2020] [Revised: 02/14/2020] [Accepted: 02/21/2020] [Indexed: 01/04/2023] Open
Abstract
Background The serum alanine aminotransferase (ALT) level is a critical parameter for evaluating liver injury in non‐alcoholic fatty liver disease (NAFLD). However, the currently accepted upper limits of normal (ULN) for serum ALT (ULN‐ALT) are debated, as they may be excessively high. Methods A total of 1638 children aged 6‐16 years, comprising 507 children with normal BMI (500 healthy children and 7 children with NAFLD), 199 overweight children, and 932 obese children, were included in the analysis. We re‐evaluated the ULN‐ALT in 500 healthy Chinese children using the 95th percentiles of serum ALT levels as revised ULN‐ALT. Fatty liver was identified by ultrasound examination. Results Significant positive correlations between serum ALT levels and body mass index (BMI) were detected in overweight boys (r = .399, P < .001), obese boys (r = .398, P < .001), and obese girls (r = .392, P < .001). The prevalence percentages of NAFLD were 93.6%, 75.8%, and 37.9% in obese boys with serum ALT levels of >50, 25‐50, and ≤25 U/L and were 81.6%, 67.9%, and 20.6% in obese girls with serum ALT levels of >40, 20‐40, and ≤20 U/L, respectively. Conclusion Serum ALT levels significantly correlated with abnormal BMI values in children, suggesting a rigorous BMI threshold is needed to establish the cutoffs for serum ULN‐ALT in children. Besides, the revised serum ULN‐ALT can uncover mild liver injury in obese children with NAFLD.
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Affiliation(s)
- Yutian Lu
- Department of Clinical Laboratory, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.,School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.,Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou, Zhejiang, China
| | - Qiongdan Wang
- Department of Clinical Laboratory, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.,School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.,Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou, Zhejiang, China
| | - Lisha Yu
- Department of Clinical Laboratory, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.,School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.,Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou, Zhejiang, China
| | - XueRui Yin
- Department of Clinical Laboratory, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.,School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.,Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou, Zhejiang, China
| | - Huijie Yang
- Department of Clinical Laboratory, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.,School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.,Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou, Zhejiang, China
| | - Xi Xu
- Department of Clinical Laboratory, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.,School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.,Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou, Zhejiang, China
| | - Ying Xia
- Department of Clinical Laboratory, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.,School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.,Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou, Zhejiang, China
| | - Yue Luo
- Department of Pediatric Endocrinology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Ying Peng
- School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.,Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou, Zhejiang, China
| | - Qigui Yu
- Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Zhanguo Chen
- Department of Clinical Laboratory, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Jian Yu
- Department of Clinical Laboratory, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Meimei Lai
- Department of Clinical Laboratory, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Nan Wu
- Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing, China
| | - Xiao-Ben Pan
- School of Medicine, Department of Basic Medical Science, Key Laboratory of Aging and Cancer Biology of Zhejiang Province, Key Laboratory of Inflammation and Immunoregulation of Hangzhou, Hangzhou Normal University, Hangzhou, Zhejiang, China
| | - Xiaoqun Zheng
- Department of Clinical Laboratory, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.,School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.,Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou, Zhejiang, China
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Johansen MJ, Gade J, Stender S, Frithioff-Bøjsøe C, Lund MAV, Chabanova E, Thomsen HS, Pedersen O, Fonvig CE, Hansen T, Holm JC. The Effect of Overweight and Obesity on Liver Biochemical Markers in Children and Adolescents. J Clin Endocrinol Metab 2020; 105:5588552. [PMID: 31617910 DOI: 10.1210/clinem/dgz010] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2019] [Accepted: 09/20/2019] [Indexed: 02/09/2023]
Abstract
BACKGROUND Elevated plasma concentrations of liver enzymes are routinely used as markers of liver injury in adults and children. Currently, the age- and sex-specific effects of adiposity on pediatric liver enzyme concentrations are unclear. METHODS We included participants from 2 cohorts of Danish children and adolescents: 1858 from a population-based cohort and 2155 with overweight or obesity, aged from 6 to 18 years. Age- and sex-specific percentile curves were calculated for fasting plasma concentrations of alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH), gamma-glutamyltransferase (GGT), bilirubin, and alkaline phosphatase (ALP) in both cohorts. Hepatic fat content was assessed by proton magnetic resonance spectroscopy in 458 participants. RESULTS Concentrations of ALT, AST, LDH, and ALP decreased with age in both girls and boys, while GGT and bilirubin were comparable across age groups in girls and increased slightly with age in boys. Children and adolescents with overweight or obesity exhibited higher concentrations of ALT in all age groups. Concentrations of ALT, and to a lesser degree GGT, increased with age in boys with overweight or obesity. Optimal ALT cut-points for diagnosing hepatic steatosis (liver fat content > 5%) was 24.5 U/L for girls (sensitivity: 55.6%, specificity: 84.0%), and 34.5 U/L for boys (sensitivity: 83.7%, specificity: 68.2%). CONCLUSIONS Pediatric normal values of liver enzymes vary with both age and sex. Overweight and obesity is associated with elevated biochemical markers of liver damage. These findings emphasize the need for prevention and treatment of overweight and obesity in children and adolescents. (J Clin Endocrinol Metab XX: 0-0, 2019).
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Affiliation(s)
- Magnus J Johansen
- The Children's Obesity Clinic, European Centre of Management (COM/EASO), Department of Pediatrics, Copenhagen University Hospital Holbæk, Holbæk, Denmark
- Department of Radiology, Herlev Gentofte Hospital, Herlev, Denmark
| | - Julie Gade
- The Children's Obesity Clinic, European Centre of Management (COM/EASO), Department of Pediatrics, Copenhagen University Hospital Holbæk, Holbæk, Denmark
- Department of Radiology, Herlev Gentofte Hospital, Herlev, Denmark
| | - Stefan Stender
- The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark
| | - Christine Frithioff-Bøjsøe
- The Children's Obesity Clinic, European Centre of Management (COM/EASO), Department of Pediatrics, Copenhagen University Hospital Holbæk, Holbæk, Denmark
- The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Morten A V Lund
- The Children's Obesity Clinic, European Centre of Management (COM/EASO), Department of Pediatrics, Copenhagen University Hospital Holbæk, Holbæk, Denmark
- Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
| | | | - Henrik S Thomsen
- Department of Radiology, Herlev Gentofte Hospital, Herlev, Denmark
- University of Copenhagen, Faculty of Health Sciences, Copenhagen, Denmark
| | - Oluf Pedersen
- The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Cilius E Fonvig
- The Children's Obesity Clinic, European Centre of Management (COM/EASO), Department of Pediatrics, Copenhagen University Hospital Holbæk, Holbæk, Denmark
- Department of Pediatrics, Kolding Hospital a part of Lillebaelt Hospital, Kolding, Denmark
| | - Torben Hansen
- The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- University of Southern Denmark, Faculty of Health Sciences, Odense, Denmark
| | - Jens-Christian Holm
- The Children's Obesity Clinic, European Centre of Management (COM/EASO), Department of Pediatrics, Copenhagen University Hospital Holbæk, Holbæk, Denmark
- The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- University of Copenhagen, Faculty of Health Sciences, Copenhagen, Denmark
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Lv S, Jiang S, Liu S, Dong Q, Xin Y, Xuan S. Noninvasive Quantitative Detection Methods of Liver Fat Content in Nonalcoholic Fatty Liver Disease. J Clin Transl Hepatol 2018; 6:217-221. [PMID: 29951367 PMCID: PMC6018305 DOI: 10.14218/jcth.2018.00021] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2018] [Revised: 05/22/2018] [Accepted: 06/14/2018] [Indexed: 12/19/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) ranges from simple steatosis to NAFLD-related liver cirrhosis and is a main cause of chronic liver diseases. Patients with nonalcoholic steatohepatitis and fibrosis are at a great risk of the progression to cirrhosis or hepatocellular carcinoma, both of which are tightly associated with liver-related mortality. Liver biopsy is still the gold standard for the diagnosis of NAFLD, but some defects, such as serious complications, sampling error and variability in histologic evaluation among pathologists, remain problematic. Therefore, noninvasive, repeatable and accurate diagnostic methods are urgently needed. Ultrasonography is a well-established and lower-cost imaging technique for the diagnosis of hepatic steatosis, especially suitable for population census, but limited by its low sensitivity to diagnose mild steatosis and being highly operator-dependent. Computed tomography also lacks the sensitivity to detect mild steatosis and small changes in fat content, and presents a potential radiation hazard. Controlled attenuation parameter based on the FibroScan® technology is a promising tool for noninvasive semiquantitative assessment of liver fat content, but the accuracy rate depends on the operator's expertise and is affected by age, width of the intercostal space, skin capsular distance and body mass index. Magnetic resonance imaging and magnetic resonance spectroscopy are regarded as the most accurate quantitative methods for measuring liver fat content in clinical practice, especially for longitudinal follow up of NAFLD patients. In this review, we mainly introduce the current imaging methods that are in use for evaluation of liver fat content and we discuss the advantages and disadvantages of each method.
