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Panganiban J, Kehar M, Ibrahim SH, Hartmann P, Sood S, Hassan S, Ramirez CM, Kohli R, Censani M, Mauney E, Cuda S, Karjoo S. Metabolic dysfunction-associated steatotic liver disease (MASLD) in children with obesity: An Obesity Medicine Association (OMA) and expert joint perspective 2025. OBESITY PILLARS 2025; 14:100164. [PMID: 40230708 PMCID: PMC11995806 DOI: 10.1016/j.obpill.2025.100164] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/27/2024] [Revised: 01/28/2025] [Accepted: 01/29/2025] [Indexed: 04/16/2025]
Abstract
Introduction This Obesity Medicine Association (OMA) Expert Joint Perspective examines steatotic liver disease (SLD), which is composed of metabolic dysfunction-associated steatotic liver disease (MASLD), and metabolic dysfunction-associated steatohepatitis (MASH) in children with obesity. The prevalence of obesity is increasing, rates have tripled since 1963 from 5 % to now 19 % of US children affected in 2018. MASLD, is the most common liver disease seen in children, can be a precursor to the development of Type 2 Diabetes (T2DM) and is the primary reason for liver transplant listing in young adults. We must be vigilant in prevention and treatment of MASLD in childhood to prevent further progression. Methods This joint clinical perspective is based upon scientific evidence, peer and clinical expertise. The medical literature was reviewed via PubMed search and appropriate articles were included in this review. This work was formulated from the collaboration of eight hepatologists/gastroenterologists with MASLD expertise and two physicians from the OMA. Results The authors who are experts in the field, determined sentinel questions often asked by clinicians regarding MASLD in children with obesity. They created a consensus and clinical guideline for clinicians on the screening, diagnosis, and treatment of MASLD associated with obesity in children. Conclusions Obesity and the comorbidity of MASLD is increasing in children, and this is a medical problem that needs to be addressed urgently. It is well known that children with metabolic associated chronic disease often continue to have these chronic diseases as adults, which leads to reduced life expectancy, quality of life, and increasing healthcare needs and financial burden. The authors of this paper recommend healthy weight reduction not only through lifestyle modification but through obesity pharmacotherapy and bariatric surgery. Therefore, this guidance reviews available therapies to achieve healthy weight reduction and reverse MASLD to prevent progressive liver fibrosis, and metabolic disease.
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Affiliation(s)
| | - Mohit Kehar
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Children's Hospital of Eastern Ontario, Ottawa, Canada
| | - Samar H. Ibrahim
- Division of Pediatric Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Phillipp Hartmann
- Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
- Division of Gastroenterology, Hepatology & Nutrition, Rady Children’s Hospital San Diego, San Diego, CA, USA
| | - Shilpa Sood
- Division of Pediatric Gastroenterology, Boston Children's Health Physicians, New York Medical College, Valhalla, NY, USA
| | - Sara Hassan
- University of Texas Southwestern, Dallas, TX, United States
| | | | - Rohit Kohli
- Children's Hospital Los Angeles, CA, United States
| | - Marisa Censani
- Weill Cornell Medicine, New York Presbyterian Hospital, New York, NY, United States
| | - Erin Mauney
- Tufts Medical Center, Boston, MA, United States
| | - Suzanne Cuda
- Alamo City Healthy Kids and Families, San Antonio, TX, United States
| | - Sara Karjoo
- Johns Hopkins All Children's Hospital, St. Petersburg, FL, United States
- University of South Florida, Tampa, FL, United States
- Florida State University, Tallahassee, FL, United States
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Karampatsou SI, Paltoglou G, Genitsaridi SM, Kassari P, Charmandari E. The Effect of a Multidisciplinary Lifestyle Intervention Program on Apelin-12, Vaspin and Resistin Concentrations in Children and Adolescents with Overweight and Obesity. Nutrients 2024; 16:3646. [PMID: 39519480 PMCID: PMC11547676 DOI: 10.3390/nu16213646] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Revised: 10/21/2024] [Accepted: 10/22/2024] [Indexed: 11/16/2024] Open
Abstract
Background: Obesity in childhood and adolescence has reached epidemic proportions in recent decades. Methods: In the present study, we determined the concentrations of apelin-12, vaspin and resistin in 106 children and adolescents with overweight or obesity before and after the implementation of a multidisciplinary, personalized lifestyle intervention program of diet, sleep and exercise for 1 year. All subjects attended our Center for the Prevention and Management of Overweight and Obesity in Childhood and Adolescence. Results: Following the lifestyle intervention, there were significant decreases in BMI (p < 0.01), apelin-12 (p < 0.05) and resistin (p < 0.01) concentrations, and an increase in vaspin (p < 0.01) concentration. Glucose was the best positive predictor of apelin-12 (b = 0.236, p < 0.05), and osteopontin was the best negative predictor of changes in apelin-12 (b = -0.299, p < 0.05). Vaspin correlated positively with adiponectin (b = 0.29, p < 0.05), while vitamin D (b = 0.621, p < 0.05) was the best positive predictor of vaspin. BMI z score (b = -0.794, p < 0.05), HDL (b = -0.284, p < 0.05) and HbA1C (b = -0.262, p < 0.05) were the best negative predictors of changes in vaspin. BMI z score was the best positive predictor of resistin (b = 0.437, p < 0.05). Conclusions: These findings suggest that apelin-12, vaspin and resistin correlate with indices of obesity, glucose, lipids and bone metabolism, while interaction with other proteins, such as osteopontin and adiponectin, was also noted. Therefore, apelin-12, vaspin and resistin may be used as biomarkers in children and adolescents with overweight and obesity.
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Affiliation(s)
- Sofia I. Karampatsou
- Division of Endocrinology, Metabolism and Diabetes, First Department of Pediatrics, National and Kapodistrian University of Athens Medical School, ‘Aghia Sophia’ Children’s Hospital, 11527 Athens, Greece; (S.I.K.); (G.P.); (S.M.G.); (P.K.)
- Department of Pediatrics, National and Kapodistrian University of Athens Nursing School, “P. and A. Kyriakou” Children’s Hospital, 11527 Athens, Greece
| | - George Paltoglou
- Division of Endocrinology, Metabolism and Diabetes, First Department of Pediatrics, National and Kapodistrian University of Athens Medical School, ‘Aghia Sophia’ Children’s Hospital, 11527 Athens, Greece; (S.I.K.); (G.P.); (S.M.G.); (P.K.)
- Second Department of Pediatrics, National and Kapodistrian University of Athens Medical School, “P. and A. Kyriakou” Children’s Hospital, 11527 Athens, Greece
| | - Sofia M. Genitsaridi
- Division of Endocrinology, Metabolism and Diabetes, First Department of Pediatrics, National and Kapodistrian University of Athens Medical School, ‘Aghia Sophia’ Children’s Hospital, 11527 Athens, Greece; (S.I.K.); (G.P.); (S.M.G.); (P.K.)
| | - Penio Kassari
- Division of Endocrinology, Metabolism and Diabetes, First Department of Pediatrics, National and Kapodistrian University of Athens Medical School, ‘Aghia Sophia’ Children’s Hospital, 11527 Athens, Greece; (S.I.K.); (G.P.); (S.M.G.); (P.K.)
- Division of Endocrinology and Metabolism, Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, Greece
| | - Evangelia Charmandari
- Division of Endocrinology, Metabolism and Diabetes, First Department of Pediatrics, National and Kapodistrian University of Athens Medical School, ‘Aghia Sophia’ Children’s Hospital, 11527 Athens, Greece; (S.I.K.); (G.P.); (S.M.G.); (P.K.)
