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Xu QY, Ren TY, Zhou YC, Xu J, Du LD, Hong DY, Zhang QR, Chu HK, Peng Z, Fan JG, Jiang L. Prevotella copri-produced 5-aminopentanoic acid promotes pediatric metabolic dysfunction-associated steatotic liver disease. Hepatobiliary Pancreat Dis Int 2025; 24:303-315. [PMID: 40057459 DOI: 10.1016/j.hbpd.2025.02.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Accepted: 02/24/2025] [Indexed: 05/03/2025]
Abstract
BACKGROUND Recent studies suggest an association between the expansion of Prevotella copri and the disease severity in children with metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to investigate the causative role and molecular mechanisms of P. copri in pediatric MASLD. METHODS C57BL/6 J mice aged 3 weeks were fed a high-fat diet (HFD) and orally administered with P. copri for 5 weeks. We assessed the key features of MASLD and the gut microbiota profile. By untargeted metabolomics on mouse fecal samples and the supernatant from P. copri culture, we identified P. copri-derived metabolite and tested its effects in vitro. RESULTS In HFD-fed mice, administration of P. copri significantly promoted liver steatosis. Genes associated with inflammation and fibrosis were significantly upregulated in the livers from the HFD + P. copri group compared with those in the livers from the HFD group. In addition, P. copri reduced gut microbial diversity, increased the proportion of Firmicutes and decreased Bacteroidota. Importantly, 5-aminopentanoic acid (5-AVA) was significantly enriched in both mouse feces from the HFD + P. copri group and the culture supernatant of P. copri. In vitro, 5-AVA aggravated palmitic acid-induced lipid accumulation in HepG2 cells and primary mouse hepatocytes. Mechanistically, P. copri-produced 5-AVA exacerbated hepatic steatosis by promoting lipogenesis and fatty acid uptake, while also reducing hepatic very-low-density lipoprotein export. CONCLUSIONS Our findings demonstrated that P. copri promotes liver steatosis in HFD-fed juvenile mice through its metabolite 5-AVA, suggesting its potential as a therapeutic target for the management of pediatric MASLD.
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Affiliation(s)
- Qing-Yang Xu
- Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
| | - Tian-Yi Ren
- Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
| | - Yong-Chang Zhou
- Shanghai Institute for Pediatric Research, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China; Shanghai Key Lab of Pediatric Gastroenterology and Nutrition, Shanghai 200092, China
| | - Juan Xu
- Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
| | - Lan-Duoduo Du
- Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
| | - Dong-Yang Hong
- Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
| | - Qian-Ren Zhang
- Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
| | - Hui-Kuan Chu
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Zhong Peng
- National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China
| | - Jian-Gao Fan
- Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China; Shanghai Key Lab of Pediatric Gastroenterology and Nutrition, Shanghai 200092, China
| | - Lu Jiang
- Shanghai Institute for Pediatric Research, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China; Shanghai Key Lab of Pediatric Gastroenterology and Nutrition, Shanghai 200092, China; Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
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Karaceper MD, Villegas MJ, Sadh S, Kawesa S, Strain J, Nair A, Dupuis A, Pothos M, Zheng MH, Kehar M. Prevalence and Risk Factors of Metabolic-Associated Fatty Liver Disease in Children with Down Syndrome at a Tertiary Care Center. J Clin Med 2025; 14:3239. [PMID: 40364270 PMCID: PMC12072516 DOI: 10.3390/jcm14093239] [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: 03/20/2025] [Revised: 04/25/2025] [Accepted: 05/04/2025] [Indexed: 05/15/2025] Open
Abstract
Background: The global rise of metabolic-associated fatty liver disease (MAFLD) in children is particularly concerning in high-risk groups such as those with Down Syndrome (DS), who have an elevated risk of obesity and insulin resistance. Despite increasing recognition of MAFLD in pediatric populations, data on its prevalence and risk factors among children with DS in Canada remain limited. Method: This retrospective study reviewed medical records of children with DS at the CHEO Down Syndrome Clinic (2013-2023). A diagnosis of MAFLD required evidence of hepatic steatosis on imaging, lab markers, or biopsy, along with the presence of metabolic risk features. Demographic, laboratory, and diagnostic data were analyzed. Results: Among 503 children with DS (231 females, 271 males; median age: 172 months), 54 (10.7%) had MAFLD. The MAFLD group was older (median age: 205 vs. 163 months, p = 0.0002) and had higher BMI (31.39 vs. 20.5, p < 0.0001). Most cases (47/54) were diagnosed via ultrasound, and 49/54 met MAFLD criteria due to excessive adiposity. Lab results showed a median ALT of 35 U/L, triglycerides of 4.4 mmol/L, and LDL cholesterol of 2.59 mmol/L. FibroScan in 13 children revealed a median transient elastography of 5.3 kPa. BMI was the strongest predictor of MAFLD (OR: 1.2, 95% CI: 1.1-1.2). Conclusions: The DS clinic-based prevalence of MAFLD underscores the need for proactive screening and early intervention. BMI was the strongest predictor, emphasizing targeted management strategies. Further research is needed to refine diagnostic approaches and improve outcomes.
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Affiliation(s)
- Maria D. Karaceper
- Division of Pediatric Medicine, Children’s Hospital of Eastern Ontario, University of Ottawa, Ottawa, ON K1H 8L1, Canada; (M.D.K.); (A.N.); (A.D.); (M.P.)
| | - Maria-Jose Villegas
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Children’s Hospital of Eastern Ontario, Ottawa, ON K1J 9B7, Canada; (M.-J.V.); (S.S.); (S.K.); (J.S.)
| | - Sanathan Sadh
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Children’s Hospital of Eastern Ontario, Ottawa, ON K1J 9B7, Canada; (M.-J.V.); (S.S.); (S.K.); (J.S.)
| | - Sierra Kawesa
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Children’s Hospital of Eastern Ontario, Ottawa, ON K1J 9B7, Canada; (M.-J.V.); (S.S.); (S.K.); (J.S.)
| | - Jamie Strain
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Children’s Hospital of Eastern Ontario, Ottawa, ON K1J 9B7, Canada; (M.-J.V.); (S.S.); (S.K.); (J.S.)
| | - Asha Nair
- Division of Pediatric Medicine, Children’s Hospital of Eastern Ontario, University of Ottawa, Ottawa, ON K1H 8L1, Canada; (M.D.K.); (A.N.); (A.D.); (M.P.)
| | - Alissa Dupuis
- Division of Pediatric Medicine, Children’s Hospital of Eastern Ontario, University of Ottawa, Ottawa, ON K1H 8L1, Canada; (M.D.K.); (A.N.); (A.D.); (M.P.)
| | - Mary Pothos
- Division of Pediatric Medicine, Children’s Hospital of Eastern Ontario, University of Ottawa, Ottawa, ON K1H 8L1, Canada; (M.D.K.); (A.N.); (A.D.); (M.P.)
| | - Ming-Hua Zheng
- MAFLD Research Center, Department of Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
- Key Laboratory of Diagnosis and Treatment for the Development of Chronic Liver Disease in Zhejiang Province, Wenzhou 325000, China
| | - Mohit Kehar
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Children’s Hospital of Eastern Ontario, Ottawa, ON K1J 9B7, Canada; (M.-J.V.); (S.S.); (S.K.); (J.S.)
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Gong X, Bai S, Lei E, Lu T, Chen Y, Cai J, Liu J. A bibliometric analysis of metabolic dysfunction-associated steatotic liver disease in children from 2004 to 2024. Front Pediatr 2025; 13:1468788. [PMID: 40356777 PMCID: PMC12066688 DOI: 10.3389/fped.2025.1468788] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Accepted: 04/14/2025] [Indexed: 05/15/2025] Open
Abstract
Background Metabolic dysfunction-associated steatotic liver disease (MASLD), once known as Non-alcoholic fatty liver disease, impacts between 3% and 10% of children and adolescents globally, as well as nearly one-third of obsessed boys and one-quarter of obsessed girls, and is the most frequent cause of pediatric liver disease associated with the obesity epidemic. With the growing attention and increasing volume of literature on pediatric MASLD, there is an urgent need for bibliometric analysis and visualization in the area of pediatric MASLD study in terms of dissecting study priorities. Methods Literature was searched in the Web of Science Core Collection database, followed by categorization, bibliometric study as well as visual analysis conducted by applying software including Citespace, VOSviewer, and the R language. The study concentrated on analyzing information related to key authors, spatial and temporal distribution, core keywords, and important citations. Results In total, 3,409 publications on pediatric MASLD were collected in the study, including 2,697 articles and 712 review articles. Between 2004 and 2024, the volume of publications had been constantly increasing per year. The country with the most numerous publications was the United States, which had extensive exchanges and collaborations with Italy, China, and England, followed by Italy. The Journal of Pediatric Gastroenterology and Nutrition had the greatest quantity of publications in this domain. The core literature was a clinical guideline. Insulin resistance, metabolic syndrome, steatohepatitis, hepatocellular carcinoma, cardiovascular risk, diabetes risk, diagnostic accuracy, lifestyle intervention, gut microbiome, probiotics, and metabolic dysfunction-associated steatotic liver disease were also hot topics and frontier trends in pediatric MASLD studies. Conclusion This research represents the inaugural application of bibliometric analysis to examine the developmental trajectory of pediatric MASLD studies over the past two decades, which reveals that the etiology, pathological changes of the liver, relationship with obesity, complications, comorbidities, diagnosis and treatments of pediatric MASLD are the key focuses and provides academic references for pediatric clinicians and scholars to grasp the hotspots, the cutting edge and the evolving trends in the area.