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Affiliation(s)
- Shujing Lv
- Medical College of Qingdao University, Qingdao, Shandong, China
| | - Sushan Jiang
- Medical College of Qingdao University, Qingdao, Shandong, China
| | - Shousheng Liu
- Digestive Disease Key Laboratory of Qingdao, Qingdao, Shandong, China
- Central Laboratories, Qingdao Municipal Hospital, Qingdao, Shandong, China
| | - Quanjiang Dong
- Central Laboratories, Qingdao Municipal Hospital, Qingdao, Shandong, China
- Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao, Shandong, China
| | - Yongning Xin
- Medical College of Qingdao University, Qingdao, Shandong, China
- Digestive Disease Key Laboratory of Qingdao, Qingdao, Shandong, China
- Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao, Shandong, China
- Department of Infectious Disease, Qingdao Municipal Hospital, Qingdao, Shandong, China
- *Correspondence to: Shiying Xuan, Department of Gastroenterology, Qingdao Municipal Hospital, 1 Jiaozhou Road, Qingdao 266011, China. Tel: +86-532-88905508, Fax: +86-532-88905293, E-mail: ; Yongning Xin, Department of Gastroenterology, Qingdao Municipal Hospital, 1 Jiaozhou Road, Qingdao 266011, Shandong, China. Tel: +86-532-82789463, Fax: +86-532-85968434, E-mail:
| | - Shiying Xuan
- Medical College of Qingdao University, Qingdao, Shandong, China
- Digestive Disease Key Laboratory of Qingdao, Qingdao, Shandong, China
- Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao, Shandong, China
- *Correspondence to: Shiying Xuan, Department of Gastroenterology, Qingdao Municipal Hospital, 1 Jiaozhou Road, Qingdao 266011, China. Tel: +86-532-88905508, Fax: +86-532-88905293, E-mail: ; Yongning Xin, Department of Gastroenterology, Qingdao Municipal Hospital, 1 Jiaozhou Road, Qingdao 266011, Shandong, China. Tel: +86-532-82789463, Fax: +86-532-85968434, E-mail:
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7
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Brandt S, Roos J, Inzaghi E, Kotnik P, Kovac J, Battelino T, Cianfarani S, Nobili V, Colajacomo M, Kratzer W, Denzer C, Fischer-Posovszky P, Wabitsch M. Circulating levels of miR-122 and nonalcoholic fatty liver disease in pre-pubertal obese children. Pediatr Obes 2018; 13:175-182. [PMID: 29271122 DOI: 10.1111/ijpo.12261] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2017] [Revised: 10/20/2017] [Accepted: 10/31/2017] [Indexed: 01/23/2023]
Abstract
OBJECTIVES The liver-specific miR-122 was proposed as biomarker for NAFLD in adults. Here, we investigated the relationship between miR-122 levels, parameters of liver metabolism and NAFLD in pre-pubertal obese children. METHODS Parameters of liver metabolism (ALT, AST and GGT) of three European cohorts were included (German cohort [n = 71; age: 11.53 ± 1.29 years; BMI z-score: 2.96 ± 0.64], Italian cohort [n = 45; age: 9.60 ± 2.11 years; BMI z-score: 3.57 ± 1.16], Slovenian cohort [n = 31; age: 7.53 ± 1.47 years; BMI z-score: 3.66 ± 0.88]). MiR-122 levels and CK18 concentrations were measured in fasting blood samples. In the German and Italian cohort, the diagnosis of NAFLD and grading of NAFLD was assessed by ultrasound. RESULTS NAFLD was diagnosed in n = 50 patients of the German cohort (29.6%) and in n = 29 patients (72.5%) of the Italian cohort. In all three cohorts, miR-122 was positively correlated with ALT and AST as well as with CK18 concentrations. MiR-122 levels were higher in children with NAFLD compared with healthy controls. CONCLUSIONS MiR-122 levels in pre-pubertal obese children could be a potential biomarker for paediatric NAFLD.
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Affiliation(s)
- S Brandt
- Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany
| | - J Roos
- Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany
| | - E Inzaghi
- Dipartimento Pediatrico Universitario Ospedaliero, Bambino Gesù Children's Hospital, Tor Vergata University, Rome, Italy
| | - P Kotnik
- University Children's Hospital, Ljubljana, University Medical Centre Ljubljana, Ljubljana, Slovenia
| | - J Kovac
- University Children's Hospital, Ljubljana, University Medical Centre Ljubljana, Ljubljana, Slovenia
| | - T Battelino
- University Children's Hospital, Ljubljana, University Medical Centre Ljubljana, Ljubljana, Slovenia
| | - S Cianfarani
- Dipartimento Pediatrico Universitario Ospedaliero, Bambino Gesù Children's Hospital, Tor Vergata University, Rome, Italy.,Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden
| | - V Nobili
- Hepato-Metabolic Disease Unit, Bambino Gesù Children's Hospital, Rome, Italy
| | - M Colajacomo
- Dipartimento Diagnostica per Immagini, Bambino Gesù Children's Hospital, Rome, Italy
| | - W Kratzer
- Department of Internal Medicine I, University Hospital Ulm, Germany
| | - C Denzer
- Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany
| | - P Fischer-Posovszky
- Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany
| | - M Wabitsch
- Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany
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Di Martino M, Pacifico L, Bezzi M, Di Miscio R, Sacconi B, Chiesa C, Catalano C. Comparison of magnetic resonance spectroscopy, proton density fat fraction and histological analysis in the quantification of liver steatosis in children and adolescents. World J Gastroenterol 2016; 22:8812-8819. [PMID: 27818597 PMCID: PMC5075556 DOI: 10.3748/wjg.v22.i39.8812] [Citation(s) in RCA: 70] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2016] [Revised: 06/30/2016] [Accepted: 08/01/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To establish a threshold value for liver fat content between healthy children and those with non-alcoholic fatty liver disease (NAFLD) by using magnetic resonance imaging (MRI), with liver biopsy serving as a reference standard.
METHODS The study was approved by the local ethics committee, and written informed consent was obtained from all participants and their legal guardians before the study began. Twenty-seven children with NAFLD underwent liver biopsy to assess the presence of nonalcoholic steatohepatitis. The assessment of liver fat fraction was performed using MRI, with a high field magnet and 2D gradient-echo and multiple-echo T1-weighted sequence with low flip angle and single-voxel point-resolved ¹H MR-Spectroscopy (¹H-MRS), corrected for T1 and T2* decays. Receiver operating characteristic curve analysis was used to determine the best cut-off value. Lin coefficient test was used to evaluate the correlation between histology, MRS and MRI-PDFF. A Mann-Whitney U-test and multivariate analysis were performed to analyze the continuous variables.
RESULTS According to MRS, the threshold value between healthy children and those with NAFLD is 6%; using MRI-PDFF, a cut-off value of 3.5% is suggested. The Lin analysis revealed a good fit between the histology and MRS as well as MRI-PDFF.
CONCLUSION MRS is an accurate and precise method for detecting NAFLD in children.
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Hamza RT, Elkabbany ZA, Shedid AM, Hamed AI, Ebrahim AO. Serum Chemerin in Obese Children and Adolescents Before and After L-Carnitine Therapy: Relation to Nonalcoholic Fatty Liver Disease and Other Features of Metabolic Syndrome. Arch Med Res 2016; 47:541-549. [DOI: 10.1016/j.arcmed.2016.11.010] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2016] [Accepted: 11/17/2016] [Indexed: 01/01/2023]
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Hatipoğlu N, Doğan S, Mazıcıoğlu MM, Kurtoğlu S. Relationship between Neck Circumference and Non-Alcoholic Fatty Liver Disease in Childhood Obesity. J Clin Res Pediatr Endocrinol 2016; 8:32-9. [PMID: 26758497 PMCID: PMC4805046 DOI: 10.4274/jcrpe.2313] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
OBJECTIVE The aim of this study was to establish the association between anthropometric parameters and non-alcoholic fatty liver disease (NAFLD) and to determine the most reliable measurement as a parameter in predicting NAFLD. METHODS Two-hundred fifty-three obese children of ages 10 to 18 years were enrolled in this study. Anthropometric data and metabolic parameters such as fasting blood glucose, insulin and lipid levels, were measured. Liver function tests were assessed. NAFLD was determined by ultrasound. RESULTS Most metabolic parameters and anthropometric indices were significantly higher in children with NAFLD. A univariate logistic regression analysis was performed, taking NAFLD status as the dependent variable and anthropometric parameters as the independent variables. NAFLD was affected significantly by the anthropometric values. The multiple logistic regression analysis showed that neck circumference (NC) was the only parameter which determined the risk in both genders. Each 1 cm increase in the NC increased the risk of NAFLD 1.544-fold (p<0.001, 95% confidence interval (CI): 1.357-2.214) in the boys and 1.733-fold (p=0.001, 95% CI: 1.185-2.012) in the girls. Receiver operating characteristic analysis was performed to compare the reliability of anthropometric measurements. NC was observed to be a better indicator. CONCLUSION Measurement of the NC was shown to be associated with NAFLD in children. We suggest the use of NC as a novel, simple, practical, and reliable anthropometric index in predicting children at risk for NAFLD.
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Affiliation(s)
- Nihal Hatipoğlu
- Erciyes University Faculty of Medicine, Department of Pediatric Endocrinology, Kayseri, Turkey, Phone: +90 352 438 00 76 E-mail:
| | - Serap Doğan
- Erciyes University Faculty of Medicine, Department of Radiology, Kayseri, Turkey
| | - M. Mümtaz Mazıcıoğlu
- Erciyes University Faculty of Medicine, Department of Family Medicine, Kayseri, Turkey
| | - Selim Kurtoğlu
- Erciyes University Faculty of Medicine, Department of Pediatric Endocrinology, Kayseri, Turkey
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11
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Schlieske C, Denzer C, Wabitsch M, Oeztuerk S, Mason RA, Thiere D, Kratzer W. Sonographically measured suprailiac adipose tissue is a useful predictor of non-alcoholic fatty liver disease in obese children and adolescents. Pediatr Obes 2015; 10:260-6. [PMID: 25251446 DOI: 10.1111/ijpo.265] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2014] [Accepted: 08/20/2014] [Indexed: 01/23/2023]
Abstract
OBJECTIVE The objective of the present study was to identify ultrasonographic and anthropometric parameters that are highly associated with the presence of non-alcoholic fatty liver disease (NAFLD) in overweight children and adolescents. METHODS A total of 447 overweight children and adolescents (body mass index, 32.4 ± 5.2 kg m(-2) ; mean age, 14.2 ± 1.9 years; range 10.1-20.3 years) were analysed. Subjects underwent ultrasound examination of the liver as well as ultrasonographic measurement of the amount of adipose tissue overlying the biceps brachii and triceps brachii muscles, and of subscapular, suprailiac and abdominal subcutaneous adipose tissue and intra-abdominal depth. Anthropometric parameters such as body mass index, waist and hip circumference were documented. RESULTS The prevalence of NAFLD was 27.1%; it was significantly associated with the above-cited anthropometric parameters (P < 0.001). Ultrasonographic findings identified a significant association between NAFLD and the amount of subscapular, suprailiac and abdominal subcutaneous adipose tissue (P < 0.001) as well as between NAFLD and intra-abdominal depth (P < 0.001). Stepwise logistic regression analysis showed only intra-abdominal depth for both gender and the deposit of subcutaneous suprailiac adipose tissue in females to be independent predictors of NAFLD. CONCLUSIONS In overweight children and adolescents, we identified intra-abdominal depth for both gender and the ultrasonographically easily determined subcutaneous suprailiac adipose tissue in females as independent predictor of NAFLD.