- Division of Endocrinology and Metabolism, Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, Greece
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Li X, He M, Yi X, Lu X, Zhu M, Xue M, Tang Y, Zhu Y. Short-chain fatty acids in nonalcoholic fatty liver disease: New prospects for short-chain fatty acids as therapeutic targets. Heliyon 2024; 10:e26991. [PMID: 38486722 PMCID: PMC10937592 DOI: 10.1016/j.heliyon.2024.e26991] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Revised: 12/28/2023] [Accepted: 02/22/2024] [Indexed: 03/17/2024] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a stress-induced liver injury related to heredity, environmental exposure and the gut microbiome metabolism. Short-chain fatty acids (SCFAs), the metabolites of gut microbiota (GM), participate in the regulation of hepatic steatosis and inflammation through the gut-liver axis, which play an important role in the alleviation of NAFLD. However, little progress has been made in systematically elucidating the mechanism of how SCFAs improve NAFLD, especially the epigenetic mechanisms and the potential therapeutic application as clinical treatment for NAFLD. Herein, we adopted PubMed and Medline to search relevant keywords such as 'SCFAs', 'NAFLD', 'gut microbiota', 'Epigenetic', 'diet', and 'prebiotic effect' to review the latest research on SCFAs in NAFLD up to November 2023. In this review, firstly, we specifically discussed the production and function of SCFAs, as well as their crosstalk coordination in the gut liver axis. Secondly, we provided an updated summary and intensive discussion of how SCFAs affect hepatic steatosis to alleviate NAFLD from the perspective of genetic and epigenetic. Thirdly, we paid attention to the pharmacological and physiological characteristics of SCFAs, and proposed a promising future direction to adopt SCFAs alone or in combination with prebiotics and related clinical drugs to prevent and treat NAFLD. Together, this review aimed to elucidate the function of SCFAs and provide new insights to the prospects of SCFAs as a therapeutic target for NAFLD.
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Affiliation(s)
- Xinyu Li
- Department of Pathophysiology, College of Basic Medical Science, Anhui Medical University, Hefei, China
| | - Maozhang He
- Department of Microbiology, College of Basic Medical Science, Anhui Medical University, Hefei, China
| | - Xinrui Yi
- Department of Pathophysiology, College of Basic Medical Science, Anhui Medical University, Hefei, China
| | - Xuejin Lu
- Department of Pathophysiology, College of Basic Medical Science, Anhui Medical University, Hefei, China
| | - Meizi Zhu
- Department of Pathophysiology, College of Basic Medical Science, Anhui Medical University, Hefei, China
| | - Min Xue
- Department of Pathophysiology, College of Basic Medical Science, Anhui Medical University, Hefei, China
| | - Yunshu Tang
- Laboratory Animal Research Center, College of Basic Medical Science, Anhui Medical University, Hefei, China
| | - Yaling Zhu
- Department of Pathophysiology, College of Basic Medical Science, Anhui Medical University, Hefei, China
- Laboratory Animal Research Center, College of Basic Medical Science, Anhui Medical University, Hefei, China
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Jayasekera D, Hartmann P. Noninvasive biomarkers in pediatric nonalcoholic fatty liver disease. World J Hepatol 2023; 15:609-640. [PMID: 37305367 PMCID: PMC10251277 DOI: 10.4254/wjh.v15.i5.609] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2023] [Revised: 03/14/2023] [Accepted: 04/10/2023] [Indexed: 05/24/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease worldwide among children and adolescents. It encompasses a spectrum of disease, from its mildest form of isolated steatosis, to nonalcoholic steatohepatitis (NASH) to liver fibrosis and cirrhosis, or end-stage liver disease. The early diagnosis of pediatric NAFLD is crucial in preventing disease progression and in improving outcomes. Currently, liver biopsy is the gold standard for diagnosing NAFLD. However, given its invasive nature, there has been significant interest in developing noninvasive methods that can be used as accurate alternatives. Here, we review noninvasive biomarkers in pediatric NAFLD, focusing primarily on the diagnostic accuracy of various biomarkers as measured by their area under the receiver operating characteristic, sensitivity, and specificity. We examine two major approaches to noninvasive biomarkers in children with NAFLD. First, the biological approach that quantifies serological biomarkers. This includes the study of individual circulating molecules as biomarkers as well as the use of composite algorithms derived from combinations of biomarkers. The second is a more physical approach that examines data measured through imaging techniques as noninvasive biomarkers for pediatric NAFLD. Each of these approaches was applied to children with NAFLD, NASH, and NAFLD with fibrosis. Finally, we suggest possible areas for future research based on current gaps in knowledge.
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Affiliation(s)
- Dulshan Jayasekera
- Department of Internal Medicine and Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, United States
| | - Phillipp Hartmann
- Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, University of California San Diego, La Jolla, CA 92093, United States.
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Jeong S, Oh YH, Choi S, Chang J, Kim SM, Park SJ, Cho Y, Son JS, Lee G, Park SM. Association of Change in Smoking Status and Subsequent Weight Change with Risk of Nonalcoholic Fatty Liver Disease. Gut Liver 2023; 17:150-158. [PMID: 36325764 PMCID: PMC9840925 DOI: 10.5009/gnl220038] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Revised: 03/05/2022] [Accepted: 03/15/2022] [Indexed: 11/06/2022] Open
Abstract
Background/Aims Smoking is considered a risk factor for the development of nonalcoholic fatty liver disease (NAFLD). However, the association of a weight change after a change in smoking status and the risk of NAFLD remains undetermined. Methods This study used the Korean National Health Insurance Service-National Sample Cohort. Based on the first (2009 to 2010) and second (2011 to 2012) health examination periods, 139,180 adults aged at least 40 years were divided into nonsmoking, smoking cessation, smoking relapse, and sustained smoking groups. NAFLD was operationally defined using the fatty liver index. The adjusted odds ratio (aOR) and 95% confidence interval (CI) were calculated using multivariable-adjusted logistic regression. Results Compared to nonsmoking with no body mass index (BMI) change, the risk of NAFLD was significantly increased among subjects with BMI gain and nonsmoking (aOR, 4.07; 95% CI, 3.77 to 4.39), smoking cessation (aOR, 5.52; 95% CI, 4.12 to 7.40), smoking relapse (aOR, 7.51; 95% CI, 4.81 to 11.72), and sustained smoking (aOR, 6.65; 95% CI, 5.33 to 8.29), whereas the risk of NAFLD was reduced among participants with BMI loss in all smoking status groups. In addition, smoking cessation (aOR, 1.76; 95% CI, 1.35 to 2.29) and sustained smoking (aOR, 1.64; 95% CI, 1.39 to 1.94) were associated with higher risk of NAFLD among participants with no BMI change. The liver enzyme levels were higher among participants with smoking cessation and BMI gain. Conclusions Monitoring and management of weight change after a change in smoking status may be a promising approach to reducing NAFLD.
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Affiliation(s)
- Seogsong Jeong
- Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea
| | - Yun Hwan Oh
- Department of Family Medicine, Jeju National University School of Medicine, Jeju, Korea
| | - Seulggie Choi
- Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea
| | - Jooyoung Chang
- Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea
| | - Sung Min Kim
- Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea
| | - Sun Jae Park
- Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea
| | - Yoosun Cho
- Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Joung Sik Son
- Department of Family Medicine, Korea University Guro Hospital, Seoul, Korea
| | - Gyeongsil Lee
- Department of Family Medicine, Seoul National University Hospital, Seoul, Korea
| | - Sang Min Park
- Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea,Department of Family Medicine, Seoul National University Hospital, Seoul, Korea,Corresponding Author Sang Min Park, ORCIDhttps://orcid.org/0000-0002-7498-4829, E-mail
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6
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Abstract
Nonalcoholic fatty liver disease (NAFLD) is becoming increasingly common as the global economy grows and living standards improve. Timely and effective preventions and treatments for NAFLD are urgently needed. Retinol-binding protein-4 (RBP4), the protein that transports retinol through the circulation, was found to be positively related to diabetes, obesity, cardiovascular disease, and other metabolic diseases. Observational studies on the association between serum RBP4 level and the prevalence of NAFLD found contradictory results. Some of the underlying mechanisms responsible for this association have been revealed, and the possible clinical implications of treating NAFLD by targeting RBP4 have been demonstrated. Future studies should focus on the predictive value of RBP4 on NAFLD development and its potential as a therapeutic target in NAFLD.