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Affiliation(s)
- Xiaowei Gong
- College of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, China
- Department of Pediatrics, Wuhan Hospital of Traditional Chinese Medicine, Wuhan, China
| | - Siyu Bai
- College of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, China
| | - Enze Lei
- College of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, China
| | - Tao Lu
- College of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, China
| | - Yao Chen
- Department of Pediatrics, Hubei Provincial Hospital of Traditional Chinese Medicine, Affiliated Hospital of Hubei University of Chinese Medicine, Wuhan, China
- Hubei Shizhen Laboratory, Wuhan, China
- Hubei Key Laboratory of Liver and Kidney Research and Application of Traditional Chinese Medicine, Wuhan, China
| | - Jianxin Cai
- Department of Pediatrics, Wuhan Hospital of Traditional Chinese Medicine, Wuhan, China
| | - Jianzhong Liu
- College of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, China
- Department of Pediatrics, Hubei Provincial Hospital of Traditional Chinese Medicine, Affiliated Hospital of Hubei University of Chinese Medicine, Wuhan, China
- Hubei Shizhen Laboratory, Wuhan, China
- Hubei Key Laboratory of Liver and Kidney Research and Application of Traditional Chinese Medicine, Wuhan, China
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Accacha S, Barillas-Cerritos J, Srivastava A, Ross F, Drewes W, Gulkarov S, De Leon J, Reiss AB. From Childhood Obesity to Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and Hyperlipidemia Through Oxidative Stress During Childhood. Metabolites 2025; 15:287. [PMID: 40422865 DOI: 10.3390/metabo15050287] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2025] [Revised: 04/16/2025] [Accepted: 04/17/2025] [Indexed: 05/28/2025] Open
Abstract
BACKGROUND/OBJECTIVES Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is rapidly becoming the most prevalent form of chronic liver disease in both pediatric and adult populations. It encompasses a wide spectrum of liver abnormalities, ranging from simple fat accumulation to severe conditions such as inflammation, fibrosis, cirrhosis, and liver cancer. Major risk factors for MASLD include obesity, insulin resistance, type 2 diabetes, and hypertriglyceridemia. METHODS This narrative review employed a comprehensive search of recent literature to identify the latest studies on the relationship between MAFLD and obesity, the health consequences and the latest treatment options to prevent long-term damage to the liver and other organs. Additionally, the article presents perspectives on diagnostic biomarkers. RESULTS Childhood obesity is linked to a multitude of comorbid conditions and remains a primary risk factor for adult obesity. This abnormal fat accumulation is known to have long-term detrimental effects into adulthood. Scientific evidence unequivocally demonstrates the role of obesity-related conditions, such as insulin resistance, dyslipidemia, and hyperglycemia, in the development and progression of MASLD. Oxidative stress, stemming from mitochondrial dysfunction, is a leading factor in MASLD. This review discusses the interconnections between oxidative stress, obesity, dyslipidemia, and MASLD. CONCLUSIONS Atherogenic dyslipidemia, oxidative stress, inflammation, insulin resistance, endothelial dysfunction, and cytokines collectively contribute to the development of MASLD. Potential treatment targets for MASLD are focused on prevention and the use of drugs to address obesity and elevated blood lipid levels.
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Affiliation(s)
- Siham Accacha
- Department of Pediatrics, NYU Grossman Long Island School of Medicine, Mineola, NY 11501, USA
| | - Julia Barillas-Cerritos
- Department of Pediatrics, NYU Grossman Long Island School of Medicine, Mineola, NY 11501, USA
| | - Ankita Srivastava
- Department of Foundations of Medicine, NYU Grossman Long Island School of Medicine, Mineola, NY 11501, USA
| | - Frances Ross
- Department of Pediatrics, NYU Grossman Long Island School of Medicine, Mineola, NY 11501, USA
| | - Wendy Drewes
- Department of Medicine, NYU Grossman Long Island School of Medicine, Mineola, NY 11501, USA
| | - Shelly Gulkarov
- Department of Foundations of Medicine, NYU Grossman Long Island School of Medicine, Mineola, NY 11501, USA
| | - Joshua De Leon
- Department of Medicine, NYU Grossman Long Island School of Medicine, Mineola, NY 11501, USA
| | - Allison B Reiss
- Department of Foundations of Medicine, NYU Grossman Long Island School of Medicine, Mineola, NY 11501, USA
- Department of Medicine, NYU Grossman Long Island School of Medicine, Mineola, NY 11501, USA
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Du L, Zhang K, Liang L, Yang Y, Lu D, Zhou Y, Ren T, Fan J, Zhang H, Wang Y, Jiang L. Multi-omics analyses of the gut microbiota and metabolites in children with metabolic dysfunction-associated steatotic liver disease. mSystems 2025; 10:e0114824. [PMID: 40084870 PMCID: PMC12013275 DOI: 10.1128/msystems.01148-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2024] [Accepted: 02/12/2025] [Indexed: 03/16/2025] Open
Abstract
The development and severity of metabolic dysfunction-associated steatotic liver disease (MASLD) in children are closely related to alterations of gut microbiota. This study aims to investigate changes in the gut microbiota signature and microbial metabolites in children with MASLD. We collected fecal samples from children and adolescents aged 6-16 years, and the presence of MASLD was diagnosed by ultrasound. We performed 16S ribosomal DNA sequencing and targeted metabolomics in 36 and 25 subjects, consisting of healthy controls, children with obesity, and children with MASLD. The α-diversity was significantly lower in children with obesity and MASLD compared with healthy controls. Linear discriminant analysis of effect size analysis identified Anaerostipes and A. hadrus as the top biomarkers differentiating the obesity group from the MASLD group. In MASLD patients with high alanine aminotransferase values (≥50 U/L for boys and 44 U/L for girls), we observed a decrease in the gut microbiota health index. MASLD patients with high shear wave elastography (E) values (≥6.2 kPa) showed an increased abundance of Ruminococcus torques, which was positively correlated with the levels of deoxycholic acid (DCA) and E values. Importantly, the mediation analysis identified positive associations between R. torques and clinical indicators of MASLD that were mediated by DCA. Overall, our study suggests that gut microbiota and metabolites are significantly altered in children with MASLD, and targeting R. torques may offer potential benefits for disease management.IMPORTANCEThis study investigated alterations in the gut microbiota signature and microbial metabolites in children with metabolic dysfunction-associated steatotic liver disease (MASLD). We found that an increased abundance of Ruminococcus torques was associated with increased levels of deoxycholic acid and the progression of MASLD, suggesting that R. torques may serve as a novel clinical target in pediatric MASLD.
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Affiliation(s)
- Landuoduo Du
- Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Department of Clinical Nutrition, College of Health Science and Technology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Kaichuang Zhang
- Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Lili Liang
- Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yi Yang
- Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Deyun Lu
- Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yongchang Zhou
- Shanghai Institute for Pediatric Research, Shanghai, China
- Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China
| | - Tianyi Ren
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jiangao Fan
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Huiwen Zhang
- Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ying Wang
- Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China
| | - Lu Jiang
- Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Institute for Pediatric Research, Shanghai, China
- Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China
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Zheng X, Zhao D, Wang L, Wang Y, Chen Y, Zhang Y. Prevalence of Metabolic Dysfunction-associated Steatotic Liver Disease and Cardiometabolic Risk Factor in US Adolescents. J Clin Endocrinol Metab 2025; 110:e1458-e1465. [PMID: 39136243 DOI: 10.1210/clinem/dgae553] [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: 04/07/2024] [Revised: 07/20/2024] [Accepted: 08/12/2024] [Indexed: 10/25/2024]
Abstract
CONTEXT Metabolic dysfunction-associated steatotic liver disease (MASLD) is widespread worldwide, and a strong link between MASLD and cardiometabolic risk factors (CMRFs) was highlighted in this study. OBJECTIVE This study characterized the prevalence of MASLD in adolescent population and overlapping CMRFs conditions in MASLD. METHODS This is a cross-sectional study of US adolescents aged 12 to 19 years in the 2017 through 2020 cycles of the National Health and Nutrition Examination Survey. The relationship between CMRFs and liver steatosis, evaluated by the median controlled attenuation parameter (CAP), was assessed. RESULTS The prevalence of MASLD in adolescents was 23.77%. Isolated overweight/obesity (35%) was the top CMRF. Non-Hispanic Black patients had the highest proportion of overweight/obesity plus elevated glucose (24%), whereas non-Hispanic Asians had the highest burden of dyslipidemia (2%, 14%, and 19%). Except for hypertension, overweight/obesity (β = 48.7; 95% CI, 43.4-54.0), hypertriglyceridemia (β = 15.5; 95% CI, 7.2-28.3), low HDL-C (β = 10.0; 95% CI, 3.1-16.9), elevated glucose (β = 6.9; 95% CI, 0.6-13.2) were all significantly associated with increased CAP values. Increased CAP was linked to the synergistic interactions between overweight/obesity and dyslipidemia or elevated glucose (overweight/obesity and elevated glucose: relative excess risk due to interaction [RERI] = 8.21, attributable proportion due to interaction [AP] = 0.45, synergy index [SI] = 1.91; overweight/obesity and hypertriglyceridemia: RERI = 19.00, AP = 0.69, SI = 3.53; overweight/obesity and low high-density lipoprotein cholesterol: RERI = 10.83, AP = 0.58, SI = 2.61). Adolescents with combination of overweight/obesity, dyslipidemia (β = 15.1; 95% CI, 0.1-30.2) and combination of overweight/obesity, dyslipidemia and elevated glucose (β = 48.0; 95% CI, 23.3-72.6) had a significantly higher CAP values. CONCLUSION The prevalence of MASLD was alarmingly high in adolescents, and overweight/obesity was the most important CMRF. Overweight/obesity and dyslipidemia or elevated glucose had positive additive interaction effects on liver steatosis.
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Affiliation(s)
- Xiaoyan Zheng
- Department of Pediatrics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
| | - Dongying Zhao
- Department of Pediatrics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
| | - Liwei Wang
- Department of Nursing, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
| | - Yiwen Wang
- Department of Pediatrics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
| | - Yan Chen
- Department of Pediatrics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
| | - Yongjun Zhang
- Department of Pediatrics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
- Shanghai Institute for Pediatric Research, Shanghai Jiao Tong University School of Medicine, Xinhua Hospital, Shanghai 200092, China
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Chen Q, Hu Q, Zhang F, Lu W, Yuan Z, Qiao F. Mechanistic evaluation of Jiu Wei Qing Zhi Gao in non-alcoholic fatty liver disease: insights from network Pharmacology and experimental validation. Hereditas 2025; 162:59. [PMID: 40221773 PMCID: PMC11992867 DOI: 10.1186/s41065-025-00427-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2025] [Accepted: 03/31/2025] [Indexed: 04/14/2025] Open
Abstract
CONTEXT Jiu Wei Qing Zhi Gao (JWQZG), a traditional Chinese medicine (TCM) formulation, is widely utilized in China for managing non-alcoholic fatty liver disease (NAFLD). OBJECTIVE This study aimed to elucidate the therapeutic mechanisms of JWQZG in the management of NAFLD. MATERIALS AND METHODS Network pharmacology was employed to predict the potential mechanisms of JWQZG in NAFLD management. In vivo experiments were conducted using C57BL/6J mice fed a high-fat diet (HFD) for 16 weeks, followed by treatment with JWQZG at three dosages (1.85, 3.7, and 7.4 g/kg/day) or metformin (150 mg/kg/day) for 8 weeks. In vitro studies utilized HepG2 cells exposed to 0.5 mM palmitic acid (PA) for 24 h to establish an NAFLD model, followed by exposure to JWQZG-containing serum at three concentrations for an additional 24 h. Western blot analysis was used to analyze the expression levels of key signaling pathway components. RESULTS Results of network pharmacology analysis identified the insulin signaling pathway as a potential mediator of the protective effects of JWQZG in NAFLD. Treatment with JWQZG markedly reduced hepatic steatosis and improved insulin resistance. This was accompanied by enhanced expression of key components in the insulin signaling pathway, including insulin receptor substrate 1 (IRS1), phosphorylated PI3K (p-PI3K), phosphorylated AKT (p-AKT), and phosphorylated GSK3β (p-GSK3β), compared to the NAFLD model group. CONCLUSIONS These findings provide robust evidence supporting the therapeutic potential of JWQZG in NAFLD and its modulation of the insulin signaling pathway. Furthermore, the study offers valuable insights for the discovery of anti-NAFLD compounds derived from TCM formulations.