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Affiliation(s)
- C Schlieske
- Department of Internal Medicine I, Center for Internal Medicine, University Hospital Ulm, Ulm, Germany
| | - C Denzer
- Divison of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, University Hospital Ulm, Ulm, Germany
| | - M Wabitsch
- Divison of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, University Hospital Ulm, Ulm, Germany
| | - S Oeztuerk
- Department of Internal Medicine I, Center for Internal Medicine, University Hospital Ulm, Ulm, Germany
| | - R A Mason
- Louis Stokes Cleveland Department, Veterans Affairs Medical Center, Cleveland, Ohio, USA
| | - D Thiere
- Divison of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, University Hospital Ulm, Ulm, Germany
| | - W Kratzer
- Department of Internal Medicine I, Center for Internal Medicine, University Hospital Ulm, Ulm, Germany
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Liu JQ, Zhang ZJ, Wang W, Lin KR, Liu G, Jiang CS, Chen ZP, Li HT, Lin WL. Risk factors for non-alcoholic fatty liver disease combined with type 2 diabetes mellitus in adolescents. Shijie Huaren Xiaohua Zazhi 2015; 23:1812-1817. [DOI: 10.11569/wcjd.v23.i11.1812] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the risk factors for non-alcoholic fatty liver disease (NAFLD) combined with type 2 diabetes mellitus (T2DM) in adolescents.
METHODS: A long-term follow-up study of 721 urban adolescents showed that there were 134 NAFLD cases and 17 cases of T2DM. Twelve NAFLD patients had combined T2DM. The risk factors for NAFLD combined with T2DM were analyzed using univariate and multivariate logistic regression analyses.
RESULTS: The NAFLD prevalence rate in urban adolescents was 18.6%. The prevalence rate in males was significantly higher than that in females (P < 0.05). The percentage of patients with a fatty liver family history, body mass index (BMI), waist-hip ratio (WHR), ratio of intra-abdominal obesity, 2 h postprandial blood glucose (2 h PBG) and rate of T2DM in NAFLD patients were significantly higher than those in non-NAFLD patients (P < 0.05). BMI, WHR, severity of fatty liver, fasting blood glucose (FBG), aspartate aminotransferase (AST), gamma glutamine transferase (γ-GT), total cholesterol (TC), and the percentages of patients with diabetes family history or fatty liver family history in NAFLD patients with T2DM were significantly higher than those in NAFLD patients without T2DM (P < 0.05). Univariate logistic regression analysis showed that age, BMI ≥ 28 kg/m2, intra-abdominal obesity, fatty liver family history and diabetes family history were significantly related to NAFLD combined with T2DM. In the following multivariate logistic regression, only BMI ≥ 28 kg/m2 and diabetes family history were significantly related to NAFLD combined with T2DM in adolescents.
CONCLUSION: The rate of T2DM in NAFLD adolescents is significantly higher than that in non-NAFLD adolescents. Obesity (BMI ≥ 28 kg/m2) and diabetes family history are risk factors for NAFLD combined with T2DM in adolescents. Controlling weight effectively is urgent to NAFLD patients with a diabetes family history in adolescents.
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Loy JJ, Youn HA, Schwack B, Kurian M, Ren Fielding C, Fielding GA. Improvement in nonalcoholic fatty liver disease and metabolic syndrome in adolescents undergoing bariatric surgery. Surg Obes Relat Dis 2014; 11:442-9. [PMID: 25820083 DOI: 10.1016/j.soard.2014.11.010] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2014] [Revised: 11/10/2014] [Accepted: 11/11/2014] [Indexed: 02/06/2023]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children. It is linked to obesity and the metabolic syndrome (MS), predisposing to future cirrhosis. The objective of this study was to demonstrate the effects that weight loss achieved with laparoscopic adjustable gastric band (LAGB) has on the metabolic parameters and NAFLD scores of obese adolescents with evidence of fatty liver disease. METHODS Adolescents undergoing LAGB were evaluated for NAFLD with evidence of fatty liver on preoperative sonogram, serum biochemistry, or both between 2005 and 2011. Primary endpoint was change in NAFLD scores after LAGB and secondary endpoint change in MS criteria. RESULTS Fifty-six out of 155 adolescents had evidence of fatty liver disease at presentation. The group consisted of 17 (30%) male and 39 (70%) females, mean age 16.1 years (range 14-17.8 yr). Preoperative body mass index (BMI) was 48.8 kg/m(2) (±7) dropping to 37.9 kg/m(2) (±8.3) at 12 months and 36.8 kg/m(2) (±8.2) at 24 months. Fifteen (27%) patients met the criteria for MS. When comparing 1-year postsurgery to presurgery, the NAFLD score decreased by an average of .68 (SD = 1.03, P<.01). The 2-year NAFLD score decreased by a mean of .38 (SD = .99, P = .01). The reoperation rate for band/port related complications was 10.7% at 2 years with no mortality. MS rates improved from 27% to 2% at 2 years (P< .01). CONCLUSIONS LAGB is a safe and effective operation for obese adolescents with NAFLD. There was significant improvement in NAFLD scores and resolution of MS.
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Affiliation(s)
- John J Loy
- NYU Langone Medical Center, Department of Bariatric Surgery, New York, New York.
| | - Heekoung A Youn
- NYU Langone Medical Center, Department of Bariatric Surgery, New York, New York
| | - Bradley Schwack
- NYU Langone Medical Center, Department of Bariatric Surgery, New York, New York
| | - Marina Kurian
- NYU Langone Medical Center, Department of Bariatric Surgery, New York, New York
| | | | - George A Fielding
- NYU Langone Medical Center, Department of Bariatric Surgery, New York, New York
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Elizondo-Montemayor L, Ugalde-Casas PA, Lam-Franco L, Bustamante-Careaga H, Serrano-González M, Gutiérrez NG, Martínez U. Association of ALT and the metabolic syndrome among Mexican children. Obes Res Clin Pract 2014; 8:e79-87. [PMID: 24548580 DOI: 10.1016/j.orcp.2012.08.191] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2011] [Revised: 02/15/2012] [Accepted: 08/10/2012] [Indexed: 12/21/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is emerging as a component of the metabolic syndrome (MetS); Hispanics being particularly predisposed. Alanine aminotransferase (ALT) is considered a marker of NAFLD. The aim of this study was to determine the prevalence and associations between ALT elevations and MetS in normal-weight, overweight and obese Mexican children and adolescents, since data in Mexico is scarce. Body mass index (BMI), waist circumference (WC), percentage body fat, blood pressure, glucose, lipid profiles, ALT and aspartate aminotransferase (AST) were measured in 236, 6-12yo normal-weight, overweight and obese Mexicans from eight public schools. The results showed that elevated ALT (>40 IU/L) was found in 17.7% of the obese and overweight population, with no gender difference. The prevalence of elevated ALT increased linearly across BMI categories (p = 0.001), from 0.0% for the normal-weight group (95%CI 0.0-8.0) to 22.4% for the obese one (95%CI 16.2-30.2). AST/ALT ratio <1 also increased linearly, as did the prevalence of MetS (p = 0.001), from 0.0% for the normal-weight group to 40.3% for the obese one. The prevalence of MetS was strongly associated with elevated ALT (p = 0.002), 50% in the elevated ALT group (95%CI 34.1-65.9) and 24.1% in the normal ALT one (95%CI 18.1-31.3). There was also a strong association between MetS and an AST/ALT ratio <1. WC was the best predictor of elevated ALT (AOR = 7.13). Pearson correlation showed that MetS components were significantly correlated with elevated ALT. Therefore elevated ALT levels were highly prevalent and strongly associated with MetS in Mexican children, it should be screened in overweight and obese children.