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Affiliation(s)
- Hangkai Huang
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, China
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Özkan EA, Sadigov A, Öztürk O. Evaluation of Serum Omentin-1, Vaspin, Leptin, Adiponectin Levels in Obese/Overweight Children and Their Relationship With Non-Alcoholic Fatty Liver Disease. Clin Nutr Res 2022; 11:194-203. [PMID: 35949560 PMCID: PMC9348910 DOI: 10.7762/cnr.2022.11.3.194] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Revised: 07/06/2022] [Accepted: 07/11/2022] [Indexed: 11/26/2022] Open
Abstract
To investigate adipokines (vaspin, omentin-1, adiponectin and leptin) and their correlation with hepatosteatosis degree in obese/overweight (O/O) children. We analyzed adipokine levels of 81 children (49 O/O, [body mass index (BMI) > 95th] and 32 non-obese (BMI = 5-85th) admitted to the pediatric outpatient clinic. Serum triglyceride, glucose, low density lipoprotein-cholesterol, total cholesterol, high density lipoprotein-cholesterol, alanine aminotransferase, aspartate aminotransferase (AST), insulin, HbA1c levels and leptin, omentin-1, vaspin, adiponectin levels were studied. O/O children with hepatosteatosis were divided into grades 1, 2 and 3 according to the degree of hepatosteatosis determined by ultrasonography. While AST (p = 0.001), triglyceride (p = 0.006), BMI percentile (p = 0.000), HOMA index (p = 0.002), systolic blood pressure (p = 0.02), leptin (p = 0.001), omentin-1 (p = 0.001), adiponectin (p = 0.001) levels were higher, vaspin level was lower (p = 0.008) in the (O/O) group compared to the controls. There was a positive correlation between HDL and vaspin, and a negative correlation between HDL and omentin-1 in the O/O group. Also it was observed that as the degree of hepatosteotosis increased, leptin (p = 0.004), omentin-1 (p = 0.001) levels were increased. There was no significant change in vaspin level (p = 0.128). The high levels of omentin-1, leptin and adiponectin have an association with the development of hepatosteatosis in O/O children.
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Affiliation(s)
- Esra Akyüz Özkan
- Ondokuz Mayıs University Medical Faculty, Department of Pediatrics, Samsun 55139, Turkey
| | - Allahverdi Sadigov
- Yozgat Bozok University Medical Faculty, Department of Pediatrics, Yozgat 66200, Turkey
| | - Osman Öztürk
- Yozgat Bozok University Medical Faculty, Department of Pediatrics, Yozgat 66200, Turkey
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Liu B, Zheng H, Liu G, Li Z. Adiponectin is Inversely Associated with Insulin Resistance in Adolescents with Nonalcoholic Fatty Liver Disease. Endocr Metab Immune Disord Drug Targets 2021; 22:631-639. [PMID: 34579641 DOI: 10.2174/1871530321666210927153831] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2021] [Revised: 08/13/2021] [Accepted: 08/16/2021] [Indexed: 12/16/2022]
Abstract
BACKGROUND Insulin resistance(IR) is confirmed as a key feature of nonalcoholic fatty liver disease (NAFLD) in children and adolescents. Numerous studies report that adiponectin (APN) levels are inversely associated with the status of IR in adults with NAFLD. This study aimed to investigate the relationship between serum total APNand homeostasis model assessment insulin resistance(HOMA-IR) in adolescents with NAFLD. METHODS 382 newly-diagnosed NAFLD adolescents, aged 9-16 years old, were enrolled and divided into 3 subgroups according to the APNtertile. Simple and multiple linear regression analyses were performed to assess the correlation between HOMA-IR and APN in boys and girls, respectively. RESULTS The HOMA-IR values tended to decrease in boys according to APN tertiles: 5.6(4.4-7.3) vs. 5.2(4.6-6.9) vs. 4.9(4.1-5.8) (P<0.01), and there was a significant difference in the HOMA-IR values among three APN tertile subgroups in girls(P<0.01).Univariate analysis showed thatbody mass index, waist circumference, weight-to-height ratio, fasting blood glucose, insulin, triglyceride, and APN were significantly associated with HOMA-IR in boys (P<0.05). In girls, body mass index, fasting blood glucose, insulin, total cholesterol, triglyceride, and APN were significantly associated with HOMA-IR (P<0.05).APN was found to be a significant determinant for HOMA-IR only in boys (β=-0.147, P<0.01). CONCLUSION Our findings showed that APN was an independent and significant determinant for increased HOMA-IR in boys with NAFLD. Further studies are needed to explore the underlying mechanisms.
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Affiliation(s)
- Bin Liu
- Department of Neurology, Shanghai Minhang Hospital, Fudan University, Shanghai. China
| | - Huan Zheng
- Department of Cardiology, Worldpath Clinic International, Shanghai. China
| | - Guanghui Liu
- Department of Endocrinology, Tongji Hospital, School of Medicine, Tongji University, Shanghai. China
| | - Zhiling Li
- Department of Pharmacy, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai. China
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Mirzaei A, Asal A, Seidkhani-Nahal A, Noori-Zadeh A. A systematic review and meta-analysis of serum resistin level and its relation to HOMA-IR score using meta-regression in nonalcoholic fatty liver disease patients. MEDITERRANEAN JOURNAL OF NUTRITION AND METABOLISM 2021. [DOI: 10.3233/mnm-210538] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) comorbidity with adipose tissue dysfunction is not new and studies have focused on how adipose tissue influences NAFLD pathophysiology. OBJECTIVE: Quantification of nature and magnitude of the association between serum resistin and also insulin resistance, by calculating pooled Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) score, with NAFLD pathophysiology was the objective of the current study. METHODS: Using systematic review and meta-analysis and standardized mean difference (SMD) as the effect size, the levels of resistin and HOMA-IR scores have been investigated in NAFLD subjects in comparison with controls in the case-control studies using random-effects models. RESULTS: This meta-analysis retrieved a total number of 665 and 522 cases and 671 and 555 control subjects until May 2020 for serum levels of resistin and HOMA-IR score until May 2020. The final analyses demonstrated that pooled SMD of resistin and HOMA-IR score was 0.687 (95% confidence interval, 0.070–1.304) and 1.368 (95% confidence interval, 1.080–1.655); respectively. Moreover, the p-value for the test of significance for each pooled SMD was examined by the z-test and calculated as 0.029 and 0.000 for resistin and HOMA-IR score (clearly considered as statistically significant). CONCLUSION: Based on the findings, the HOMA-IR score and the serum levels of resistin in NAFLD subjects are associated with disease pathogenesis.
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Affiliation(s)
- Asad Mirzaei
- Department of Medical Parasitology, Faculty of Paramedicine, Ilam University of Medical Sciences, Ilam, Iran
- Zoonotic Diseases Research Center, Ilam University of Medical Sciences, Ilam, Iran
| | - Asma Asal
- Student Research Committee, Ilam University of Medical Sciences, Ilam, Iran
| | - Ali Seidkhani-Nahal
- Department of Clinical Biochemistry, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran
| | - Ali Noori-Zadeh
- Student Research Committee, Ilam University of Medical Sciences, Ilam, Iran
- Department of Clinical Biochemistry, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran
- Department of Clinical Biochemistry, Faculty of Allied Medical Sciences, Ilam University of Medical Sciences, Ilam, Iran
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Chang E, Chang JS, Kong ID, Baik SK, Kim MY, Park KS. Multidimensional Biomarker Analysis Including Mitochondrial Stress Indicators for Nonalcoholic Fatty Liver Disease. Gut Liver 2021; 16:171-189. [PMID: 34420934 PMCID: PMC8924798 DOI: 10.5009/gnl210106] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Revised: 06/15/2021] [Accepted: 06/22/2021] [Indexed: 11/22/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is accompanied by a complex and multifactorial pathogenesis with sequential progressions from inflammation to fibrosis and then to cancer. This heterogeneity interferes with the development of precise diagnostic and prognostic strategies for NAFLD. The current approach for the diagnosis of simple steatosis, steatohepatitis, and cirrhosis mainly consists of ultrasonography, magnetic resonance imaging, elastography, and various serological analyses. However, individual dry and wet biomarkers have limitations demanding an integrative approach for the assessment of disease progression. Here, we review diagnostic strategies for simple steatosis, steatohepatitis and hepatic fibrosis, followed by potential biomarkers associated with fat accumulation and mitochondrial stress. For mitochondrial stress indicators, we focused on fibroblast growth factor 21 (FGF21), growth differentiation factor 15 (GDF15), angiopoietin-related growth factor and mitochondrial-derived peptides. Each biomarker may not strongly indicate the severity of steatosis or steatohepatitis. Instead, multidimensional analysis of different groups of biomarkers based on pathogenic mechanisms may provide decisive diagnostic/prognostic information to develop a therapeutic plan for patients with NAFLD. For this purpose, mitochondrial stress indicators, such as FGF21 or GDF15, could be an important component in the multiplexed and contextual interpretation of NAFLD. Further validation of the integrative evaluation of mitochondrial stress indicators combined with other biomarkers is needed in the diagnosis/prognosis of NAFLD.