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Affiliation(s)
- Qinlei Chen
- Department of Infectious Diseases, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210001, China
| | - Qianfeng Hu
- Nanjing University of Chinese Medicine, Nanjing, China, 210046
| | - Fan Zhang
- Department of Infectious Diseases, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210001, China
| | - Weiting Lu
- Department of Infectious Diseases, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210001, China
| | - Zheng Yuan
- Department of Infectious Diseases, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210001, China.
| | - Fei Qiao
- Department of Infectious Diseases, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210001, China.
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Zapata JK, Gómez-Ambrosi J, Frühbeck G. Childhood obesity: The threatening apprentice of the adiposity empire. Rev Endocr Metab Disord 2025:10.1007/s11154-025-09959-4. [PMID: 40195232 DOI: 10.1007/s11154-025-09959-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/18/2025] [Indexed: 04/09/2025]
Abstract
Childhood obesity is a global health problem, with its prevalence having tripled since 1975. The increase in its prevalence has been predominantly in developing countries, but also in those with high economic status. Nowadays, there are multiple obesity definitions, however, one of the most accurate is the one which defines obesity as the accumulation of excessive body adiposity and not as an body weight excess. Nevertheless, the body mass index (BMI) is the most frequently used tool for its classification, according to the cut-off points established by the Center for Disease Control and World Health Organization tables. In children and adolescents an adiposity excess is related to the appearance of cardiovascular disease in adulthood and with many comorbidities such as metabolic syndrome, insulin resistance, type 2 diabetes, hypertension and metabolic dysfunction-associated steatotic liver disease, among others. Currently, there is still controversy about which is the ideal indicator for measuring overweight and obesity. BMI is still used as a standardized measure but may miss cases in which body composition is pathological despite a BMI within the normal-weight category. An adequate knowledge of the impact on health of dysfunctional adiposity as well as its accurate diagnosis will allow health professionals to address this condition in a more precise and comprehensive manner, and substantially improve the associated cardiometabolic risk and prognosis.
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Affiliation(s)
- J Karina Zapata
- Department of Endocrinology and Nutrition, Clínica Universidad de Navarra, Pamplona, Spain
| | - Javier Gómez-Ambrosi
- Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain.
- Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Pamplona, Spain.
- Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.
| | - Gema Frühbeck
- Department of Endocrinology and Nutrition, Clínica Universidad de Navarra, Pamplona, Spain.
- Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain.
- Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Pamplona, Spain.
- Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.
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Zhang Y, Ju F, Yan L, Shen X, Guo S, Yu M, Cao Y, Wang W. Elevated Porcupine Disrupts Lipid Metabolism and Promotes Inflammatory Response in MASLD. Liver Int 2025; 45:e16130. [PMID: 39403838 DOI: 10.1111/liv.16130] [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: 03/29/2024] [Revised: 09/26/2024] [Accepted: 09/29/2024] [Indexed: 03/11/2025]
Abstract
BACKGROUND AND AIMS Metabolic dysfunction-associated steatotic liver disease (MASLD) presents a high incidence globally and is a major cause of cirrhosis and hepatocellular carcinoma, lacking of efficient interventions. Patients with MASLD exhibit exceeded serum levels of palmitic acid (PA). However, the association between PA and MASLD remains obscure. METHODS Gene expression omnibus dataset analysis, western blotting, mRNA-sequencing, RT-qPCR, a click chemistry-immunoprecipitation-immunofluorescence system, ELISA, lipid extraction and UHPLC-MS/MS analysis, CyTOF mass cytometry, gene knockdown via lentivirus-mediated shRNA, and high-fat methionine and choline-deficient diet-fed WT and db/db mice models were used to reveal the expression and functions of Porcupine in MASLD development both in vitro and in vivo. RESULTS Our findings show that PA, as a crucial substrate for protein palmitoylation, induced the expression of palmitoyltransferase Porcupine in a time-dependent manner. This induction was closely associated with dysregulated lipid metabolism and stimulated inflammatory response observed in vitro. Porcupine protein levels were significantly increased in liver tissues from both MASLD mice models, which was predominantly localised in lipid droplet-rich hepatocytes. Pharmacological inhibition of Porcupine by Wnt974 markedly ameliorated the aberrant lipid accumulation and inflammatory response in mouse livers. Furthermore, increased Porcupine positively correlated with CD36 at protein levels, and its inhibition or knockdown decreased CD36 protein levels via mechanisms irrelevant to transcriptional regulation, but primarily dependent on protein palmitoylation. CONCLUSIONS The current study reveals that PA-induced Porcupine disrupts lipid metabolism and promotes inflammatory response during MASLD development, which can be ameliorated by the Porcupine inhibitor Wnt974. Therefore, Porcupine may be a potential pharmacological target for the treatment of MASLD.
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Affiliation(s)
- Yalin Zhang
- Department of Pharmacology and School of Basic Medicine Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, China
| | - Fengyu Ju
- Department of Pharmacology and School of Basic Medicine Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, China
| | - Li Yan
- Department of Pharmacology and School of Basic Medicine Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, China
| | - Xin Shen
- Department of Pharmacology and School of Basic Medicine Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, China
| | - Shiqing Guo
- Department of Pharmacology and School of Basic Medicine Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, China
| | - Muchen Yu
- Department of Pharmacology and School of Basic Medicine Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, China
| | - Yujia Cao
- Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
| | - Wenhui Wang
- Department of Pharmacology and School of Basic Medicine Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, China
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Buytaert M, Declercq D, Depoorter F, Cosijn Z, Devisscher L, Raevens S, Verhelst X, Van Vlierberghe H, Geerts A, De Bruyne R, Lefere S. The association of ultra-processed food intake with adolescent metabolic dysfunction-associated steatotic liver disease in the NHANES. Pediatr Obes 2025; 20:e13174. [PMID: 39340247 DOI: 10.1111/ijpo.13174] [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: 03/26/2024] [Revised: 08/01/2024] [Accepted: 08/26/2024] [Indexed: 09/30/2024]
Abstract
INTRODUCTION Metabolic dysfunction-associated steatotic liver disease (MASLD) has become a major public health concern. A thorough analysis of the link between ultra-processed food (UPF) intake and MASLD in the adolescent population is lacking. METHODS Adolescent participants of the National Health and Nutrition Examination Survey (NHANES) pre-pandemic cohort were included. Different controlled attenuation parameter (CAP) cut-offs were used to assess MASLD. The percentage energy intake of UPF, categorized according to the NOVA classification, to total energy intake was taken as the main outcome marker. Structural equation modelling (SEM) was used to better quantify the causal connection between UPF and liver steatosis. RESULTS UPF consumption constituted a median 75% (62-86) of total energy intake. There was no significant correlation between UPF intake and CAP (ρ = 0.061, p = 0.091). The median proportion UPF intake was not associated with steatosis severity. SEM similarly yielded a weak and non-significant correlation of 0.078. In participants with MASLD, total energy intake was significantly higher (p < 0.001) and sugar-containing beverage (SCB) consumption showed a non-significant trend towards higher consumption. CONCLUSIONS No clinically relevant association between UPF intake and MASLD in adolescents could be demonstrated. Our results nonetheless suggest that total energy intake and consumption of SCBs are important contributors to paediatric obesity and MASLD.
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Affiliation(s)
- Maarten Buytaert
- Department of Internal Medicine and Pediatrics, Hepatology Research Unit, Ghent University, Ghent, Belgium
- Liver Research Center Ghent, Ghent University Hospital, Ghent, Belgium
| | - Dimitri Declercq
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
- Center for Nutrition and Dietetics, Ghent University Hospital, Ghent, Belgium
| | - Fleur Depoorter
- Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
| | - Zerlina Cosijn
- Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
| | - Lindsey Devisscher
- Liver Research Center Ghent, Ghent University Hospital, Ghent, Belgium
- Department of Basic and Applied Medical Sciences, Gut-Liver Immunopharmacology Unit, Ghent University, Ghent, Belgium
| | - Sarah Raevens
- Department of Internal Medicine and Pediatrics, Hepatology Research Unit, Ghent University, Ghent, Belgium
- Liver Research Center Ghent, Ghent University Hospital, Ghent, Belgium
| | - Xavier Verhelst
- Department of Internal Medicine and Pediatrics, Hepatology Research Unit, Ghent University, Ghent, Belgium
- Liver Research Center Ghent, Ghent University Hospital, Ghent, Belgium
| | - Hans Van Vlierberghe
- Department of Internal Medicine and Pediatrics, Hepatology Research Unit, Ghent University, Ghent, Belgium
- Liver Research Center Ghent, Ghent University Hospital, Ghent, Belgium
| | - Anja Geerts
- Department of Internal Medicine and Pediatrics, Hepatology Research Unit, Ghent University, Ghent, Belgium
- Liver Research Center Ghent, Ghent University Hospital, Ghent, Belgium
| | - Ruth De Bruyne
- Liver Research Center Ghent, Ghent University Hospital, Ghent, Belgium
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Ghent University Hospital, Ghent, Belgium
| | - Sander Lefere
- Department of Internal Medicine and Pediatrics, Hepatology Research Unit, Ghent University, Ghent, Belgium
- Liver Research Center Ghent, Ghent University Hospital, Ghent, Belgium
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Lefere S, Mosca A, Hudert C, Dupont E, Fitzpatrick E, Kyrana E, Dhawan A, Kalveram L, Pietrobattista A, Geerts A, De Bruyne R. Development and validation of pFIB scores for exclusion of significant liver fibrosis in pediatric MASLD. Hepatology 2025; 81:1276-1287. [PMID: 39028885 DOI: 10.1097/hep.0000000000001016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Accepted: 07/01/2024] [Indexed: 07/21/2024]
Abstract
BACKGROUND AND AIMS Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent pediatric liver disease, yet accurate risk scores for referral of children/adolescents with suspected clinically significant liver fibrosis are currently lacking. APPROACH AND RESULTS Clinical and biochemical variables were collected in a prospective cohort of 327 children and adolescents with severe obesity, in whom liver fibrosis was evaluated by transient elastography. Logistic regression was performed to establish continuous (pFIB-c) and simplified (pFIB-6) diagnostic scores that accurately exclude significant (≥F2) fibrosis. Performance for each was compared to established noninvve fibrosis scores. These scores were validated in elastography (n=504) and multiple biopsy-proven MASLD (n=261) cohorts. Patient sex, ethnicity, weight z-score, homeostatic model assessment of insulin resistance index, ALT, and presence of hypertension were included in the scores. The pFIB-c and pFIB-6 exhibited good discriminatory capacity (c-statistic of 0.839 and 0.826), outperforming existing indices. Negative predictive values were >90% for both scores in the derivation and elastography validation cohorts. Performance in the histological cohorts varied (AUROCs for the pFIB-c between 0.710 and 0.770), as the scores were less accurate when applied to populations in tertiary referral centers characterized by a high prevalence of significant fibrosis and high ALT levels. CONCLUSIONS Analyzing several cohorts totaling approximately 1100 children and adolescents, we developed novel risk scores incorporating readily available clinical variables. In accordance with the aim of excluding pediatric MASLD-associated fibrosis, the scores performed better in nonselected cohorts of children and adolescents living with obesity than in patients referred to tertiary liver units.