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Affiliation(s)
- Leticia Elizondo-Montemayor
- Clinical Nutrition and Obesity Research Center, School of Medicine and Health Sciences, Instituto Tecnológico y de Estudios Superiores de Monterrey, Av. Morones Prieto 3000 Pte. Col., Los Doctores, C.P. 64710 Monterrey, N.L., Mexico.
| | - Patricia A Ugalde-Casas
- Clinical Nutrition and Obesity Research Center, School of Medicine and Health Sciences, Instituto Tecnológico y de Estudios Superiores de Monterrey, Av. Morones Prieto 3000 Pte. Col., Los Doctores, C.P. 64710 Monterrey, N.L., Mexico
| | - Lorena Lam-Franco
- Clinical Nutrition and Obesity Research Center, School of Medicine and Health Sciences, Instituto Tecnológico y de Estudios Superiores de Monterrey, Av. Morones Prieto 3000 Pte. Col., Los Doctores, C.P. 64710 Monterrey, N.L., Mexico
| | - Humberto Bustamante-Careaga
- Clinical Nutrition and Obesity Research Center, School of Medicine and Health Sciences, Instituto Tecnológico y de Estudios Superiores de Monterrey, Av. Morones Prieto 3000 Pte. Col., Los Doctores, C.P. 64710 Monterrey, N.L., Mexico
| | - Mónica Serrano-González
- Clinical Nutrition and Obesity Research Center, School of Medicine and Health Sciences, Instituto Tecnológico y de Estudios Superiores de Monterrey, Av. Morones Prieto 3000 Pte. Col., Los Doctores, C.P. 64710 Monterrey, N.L., Mexico
| | - Norma G Gutiérrez
- Clinical Nutrition and Obesity Research Center, School of Medicine and Health Sciences, Instituto Tecnológico y de Estudios Superiores de Monterrey, Av. Morones Prieto 3000 Pte. Col., Los Doctores, C.P. 64710 Monterrey, N.L., Mexico
| | - Ubaldo Martínez
- Clinical Nutrition and Obesity Research Center, School of Medicine and Health Sciences, Instituto Tecnológico y de Estudios Superiores de Monterrey, Av. Morones Prieto 3000 Pte. Col., Los Doctores, C.P. 64710 Monterrey, N.L., Mexico
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Antunes BDMM, Monteiro PA, Silveira LS, Cayres SU, Silva CBD, F IF. Effect of concurrent training on risk factors and hepatic steatosis in obese adolescents. REVISTA PAULISTA DE PEDIATRIA 2014; 31:371-6. [PMID: 24142321 PMCID: PMC4182972 DOI: 10.1590/s0103-05822013000300015] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/22/2012] [Accepted: 10/11/2012] [Indexed: 11/22/2022]
Abstract
OBJECTIVE To analyze the effects of a 20-week concurrent training on the variables of
body composition, lipid profile, and fatty liver diagnosis in obese
adolescents. METHODS An open clinical trial was carried out with 34 obese adolescents aged
between 12 and 15 years. Total body fat, trunk fat mass, total cholesterol
and its fractions (HDL, LDL and VLDL), and triglycerides were analyzed; an
upper abdominal ultrasound was performed in order to diagnose fatty liver.
The participants underwent concurrent training (association of weight
training with aerobic training) three times per week, lasting one hour for
20 weeks. Statistical analysis included paired Studentâ€(tm)s t-test and
frequency analysis in order to verify the relative and absolute reductions
of fatty liver diagnosis, being significant p<0.05. RESULTS The studied adolescents showed statistically significant improvement in body
composition, with a decrease of total body fat percentage, total fat mass,
trunk fat, and an a increase in the lean body mass. They also presented
reduced size of liver lobes, decrease in total cholesterol and in
LDL-cholesterol, with a lower prevalence of fatty liver. CONCLUSIONS The concurrent training was effective for promoting significant improvements
in body fat composition and lipid profile variables, besides reducing fatty
liver prevalence rate.
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Engelmann G, Hoffmann GF, Grulich-Henn J, Teufel U. Alanine aminotransferase elevation in obese infants and children: a marker of early onset non alcoholic Fatty liver disease. HEPATITIS MONTHLY 2014; 14:e14112. [PMID: 24748893 PMCID: PMC3989734 DOI: 10.5812/hepatmon.14112] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/30/2014] [Revised: 02/21/2014] [Accepted: 02/28/2014] [Indexed: 02/07/2023]
Abstract
BACKGROUND Elevated aminotransferases serve as surrogate markers of non-alcoholic fatty liver disease, a feature commonly associated with the metabolic syndrome. Studies on the prevalence of fatty liver disease in obese children comprise small patient samples or focus on those patients with liver enzyme elevation. OBJECTIVES We have prospectively analyzed liver enzymes in all overweight and obese children coming to our tertiary care centre. PATIENTS AND METHODS In a prospective study 224 healthy, overweight or obese children aged 1 - 12 years were examined. Body Mass Index-Standard Deviation Score, alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl-transpeptidase were measured. RESULTS Elevated alanine aminotransferase was observed in 29% of children. 26 % of obese and 30 % of overweight children had liver enzyme elevations. Obese children had significantly higher alanine aminotransferase levels than overweight children (0.9 vs. 0.7 times the Upper Limit of Normal; P = 0.04). CONCLUSIONS Elevation of liver enzymes appears in 29 % obese children in a tertiary care centre. Absolute alanine aminotransferase levels are significantly higher in obese than in overweight children. Even obese children with normal liver enzymes show signs of fatty liver disease as demonstrated by liver enzymes at the upper limit of normal.
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Affiliation(s)
- Guido Engelmann
- Department of Pediatrics, Lukas Hospital, Neuss, Germany
- Corresponding Author: Guido Engelmann, Department of Pediatrics, Lukas Hospital, Preussen Str 84, D-41464 Neuss, Germany. Tel: +49-21318883500, Fax: +49-21318883599, E-mail:
| | | | | | - Ulrike Teufel
- Department of Pediatrics, University of Heidelberg, Heidelberg, Germany
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Kelly AS, Barlow SE, Rao G, Inge TH, Hayman LL, Steinberger J, Urbina EM, Ewing LJ, Daniels SR. Severe obesity in children and adolescents: identification, associated health risks, and treatment approaches: a scientific statement from the American Heart Association. Circulation 2013; 128:1689-712. [PMID: 24016455 DOI: 10.1161/cir.0b013e3182a5cfb3] [Citation(s) in RCA: 736] [Impact Index Per Article: 61.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Severe obesity afflicts between 4% and 6% of all youth in the United States, and the prevalence is increasing. Despite the serious immediate and long-term cardiovascular, metabolic, and other health consequences of severe pediatric obesity, current treatments are limited in effectiveness and lack widespread availability. Lifestyle modification/behavior-based treatment interventions in youth with severe obesity have demonstrated modest improvement in body mass index status, but participants have generally remained severely obese and often regained weight after the conclusion of the treatment programs. The role of medical management is minimal, because only 1 medication is currently approved for the treatment of obesity in adolescents. Bariatric surgery has generally been effective in reducing body mass index and improving cardiovascular and metabolic risk factors; however, reports of long-term outcomes are few, many youth with severe obesity do not qualify for surgery, and access is limited by lack of insurance coverage. To begin to address these challenges, the purposes of this scientific statement are to (1) provide justification for and recommend a standardized definition of severe obesity in children and adolescents; (2) raise awareness of this serious and growing problem by summarizing the current literature in this area in terms of the epidemiology and trends, associated health risks (immediate and long-term), and challenges and shortcomings of currently available treatment options; and (3) highlight areas in need of future research. Innovative behavior-based treatment, minimally invasive procedures, and medications currently under development all need to be evaluated for their efficacy and safety in this group of patients with high medical and psychosocial risks.
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[Non-alcoholic fatty liver disease in obese children and adolescents]. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2013; 56:517-27. [PMID: 23529597 DOI: 10.1007/s00103-012-1639-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in children and adolescents in industrialized countries. Recent studies have demonstrated a prevalence rate of NAFLD in overweight and obese children and adolescents in Germany of up to 30%. The spectrum of NAFLD ranges from pure fatty infiltration (simple steatosis) to inflammation (steatohepatitis, synonymous NASH) to fibrosis and cirrhosis. Age, gender, ethnicity, insulin resistance, and sex steroids are implicated in the pathogenesis of NAFLD in childhood and adolescence. Moreover, NAFLD in the pediatric age group is associated with marked cardiovascular comorbidities. This review focuses on current data regarding epidemiology, pathophysiology, comorbidities, and treatment of NAFLD in children and adolescents.
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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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Rorat M, Jurek T, Kuchar E, Szenborn L, Golema W, Halon A. Liver steatosis in Polish children assessed by medicolegal autopsies. World J Pediatr 2013; 9:68-72. [PMID: 23275099 DOI: 10.1007/s12519-012-0387-8] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2011] [Accepted: 03/15/2012] [Indexed: 12/18/2022]
Abstract
BACKGROUND Cases of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are increasing in the pediatric population. Their growing prevalence coincides with the obesity epidemic. Assessment of the incidence requires liver biopsies on a representative population sample, which are hampered by the absence of indications for invasive examination on children without clinical symptoms. The aim of the current study was to assess the incidence of liver steatosis in the population of children up to 18 years old from Lower Silesia. METHODS We retrospectively reviewed 342 medico-legal autopsy reports from 2000 to 2009. We separated a group of 256 children whose death was caused by trauma. Liver steatosis was diagnosed according to the results of histopathological examinations and typical macroscopic imaging. RESULTS In the 265 children who died from trauma, liver steatosis was reported in 11 (4.2%) children (6 boys) aged between 6 months and 18 years old. Six of the 11 children (54.5%) were found to be overweight. In all 342 children, steatosis was found in 18 (5.3%) children (13 boys), while NASH was diagnosed in 1 (0.3%). Excess body weight was observed in 55.6% (10/18) of children with steatosis. CONCLUSIONS Liver steatosis can occur at any age, even in infancy. Being overweight is a very important risk factor. Gross examination of the liver is insufficient for the diagnosis of steatosis because of its lower sensitivity and specificity. Verification of liver steatosis requires reference histopathological examination.
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Affiliation(s)
- Marta Rorat
- Department of Forensic Medicine, Wroclaw Medical University, Wroclaw, Poland.