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Affiliation(s)
- Eunha Chang
- Department of Physiology, Yonsei University Wonju College of Medicine, Wonju, Korea.,Department of Mitohormesis Research Center, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Jae Seung Chang
- Department of Mitohormesis Research Center, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - In Deok Kong
- Department of Physiology, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Soon Koo Baik
- Department of Mitohormesis Research Center, Yonsei University Wonju College of Medicine, Wonju, Korea.,Department of Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Moon Young Kim
- Department of Mitohormesis Research Center, Yonsei University Wonju College of Medicine, Wonju, Korea.,Department of Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Kyu-Sang Park
- Department of Physiology, Yonsei University Wonju College of Medicine, Wonju, Korea.,Department of Mitohormesis Research Center, Yonsei University Wonju College of Medicine, Wonju, Korea
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11
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Kim Y. Emerging Treatment Options for Sarcopenia in Chronic Liver Disease. Life (Basel) 2021; 11:life11030250. [PMID: 33803020 PMCID: PMC8002763 DOI: 10.3390/life11030250] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 03/13/2021] [Accepted: 03/15/2021] [Indexed: 12/17/2022] Open
Abstract
Sarcopenia is characterized by a skeletal muscle disorder with progressive and generalized loss of muscle mass and function, and it increases the risk of adverse outcomes with considerable prevalence in patients with chronic liver disease. Sarcopenia in chronic liver disease underlies complicated and multifactorial mechanisms for pathogenesis, including alterations in protein turnover, hyperammonemia, energy disposal, hormonal changes, and chronic inflammation. The key contribution to sarcopenia in patients with chronic liver diseases can be the hyperammonemia-induced upregulation of myostatin, which causes muscle atrophy via the expression of atrophy-related genes. Several clinical studies on emerging treatment options for sarcopenia have been reported, but only a few have focused on patients with chronic liver diseases, with mostly nutritional and behavioral interventions being carried out. The inhibition of the myostatin-activin receptor signaling pathway and hormonal therapy might be the most promising therapeutic options in combination with an ammonia-lowering approach in sarcopenic patients with chronic liver diseases. This review focuses on current and emerging treatment options for sarcopenia in chronic liver diseases with underlying mechanisms to counteract this condition.
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Affiliation(s)
- Yun Kim
- Hanyang Medicine-Engineering-Bio Collaborative & Comprehensive Center for Drug Development, Hanyang University, Seoul 04763, Korea
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12
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Suri A, Song E, van Nispen J, Voigt M, Armstrong A, Murali V, Jain A. Advances in the Epidemiology, Diagnosis, and Management of Pediatric Fatty Liver Disease. Clin Ther 2021; 43:438-454. [PMID: 33597074 DOI: 10.1016/j.clinthera.2021.01.006] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Revised: 12/28/2020] [Accepted: 01/04/2021] [Indexed: 02/07/2023]
Abstract
PURPOSE Nonalcoholic fatty liver (NAFL) is a major contributor to pediatric liver disease. This review evaluated the current literature on prevalence, screening, diagnosis, and management of NAFL in children and explored recent advances in the field of pediatric NAFL. METHODS A PubMed search was performed for manuscripts describing disease burden, diagnosis, and management strategies in pediatric NAFL published within the past 15 years. Systematic reviews, clinical practice guidelines, randomized controlled trials, and cohort and case-control studies were reviewed for the purpose of this article. FINDINGS The prevalence of NAFL in children is increasing. It is a leading cause of liver-related morbidity and mortality in children. Screening and diagnosis of NAFL in children are a challenge. Lifestyle changes and exercise are the cornerstones of the management of NAFL. IMPLICATIONS Further research is needed to develop better screening and diagnostic tools for pediatric NAFL, including noninvasive diagnostics. NAFL therapeutics is another area of much-needed, ongoing research.
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Affiliation(s)
- Anandini Suri
- Department of Pediatrics, School of Medicine, St. Louis University, St. Louis, Missouri, USA.
| | - Eric Song
- Department of Pediatrics, School of Medicine, St. Louis University, St. Louis, Missouri, USA
| | - Johan van Nispen
- Department of Pediatrics, School of Medicine, St. Louis University, St. Louis, Missouri, USA
| | - Marcus Voigt
- Department of Pediatrics, School of Medicine, St. Louis University, St. Louis, Missouri, USA
| | - Austin Armstrong
- Department of Pediatrics, School of Medicine, St. Louis University, St. Louis, Missouri, USA
| | - Vidul Murali
- Department of Pediatrics, School of Medicine, St. Louis University, St. Louis, Missouri, USA
| | - Ajay Jain
- Department of Pediatrics, School of Medicine, St. Louis University, St. Louis, Missouri, USA
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Du YX, Chen SN, Zhu HL, Niu X, Li J, Fan YW, Deng ZY. Consumption of Interesterified Medium- and Long-Chain Triacylglycerols Improves Lipid Metabolism and Reduces Inflammation in High-Fat Diet-Induced Obese Rats. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2020; 68:8255-8262. [PMID: 32643946 DOI: 10.1021/acs.jafc.0c03103] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
Medium- and long-chain triacylglycerols (MLCTs) were synthesized from rapeseed oil (RO), one kind of commonly used edible long-chain triacylglycerols (TGs), and then delivered to high-fat diet (HFD)-induced obese rats. Compared with RO, MLCT consumption exhibited more potent effects on reducing body and tissue weight gains, plasma TG, and total cholesterol (TC) levels and on improving hepatic TG, TC, fatty acid synthase, acetyl-CoA carboxylase, and lipoprteinlipase contents. Meanwhile, lower amounts of tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1, and endotoxin in plasma, lower levels of interleukin-6 and TNF-α, and higher levels of interleukin-10 in both livers and white adipose tissues were detected in MLCT-fed rats. MLCT intake also remarkably suppressed the size of adipocytes and the number of macrophages. In conclusion, our study suggested that the interesterified MLCT was more efficacious in improving the lipid metabolism and inflammation in HFD-induced obese rats than RO.
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Affiliation(s)
- Ying-Xue Du
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China
| | - Sun-Ni Chen
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China
| | - Hong-Lin Zhu
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China
| | - Xian Niu
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China
| | - Jing Li
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China
| | - Ya-Wei Fan
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China
| | - Ze-Yuan Deng
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China
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Heydari M, Cornide-Petronio ME, Jiménez-Castro MB, Peralta C. Data on Adiponectin from 2010 to 2020: Therapeutic Target and Prognostic Factor for Liver Diseases? Int J Mol Sci 2020; 21:5242. [PMID: 32718097 PMCID: PMC7432057 DOI: 10.3390/ijms21155242] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Revised: 07/15/2020] [Accepted: 07/22/2020] [Indexed: 12/13/2022] Open
Abstract
The review describes the role of adiponectin in liver diseases in the presence and absence of surgery reported in the literature in the last ten years. The most updated therapeutic strategies based on the regulation of adiponectin including pharmacological and surgical interventions and adiponectin knockout rodents, as well as some of the scientific controversies in this field, are described. Whether adiponectin could be a potential therapeutic target for the treatment of liver diseases and patients submitted to hepatic resection or liver transplantation are discussed. Furthermore, preclinical and clinical data on the mechanism of action of adiponectin in different liver diseases (nonalcoholic fatty disease, alcoholic liver disease, nonalcoholic steatohepatitis, liver cirrhosis and hepatocellular carcinoma) in the absence or presence of surgery are evaluated in order to establish potential targets that might be useful for the treatment of liver disease as well as in the practice of liver surgery associated with the hepatic resections of tumors and liver transplantation.