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Affiliation(s)
- Sander Lefere
- Hepatology Research Unit, Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
- Liver Research Center Ghent, Ghent University Hospital, Ghent, Belgium
| | - Antonella Mosca
- Hepatogastroenterology, Nutrition, Digestive Endoscopy and Liver Transplant Unit, Bambino Gesù Children's Hospital, Rome, Italy
| | - Christian Hudert
- Department of Pediatric Gastroenterology, Nephrology and Metabolic Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | | | - Emer Fitzpatrick
- Paediatric Liver, GI and Nutrition Centre, King's College Hospital, London, United Kingdom
- Department of Gastroenterology, Hepatology and Nutrition, Children's Health Ireland and University College Dublin, Ireland
| | - Eirini Kyrana
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Anil Dhawan
- Paediatric Liver, GI and Nutrition Centre, King's College Hospital, London, United Kingdom
| | - Laura Kalveram
- Department of Pediatric Gastroenterology, Nephrology and Metabolic Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Andrea Pietrobattista
- Hepatogastroenterology, Nutrition, Digestive Endoscopy and Liver Transplant Unit, Bambino Gesù Children's Hospital, Rome, Italy
| | - Anja Geerts
- Hepatology Research Unit, Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
- Liver Research Center Ghent, Ghent University Hospital, Ghent, Belgium
| | - Ruth De Bruyne
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Ghent University, Ghent, Belgium
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Zhang QR, Dong Y, Fan JG. Early-life exposure to gestational diabetes mellitus predisposes offspring to pediatric nonalcoholic fatty liver disease. Hepatobiliary Pancreat Dis Int 2025; 24:128-137. [PMID: 38195352 DOI: 10.1016/j.hbpd.2023.12.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2023] [Accepted: 12/28/2023] [Indexed: 01/11/2024]
Abstract
Nonalcoholic fatty liver disease (NAFLD) has emerged as the prevailing chronic liver disease in the pediatric population due to the global obesity pandemic. Evidence shows that prenatal and postnatal exposure to maternal abnormalities leads to a higher risk of pediatric NAFLD through persistent alterations in developmental programming. Gestational diabetes mellitus (GDM) is a hyperglycemic syndrome which has become the most prevalent complication in pregnant women. An increasing number of both epidemiologic investigations and animal model studies have validated adverse and long-term outcomes in offspring following GDM exposure in utero. Similarly, GDM is considered a crucial risk factor for pediatric NAFLD. This review aimed to summarize currently published studies concerning the inductive roles of GDM in offspring NAFLD development during childhood and adolescence. Dysregulations in hepatic lipid metabolism and gut microbiota in offspring, as well as dysfunctions in the placenta are potential factors in the pathogenesis of GDM-associated pediatric NAFLD. In addition, potentially effective interventions for GDM-associated offspring NAFLD are also discussed in this review. However, most of these therapeutic approaches still require further clinical research for validation.
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Affiliation(s)
- Qian-Ren Zhang
- Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
| | - Yan Dong
- Department of Endocrinology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China; Shanghai Institute for Pediatric Research, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
| | - Jian-Gao Fan
- Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China; Shanghai Key Lab of Pediatric Gastroenterology and Nutrition, Shanghai 200092, China.
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Ashraf H, Anushiravani A, Rayatpisheh M, Hamidi Alamdari D, Hossieni A, Kazeminezhad B. Association between oxidative stress and liver fibrosis severity in non-alcoholic fatty liver disease: insights from the pro-oxidant antioxidant balance method in a population from Tehran and Mashhad, Iran. Front Med (Lausanne) 2025; 12:1539605. [PMID: 40144874 PMCID: PMC11936954 DOI: 10.3389/fmed.2025.1539605] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2024] [Accepted: 02/24/2025] [Indexed: 03/28/2025] Open
Abstract
Background The exact mechanisms of non-alcoholic fatty liver disease (NAFLD), recently redefined as metabolic dysfunction-associated steatotic liver disease (MASLD), remain unclear. However, oxidative stress is recognized as a factor across all stages of NAFLD. The Pro-oxidant Antioxidant Balance (PAB) method is an important clinical tool that provides an assessment of the balance between oxidants and antioxidant. We aimed to explore oxidative stress in NAFLD using the PAB method. Methods Individuals with NAFLD were recruited in 2021. Eligible participants underwent detailed assessments, including liver elastography for fibrosis evaluation. Blood samples (5 mL) were collected to measure serum PAB levels. The METAVIR score, derived from FibroScan measurements of liver stiffness, categorized fibrosis severity from F0 (no fibrosis) to F4 (advanced fibrosis or cirrhosis). Results The study included 102 participants, with a mean age of 50.12 ± 10.03 years. Significant correlations were observed between FibroScan scores and variables such as age, body mass index (BMI), history of chronic diseases, and family history of NAFLD. PAB levels were notably higher in patients with advanced fibrosis (F2 and F3 groups: 86.32 ± 25.53) compared to those in early stages (F0 and F1 groups: 45.36 ± 21.29). Moreover, FibroScan scores showed a significant positive association with PAB values (odds ratio [OR]: 1.07; 95% confidence interval (CI): 1.04, 1.10), even after adjusting for confounding variables (OR: 1.13; 95% CI: 1.07, 1.18). Conclusion Elevated PAB levels were strongly associated with advanced stages of liver fibrosis in NAFLD patients, reflecting increased oxidative stress with disease progression. These results highlight the potential of PAB as a marker for monitoring oxidative stress and disease severity in NAFLD. Nevertheless, further large-scale studies are warranted.
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Affiliation(s)
- Hami Ashraf
- Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Innovative Laboratory Assays in Biomedicine Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amir Anushiravani
- Digestive Diseases Research Institute, Tehran University of Medical Science, Tehran, Iran
| | - Maryam Rayatpisheh
- Digestive Diseases Research Institute, Tehran University of Medical Science, Tehran, Iran
| | | | - Arianaz Hossieni
- Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Innovative Laboratory Assays in Biomedicine Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Behrang Kazeminezhad
- Modarres Hospital, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Du H, Huang J, Wang Y, Wang C, Wang Y, Hou L, Li Y, Li Y, Su Q. Analyzing MASLD interventional clinical trial registration based on the ClinicalTrials.gov database. BMC Gastroenterol 2025; 25:148. [PMID: 40055604 PMCID: PMC11887356 DOI: 10.1186/s12876-025-03732-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2024] [Accepted: 02/25/2025] [Indexed: 05/13/2025] Open
Abstract
OBJECTIVE With the rising incidence of MASLD, extensive drug research has been conducted in clinical trials. The study examined the design principles and research objectives of MASLD therapeutics, in order to offer guidance to clinical trial participants and decision makers. METHODS By searching the clinical research trial data registered on clinicaltrials.gov platform, 1209 interventional clinical trials were screened. These trials were subsequently evaluated based on clinical stage, trial design, intervention modalities, outcome metrics, and other pertinent factors. RESULTS A total of 1,209 trials were included, of which 199 were registered from 2000 to 2012 (16.46%) and 1010 were registered from 2013 to 2024 (83.54%), reflecting the growing body of research on MASLD. Regarding the intervention model type, single-group designs were employed in 232 (19.19%) trials, and parallel designs were employed in 873(72.21%). A total of 13 trials were early phase 1 (1.08%), 152 (12.57%) were phase 1, 34 (2.81%) were phase 1/phase 2, 301 were phase 2 (24.90%), 19 (1.57%) were phase 2/phase 3, 72 (5.96%) were phase 3, and 84 (6.95%) were phase 4. Within these trials, the three primary clinical outcomes for drug interventions were hepatic histological improvement, hepatic fat content and adverse events. Furthermore, 140 drug interventional trials with results for therapeutic purposes (This accounted for 88.61% of the 158 drug interventional trials with results) primarily aimed to improve MASLD through mechanisms such as metabolic and energy balance, inflammatory and immunomodulatory, and lipid reduction, targeting primarily PPAR, FXR, ACC and GLP-1. CONCLUSION This study suggests the basic characteristics of global MASLD clinical trial design, and the current global interventional clinical trials are mainly focused on drug-related treatments, and drugs to improve inflammation and metabolism are still the first choice for MASLD drug intervention studies.