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Importance of the liver ultrasound scores in pubertal obese children with nonalcoholic fatty liver disease. Clin Imaging 2012; 37:504-8. [PMID: 23601769 DOI: 10.1016/j.clinimag.2012.07.011] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2012] [Accepted: 07/25/2012] [Indexed: 02/07/2023]
Abstract
AIM The purpose of our study was to determine the relationship between liver ultrasound scores and insulin sensitivity in a population of obese children with nonalcoholic fatty liver disease (NAFLD) and the relationships between other metabolic features and ultrasound scores. METHODS One hundred sixty-nine obese adolescents, 96 girls, and 73 boys (mean age: 12.7 ± 1.3 years, mean body mass index: 26.3 ± 4.6) were enrolled the study. The obese subjects were divided into 2 groups based on their pubertal status. Ultrasonography findings were scored in this study included hepatorenal echo contrast, liver brightness, deep attenuation, and vascular blurring. Scores ranged from 0 to 6 points, and NAFLD was defined if ultrasound score was ≥ 1. Insulin resistance was evaluated by homeostasis model assessment (HOMA-IR) from fasting samples. RESULTS Prevalence of NAFLD in pubertal children (61.9%) had significantly higher than pre-pubertal children (40.8%) (P=.008). Transaminases ratio was significantly correlated in both prepubertal (r=0.231; P=.03) and pubertal (r=0.628, P=0.017) groups. HOMA-IR values were elevated in both groups; however, liver ultrasound score was positively correlated with HOMA-IR (r=0.735, P=.014) in pubertal children. CONCLUSION NAFLD prevalence among obese children is quite high, especially pubertal adolescents than prepubertal children. We demonstrated an association between insulin resistance and NAFLD ultrasound scoring in pubertal obese children. We suggested that ultrasound examination of the liver be included in the routine check-up of the pubertal obese children with insulin resistance to allow the detection of NAFLD at an early stage.
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Abstract
Non-alcoholic fatty liver disease (NAFLD) is rapidly increasing in the Asia-Pacific and affects up to 30 % of the general population. In younger children, prevalence has been reported to be between 2.1 and 4.5 %. The prevalence of NAFLD increases with increasing age. NAFLD is more prevalent in men than women, but this trend fades in older age group. NAFLD is one of the most common causes of raised serum ALT levels and the latter is closely related to the presence of features of metabolic syndrome. NAFLD may contribute to metabolic syndrome in a similar way as visceral adiposity and can be an early predictor of metabolic disorders. NAFLD increases the risk of developing diabetes mellitus and is closely related to degree of glucose intolerance. A significant proportion of patients with NAFLD have impaired glucose tolerance or diabetes mellitus but with normal fasting blood glucose, highlighting the importance of oral glucose tolerance test in NAFLD patients with normal fasting blood glucose. Besides liver-related complications, NAFLD has been associated with cardiovascular complications, hyperuricemia, gout, chronic kidney disease, gallstone disease, colorectal adenomatous polyp, and polycystic ovarian syndrome. NAFLD seems to be related to host metabolic factors rather than viral factors and does not seem to affect severity of the liver disease in patients with chronic hepatitis B. On the other hand, hepatic steatosis may be related to both host metabolic and viral factors in patients with chronic hepatitis C and seems to adversely impact on the severity of liver disease and possibly response to antiviral therapy.
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Nseir W, Shalata A, Marmor A, Assy N. Mechanisms linking nonalcoholic fatty liver disease with coronary artery disease. Dig Dis Sci 2011; 56:3439-49. [PMID: 21655948 DOI: 10.1007/s10620-011-1767-y] [Citation(s) in RCA: 64] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2011] [Accepted: 05/18/2011] [Indexed: 02/08/2023]
Abstract
The most common cause of death in patients with nonalcoholic fatty liver disease (NAFLD) is coronary artery disease (CAD), not chronic liver disease. Fatty liver increases cardiovascular risk by classical (dyslipidemia, hypertension, diabetes) and by less conventional mechanisms. Common pathways involved in the pathogenesis of fatty liver and CAD includes hepatic insulin resistance and sub clinical inflammation. The hepatic insulin resistance state of fatty liver infiltration is characterized by increased FFA, which causes lipotoxicity and impairs endothelium-dependent vasodilatation, increases oxidative stress, and has a cardio toxic effect. Additional metabolic risk factors include leptin, adiponectin, pro inflammatory cytokines [such as IL-6, C-reactive protein and plasminogen activator inhibitor-1 (PAI-1)], which together lead to increased oxidative stress and endothelial dysfunction, finally promoting coronary artery disease (CAD). When classical risk factors are superimposed on fatty liver accumulation, they may further increase the new metabolic risk factors, exacerbating CAD. The clinical implication is that patients with NAFLD are at higher risk (steatohepatitis, diabetes, obesity, atherogenic dyslipidemia) and should undergo periodic cardiovascular risk assessment including the Framingham score, cardiac effort test, and measurement of intimae-media thickening of the carotids arteries. This may improve risk stratification for CAD.
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Affiliation(s)
- W Nseir
- Department of Internal Medicine, Holy Family Hospital, Nazareth, Israel
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Abstract
The incidence of childhood obesity ranges today from approximately 8% to 17%, and is an increasing issue in developed and developing countries. This disease will become increasingly significant in paediatric anaesthesia. Obese children not only have anaesthesia-relevant co-existing diseases, that are, asthma and hypertension, but also have a higher incidence of anaesthesia-related complication. This review covers current definition and some epidemiology of childhood obesity. It summarises potential co-morbidities and provides details for preoperative evaluation, anaesthetic management and prevention of perioperative complications.
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Affiliation(s)
- Claudia Philippi-Höhne
- University of Leipzig, Department of Anesthesiology and Intensive Care Medicine, Liebigstrasse 20, 04103 Leipzig, Germany.
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vd Baan-Slootweg OH, Liem O, Bekkali N, van Aalderen WMC, Rijcken THP, Di Lorenzo C, Benninga MA. Constipation and colonic transit times in children with morbid obesity. J Pediatr Gastroenterol Nutr 2011; 52:442-5. [PMID: 21240026 DOI: 10.1097/mpg.0b013e3181ef8e3c] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
OBJECTIVES The aim of the study was to determine the frequency of functional constipation according to the Rome III criteria in children with morbid obesity and to evaluate by measuring colonic transit times (CTTs) whether decreased colonic motility is present in these children. PATIENTS AND METHODS Ninety-one children with morbid obesity ages 8 to 18 years, entering a prospective, randomized controlled study evaluating the effect of an outpatient versus inpatient treatment program of obesity, participated. All of the children filled out a standardized questionnaire regarding their bowel habits, and CTTs were measured using radioopaque markers. Food diaries were also recorded to evaluate their diet. RESULTS A total of 19 children (21%) had functional constipation according to the Rome III criteria, whereas 1 child had functional nonretentive fecal incontinence. Total CTT exceeded 62 hours in only 10.5% of the children with constipation, and among them, 2 had a total CTT of >100 hours. In the nonconstipated group 8.3% had a delayed CTT. Furthermore, no difference was found between the diet of children with or without constipation, specifically not with respect to fiber and fat intake. CONCLUSIONS Our study confirms a high frequency of functional constipation in children with obesity, using the Rome III criteria. However, abnormal colonic motility, as measured by CTT, was delayed in only a minority of patients. No relation was found between constipation in these children and fiber or fat intake.
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Affiliation(s)
- Olga H vd Baan-Slootweg
- Department of Pediatric Gastroenterology and Nutrition, Emma's Children's Hospital/AMC, Amsterdam, the Netherlands
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Silva GH, Hessel G, Coelho KIR, Escanhoela CAF. Steatosis of indeterminate cause in a pediatric group: is it a primary mitochondrial hepatopathy? SAO PAULO MED J 2011; 129:217-23. [PMID: 21971896 PMCID: PMC10896015 DOI: 10.1590/s1516-31802011000400004] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2010] [Revised: 08/30/2010] [Accepted: 03/28/2011] [Indexed: 01/07/2023] Open
Abstract
CONTEXT AND OBJECTIVE In children, hepatic steatosis may be related to inborn errors of metabolism (IEMs) or to non-alcoholic fatty liver disease (NAFLD). The aim of this study was to assess and characterize steatosis of indeterminate cause through morphological and morphometric analysis of liver tissue. DESIGN AND SETTING Cross-sectional study at the Departments of Pathology of Faculdade de Ciências Médicas, Universidade Estadual de Campinas (FCM-Unicamp) and Faculdade de Medicina de Botucatu, Universidade Estadual Paulista (FMB-Unesp). METHODS Eighteen consecutive liver biopsies obtained from 16 patients of ages ranging from 3 months to 12 years and nine months that were inserted in a database in the study period were analyzed using optical microscopy and transmission electron microscopy. Through electron microscopy, the mitochondrial density and mean mitochondrial surface area were determined in hepatocytes. Ten patients ranging in age from 1 to 14 years were used as a control group. RESULTS "Pure" steatosis was detected, unaccompanied by fibrosis or any other histological alteration. Microvesicular steatosis predominated, with a significant increase in mean mitochondrial surface area. CONCLUSION Microvesicular steatosis may be related to primary mitochondrial hepatopathy, especially due to reduction of β-oxidation or partial stagnation of oxidative phosphorylation. For these reasons, this form of steatosis (which should not be called "pure") is likely to represent an initial stage in the broad spectrum of NAFLD. We have drawn attention to cases of steatosis in the pediatric group, in which the microvesicular form predominates, since this may be associated with mitochondrial disorders.
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Affiliation(s)
- Gustavo Henrique Silva
- Department of Pediatrics, Universidade Estadual de Campinas, Campinas, São Paulo, Brazil.