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Affiliation(s)
- Misaq Heydari
- Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), 08036 Barcelona, Spain; (M.H.); (M.E.C.-P.)
| | | | - Mónica B. Jiménez-Castro
- Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), 08036 Barcelona, Spain; (M.H.); (M.E.C.-P.)
| | - Carmen Peralta
- Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), 08036 Barcelona, Spain; (M.H.); (M.E.C.-P.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 08036 Barcelona, Spain
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Overview of the Pathogenesis, Genetic, and Non-Invasive Clinical, Biochemical, and Scoring Methods in the Assessment of NAFLD. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2019; 16:ijerph16193570. [PMID: 31554274 PMCID: PMC6801903 DOI: 10.3390/ijerph16193570] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/31/2019] [Revised: 09/16/2019] [Accepted: 09/20/2019] [Indexed: 02/06/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease worldwide. It represents a range of disorders, including simple steatosis, nonalcoholic steatohepatitis (NASH), and liver cirrhosis, and its prevalence continues to rise. In some cases, hepatocellular carcinoma (HCC) may develop. The develop;ment of non-invasive diagnostic and screening tools is needed, in order to reduce the frequency of liver biopsies. The most promising methods are those able to exclude advanced fibrosis and quantify steatosis. In this study, new perspective markers for inflammation, oxidative stress, apoptosis, and fibrogenesis; emerging scoring models for detecting hepatic steatosis and fibrosis; and new genetic, epigenetic, and multiomic studies are discussed. As isolated biochemical parameters are not specific or sensitive enough to predict the presence of NASH and fibrosis, there is a tendency to use various markers and combine them into mathematical algorithms. Several predictive models and scoring systems have been developed. Current data suggests that panels of markers (NAFLD fibrosis score, Fib-4 score, BARD score, and others) are useful diagnostic modalities to minimize the number of liver biopsies. The review unveils pathophysiological aspects related to new trends in current non-invasive biochemical, genetic, and scoring methods, and provides insight into their diagnostic accuracies and suitability in clinical practice.
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Liu J, Xing J, Wang B, Wei C, Yang R, Zhu Y, Qiu H. Correlation Between Adiponectin Gene rs1501299 Polymorphism and Nonalcoholic Fatty Liver Disease Susceptibility: A Systematic Review and Meta-Analysis. Med Sci Monit 2019; 25:1078-1086. [PMID: 30735485 PMCID: PMC6376635 DOI: 10.12659/msm.912737] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Background Metabolic related nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver diseases around the world. A single nucleotide polymorphism (SNP) rs1501299 (+276G>T) in the adiponectin gene has been recently revealed to be responsible for susceptibility to NAFLD. This meta-analysis intended to assess the association risk of NAFLD and rs1501299 polymorphism. Material/Methods We conducted a literature search on PubMed, Embase, and Cochrane Library databases. All involved studies were selected based on our search criteria. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to quantify the strength of the association. Subgroup analysis considered the effects of ethnicity, subject scope, and source of control. Publication bias was assessed by Begg’s tests. Results Eight qualified case-control studies with 1639 patients and 1426 controls demonstrated a significant correlation between rs1501299 polymorphism in adiponectin and NAFLD under the dominant model (OR=1.18, 95% CI=1.02–1.36), allelic contrast (OR=1.21, 95% CI=1.09–1.36), homozygote comparison (OR=1.63, 95% CI=1.26–2.01) and the recessive allele model (OR=1.58, 95% CI=1.23–2.02) with evident heterogeneity. No association was observed between the risk of NAFLD and the genotypic variants in heterozygote comparison (OR=1.11, 95% CI=0.95–1.29) without heterogeneity. Subgroup analysis suggested that the sample size could be the potential source of heterogeneity. Source of control was not the reason for between-study heterogeneity and further sensitivity analysis and publication bias revealed good consistency and symmetry in the pooling studies. Conclusions Results from our current meta-analysis gave insight into the correlation between rs1501299 polymorphism and the risk of NAFLD, indicating the variant of rs1501299 might be related to increased NAFLD susceptibility.
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Affiliation(s)
- Jiaxing Liu
- Bayi College of People's Liberation Army (PLA), Anhui Medical University, Nanjing, Jiangsu, China (mainland)
| | - Jicheng Xing
- Department of Clinical Laboratory, The 81st Hospital of People's Liberation Army (PLA), Nanjing, Jiangsu, China (mainland)
| | - Bing Wang
- Department of Clinical Laboratory, The 81st Hospital of People's Liberation Army (PLA), Nanjing, Jiangsu, China (mainland)
| | - Changyong Wei
- Department of Hematology and Medical Oncology, School of Medicine, Emory University, Atlanta, GA, USA
| | - Ruining Yang
- Department of Clinical Laboratory, The 81st Hospital of People's Liberation Army (PLA), Nanjing, Jiangsu, China (mainland)
| | - Yuerong Zhu
- Department of Clinical Laboratory, The 81st Hospital of People's Liberation Army (PLA), Nanjing, Jiangsu, China (mainland)
| | - Hong Qiu
- Department of Clinical Laboratory, The 81st Hospital of People's Liberation Army (PLA), Nanjing, Jiangsu, China (mainland)
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BALTIERI L, CHAIM EA, CHAIM FDM, UTRINI MP, GESTIC MA, CAZZO E. CORRELATION BETWEEN NONALCOHOLIC FATTY LIVER DISEASE FEATURES AND LEVELS OF ADIPOKINES AND INFLAMMATORY CYTOKINES AMONG MORBIDLY OBESE INDIVIDUALS. ARQUIVOS DE GASTROENTEROLOGIA 2018; 55:247-251. [PMID: 30540086 DOI: 10.1590/s0004-2803.201800000-62] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/19/2018] [Accepted: 05/28/2018] [Indexed: 01/01/2023]
Abstract
ABSTRACT BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the commonest hepatopathy worldwide. OBJECTIVE: To investigate the correlations between NAFLD histopathological features and the levels of adipokines (adiponectin, leptin, and resistin) and circulating inflammatory markers (interleukin-6 [IL-6], interleukin-8 [IL-8], tumor necrosis factor alpha [TNF-α], and C-reactive protein [CRP]). METHODS: This is an exploratory cross-sectional study, which enrolled 19 women with obesity who underwent bariatric surgery. Biochemical characteristics evaluated included the levels of adiponectin, leptin, resistin, IL-6, IL-8, TNF-α, and CRP. NAFLD was assessed through histological examination of liver biopsies carried out during the surgical procedures. RESULTS: The mean age of the study group was 37.3±8.2 years old; mean BMI was 36.2±2.5 kg/m2. Among individuals with liver fibrosis, the levels of IL-8 were significantly higher (24.4 ± 9.7 versus 12.7 ± 6.6; P=0.016726). The intensity of fibrosis presented a significant negative correlation with the levels of adiponectin (R= -0.49379; P=0.03166); i.e. the higher the levels of adiponectin, the lower the intensity of fibrosis. The intensity of steatohepatitis presented a significant negative correlation with the levels of adiponectin (R= -0.562321; P=0.01221); this means that the higher the levels of adiponectin, the lower the intensity of steatohepatitis. CONCLUSION: Adiponectin levels were inversely correlated with the severity of fibrosis and steatohepatitis, whereas IL-8 levels were higher in individuals with liver fibrosis among individuals with obesity and NAFLD undergoing bariatric surgery. The use of these markers to assess NAFLD may bring significant information within similar populations.