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Affiliation(s)
- Hui Du
- Department of Infectious, Longhua Hospital, Affiliated to Shanghai University of Traditional Chinese Medicine, #725 Wanping South Road, Xuhui District, Shanghai, 200032, People's Republic of China
| | - Jihan Huang
- Center for Drug Clinical Research, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People's Republic of China
| | - Youhua Wang
- Department of Infectious, Longhua Hospital, Affiliated to Shanghai University of Traditional Chinese Medicine, #725 Wanping South Road, Xuhui District, Shanghai, 200032, People's Republic of China
| | - Chunyan Wang
- Department of Infectious, Longhua Hospital, Affiliated to Shanghai University of Traditional Chinese Medicine, #725 Wanping South Road, Xuhui District, Shanghai, 200032, People's Republic of China
| | - Yiqun Wang
- Department of Traditional Chinese Medicine, Shanghai Public Health Clinical Center, Shanghai, 200083, People's Republic of China
| | - Luming Hou
- Department of Infectious, Longhua Hospital, Affiliated to Shanghai University of Traditional Chinese Medicine, #725 Wanping South Road, Xuhui District, Shanghai, 200032, People's Republic of China
| | - Yali Li
- Department of Infectious, Longhua Hospital, Affiliated to Shanghai University of Traditional Chinese Medicine, #725 Wanping South Road, Xuhui District, Shanghai, 200032, People's Republic of China
| | - Ying Li
- Department of Infectious, Longhua Hospital, Affiliated to Shanghai University of Traditional Chinese Medicine, #725 Wanping South Road, Xuhui District, Shanghai, 200032, People's Republic of China.
| | - Qianmin Su
- Department of Computer Science, School of Electrical and Electronic Engineering, Shanghai University of Engineering Science, #333 Longteng Road, Songjiang District, Shanghai, 201620, People's Republic of China.
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Liu X, Ma S, Li J, Song M, Li Y, Qi Y, Liu F, Fang Z, Zheng R. Clinical Features and Plasma Metabolites Analysis in Obese Chinese Children With Nonalcoholic Fatty Liver Disease. J Endocr Soc 2025; 9:bvaf032. [PMID: 40104566 PMCID: PMC11914974 DOI: 10.1210/jendso/bvaf032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Indexed: 03/20/2025] Open
Abstract
Objective This study aimed to investigate the clinical characteristics and plasma metabolites of nonalcoholic fatty liver disease (NAFLD) in obese Chinese children and to develop machine learning-based NAFLD diagnostic models. Methods We recruited 222 obese children aged 4 to 17 years and divided them into an obese control group and an obese NAFLD group based on liver ultrasonography. Mass spectrometry metabolomic analysis was used to measure 106 metabolites in plasma. Binary logistic regression was used to identify NAFLD-related clinical variables. NAFLD-specific metabolites were illustrated via volcano plots, cluster heatmaps, and metabolic network diagrams. Additionally, we applied 8 machine learning methods to construct 3 diagnostic models based on clinical variables, metabolites, and clinical variables combined with metabolites. Results By evaluating clinical variables and plasma metabolites, we identified 16 clinical variables and 14 plasma metabolites closely associated with NAFLD. We discovered that the level of 18:0 to 22:6 phosphatidylethanolamines was positively correlated with the levels of total cholesterol, triglyceride-glucose index, and triglyceride to high-density lipoprotein cholesterol ratio, whereas the level of glycocholic acid was positively correlated with the levels of alanine aminotransferase, gamma-glutamyl transferase, insulin, and the homeostasis model assessment of insulin resistance. Additionally, we successfully developed 3 NAFLD diagnostic models that showed excellent diagnostic performance (areas under the receiver operating characteristic curves of 0.917, 0.954, and 0.957, respectively). Conclusions We identified 16 clinical variables and 14 plasma metabolites associated with NAFLD in obese Chinese children. Diagnostic models using these features showed excellent performance, indicating their potential for diagnosis.
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Affiliation(s)
- Xiaoxiao Liu
- Department of Pediatrics, Tianjin Medical University General Hospital, Tianjin 300000, China
| | - Shifeng Ma
- Department of Pediatrics, Tianjin Medical University General Hospital, Tianjin 300000, China
| | - Jing Li
- Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin 300000, China
- Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin 300000, China
- Tianjin Center for International Collaborative Research on Environment, Nutrition and Public Health, Tianjin 300000, China
| | - Mingkun Song
- Department of Pediatrics, Tianjin Medical University General Hospital, Tianjin 300000, China
| | - Yun Li
- Department of Pediatrics, Tianjin Medical University General Hospital, Tianjin 300000, China
| | - Yingyi Qi
- Department of Pediatrics, Tianjin Medical University General Hospital, Tianjin 300000, China
| | - Fei Liu
- Department of Pediatrics, Tianjin Medical University General Hospital, Tianjin 300000, China
| | - Zhongze Fang
- Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin 300000, China
- Tianjin Center for International Collaborative Research on Environment, Nutrition and Public Health, Tianjin 300000, China
- Department of Toxicology and Sanitary Chemistry, School of Public Health, Tianjin Medical University, Tianjin 300000, China
| | - Rongxiu Zheng
- Department of Pediatrics, Tianjin Medical University General Hospital, Tianjin 300000, China
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Fajrudheen M, Mahapatro S, Panigrahi MK, Naik S, Satapathy AK. Noninvasive Assessment of Nonalcoholic Fatty Liver Disease in Children with Overweight and Obesity by Transient Elastography. Indian J Endocrinol Metab 2025; 29:230-236. [PMID: 40416463 PMCID: PMC12101759 DOI: 10.4103/ijem.ijem_150_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2024] [Revised: 08/03/2024] [Accepted: 12/09/2024] [Indexed: 05/27/2025] Open
Abstract
Introduction Childhood obesity and nonalcoholic fatty liver disease (NAFLD) are emerging as significant health concerns. While liver biopsy remains the gold standard for diagnosis, there is a pressing need for a noninvasive alternative to identify early fibrosis. Methods A cross-sectional investigation was carried out from January 2020 to December 2021 involving overweight and obese children attending the pediatric outpatient department (OPD). The aim is to determine the occurrence of fibrotic and steatotic changes in the liver of overweight and obese children using transient elastography (TE) and to establish correlations between TE results, Pediatric NAFLD Fibrosis Index (PNFI), and other biochemical parameters. TE was utilized to assess both fibrotic and steatosis changes, while ultrasound (USG) was employed to detect steatosis in the liver. Results Two hundred and fifty-nine eligible children participated in the study. Mean age of the study cohort was 10.8 years, with males constituting 63%. Mean Z score for BMI was 1.71 ± 0.57. Fibrosis was detected in 29.3% of children by TE, while steatosis was observed in 27.7% of children. Steatosis was identified in 23.8% of cases through USG. BMI Z score, ALT (Alanine aminotransferase), AST and PNFI score exhibited significant associations with grades of liver fibrosis and steatosis as determined by TE, as well as with grades of steatosis according to USG findings. Conclusion A notable prevalence of increased liver stiffness was observed in overweight and obese children. TE proves to be a valuable tool in identifying fibrotic and steatotic changes in these children, complementing existing noninvasive modalities.
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Affiliation(s)
- Mohamed Fajrudheen
- Department of Pediatrics, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India
| | - Samarendra Mahapatro
- Department of Pediatrics, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India
| | - Manas K. Panigrahi
- Department of Gastroenterology, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India
| | - Suprava Naik
- Department of Radiodiagnosis, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India
| | - Amit K. Satapathy
- Department of Pediatrics, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India
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Bornia Matavelli C, Echeverria LS, Pereira LM, Chrispim I, Mounzer DLS, Chaim FDM, Chaim EA, Utrini MP, Gestic MA, Callejas-Neto F, Cazzo E. Short-Term Evolution of MASLD Following Roux-en-Y Gastric Bypass: A Focus on Fibrotic MASH. Obes Surg 2025; 35:926-933. [PMID: 39870941 DOI: 10.1007/s11695-025-07688-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Revised: 12/23/2024] [Accepted: 01/11/2025] [Indexed: 01/29/2025]
Abstract
BACKGROUND Metabolic dysfunction-associated steatotic liver disease (MASLD) includes simple steatosis and metabolic dysfuncion-associated steatohepatitis (MASH), with fibrosis in MASH serving as a critical prognostic marker. This study investigates the effects of Roux-en-Y gastric bypass (RYGB) on fibrotic MASH, assessed using the fibrotic NASH index (FNI) and the non-invasive NASH detection score (NI-NASH-DS), as well as provides further data on the diagnostic accuracy of both scores. METHODS A retrospective cohort study was conducted involving 104 individuals (91.3% female, mean age 39.4 ± 8.6 years) who underwent RYGB. Histopathological evaluations during surgery identified fibrotic MASH, and FNI and NI-NASH-DS values were calculated at baseline and 1 year post-surgery. RESULTS At the time of surgery, participants had a mean BMI of 35.3 ± 2.8 kg/m2, which decreased to 27.1 ± 4.0 kg/m2 1 year after surgery. The mean % total weight loss (%TWL) was 23.8 ± 10.1%, and the mean % excess weight loss (%EWL) was 82.4 ± 37.3%. Fibrotic MASH was present in 17.3% of participants pre-operatively. The mean FNI score significantly decreased after surgery (p < 0.0001). Female gender (p < 0.001) and histological evidence of lobular inflammation (p < 0.001) were independently associated with the improvement of FNI. The FNI demonstrated high diagnostic accuracy (sensitivity: 61.1%, specificity: 96.4%, overall accuracy: 90.2%). NI-NASH-DS had a 60% accuracy in detecting MASH, alongside an 85.9% specificity. CONCLUSIONS RYGB seemingly promotes improvement of fibrotic MASH as evaluated by FNI, highlighting its potential as a therapeutic intervention to mitigate MASLD progression. Both FNI and NI-NASH-DS are helpful and inexpensive tools for assessing MASH.