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El-Koofy NM, El-Karaksy HM, Mandour IM, Anwar GM, El-Raziky MS, El-Hennawy AM. Genetic polymorphisms in non-alcoholic fatty liver disease in obese Egyptian children. Saudi J Gastroenterol 2011; 17:265-70. [PMID: 21727734 PMCID: PMC3133985 DOI: 10.4103/1319-3767.82582] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
BACKGROUND/AIM Polymorphisms in the promoter of microsomal triglyceride transfer protein (MTP) lead to decreased MTP transcription, less export of triglyceride from hepatocytes, and greater intracellular triglyceride accumulation. Therefore, functional polymorphisms in MTP may be involved in determining susceptibility to nonalcoholic steatohepatitis (NASH). The aim of this study is to examine the effect of some genetic influences among a group of obese Egyptian children. PATIENTS AND METHODS A cross-sectional study was conducted on 76 overweight and obese children presenting to the Pediatric Endocrinology Unit, Cairo University Children's Hospital, Egypt, as well as on 20 healthy controls. Anthropometric measurements were taken for all the patients and they underwent clinical examination, ultrasonographic examination of the liver, and liver biopsy when appropriate. Liver functions, blood glucose, serum insulin, C-peptide, and lipid profile were assessed and HOMA-IR calculated. Blood samples from biopsy-proven NASH patients and controls were analyzed by polymerase chain reaction (PCR) and restriction fragment length polymorphism for the -493 G/T polymorphism in the promoter of MTP and the 1183 T/C polymorphism in the mitochondrial targeting sequence of manganese superoxide dismutase (MnSOD). RESULTS Eight had biopsy-proven simple steatosis and 7 had NASH. NASH patients had a much higher incidence of the MTP G/G genotype (P = 0.002, CI: 2.9-392) compared with the controls. NASH patients also had a 100% prevalence of the MnSOD T/T genotype. CONCLUSION Certain genotypes in MTP and MnSOD are significantly more prevalent among obese children with NASH and may be responsible for such a phenotype.
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Affiliation(s)
- Nehal M. El-Koofy
- Department of Pediatrics, Cairo University, Egypt,Address for correspondence: Dr. Nehal Mohammed El-Koofy, Department of Pediatrices, Cairo University, Egypt. E-mail:
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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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Ozkol M, Ersoy B, Kasirga E, Taneli F, Bostanci IE, Ozhan B. Metabolic predictors for early identification of fatty liver using doppler and B-mode ultrasonography in overweight and obese adolescents. Eur J Pediatr 2010; 169:1345-52. [PMID: 20499088 DOI: 10.1007/s00431-010-1227-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2010] [Accepted: 05/12/2010] [Indexed: 12/15/2022]
Abstract
(1) to evaluate the frequency of asymptomatic fatty liver disease (FLD) using both Doppler and B-mode ultrasound (US) in overweight and obese adolescents; (2) to compare metabolic findings of fatty liver (FL) assessed by two methods; and (3) to evaluate metabolic predictors of FL shown by these methods. Fifty-nine overweight and obese adolescents aged between 9.0 and 17.0 years and 41 non-obese healthy adolescents were included in this study. B-mode and right hepatic vein Doppler ultrasonography (US) were performed and anthropometric indices, lipid profiles, and adiponectin levels were evaluated in all adolescents. HDL-C levels were significantly lower in patients with FL detected by Doppler US compared to patients without FL (p < 0.05). HDL-C levels were inversely correlated with presence of FL assessed by two methods (r = -0.285, p = 0.004; r = -0.328, p = 0.001, respectively) and adiponectin levels were correlated with presence of FL only detected by B-mode US (r = -0.263, p = 0.008). Adiponectin levels were significantly lower in patients with FL than those without FL assessed by B-Mode US (p = 0.049). Multiple regression analysis revealed that HDL-C levels was the most important predictor of FL assessed by Doppler US (p = 0.027), while body mass index was the determinant of FL assessed by two methods (p < 0.001) in asymptomatic overweight and obese adolescents. It was found that FLD, identified by both B-mode and Doppler US, is seen frequently in asymptomatic overweight and obese adolescents. Elevated BMI is associated with increased risk of FL assessed by two ultrasonographic methods. When using Doppler US, low HDL-C levels can be used as a good predictor for presence of FLD in overweight and obese adolescents.
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Affiliation(s)
- Mine Ozkol
- Department of Radiology, Medical School, Celal Bayar University, Manisa, Turkey
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Gender difference of alanine aminotransferase elevation may be associated with higher hemoglobin levels among male adolescents. PLoS One 2010; 5:e13269. [PMID: 20967274 PMCID: PMC2953507 DOI: 10.1371/journal.pone.0013269] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2010] [Accepted: 09/14/2010] [Indexed: 01/20/2023] Open
Abstract
BACKGROUND To explore the gender difference of ALT elevation and its association with high hemoglobin levels. METHODS A cross-sectional study of 3547 adolescents (2005 females, mean age of 16.5?.3 years) who were negative for hepatitis B surface antigen received health checkups in 2006. Body mass index (BMI), levels of hemoglobin, ALT and cholesterol were measured. ALT >42 U/L was defined as elevated ALT. Elevated ALT levels were detected in 112 of the 3547 participants (3.3%), more prevalent in males than in females (5.4% vs. 1.4%, p<0.001). Hemoglobin levels had a significant linear correlation with ALT levels in both genders. Abnormal ALT started to occur if hemoglobin >11 g/dl in females or >13.5 g/dl in males, but the cumulative cases of elevated ALT increased more quickly in males. Proportion of elevated ALT increased as either the BMI or hemoglobin level rise, more apparent in male adolescents. Logistic regression modeling showed odds ratio (95% confidence interval) were 24.7 (15.0-40.6) for BMI ≥27 kg/m(2); 5.5 (2.9-10.4) for BMI 24-27 kg/m(2); 2.7 (1.3-5.5) for Q5 (top 20th percentile) hemoglobin level; and 2.6 (1.6-4.1) for male gender. Further separately fitting the logistic models for two genders, the significance of Q5 hemoglobin level only appeared in the males. CONCLUSIONS High hemoglobin level is a significant risk factor of ALT elevation after control hepatitis B, obesity and gender. Males have greater risk of abnormal liver function which may be associated with higher hemoglobin levels.
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Caserta CA, Pendino GM, Amante A, Vacalebre C, Fiorillo MT, Surace P, Messineo A, Surace M, Alicante S, Cotichini R, Zuin M, Rosmini F, Mele A, Marcucci F. Cardiovascular risk factors, nonalcoholic fatty liver disease, and carotid artery intima-media thickness in an adolescent population in southern Italy. Am J Epidemiol 2010; 171:1195-202. [PMID: 20457571 DOI: 10.1093/aje/kwq073] [Citation(s) in RCA: 67] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
The objective of this study was to determine, in an adolescent population, the prevalence of nonalcoholic fatty liver disease (NAFLD) and the association of NAFLD and cardiovascular risk factors with carotid artery intima-media thickness (IMT), a marker of subclinical atherosclerosis. The authors conducted a population-based study among 642 randomly selected adolescents aged 11-13 years in Reggio Calabria, southern Italy, between November 2007 and October 2008. Prevalences of overweight and obesity were 30.5% and 13.5%, respectively. The overall prevalence of NAFLD was 12.5%, increasing to 23.0% in overweight/obese adolescents. In univariate analysis, increased IMT was positively associated with the presence of NAFLD, body mass index (BMI), waist circumference, systolic blood pressure (all P's < 0.001), diastolic blood pressure (P = 0.006), gamma-glutamyl transpeptidase (P = 0.006), alanine aminotransferase (P = 0.007), and C-reactive protein (P = 0.008) and was inversely associated with high density lipoprotein cholesterol (P < 0.001). In multivariate analysis, NAFLD (P = 0.002), BMI (P = 0.004), waist circumference (P = 0.003), and systolic blood pressure (P = 0.005) retained significant associations. The authors conclude that NAFLD, BMI, waist circumference, and systolic blood pressure are independent markers of increased IMT in a random sample of adolescents.
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Nelson RA, Bremer AA. Insulin resistance and metabolic syndrome in the pediatric population. Metab Syndr Relat Disord 2010; 8:1-14. [PMID: 19943799 DOI: 10.1089/met.2009.0068] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The metabolic syndrome is a constellation of specific anthropometric, physiological, and biochemical abnormalities predisposing affected individuals to the development of diabetes and cardiovascular disease. The syndrome is well described in the adult literature. However, its description in the pediatric literature is more limited. Due in large part to the normal physiological changes that occur in children and adolescents with respect to growth and puberty, investigators have also struggled to establish a standard definition of the syndrome in the pediatric age group, hindering coordinated research efforts. However, whatever definition of the syndrome is used, the prevalence of the metabolic syndrome in the pediatric age group has increased worldwide. Insulin resistance is the principal metabolic abnormality that is common to the development of the metabolic syndrome in both children and adults. This review summarizes current research regarding the pathophysiology of insulin resistance and how this may contribute to specific abnormalities seen in children and adolescents with the metabolic syndrome. Specifically, insulin resistance in pediatric patients is correlated with cardiovascular risk factors such as elevated blood pressure, dyslipidemia, and type 2 diabetes mellitus, all of which are significant risk factors for adult disease. In addition, current treatment and prevention strategies, including lifestyle modifications, pharmacologic agents, and certain surgical therapies, are highlighted. The need for collaborative changes at the family, school, city, state, and national levels to address the growing prevalence of the metabolic syndrome in the pediatric age group is also reviewed.