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Paplińska-Goryca M, Rubinsztajn R, Nejman-Gryz P, Przybyłowski T, Krenke R, Chazan R. The association between serological features of chronic Chlamydia pneumoniae infection and markers of systemic inflammation and nutrition in COPD patients. Scandinavian Journal of Clinical and Laboratory Investigation 2017; 77:644-650. [PMID: 29069917 DOI: 10.1080/00365513.2017.1393694] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
INTRODUCTION Chlamydia pneumoniae is an obligatory human pathogen involved in lower and upper airway infections, including pneumonia, bronchitis. Asymptomatic C. pneumoniae carriage is also relatively common. The association of C. pneumoniae infections with the chronic obstructive pulmonary disease (COPD) course is unclear. OBJECTIVES The aim of the study was to investigate the association between chronic C. pneumoniae infection and clinical features of COPD, markers of inflammation and metabolic dysfunction. PATIENTS AND METHODS The study included 59 patients with stable COPD who had no, or had ≥2 acute exacerbations during last year. The level of IgA and IgG antibody against C. pneumoniae, IL-6, IL-8, resistin, insulin, adiponectin and acyl ghrelin was measured in serum by enzyme-linked immunosorbent assay (ELISA). RESULTS No differences in clinical and functional data were observed between COPD patients without serological features of C. pneumoniae infection and chronic C. pneumoniae infection. The level of anti C. pneumoniae IgA significantly correlated with IL-8, IL-6, resistin concentration in group of frequent exacerbators. IgG level correlated negatively with acetyl ghrelin and body mass index (BMI) in patients without frequent exacerbations, in contrast to frequent COPD exacerbation group where significant correlations between IgG level and BMI was demonstrated. Serum IL-6 correlated positively with resistin and insulin and negatively with adiponectin in group of patients with serological features of chronic C. pneumoniae infection only. CONCLUSIONS Our study showed that chronic C. pneumoniae infection does not influence the clinical course of COPD in the both study groups. Chronic C. pneumoniae infections might be associated with a distinct COPD phenotype that affects metabolic dysfunction.
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Affiliation(s)
- Magdalena Paplińska-Goryca
- a Department of Internal Medicine, Pulmonary Diseases and Allergy , Medical University of Warsaw , Warsaw , Poland
| | - Renata Rubinsztajn
- a Department of Internal Medicine, Pulmonary Diseases and Allergy , Medical University of Warsaw , Warsaw , Poland
| | - Patrycja Nejman-Gryz
- a Department of Internal Medicine, Pulmonary Diseases and Allergy , Medical University of Warsaw , Warsaw , Poland
| | - Tadeusz Przybyłowski
- a Department of Internal Medicine, Pulmonary Diseases and Allergy , Medical University of Warsaw , Warsaw , Poland
| | - Rafał Krenke
- a Department of Internal Medicine, Pulmonary Diseases and Allergy , Medical University of Warsaw , Warsaw , Poland
| | - Ryszarda Chazan
- a Department of Internal Medicine, Pulmonary Diseases and Allergy , Medical University of Warsaw , Warsaw , Poland
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Simpson J, Smith AD, Fraser A, Sattar N, Callaway M, Lindsay RS, Lawlor DA, Nelson SM. Cord Blood Adipokines and Lipids and Adolescent Nonalcoholic Fatty Liver Disease. J Clin Endocrinol Metab 2016; 101:4661-4668. [PMID: 27648968 PMCID: PMC5155695 DOI: 10.1210/jc.2016-2604] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2016] [Accepted: 09/15/2016] [Indexed: 12/14/2022]
Abstract
CONTEXT Maternal adiposity in pregnancy is associated with offspring adiposity and metabolic dysfunction postnatally, including greater risk of nonalcoholic fatty liver disease (NAFLD). Recent genetic analyses suggest a causal effect of greater maternal body mass index on offspring birth weight and ponderal index, but the relative roles of the environment in utero or later in life remains unclear. OBJECTIVE We sought to determine whether markers of infant adiposity (birth weight, umbilical cord blood leptin, adiponectin, and lipids) were associated with markers of NAFLD in adolescence. DESIGN, SETTING, AND PARTICIPANTS This was a UK prospective birth cohort with 17 years of follow-up with liver function tests (aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase) (n = 1037 participants), and ultrasound scan assessed liver fat, volume, and sheer velocity at age 17 (n = 541 participants). Missing covariate data were imputed. MAIN OUTCOMES Ultrasound and biochemical measures of NAFLD were measured. RESULTS Birth weight, cord blood leptin, and adiponectin were not associated with a diagnosis of NAFLD. In adjusted analyses, 2 of 42 associations attained conventional 5% levels of significance. Birth weight was positively associated with liver volume (1.0% greater per 100 g [95% confidence interval 0.5%-2.0%]). Cord high-density lipoprotein-cholesterol was positively associated with alanine aminotransferase (11.6% higher per 1 mmol/L [95% confidence interval 0.3, 23.4]); however, this association was primarily mediated via offspring adiposity. CONCLUSIONS In this extensive analysis, we found little evidence measurements of infant fat mass and birth size were related to adolescent markers of NAFLD. The association between birth weight and adolescent liver volume may indicate the contribution of greater organ size to birth weight and tracking of organ size.
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Affiliation(s)
- Joy Simpson
- School of Medicine (J.S., S.M.N.), University of Glasgow, Glasgow G31 2ER, United Kingdom; Medical Research Council Integrative Epidemiology Unit (A.D.S., A.F., D.A.L.), School of Social and Community Medicine (A.D.S., A.F., D.A.L.), University of Bristol, Bristol BS13NY United Kingdom; Institute of Cardiovascular and Metabolic Medicine (N.S., R.S.L.), British Heart Foundation Glasgow Cardiovascular Research Centre, Glasgow G61 1QH, United Kingdom; and University Hospitals Bristol National Health Service Foundation Trust (M.C.), Bristol BS1 3NY, United Kingdom
| | - Andrew D Smith
- School of Medicine (J.S., S.M.N.), University of Glasgow, Glasgow G31 2ER, United Kingdom; Medical Research Council Integrative Epidemiology Unit (A.D.S., A.F., D.A.L.), School of Social and Community Medicine (A.D.S., A.F., D.A.L.), University of Bristol, Bristol BS13NY United Kingdom; Institute of Cardiovascular and Metabolic Medicine (N.S., R.S.L.), British Heart Foundation Glasgow Cardiovascular Research Centre, Glasgow G61 1QH, United Kingdom; and University Hospitals Bristol National Health Service Foundation Trust (M.C.), Bristol BS1 3NY, United Kingdom
| | - Abigail Fraser
- School of Medicine (J.S., S.M.N.), University of Glasgow, Glasgow G31 2ER, United Kingdom; Medical Research Council Integrative Epidemiology Unit (A.D.S., A.F., D.A.L.), School of Social and Community Medicine (A.D.S., A.F., D.A.L.), University of Bristol, Bristol BS13NY United Kingdom; Institute of Cardiovascular and Metabolic Medicine (N.S., R.S.L.), British Heart Foundation Glasgow Cardiovascular Research Centre, Glasgow G61 1QH, United Kingdom; and University Hospitals Bristol National Health Service Foundation Trust (M.C.), Bristol BS1 3NY, United Kingdom
| | - Naveed Sattar
- School of Medicine (J.S., S.M.N.), University of Glasgow, Glasgow G31 2ER, United Kingdom; Medical Research Council Integrative Epidemiology Unit (A.D.S., A.F., D.A.L.), School of Social and Community Medicine (A.D.S., A.F., D.A.L.), University of Bristol, Bristol BS13NY United Kingdom; Institute of Cardiovascular and Metabolic Medicine (N.S., R.S.L.), British Heart Foundation Glasgow Cardiovascular Research Centre, Glasgow G61 1QH, United Kingdom; and University Hospitals Bristol National Health Service Foundation Trust (M.C.), Bristol BS1 3NY, United Kingdom
| | - Mark Callaway
- School of Medicine (J.S., S.M.N.), University of Glasgow, Glasgow G31 2ER, United Kingdom; Medical Research Council Integrative Epidemiology Unit (A.D.S., A.F., D.A.L.), School of Social and Community Medicine (A.D.S., A.F., D.A.L.), University of Bristol, Bristol BS13NY United Kingdom; Institute of Cardiovascular and Metabolic Medicine (N.S., R.S.L.), British Heart Foundation Glasgow Cardiovascular Research Centre, Glasgow G61 1QH, United Kingdom; and University Hospitals Bristol National Health Service Foundation Trust (M.C.), Bristol BS1 3NY, United Kingdom