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Wang Y, Yang S, Zhang S, Yang Y, Li S, Zhang M, Li X, Bai H, Luo P, Yuan Y. The value of sex hormones and sex hormone-binding globulin in metabolic dysfunction-associated fatty liver disease among boys with obesity. Front Endocrinol (Lausanne) 2025; 16:1446049. [PMID: 39980852 PMCID: PMC11839430 DOI: 10.3389/fendo.2025.1446049] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2024] [Accepted: 01/15/2025] [Indexed: 02/22/2025] Open
Abstract
Objective This study aims to investigate the relationship between metabolic dysfunction-associated fatty liver disease (MAFLD) and sex hormones and sex hormone-binding globulin (SHBG) in boys with obesity. Methods Retrospective analysis of metabolic indicators and sex hormone levels in boys with obesity who sought medical attention at the First People's Hospital of Lianyungang City from January 2020 to December 2023. Based on abdominal ultrasound results, they were categorized into a simple obesity group and MAFLD group, and differences between the two groups were compared. Utilizing logistic regression analysis to explore the risk factors for developing MAFLD, and through the construction of Receiver Operating Characteristic (ROC) curves, conducting a preliminary assessment of the diagnostic value for MAFLD. Results A total of 155 male children with obesity were included in the study, mean age of 11.07 ± 1.53 years. Children in the MAFLD group had higher levels of height[(159.49 ± 12.73)cm vs.(155.55 ± 10.50)cm], weight[(82.32 ± 18.75)kg vs.(68.28 ± 15.00)kg], BMI[(32.08 ± 4.49)kg/m2 vs.(27.85 ± 4.21)kg/m2],fasting insulin[33.42(24.07,43.93)uIU/ml vs.23.91(15.72,31.52)uIU/ml],HOMA-IR[7.27(5.26,10.71) vs.4.87(3.27,6.86)],fastingC-peptide[1409.00(1175.00,1668.00)pmol/L vs.1020.00(849.05,1303.00)pmol/L], WBC[(7.85 ± 1.80)×109/L vs.(7.15 ± 1.42)×109/L], HbA1c[5.40(5.30,5.70)% vs.(5.30(5.20,5.60)%],ALT[48.00(27.00,80.00)U/L vs.19.00(15.00,26.50)U/L], and AST[31.00(24.00,60.00)U/L vs.21.00(18.50, 26.00)U/L] compared to the simple obesity group (P<0.05). Children in the MAFLD group had lower levels of HDL[(1.05 ± 0.21)mmol/L vs.(1.16 ± 0.26)mmol/L], testosterone [42.41(30.33,143.28)ng/dl vs.125.41(23.41,221.57)ng/dl], and SHBG[13.20(9.10,17.30)nmol/l vs.19.60(13.50,29.85)nmol/l] compared to the simple obesity group (P<0.05). Logistic regression showed that BMI, testosterone, and SHBG were independent risk factors for MAFLD in boys, and ROC curve analysis indicated their potential value in the early diagnosis of MAFLD. Conclusion BMI, testosterone, and SHBG are independent risk factors for the occurrence of MAFLD in boys with obesity. To control the occurrence of MAFLD, it is essential to address the root cause of the high growth rate of obesity. The roles of testosterone and SHBG in MAFLD merit further research.
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Affiliation(s)
- Ying Wang
- Pediatric Endocrinology Department, The First People’s Hospital of Lianyungang, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, China
| | - Shuyi Yang
- Pediatric Endocrinology Department, The First People’s Hospital of Lianyungang, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, China
| | - Suming Zhang
- Pediatric Endocrinology Department, The First People’s Hospital of Lianyungang, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, China
- Department of Pediatrics, Lianyungang Municipal Oriental Hospital, Lianyungang, China
| | - Ye Yang
- Pediatric Endocrinology Department, The First People’s Hospital of Lianyungang, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, China
| | - Siqing Li
- Pediatric Endocrinology Department, The First People’s Hospital of Lianyungang, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, China
- Pediatric Endocrinology Department, The First People’s Hospital of Lianyungang, Lianyungang Clinical College of Nanjing Medical University, Lianyungang, China
| | - Meiyu Zhang
- Pediatric Endocrinology Department, The First People’s Hospital of Lianyungang, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, China
- Pediatric Endocrinology Department, The First People’s Hospital of Lianyungang, Lianyungang Clinical College of Nanjing Medical University, Lianyungang, China
| | - Xiaona Li
- Pediatric Endocrinology Department, The First People’s Hospital of Lianyungang, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, China
| | - Hua Bai
- Pediatric Endocrinology Department, The First People’s Hospital of Lianyungang, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, China
| | - Peiliang Luo
- Pediatric Endocrinology Department, The First People’s Hospital of Lianyungang, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, China
| | - Yingdi Yuan
- Pediatric Endocrinology Department, The First People’s Hospital of Lianyungang, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, China
- Pediatric Endocrinology Department, The First People’s Hospital of Lianyungang, Lianyungang Clinical College of Nanjing Medical University, Lianyungang, China
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Arteaga I, Chacón C, Martínez-Escudé A, Rojano IR, Diez-Fadrique G, Carmona-Cervelló M, Torán-Monserrat P. Evaluating Pediatric NAFLD with Controlled Attenuation Parameter: A Comprehensive Narrative Review. Diagnostics (Basel) 2025; 15:299. [PMID: 39941229 PMCID: PMC11816681 DOI: 10.3390/diagnostics15030299] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2024] [Revised: 01/09/2025] [Accepted: 01/24/2025] [Indexed: 02/16/2025] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) in the pediatric population has emerged as a significant health concern due to its alarming rise in prevalence. In children, the characteristics of the disease differ from those seen in adults. NAFLD may progress to more severe liver disease in children compared to adults with similar profiles. Liver biopsy remains the gold standard for diagnosis; its invasive nature and high cost limit its use as a first-line tool. Alternatively, magnetic resonance imaging (MRI) techniques, such as magnetic resonance imaging-estimated liver proton density fat fraction (MRI-PDFF), have shown a good correlation with the degree of histological steatosis, although their use is limited by high costs and limited accessibility. Controlled attenuation parameter (CAP), integrated with vibration-controlled transient elastography (VCTE) (FibroScan®), is a novel non-invasive, accessible, and effective method for diagnosing hepatic steatosis. In this article, we reviewed the existing literature on the diagnostic accuracy of CAP in pediatric NAFLD. The PubMed and EMBASE databases were searched. Seven relevant studies were identified, conducted in pediatric hospital populations with specific demographic characteristics. Two of these studies compared CAP with liver biopsy, one compared CAP with liver biopsy and MRI-PDFF, and the remaining four compared CAP with MRI. Overall, CAP proved to be accurate in detecting the presence or absence of fatty infiltration, positioning it as a promising tool to simplify the diagnosis of NAFLD in children. However, further studies in larger populations are needed to confirm these findings and facilitate its implementation in routine clinical practice.
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Affiliation(s)
- Ingrid Arteaga
- Unitat de Suport a la Recerca (USR) Metropolitana Nord, Fundació Institut Universitari d’Investigació en Atenció Primària Jordi Gol i Gurina (IDIAP Jordi Gol), 08303 Mataró, Spain; (I.A.); (C.C.); (A.M.-E.); (I.R.R.); (G.D.-F.); (M.C.-C.)
- Grup de Recerca en Malalties Hepàtiques a l’Atenció Primària (GRemHAp), IDIAP Jordi Gol, USR Metro-Nord, 08303 Mataró, Spain
- Primary Healthcare Center Vall del Tenes, Gerència d’Àmbit d’Atenció Primària Metropolitana Nord, Institut Català de la Salut, 08186 Llicà d’Amunt, Spain
| | - Carla Chacón
- Unitat de Suport a la Recerca (USR) Metropolitana Nord, Fundació Institut Universitari d’Investigació en Atenció Primària Jordi Gol i Gurina (IDIAP Jordi Gol), 08303 Mataró, Spain; (I.A.); (C.C.); (A.M.-E.); (I.R.R.); (G.D.-F.); (M.C.-C.)
- Grup de Recerca en Malalties Hepàtiques a l’Atenció Primària (GRemHAp), IDIAP Jordi Gol, USR Metro-Nord, 08303 Mataró, Spain
- Ph.D. Programme in Medicine and Translational Research, Faculty of Medicine, University of Barcelona, 08193 Barcelona, Spain
| | - Alba Martínez-Escudé
- Unitat de Suport a la Recerca (USR) Metropolitana Nord, Fundació Institut Universitari d’Investigació en Atenció Primària Jordi Gol i Gurina (IDIAP Jordi Gol), 08303 Mataró, Spain; (I.A.); (C.C.); (A.M.-E.); (I.R.R.); (G.D.-F.); (M.C.-C.)
- Grup de Recerca en Malalties Hepàtiques a l’Atenció Primària (GRemHAp), IDIAP Jordi Gol, USR Metro-Nord, 08303 Mataró, Spain
- Primary Healthcare Center La Llagosta, Gerència d’Àmbit d’Atenció Primària Metropolitana Nord, Institut Català de la Salut, 08120 La Llagosta, Spain
- Department of Medicine, Faculty of Medicine, Autonomous University of Barcelona, 08193 Bellaterra, Spain
| | - Irene Ruiz Rojano
- Unitat de Suport a la Recerca (USR) Metropolitana Nord, Fundació Institut Universitari d’Investigació en Atenció Primària Jordi Gol i Gurina (IDIAP Jordi Gol), 08303 Mataró, Spain; (I.A.); (C.C.); (A.M.-E.); (I.R.R.); (G.D.-F.); (M.C.-C.)
- Grup de Recerca en Malalties Hepàtiques a l’Atenció Primària (GRemHAp), IDIAP Jordi Gol, USR Metro-Nord, 08303 Mataró, Spain
- Primary Healthcare Center Dr. Barraquer, Gerència d’Àmbit d’Atenció Primària Metropolitana Nord, Institut Català de la Salut, 08930 Sant Adrià del Besos, Spain
| | - Galadriel Diez-Fadrique
- Unitat de Suport a la Recerca (USR) Metropolitana Nord, Fundació Institut Universitari d’Investigació en Atenció Primària Jordi Gol i Gurina (IDIAP Jordi Gol), 08303 Mataró, Spain; (I.A.); (C.C.); (A.M.-E.); (I.R.R.); (G.D.-F.); (M.C.-C.)
| | - Meritxell Carmona-Cervelló
- Unitat de Suport a la Recerca (USR) Metropolitana Nord, Fundació Institut Universitari d’Investigació en Atenció Primària Jordi Gol i Gurina (IDIAP Jordi Gol), 08303 Mataró, Spain; (I.A.); (C.C.); (A.M.-E.); (I.R.R.); (G.D.-F.); (M.C.-C.)
| | - Pere Torán-Monserrat
- Unitat de Suport a la Recerca (USR) Metropolitana Nord, Fundació Institut Universitari d’Investigació en Atenció Primària Jordi Gol i Gurina (IDIAP Jordi Gol), 08303 Mataró, Spain; (I.A.); (C.C.); (A.M.-E.); (I.R.R.); (G.D.-F.); (M.C.-C.)