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Affiliation(s)
- Rachel A Nelson
- Department of Pediatrics, University of California Davis Medical Center, Sacramento, California 95817-2208, USA
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Non-alcoholic fatty liver disease: the hepatic consequence of obesity and the metabolic syndrome. Proc Nutr Soc 2010; 69:211-20. [DOI: 10.1017/s0029665110000030] [Citation(s) in RCA: 157] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is now the most common liver disease in both adults and children worldwide. As a disease spectrum, NAFLD may progress from simple steatosis to steatohepatitis, advanced fibrosis and cirrhosis. An estimated 20–35% of the general population has steatosis, 10% of whom will develop the more progressive non-alcoholic steatohepatitis associated with markedly increased risk of cardiovascular- and liver-related mortality. Development of NAFLD is strongly linked to components of the metabolic syndrome including obesity, insulin resistance, dyslipidaemia and type 2 diabetes. The recognition that NAFLD is an independent risk factor for CVD is a major public health concern. There is a great need for a sensitive non-invasive test for the early detection and assessment of the stage of NAFLD that could also be used to monitor response to treatment. The cellular and molecular aetiology of NAFLD is multi-factorial; genetic polymorphisms influencing NAFLD have been identified and nutrition is a modifiable environmental factor influencing NAFLD progression. Weight loss through diet and exercise is the primary recommendation in the clinical management of NAFLD. The application of systems biology to the identification of NAFLD biomarkers and factors involved in NAFLD progression is an area of promising research.
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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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Denzer C, Thiere D, Muche R, Koenig W, Mayer H, Kratzer W, Wabitsch M. Gender-specific prevalences of fatty liver in obese children and adolescents: roles of body fat distribution, sex steroids, and insulin resistance. J Clin Endocrinol Metab 2009; 94:3872-81. [PMID: 19773396 DOI: 10.1210/jc.2009-1125] [Citation(s) in RCA: 90] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
CONTEXT Nonalcoholic fatty liver disease (NAFLD) is known to have a gender-dimorphic prevalence in obese children. Less information is available on predictive factors for NAFLD in obese youths. OBJECTIVE The aim of the study was to examine the prevalence pattern and to identify clinical and laboratory markers associated with the risk for NAFLD. DESIGN This was a cross-sectional study. SETTING The study setting was a rehabilitation clinic. STUDY PARTICIPANTS A total of 532 obese subjects (291 girls) aged 8-19 yr participated in the study. MAIN MEASUREMENTS Steatosis hepatis and visceral fat mass were determined by ultrasound. Laboratory tests included serum lipids, adiponectin, high-sensitivity C-reactive protein, sex steroids, and an oral glucose tolerance test. RESULTS Prevalence of hepatic steatosis was significantly higher in boys (41.1%) than in girls (17.2%) and was highest in postpubertal boys (51.2%) and lowest in postpubertal girls (12.2%). Severity of steatosis was associated with increased visceral fat mass, insulin resistance, lower adiponectin levels, and higher blood pressure. Three factors were extracted from the panel of investigated parameters by principal component analysis. Logistic regression analysis revealed significant associations of simple steatosis with the "insulin resistance and visceral fat" factor and the "body fat distribution and inflammation" factor in both genders and additionally with the "steroid hormones" factor in girls. Risk for steatosis hepatis with concomitantly elevated ALT was associated only with "insulin resistance and visceral fat" in girls and with all three factors in boys. CONCLUSION Our results suggest significant associations of NAFLD with markers of visceral obesity and insulin resistance in both genders and gender-specific associations with parameters of body fat distribution and sex steroids.
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Affiliation(s)
- Christian Denzer
- Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, University Hospital of Ulm, D-89075 Ulm, Germany
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Salameh N, Larrat B, Abarca-Quinones J, Pallu S, Dorvillius M, Leclercq I, Fink M, Sinkus R, Van Beers BE. Early Detection of Steatohepatitis in Fatty Rat Liver by Using MR Elastography. Radiology 2009; 253:90-7. [DOI: 10.1148/radiol.2523081817] [Citation(s) in RCA: 116] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
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Abstract
Metabolic consequences of obesity including insulin resistance, type 2 diabetes mellitus, hyperlipidemia, hypertension, polycystic ovarian syndrome, and non-alcoholic fatty liver infiltration are rapidly emerging in the pediatric population. Identifying effective strategies for identifying and treating these obesity related comorbidities in children are crucial to the prevention of future cardiovascular disease and poor health outcomes.This review discusses the pathophysiologic connections between obesity, metabolic disease and cardiovascular risk. Current evidence and recommendations for screening and treatment for the metabolic consequences of pediatric obesity are reviewed.
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Affiliation(s)
- Katie Larson Ode
- Division of Pediatric Endocrinology, University of Minnesota, 420 Delaware Street SE, MMC 404, Minneapolis, MN 55455, USA.
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Reinehr T, Schmidt C, de Sousa G, Andler W. Association between leptin and transaminases: 1-year follow-up study in 180 overweight children. Metabolism 2009; 58:497-503. [PMID: 19303970 DOI: 10.1016/j.metabol.2008.11.007] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2008] [Accepted: 11/18/2008] [Indexed: 01/14/2023]
Abstract
Leptin and insulin resistance are being discussed to be involved in the pathogenesis of nonalcoholic fatty liver disease, which is frequently characterized by moderately elevated transaminases. However, longitudinal studies proving an association between leptin, insulin resistance, and transaminases are scarce. We examined weight status, aspartate aminotransferase (AST), alanine aminotransferase (ALT), leptin, glucose, and insulin in 180 overweight children at baseline and 1 year later. Relationships between these parameters at baseline and their changes in the course of 1 year were determined by multiple regression analysis adjusted for age, sex, pubertal stage, and body mass index (BMI). Leptin but not homeostasis model assessment of insulin resistance index correlated significantly to transaminases in both cross-sectional and longitudinal analyses. The same findings were observed in 30 children with suspected nonalcoholic fatty liver disease by ultrasound. The 130 children who participated in a 1-year lifestyle intervention reduced their overweight (standard deviation score [SDS]-BMI, -0.37 +/- 0.11). In the course of 1 year, their changes of transaminases depended on change of weight status (SDS-BMI decrease >0.5: ALT 12 [10-15] --> 9 [8-13] U/L, AST 11 [9-12] --> 9 [8-12] U/L; SDS-BMI decrease >0 but <or=0.5: ALT 14 [11-18] --> 16 [12-26] U/L, AST 10 [8-14] --> 10 [8-24] U/L; no SDS-BMI decrease: ALT 13 [11-20] --> 20[13-33] U/L, AST 11 [9-21] --> 15 [9-24] U/L; data as median and interquartile range). The 50 children without intervention increased their SDS-BMI (+0.02 +/- 0.18) and transaminases (ALT 14 [11-18] --> 19 [15-25] U/L, AST 10 [8-15] --> 16 [10-25] U/L). These findings suggest that leptin may be involved in the pathogenesis of liver diseases. However, to test this hypothesis, careful histologic assessments in correlation to leptin levels are needed.
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Affiliation(s)
- Thomas Reinehr
- Vestische Hospital for Children and Adolescents, University of Witten-Herdecke, 45711 Datteln, Germany.
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Alavian SM, Mohammad-Alizadeh AH, Esna-Ashari F, Ardalan G, Hajarizadeh B. Non-alcoholic fatty liver disease prevalence among school-aged children and adolescents in Iran and its association with biochemical and anthropometric measures. Liver Int 2009; 29:159-63. [PMID: 18492015 DOI: 10.1111/j.1478-3231.2008.01790.x] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
OBJECTIVE To investigate the prevalence of non-alcoholic fatty liver disease (NAFLD) as well as the determination of associated metabolic abnormalities in Iranian school-aged children and adolescents. METHOD Data were obtained from 966 children aged 7-18 years in Iran by a cross-sectional survey in 2007. These children were subjected to a complete anthropometric and laboratory measurement and abdominal ultrasonography for liver echogenicity and size. A questionnaire was also used to obtain information on demographical and medical history, dietary habit, alcohol consumption and cigarette smoking. RESULTS Fatty liver was diagnosed by ultrasound in 7.1% of children. The prevalence of elevated alanine aminotransferase (ALT) was 1.8%. NAFLD was significantly more common in the older group (12.5 against 3.5%, P<0.0001). The odds ratios (OR) (95% confidence interval) for NAFLD in children having elevated ALT, high fasting insulin, total cholesterol, low density lipoprotein (LDL) cholesterol, triglyceride and insulin resistance (IR) were 10.9 (3.9-30.4), 2.8 (1.6-4.8), 2.8 (1.5-5.1), 2.8 (1.5-5.3), 2.5 (1.3-4.8) and 4.4 (1.6-12.3) respectively. Therefore, NAFLD was significantly associated with increasing age, ALT, fasting insulin, total cholesterol, LDL cholesterol, triglyceride and IR. In multiple logistic regression analysis, ALT (OR=1.2; P<0.01), total cholesterol (OR=1.01; P<0.01) and waist circumference (OR=1.14, P<0.0001) were independent metabolic factors predictive of NAFLD after adjustment for other variables. CONCLUSION There was a strong relationship between NAFLD and the abnormal metabolic variables in children. It will be very useful if children are assessed for variables such as waist circumference, fasting blood sugar, fasting insulin and serum lipid profile in order to screen those susceptible to NAFLD.
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Affiliation(s)
- Seyed-Moayed Alavian
- Baqiyatallah Research Center for Gastroenterology and Liver Diseases (BRCGL), Baqiyatallah University of Medical Sciences, Tehran Hepatitis Center, Tehran, Iran.