| | - Robert S Lindsay
- School of Medicine (J.S., S.M.N.), University of Glasgow, Glasgow G31 2ER, United Kingdom; Medical Research Council Integrative Epidemiology Unit (A.D.S., A.F., D.A.L.), School of Social and Community Medicine (A.D.S., A.F., D.A.L.), University of Bristol, Bristol BS13NY United Kingdom; Institute of Cardiovascular and Metabolic Medicine (N.S., R.S.L.), British Heart Foundation Glasgow Cardiovascular Research Centre, Glasgow G61 1QH, United Kingdom; and University Hospitals Bristol National Health Service Foundation Trust (M.C.), Bristol BS1 3NY, United Kingdom
| | - Debbie A Lawlor
- School of Medicine (J.S., S.M.N.), University of Glasgow, Glasgow G31 2ER, United Kingdom; Medical Research Council Integrative Epidemiology Unit (A.D.S., A.F., D.A.L.), School of Social and Community Medicine (A.D.S., A.F., D.A.L.), University of Bristol, Bristol BS13NY United Kingdom; Institute of Cardiovascular and Metabolic Medicine (N.S., R.S.L.), British Heart Foundation Glasgow Cardiovascular Research Centre, Glasgow G61 1QH, United Kingdom; and University Hospitals Bristol National Health Service Foundation Trust (M.C.), Bristol BS1 3NY, United Kingdom
| | - Scott M Nelson
- School of Medicine (J.S., S.M.N.), University of Glasgow, Glasgow G31 2ER, United Kingdom; Medical Research Council Integrative Epidemiology Unit (A.D.S., A.F., D.A.L.), School of Social and Community Medicine (A.D.S., A.F., D.A.L.), University of Bristol, Bristol BS13NY United Kingdom; Institute of Cardiovascular and Metabolic Medicine (N.S., R.S.L.), British Heart Foundation Glasgow Cardiovascular Research Centre, Glasgow G61 1QH, United Kingdom; and University Hospitals Bristol National Health Service Foundation Trust (M.C.), Bristol BS1 3NY, United Kingdom
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Lin S, Ji W. Association between insulin resistance and estrogen in sexual precocity of obese children. Exp Ther Med 2016; 12:2497-2500. [PMID: 27703507 PMCID: PMC5038903 DOI: 10.3892/etm.2016.3663] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2016] [Accepted: 06/28/2016] [Indexed: 01/24/2023] Open
Abstract
The aim of the study was to examine the association between sexual precocity and high-molecular weight (HMW)-adiponectin and investigate the correlation of insulin resistance and estrogen levels in obese children. In total, 60 obese children (30 boys and 30 girls) with sexual precocity were included in group A, 60 obese children (30 boys and 30 girls) without sexual precocity were included in group B, and 60 average weight children (30 boys and 30 girls) were included in group C. The levels of HMW adiponectin, fasting blood glucose, fasting insulin, luteinizing hormone (LH) peak, estradiol and testosterone were measured. The results showed that the HMW-adiponectin level of group A was the lowest and that of group C was the highest. The difference was statistically significant (P<0.05). The homeostasis model assessment of insulin resistance (HOMA-IR) and estradiol levels of group A were significantly higher than those of group B, and group B was higher than that of group C. LH peak and testosterone levels of group A were the lowest while those of group C were the highest. The differences were statistically significant (P<0.05). A subgroup analysis showed that the above results were more significant in girls. The Pearson correlation analysis revealed that the level of HMW-adiponectin was negatively correlated with HOMA-IR and estradiol (P<0.05), and positively correlated with the LH peak (P<0.05). In conclusion, sexual precocity of obese children may be associated with insulin resistance, and the link may be HMW-adiponectin.
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Affiliation(s)
- Shixia Lin
- Department of Paediatrics, Jiangyin Hospital Affiliated to Medical School of Southeast University, Jiangyin, Jiangsu 214499, P.R. China; Department of Paediatrics, Children's Hospital Affiliated to Soochow University, Suzhou, Jiangsu 215003, P.R. China
| | - Wei Ji
- Department of Paediatrics, Children's Hospital Affiliated to Soochow University, Suzhou, Jiangsu 215003, P.R. China
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Robberecht H, Hermans N. Biomarkers of Metabolic Syndrome: Biochemical Background and Clinical Significance. Metab Syndr Relat Disord 2016; 14:47-93. [PMID: 26808223 DOI: 10.1089/met.2015.0113] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Biomarkers of the metabolic syndrome are divided into four subgroups. Although dividing them in groups has some limitations, it can be used to draw some conclusions. In a first part, the dyslipidemias and markers of oxidative stress are discussed, while inflammatory markers and cardiometabolic biomarkers are reviewed in a second part. For most of them, the biochemical background and clinical significance are discussed, although here also a well-cut separation cannot always be made. Altered levels cannot always be claimed as the cause, risk, or consequence of the syndrome. Several factors are interrelated to each other and act in a concerted, antagonistic, synergistic, or modulating way. Most important conclusions are summarized at the end of every reviewed subgroup. Genetic biomarkers or influences of various food components on concentration levels are not included in this review article.
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Affiliation(s)
- Harry Robberecht
- Department of Pharmaceutical Sciences, NatuRA (Natural Products and Food Research and Analysis), University of Antwerp , Wilrijk, Antwerp, Belgium
| | - Nina Hermans
- Department of Pharmaceutical Sciences, NatuRA (Natural Products and Food Research and Analysis), University of Antwerp , Wilrijk, Antwerp, Belgium
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Zhang CX, Guo LK, Qin YM, Li GY. Interaction of Polymorphisms of Resistin Gene Promoter -420C/G, Glutathione Peroxidase -1 Gene Pro198Leu and Cigarette Smoking in Nonalcoholic Fatty Liver Disease. Chin Med J (Engl) 2015; 128:2467-73. [PMID: 26365964 PMCID: PMC4725550 DOI: 10.4103/0366-6999.164931] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Many studies have suggested that cigarette smoking and polymorphisms of resistin and glutathione peroxidase-1 (GPx-1) genes are closely correlated with the pathogenesis of nonalcoholic fatty liver disease (NAFLD). However, few reports have investigated these associations with respect to NAFLD susceptibility. We, therefore, examined the distribution of polymorphisms in GPx-1 and resistin genes in NAFLD patients and healthy controls and analyzed the relationship between these polymorphisms and smoking status. METHODS Nine hundred NAFLD patients and 900 healthy controls were selected, and the genetic polymorphisms of resistin gene promoter-420C/G and GPx-1 gene Pro198Leu were analyzed by polymorphism-polymerase chain reaction (PCR) in DNA extracted from peripheral blood leukocytes. Interactions between the two mutants and the gene-environment interaction with cigarette smoking were also analyzed. RESULTS Genotype frequencies of -420C/G (GG) and Pro198Leu (LL) were significantly higher in NAFLD cases (49.56% and 50.11%, respectively) compared with healthy controls (23.67% and 24.22%, respectively) (P = 0.0069; P = 0.0072). Moreover, the risk of NAFLD with -420C/G (GG) was significantly higher than in controls (odds ratio [OR] =3.1685, 95% confidence interval (CI) =1.9366-5.2073). Individuals carrying Pro198Leu (LL) had a high risk of NAFLD (OR = 3.1424, 95% CI = 1.7951-5.2367). Combined analysis of the polymorphisms showed that the -420C/G (GG)/Pro198Leu (LL) genotype was significantly more common in the NAFLD group than in the control group (39.44% vs. 12.78%, respectively, P = 0.0054), while individuals with -420C/G (GG)/Pro198Leu (LL) had a high risk of NAFLD (OR = 5.0357, 95% CI = 3.1852-7.8106). Moreover, the cigarette smoking rate in the NAFLD group was significantly higher than in the control group (OR = 1.8990, P = 0.0083 in the smoking index (SI) ≤400 subgroup; OR = 5.0937, P = 0.0051 in the SI >400 subgroup), and statistical analysis suggested a positive interaction between cigarette smoking and -420C/G (GG) (γ = 5.6018 in the SI ≤400 subgroup; γ = 4.4770 in the SI >400 subgroup) and Pro198Leu (LL) (γ = 5.7715 in the SI ≤400 subgroup; γ = 4.5985 in the SI >400 subgroup) in increasing the risk of NAFLD. CONCLUSION NAFLD risk factors include -420C/G (GG), Pro198Leu (LL) and cigarette smoking, and these three factors have a significant additive effect on NAFLD risk.