- Grup de Recerca en Malalties Hepàtiques a l’Atenció Primària (GRemHAp), IDIAP Jordi Gol, USR Metro-Nord, 08303 Mataró, Spain
- Germans Trias i Pujol Research Institute (IGTP), 08916 Badalona, Spain
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Mahmoudi A, Butler AE, Orekhov AN, Jamialahmadi T, Sahebkar A. Statins as a Potential Treatment for Non-alcoholic Fatty Liver Disease: Target Deconvolution using Protein-protein Interaction Network Analysis. Curr Med Chem 2025; 32:1355-1377. [PMID: 37644746 DOI: 10.2174/0929867331666230829164832] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Revised: 06/28/2023] [Accepted: 07/18/2023] [Indexed: 08/31/2023]
Abstract
BACKGROUND The hallmark of non-alcoholic fatty liver disease (NAFLD) is aberrant buildup of triglycerides (TGs) in hepatocytes. Many genes promote NAFLD development. Using bioinformatics tools, we investigated the possible effect of statins on genes involved in NAFLD progression. METHODS Protein interactions of statins and NAFLD were searched in gene-drug and gene-disease databases. A Protein-Protein interaction (PPI) network was constructed to find hub genes and Molecular Complex Detection (MCODE) of NAFLD-related genes. Shared protein targets between protein targets of statins and NAFLD-associated genes were identified. Next, targets of each statin were assayed with all modular clusters in the MCODEs related to NAFLD. Biological process and pathway enrichment analysis for shared proteins was performed. RESULTS Screening protein targets for conventional statins and curated NAFLD-related genes identified 343 protein targets and 70 genes, respectively. A Venn diagram of NAFLD-related genes and protein targets of statins showed 24 shared proteins. The biological pathways on KEGG enrichment associated with the 24 shared protein sets were evaluated and included cytokine-cytokine receptor interaction, adipocytokine, PPAR, TNF and AMPK signaling pathways. Gene Ontology analysis showed major involvement in lipid metabolic process regulation and inflammatory response. PPI network analysis of 70 protein targets indicated 13 hub genes (PPARA, IL4, CAT, LEP, SREBF1, PRKCA, CYP2E1, NFE2L2, PTEN, NR1H4, ADIPOQ, GSTP1 and TGFB1). Comparing all seven statins with the three MCODE clusterings and 13 hub genes revealed that simvastatin as the most associated statin with NAFLD. CONCLUSION Simvastatin has the most impact on NAFLD-related genes versus other statins.
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Affiliation(s)
- Ali Mahmoudi
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Alexandra E Butler
- Department of Medical Sciences, Royal College of Surgeons in Ireland Bahrain, Adliya, Bahrain
| | - Alexander N Orekhov
- Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 8 Baltiiskaya Street, Moscow 125315, Russia
- Institute for Atherosclerosis Research, Osennyaya Street 4-1-207, Moscow 121609, Russia
| | - Tannaz Jamialahmadi
- International UNESCO Center for Health-Related Basic Sciences and Human Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
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El-Kassas M, Othman HA, Elbadry M, Alswat K, Yilmaz Y. Risk Stratification of Patients with Metabolic Dysfunction-associated Steatotic Liver Disease: Steatohepatitis, Fibrosis, and Hepatocellular Carcinoma. J Clin Exp Hepatol 2025; 15:102415. [DOI: 10.1016/j.jceh.2024.102415] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/03/2025] Open
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22
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Orozco Morales JA, Medina Urrutia AX, Tamayo MT, Reyes Barrera J, Galarza EJ, Juárez Rojas JG, Dies Suarez P, Méndez Sánchez N, Díaz Orozco LE, Velázquez-López L, Medina Bravo P. Impact of metabolic-associated fatty liver disease on the cholesterol efflux capacity of high-density lipoproteins in adolescents with type 2 diabetes. Front Pediatr 2024; 12:1462406. [PMID: 39776642 PMCID: PMC11703661 DOI: 10.3389/fped.2024.1462406] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Accepted: 11/05/2024] [Indexed: 01/11/2025] Open
Abstract
CONTEXT Type 2 diabetes (DM2) is an emerging disease in the pediatric population. DM2 is associated with metabolic-associated fatty liver disease (MAFLD). High-density lipoproteins (HDLs) are lipoproteins that are believed to have atheroprotective properties that reduce the risk of cardiovascular disease (CVD). Current evidence suggests that the physicochemical and functional features of HDLs may play a key role in the pathogenesis of atherosclerosis. OBJECTIVE We aimed to assess the impact of MAFLD on cholesterol efflux capacity (CEC) in adolescents with DM2. DESIGN A cross-sectional study. SETTING Attention clinic for Children with Diabetes of the Hospital Infantil de México Federico Gómez. PATIENTS OR OTHER PARTICIPANTS This study included a total of 70 adolescents, 47 of which had DM2 and 23 were healthy individuals. INTERVENTIONS The presence of MAFLD was determined by MR spectroscopy with proton density fat fraction. We compared the distribution of HDL subtypes (HDL2b, HDL2a, HDL3a, HDL3b, and HDL3c) and the chemical composition of HDLs (total protein, triglycerides, phospholipids, cholesteryl esters, and free cholesterol). HDL functionality was determined by the CEC, measuring the fluorescent cholesterol efflux from J774 macrophage cells. MAIN OUTCOME MEASURES We were expecting to observe a decrease in HDL efflux capacity in adolescents with type 2 diabetes and MAFLD. RESULTS In our study, we observed a prevalence of MAFLD in 66% of adolescents with DM2, similar to that reported in other international studies (60%-80%). In the population with DM2 and MAFLD, we did not observe a decrease in CEC. Initially we found a slight elevation of CEC in adolescents with DM2, however, with the increase in liver fat, a little decrease is observed, which could explain a probable metabolic phenomenon, since the physicochemical composition and distribution of the particles is associated with the percentage of liver fat. A positive correlation between the percentage of liver fat and the concentration of HDL2b (p = 0.011), HDL2a (p = 0.014) and average particle size (p = 0.011) and the proportion of triglycerides inside the particles (p = 0.007). Likewise, negative correlation were found with the percentage of liver fat, cholesterol esters (p = 0.010) and free cholesterol of the particles (p < 0.001). We observed a positive correlation between CEC and the percentage of triglycerides (p = 0.007), and a negative correlation with the percentage of cholesterol esters (p = 0.05) inside the HDL's particles. CONCLUSIONS In this group of adolescents with DM2, the presence of MAFLD was not associated with CEC; however, it is associated with abnormalities in the distribution and lipid composition of HDL particles. The momentum generated by the original proposal for MAFLD in the adult population and following the recommendations for pediatric MAFLD will be a step forward in helping to study the impact of MAFLD on the atheroprotective properties of HDL in the pediatric population.
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Affiliation(s)
- José Antonio Orozco Morales
- Department of Endocrinology, Hospital Infantil de México Federico Gómez, Mexico City, Mexico
- Odontological and Health Sciences, UniversidadNacional Autónoma de México, Mexico City, Mexico
| | | | - Margarita Torres Tamayo
- Department of Endocrinology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico
- Supervision Coordination of IMSS-BIENESTAR, Mexican Social Security Institute (Instituto Mexicano del Seguro Social, IMSS), Mexico City, Mexico
| | - Juan Reyes Barrera
- Department of Endocrinology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico
| | - Esteban Jorge Galarza
- Department of Endocrinology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico
| | | | - Pilar Dies Suarez
- Department of Imaging, Hospital Infantil de México Federico Gómez, Mexico City, Mexico
| | - Nahum Méndez Sánchez
- Faculty of Medicine, Universidad Nacional Autónoma de México, Mexico City, Mexico
- Liver Research Unit, Fundación Clínica Médica Sur, Mexico City, Mexico
| | - Luis Enrique Díaz Orozco
- Faculty of Medicine, Universidad Nacional Autónoma de México, Mexico City, Mexico
- Liver Research Unit, Fundación Clínica Médica Sur, Mexico City, Mexico
| | - Lubia Velázquez-López
- Clinical Epidemiology Research Unit, Hospital Carlos Mac Gregor Sánchez Navarro, Mexican Social Security Institute (Instituto Mexicano del Seguro Social, IMSS), Mexico City, Mexico
| | - Patricia Medina Bravo
- Department of Endocrinology, Hospital Infantil de México Federico Gómez, Mexico City, Mexico
- Faculty of Medicine, Universidad Nacional Autónoma de México, Mexico City, Mexico
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Lin Y, Ye H, Chen Y, Zhang R, Chen Y, Ou W. Integrative Analyses of Genes of Pediatric Non-alcoholic Fatty Liver Disease Associated with Energy Metabolism. Dig Dis Sci 2024; 69:4373-4391. [PMID: 39496907 PMCID: PMC11602812 DOI: 10.1007/s10620-024-08702-4] [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: 04/04/2024] [Accepted: 10/18/2024] [Indexed: 11/06/2024]
Abstract
BACKGROUND Pediatric non-alcoholic fatty liver disease (NAFLD) is a chronic steatosis of the liver associated with energy metabolism in children and adolescents, failure to intervene promptly can elevate the risk of developing hepatocellular carcinoma. Therefore, this study aimed to understand the underlying mechanism of pediatric NAFLD and investigate potential biomarkers and therapeutic targets. METHODS We investigated genes using the GSE185051 data set related to energy metabolism from the GeneCards database, constructed protein-protein interaction network, identified hub genes and established networks representing interactions between these hub genes and miRNA, RNA-binding proteins, transcription factors, and drugs. Subsequently, we performed Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis, Gene Set Enrichment Analysis (GSEA), and immune infiltration analysis. RESULTS Our analysis identified 9 hub genes through the PPI network. The target molecules were identified through the interaction network between hub genes and miRNAs, RNA-binding proteins, transcription factors, and drugs. GO analysis revealed that hub genes were associated with oxidative stress responses and other pathways. KEGG analysis highlighted their involvement in pathways such as insulin resistance, among others. GSEA revealed that hub genes were highly enriched in pathways related to Omega-9 fatty acid synthesis, among others. Immune infiltration analysis suggested that mast cells and T follicular helper cells play significant roles in the pathogenesis of NAFLD. CONCLUSION We identified the hub genes in pediatric NAFLD closely related to energy metabolism. These findings offer the potential for identifying potential novel diagnostic biomarkers, and establishing therapeutic targets for pediatric NAFLD.