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Tominaga K, Fujimoto E, Suzuki K, Hayashi M, Ichikawa M, Inaba Y. Prevalence of non-alcoholic fatty liver disease in children and relationship to metabolic syndrome, insulin resistance, and waist circumference. Environ Health Prev Med 2009; 14:142-9. [PMID: 19568858 DOI: 10.1007/s12199-008-0074-5] [Citation(s) in RCA: 53] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2008] [Accepted: 12/22/2008] [Indexed: 01/01/2023] Open
Abstract
OBJECTIVES To investigate the prevalence of non-alcoholic fatty liver disease (NAFLD) in children and its relationship to metabolic syndrome, insulin resistance, and waist circumference (WC). METHODS This was a population-based cross-sectional, case-control study. Cases were selected among students of a primary and junior high school, respectively, and age- and sex-matched control subjects were selected randomly (ratio of cases to control subject was 37:113). RESULTS Of the 846 students, aged between 6 and 15 years, enrolled in the study and screened by ultrasonography, 37 children were diagnosed as having NAFLD (score >/= 1). There was a significant sex difference in the prevalence of NAFLD(P = 0.003). The trend test revealed a strong dose-response relationship (P < 0.001) between pediatric NAFLD and the number of the proposed components of pediatric metabolic syndrome in Japan (MetS-JC), such as a clustering of the components of MetS-JC. Additionally, the linear trend of the odds ratios (ORs) with increasing percentile of the homeostasis model assessment-insulin resistance (HOMA-IR) was statistically significant (P < 0.001). However, when WC was added to the logistic model, the ORs were no longer significant, whereas WC turned out to be an independent risk factor for NAFLD regardless of the HOMA-IR index. CONCLUSION The prevalence of NAFLD in children and adolescents is closely related to metabolic syndrome, insulin resistance, and WC.
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Affiliation(s)
- Kunihiko Tominaga
- Department of Epidemiology and Environmental Health, Juntendo University School of Medicine, Juntendo University, Tokyo, Japan,
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Rocha R, Cotrim HP, Bitencourt AGV, Barbosa DBV, Santos AS, Almeida ADM, Cunha B, Guimarães I. Nonalcoholic fatty liver disease in asymptomatic Brazilian adolescents. World J Gastroenterol 2009; 15:473-7. [PMID: 19152453 PMCID: PMC2653370 DOI: 10.3748/wjg.15.473] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the prevalence and clinical characteristics of Nonalcoholic fatty liver disease (NAFLD) among asymptomatic Brazilian adolescents. METHODS Transversal observational study included asymptomatic adolescents with central obesity from private and public schools in Salvador-Bahia, northeastern Brazil. The children answered a questionnaire that included age, gender, race, and medical history, and were submitted to a complete physical exam and abdominal ultrasound. Biochemical exams included: ALT, AST, GGT, C reactive protein (CRP), fasting glucose, insulin, cholesterol and triglycerides. Criteria for NAFLD included: the presence of steatosis in ultrasound and/or high level of ALT, negative or occasional historic of intake of alcohol (<or= 140 g/wk), negative investigation for hepatitis A, B, C, auto-immune hepatitis, Wilson disease and hemochromatosis. RESULTS From October, 2005 to October, 2006, the study included 1801 subjects between 11 and 18 years of age and a mean age of 13.7+/-2.0 years. One hundred ninety-nine had central obesity. The prevalence of NAFLD was 2.3%, most of whom were male and white. Insulin resistance (IR) was observed in 22.9% of them and had positive correlations with ALT and GGT (P<0.05). Elevated CRP was observed in 6.9% of the cases; however, it was not associated with WC, IR or liver enzymes. CONCLUSION The prevalence of NAFLD in Brazilian adolescents was low. The ethnicity may have influence this frequency in the population studied, which had a large proportion of African descendents.
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Affiliation(s)
- Raquel Rocha
- Federal University of Bahia, School of Medicine, Bahia 40110-150, Brazil.
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Fabbrini E, deHaseth D, Deivanayagam S, Mohammed BS, Vitola BE, Klein S. Alterations in fatty acid kinetics in obese adolescents with increased intrahepatic triglyceride content. Obesity (Silver Spring) 2009; 17:25-9. [PMID: 18948971 PMCID: PMC2649753 DOI: 10.1038/oby.2008.494] [Citation(s) in RCA: 67] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
OBJECTIVE It has been hypothesized that excessive fatty acid availability contributes to steatosis and the metabolic abnormalities associated with nonalcoholic fatty liver disease (NAFLD). The purpose of this study was to evaluate whether adipose tissue lipolytic activity and the rate of fatty acid release into plasma are increased in obese adolescents with NAFLD. METHODS Palmitate kinetics were determined in obese adolescents with normal (n = 9; BMI = 37 +/- 2 kg/m(2); intrahepatic triglyceride (IHTG) or= 10% of liver volume) IHTG content during the basal state (postabsorptive condition) and during physiological hyperinsulinemia (postprandial condition). Both groups were matched on body weight, BMI, percent body fat, age, sex, and Tanner stage. The hyperinsulinemic-euglycemic clamp procedure, in conjunction with a deuterated palmitate tracer infusion, was used to determine free-fatty acid (FFA) kinetics, and magnetic resonance spectroscopy was used to determine IHTG content. RESULTS The rate of whole-body palmitate release into plasma was greater in subjects with NAFLD than those with normal IHTG content during basal conditions, (87 +/- 7 vs. 127 +/- 13 micromol/min; P < 0.01) and during physiological hyperinsulinemia, (24 +/- 2 vs. 44 +/- 8 micromol/min; P < 0.01). DISCUSSION These results demonstrate that adipose tissue lipolytic activity is increased in obese adolescents with NAFLD and results in an increase in the rate of fatty acid release into plasma throughout the day. This continual excess in fatty acid flux supports the hypothesis that adipose insulin resistance is involved in the pathogenesis of steatosis and contributes to the metabolic complications associated with NAFLD.
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Affiliation(s)
- Elisa Fabbrini
- Center for Human Nutrition, Washington University School of Medicine, St. Louis, Missouri, USA
- Department of Medical Pathophysiology, University of Rome “La Sapienza,” Rome, Italy
| | - Dinky deHaseth
- Center for Human Nutrition, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Sheela Deivanayagam
- Center for Human Nutrition, Washington University School of Medicine, St. Louis, Missouri, USA
- Division of Pediatric Gastroenterology, Washington University School of Medicine, St. Louis, Missouri, USA
| | - B. Selma Mohammed
- Center for Human Nutrition, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Bernadette E. Vitola
- Center for Human Nutrition, Washington University School of Medicine, St. Louis, Missouri, USA
- Division of Pediatric Gastroenterology, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Samuel Klein
- Center for Human Nutrition, Washington University School of Medicine, St. Louis, Missouri, USA
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Abstract
Nonalcoholic fatty liver disease (NAFLD) is an obesity-associated liver disease found in 3% to 9% of children in the United States. NAFLD represents a spectrum of liver disease and is frequently associated with features of the metabolic syndrome. Nutrition's role in NAFLD is complex. It does not appear that overweight children with NAFLD have an unusual diet compared with their overweight counterparts without NAFLD. It is more likely that they have increased genetic susceptibility to the general poor diet and state of positive calorie balance currently found in many children. The available treatment studies using nutrition counseling and increased physical activity are promising. We recommend initiating sustainable family-oriented lifestyle changes in all children with NAFLD.
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Affiliation(s)
- Miriam B Vos
- Department of Pediatrics, Emory University, 2015 Uppergate Drive NE, Atlanta, GA 30322, USA.
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Abstract
Nonalcoholic fatty liver disease (NAFLD) is an obesity-associated liver disease found in 3% to 9% of children in the United States. NAFLD represents a spectrum of liver disease and is frequently associated with features of the metabolic syndrome. Nutrition's role in NAFLD is complex. It does not appear that overweight children with NAFLD have an unusual diet compared with their overweight counterparts without NAFLD. It is more likely that they have increased genetic susceptibility to the general poor diet and state of positive calorie balance currently found in many children. The available treatment studies using nutrition counseling and increased physical activity are promising. We recommend initiating sustainable family-oriented lifestyle changes in all children with NAFLD.
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Affiliation(s)
- Miriam B Vos
- Department of Pediatrics, Emory University, 2015 Uppergate Drive NE, Atlanta, GA 30322, USA.
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MRI in identifying hepatic steatosis in obese children and relation to ultrasonography and metabolic findings. J Pediatr Gastroenterol Nutr 2008; 47:493-9. [PMID: 18852643 DOI: 10.1097/mpg.0b013e31817b6e10] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
OBJECTIVES The aim of this study was to identify nonalcoholic fatty liver in obese children by magnetic resonance imaging (MRI) and to compare the findings with the data from ultrasonography and from clinical and laboratory testing. PATIENTS AND METHODS Sixty obese children, 6 to 14 years old, underwent hepatic MRI and abdominal ultrasonography. Biochemistry determinations included serum aminotransferases, lipid profile, glucose, and insulin. Anthropometry included body mass index, total and trunk fat, and fat-free mass obtained by dual-energy radiographic absorptiometry. Hepatic steatosis, judged as hepatic fat fraction by MRI, was >or=9%. RESULTS By MRI, 14 (23%) children had hepatic steatosis; of those, 5 had a fat fraction of 9% to 18%, and 9 had a fat fraction >18%. At univariate analysis, fat fraction was positively associated with being male, serum alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyltransferase, body mass index z score, insulin, systolic pressure, and total and trunk fat mass. Hepatic steatosis was independently associated with alanine aminotransferase (P < 0.01). Overall, liver echogenicity on ultrasonography correlated well with fat fraction by MRI (correlation coefficient 0.527, P < 0.0001). Among the 27 children with increased liver echogenicity, 13 (48%) had hepatic fat fraction >or=9%, and 89% of children with echogenicity graded 2 or 3 had fat fraction >18%. All of the children (n = 9) with fat fraction >18% had increased liver echogenicity, and in 8 of them it was graded 2 or 3, but the MRI fat fraction ranged greatly (28%-45%). CONCLUSIONS In obese children, nonalcoholic hepatic steatosis may be associated with the metabolic syndrome. Ultrasonography may be valuable in identifying high hepatic fat accumulation, but its ability to identify lower fat accumulation in the liver is scanty compared with MRI.
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