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Affiliation(s)
- Chao-Xian Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, China,Address for correspondence: Prof. Chao-Xian Zhang, Department of Gastroenterology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, China E-Mail:
| | - Li-Ke Guo
- Depatment of Stomatology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, China
| | - Yong-Mei Qin
- Department of Gastroenterology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, China
| | - Guang-Yan Li
- Department of Gastroenterology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, China
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Alterio A, Alisi A, Liccardo D, Nobili V. Non-alcoholic fatty liver and metabolic syndrome in children: a vicious circle. Horm Res Paediatr 2015; 82:283-9. [PMID: 25324136 DOI: 10.1159/000365192] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2014] [Accepted: 06/10/2014] [Indexed: 11/19/2022] Open
Abstract
During the last decade, paediatricians have observed a dramatic increase of non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MS) in children. Furthermore, several lines of evidence have reported that a large part of children with NAFLD presents one or more traits of MS making plausible that, in the coming years, these subjects may present a rapid course of disease towards more severe cirrhosis and cardiovascular disease. Genetic susceptibility and the pressure of intrauterine environment and lifestyle are all crucial to activate molecular machinery that leads to development of NAFLD and MS in childhood. In this scenario, central obesity and consequent adipose tissue inflammation are critical to promote both MS-associated metabolic dysfunctions and NAFLD-related hepatic damage. An excessive dietary intake may in fact cause a specific lipid partitioning and induce metabolic stressors, which in turn promote insulin resistance and the release of several circulating factors. These molecules, on the one hand, trigger steatosis and the inflammatory response that characterize liver damage in NAFLD, and on the other hand contribute to the onset of other features of MS. This review provides an overview of current genetic, pathogenetic and clinical evidence of the vicious circle created by NAFLD and MS in children.
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Affiliation(s)
- Arianna Alterio
- Hepato-Metabolic Disease Unit and Liver Research Unit, 'Bambino Gesù' Children's Hospital, IRCCS, Rome, Italy
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Asimakopoulou A, Weiskirchen R. Lipocalin 2 in the pathogenesis of fatty liver disease and nonalcoholic steatohepatitis. ACTA ACUST UNITED AC 2015. [DOI: 10.2217/clp.14.65] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Which metabolic syndrome criteria best predict non-alcoholic fatty liver disease in children? Eat Weight Disord 2014; 19:495-501. [PMID: 24844310 DOI: 10.1007/s40519-014-0129-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2013] [Accepted: 04/23/2014] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVE The aim of this study was to identify which metabolic syndrome criteria (WHO or IDF) better reflect the presence of non-alcoholic fatty liver disease (NAFLD) and to determine the prevalence of metabolic syndrome (MS) and NAFLD. METHODS Two hundred and seventeen obese children and adolescents, 8-15 years of age (body mass index >95 p), were included in the study. Anthropometric measurements, blood pressure measurements, an oral glucose tolerance test and lipid profile were measured. MS was diagnosed according to WHO and IDF criteria. NAFLD risk ratio was assessed according to the two MS criteria. RESULTS The prevalence of MS according to the IDF criteria was 43.3 %, and according to WHO criteria it was 55.2 %. NAFLD prevalence in the metabolic syndrome group according to IDF criteria was 25.5 % and this was statistically significant (p = 0.007). The prevalence of NAFLD was 20.8 % in the group with MS according to WHO criteria and this was not a statistically significant difference (p = 0.15). NAFLD hazard ratios were 7.06 (95 % CI 1.29-5.50) in the MS group according to IDF criteria and 2.02 (95 % CI 0.81-3.53) in the group with metabolic syndrome according to WHO criteria. IDF criteria were found to have a higher odds ratio. CONCLUSION The prevalence of MS depends on the diagnostic criteria used. IDF criteria give the best measure for the presence of NAFLD. NAFLD might be important as diagnostic criterion for MS.
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Ibarra-Reynoso LDR, Pisarchyk L, Pérez-Luque EL, Garay-Sevilla ME, Malacara JM. Whole-body and hepatic insulin resistance in obese children. PLoS One 2014; 9:e113576. [PMID: 25411786 PMCID: PMC4239088 DOI: 10.1371/journal.pone.0113576] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2014] [Accepted: 10/25/2014] [Indexed: 12/11/2022] Open
Abstract
Background Insulin resistance may be assessed as whole body or hepatic. Objective To study factors associated with both types of insulin resistance. Methods Cross-sectional study of 182 obese children. Somatometric measurements were registered, and the following three adiposity indexes were compared: BMI, waist-to-height ratio and visceral adiposity. Whole-body insulin resistance was evaluated using HOMA-IR, with 2.5 as the cut-off point. Hepatic insulin resistance was considered for IGFBP-1 level quartiles 1 to 3 (<6.67 ng/ml). We determined metabolite and hormone levels and performed a liver ultrasound. Results The majority, 73.1%, of obese children had whole-body insulin resistance and hepatic insulin resistance, while 7% did not have either type. HOMA-IR was negatively associated with IGFBP-1 and positively associated with BMI, triglycerides, leptin and mother's BMI. Girls had increased HOMA-IR. IGFBP-1 was negatively associated with waist-to-height ratio, age, leptin, HOMA-IR and IGF-I. We did not find HOMA-IR or IGFBP-1 associated with fatty liver. Conclusion In school-aged children, BMI is the best metric to predict whole-body insulin resistance, and waist-to-height ratio is the best predictor of hepatic insulin resistance, indicating that central obesity is important for hepatic insulin resistance. The reciprocal negative association of IGFBP-1 and HOMA-IR may represent a strong interaction of the physiological processes of both whole-body and hepatic insulin resistance.
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Affiliation(s)
| | - Liudmila Pisarchyk
- Department of Medical Sciences, University of Guanajuato, Campus León, 20 de Enero 929, León Guanajuato, México
| | - Elva Leticia Pérez-Luque
- Department of Medical Sciences, University of Guanajuato, Campus León, 20 de Enero 929, León Guanajuato, México
| | - Ma. Eugenia Garay-Sevilla
- Department of Medical Sciences, University of Guanajuato, Campus León, 20 de Enero 929, León Guanajuato, México
- * E-mail:
| | - Juan Manuel Malacara
- Department of Medical Sciences, University of Guanajuato, Campus León, 20 de Enero 929, León Guanajuato, México
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Abstract
Fatty liver is a growing health problem worldwide. It might evolve to nonalcoholic steatohepatitis, cirrhosis and cause hepatocellular carcinoma. This disease, which has increased because of eating habits, changes in food content and lifestyle, affects people from childhood. The most important risk factors are obesity and insulin resistance. Besides these factors, gender, ethnicity, genetic predisposition and some medical problems are also important. Cirrhosis in children is rare but is reported. Nonalcoholic fatty liver disease (NAFLD) has no specific symptoms or signs but should be considered in obese children. NAFLD does not have a proven treatment. Weight loss with family based treatments is the most acceptable management. Exercise and an applicable diet with low glycemic index and appropriate calorie intake are preferred. Drugs are promising but not sufficient in children for today.
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