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Affiliation(s)
- Yijun Lin
- Department of Pediatrics, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, No.18, Daoshan Road, Gulou District, Fuzhou, 350001, Fujian, China
- Department of Pediatrics, Fujian Children's Hospital (Fujian Branch of Shanghai Children's Medical Center), Fuzhou, China
| | - Hong Ye
- Department of Pediatrics, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, No.18, Daoshan Road, Gulou District, Fuzhou, 350001, Fujian, China.
- Department of Pediatrics, Fujian Children's Hospital (Fujian Branch of Shanghai Children's Medical Center), Fuzhou, China.
| | - Yan Chen
- Department of Pediatrics, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, No.18, Daoshan Road, Gulou District, Fuzhou, 350001, Fujian, China
- Department of Pediatrics, Fujian Children's Hospital (Fujian Branch of Shanghai Children's Medical Center), Fuzhou, China
| | - Rui Zhang
- Department of Pediatrics, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, No.18, Daoshan Road, Gulou District, Fuzhou, 350001, Fujian, China
- Department of Pediatrics, Fujian Children's Hospital (Fujian Branch of Shanghai Children's Medical Center), Fuzhou, China
| | - Yuyun Chen
- Department of Pediatrics, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, No.18, Daoshan Road, Gulou District, Fuzhou, 350001, Fujian, China
- Department of Pediatrics, Fujian Children's Hospital (Fujian Branch of Shanghai Children's Medical Center), Fuzhou, China
| | - Weijie Ou
- Department of Pediatrics, Fujian Children's Hospital (Fujian Branch of Shanghai Children's Medical Center), Fuzhou, China
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Jiang L, Xu QY, Zhou YC, Xu J, Fan JG. Spatial Transcriptomics Reveals the Transcriptomic Signatures in a Mouse Model of Pediatric Metabolic Dysfunction-Associated Steatohepatitis. THE AMERICAN JOURNAL OF PATHOLOGY 2024; 194:2341-2355. [PMID: 39222909 DOI: 10.1016/j.ajpath.2024.08.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/07/2024] [Revised: 07/24/2024] [Accepted: 08/16/2024] [Indexed: 09/04/2024]
Abstract
Metabolic dysfunction-associated steatohepatitis (MASH) is considered the progressive form of metabolic dysfunction-associated steatotic liver disease, which is the leading cause of chronic liver disease in children. However, the pathogenesis of pediatric MASH remains poorly understood because of the lack of animal models. In this study, a mouse model of pediatric MASH was developed and its hepatic transcriptomic profile was characterized using spatial transcriptomics technology. C57BL/6J mice were fed a Western diet (WD) along with weekly injections of carbon tetrachloride (CCl4) from the age of 3 weeks and lasting up to 8 weeks. After 5 weeks of feeding, WD + CCl4-treated mice showed significant liver injury without the development of insulin resistance. Histologically, WD + CCl4 induced key features of type 2 MASH, the most common type observed in children, characterized by liver steatosis, portal inflammation, and portal fibrosis. Spatial transcriptomics analysis of liver tissues indicated that cluster 0 in the mouse from the WD + CCl4 group was enriched in pathways associated with lipid metabolism. Further investigation revealed that cytochrome p450 2E1 was the top marker gene of cluster 0, and its expression was increased in the periportal area of mice from the WD + CCl4 group. These findings suggest that this mouse model of pediatric MASH mirrors the histologic features of human MASH, and the up-regulation of cytochrome p450 2E1 may be linked to the disease pathogenesis.
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Affiliation(s)
- Lu Jiang
- Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Institute for Pediatric Research, Shanghai, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China
| | - Qing-Yang Xu
- Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | | | - Juan Xu
- Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jian-Gao Fan
- Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China; Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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Wei J, Luo J, Yang F, Dai W, Huang Z, Yan Y, Luo M. Comparative genomic and metabolomic analysis reveals the potential of a newly isolated Enterococcus faecium B6 involved in lipogenic effects. Gene 2024; 927:148668. [PMID: 38852695 DOI: 10.1016/j.gene.2024.148668] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2024] [Revised: 06/01/2024] [Accepted: 06/06/2024] [Indexed: 06/11/2024]
Abstract
Evidence has indicated that Enterococcus plays a vital role in non-alcoholic fatty liver disease (NAFLD) development. However, the microbial genetic basis and metabolic potential in the disease are yet unknown. We previously isolated a bacteria Enterococcus faecium B6 (E. faecium B6) from children with NAFLD for the first time. Here, we aim to systematically investigate the potential of strain B6 in lipogenic effects. The lipogenic effects of strain B6 were explored in vitro and in vivo. The genomic and functional characterizations were investigated by whole-genome sequencing and comparative genomic analysis. Moreover, the metabolite profiles were unraveled by an untargeted metabolomic analysis. We demonstrated that strain B6 could effectively induce lipogenic effects in the liver of mice. Strain B6 contained a circular chromosome and two circular plasmids and posed various functions. Compared to the other two probiotic strains of E. faecium, strain B6 exhibited unique functions in pathways of ABC transporters, phosphotransferase system, and amino sugar and nucleotide sugar metabolism. Moreover, strain B6 produced several metabolites, mainly enriched in the protein digestion and absorption pathway. The unique potential of strain B6 in lipogenic effects was probably associated with glycolysis, fatty acid synthesis, and glutamine and choline transport. This study pioneeringly revealed the metabolic characteristics and specific detrimental traits of strain B6. The findings provided new insights into the underlying mechanisms of E. faecium in lipogenic effects, and laid essential foundations for further understanding of E. faecium-related disease.
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Affiliation(s)
- Jia Wei
- Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University, Changsha 410078, Hunan, China
| | - Jiayou Luo
- Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University, Changsha 410078, Hunan, China
| | - Fei Yang
- Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, University of South China, Hengyang 421001, Hunan, China
| | - Wen Dai
- Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University, Changsha 410078, Hunan, China
| | - Zhihang Huang
- Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University, Changsha 410078, Hunan, China
| | - Yulin Yan
- Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University, Changsha 410078, Hunan, China
| | - Miyang Luo
- Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University, Changsha 410078, Hunan, China.
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Mallet M, Silaghi CA, Sultanik P, Conti F, Rudler M, Ratziu V, Thabut D, Pais R. Current challenges and future perspectives in treating patients with NAFLD-related cirrhosis. Hepatology 2024; 80:1270-1290. [PMID: 37183906 DOI: 10.1097/hep.0000000000000456] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Accepted: 04/20/2023] [Indexed: 05/16/2023]
Abstract
Despite the slow, progressive nature of NAFLD, the number of patients with NAFLD-related cirrhosis has significantly increased. Although the management of patients with cirrhosis is constantly evolving, improving the prognosis of patients with NAFLD-related cirrhosis is a challenge because it is situated at the crossroads between the liver, the metabolic, and the cardiovascular diseases. Therefore, the therapeutic interventions should not only target the liver but also the associated cardiometabolic conditions and should be adapted accordingly. The objective of the current review is to critically discuss the particularities in the management of patients with NAFLD-related cirrhosis. We relied on the recommendations of scientific societies and discussed them in the specific context of NAFLD cirrhosis and the surrounding cardiometabolic milieu. Herein, we covered the following aspects: (1) the weight loss strategies through lifestyle interventions to avoid sarcopenia and improve portal hypertension; (2) the optimal control of metabolic comorbidities in particular type 2 diabetes aimed not only to improve cardiovascular morbidity/mortality but also to lower the incidence of cirrhosis-related complications (we discussed various aspects related to the safety of oral antidiabetic drugs in cirrhosis); (3) the challenges in performing bariatric surgery in patients with cirrhosis related to the portal hypertension and the risk of cirrhosis decompensation; (4) the particularities in the diagnosis and management of the portal hypertension and the difficulties in managing patients awaiting for liver transplantation; and (5) the difficulties in developing drugs and conducting clinical trials in patients with NAFLD-related cirrhosis. Moreover, we discussed the emerging options to overcome these obstacles.
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Affiliation(s)
- Maxime Mallet
- Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Service d'hepato-gastroentérologie, Hôpital Pitié-Salpêtrière, Paris, France
| | - Cristina Alina Silaghi
- Department of Endocrinology, "Iuliu Hatieganu" University of Medicine and Pharmacy Cluj-Napoca, Roumanie
| | - Philippe Sultanik
- Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Service d'hepato-gastroentérologie, Hôpital Pitié-Salpêtrière, Paris, France
- Brain Liver Pitié-Salpêtrière Study Group (BLIPS), Paris, France
| | - Filomena Conti
- Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Service d'hepato-gastroentérologie, Hôpital Pitié-Salpêtrière, Paris, France
- Centre de Recherche Saint Antoine, INSERM UMRS_938 Paris, France
| | - Marika Rudler
- Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Service d'hepato-gastroentérologie, Hôpital Pitié-Salpêtrière, Paris, France
- Brain Liver Pitié-Salpêtrière Study Group (BLIPS), Paris, France
- Centre de Recherche Saint Antoine, INSERM UMRS_938 Paris, France
- Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
| | - Vlad Ratziu
- Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Service d'hepato-gastroentérologie, Hôpital Pitié-Salpêtrière, Paris, France
- Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
- INSERM UMRS 1138 CRC, Paris, France
| | - Dominique Thabut
- Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Service d'hepato-gastroentérologie, Hôpital Pitié-Salpêtrière, Paris, France
- Brain Liver Pitié-Salpêtrière Study Group (BLIPS), Paris, France
- Centre de Recherche Saint Antoine, INSERM UMRS_938 Paris, France
| | - Raluca Pais
- Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Service d'hepato-gastroentérologie, Hôpital Pitié-Salpêtrière, Paris, France
- Centre de Recherche Saint Antoine, INSERM UMRS_938 Paris, France
- Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
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Akhgarjand C, Entezarian M, Samavat S, Tavakoli A, Anoushirvani A, Asghari G, Yusbashian E, Dehghan P, Mirmiran P, Imani H. The association of fructose and fiber consumption and physical activity with non-alcoholic fatty liver disease in children and adolescents: a cross-sectional study. BMC Nutr 2024; 10:140. [PMID: 39434194 PMCID: PMC11494766 DOI: 10.1186/s40795-024-00943-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2024] [Accepted: 09/30/2024] [Indexed: 10/23/2024] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is emerging as the most prevalent liver disease in overweight and obese children. While no cure exists, dietary and lifestyle modifications have been shown to improve the condition. This study investigates the relationship between fructose and fiber consumption, physical activity, and NAFLD in children. METHODS A cross-sectional study was conducted on 378 overweight and obese children aged 6-13 years. NAFLD diagnosis was confirmed via ultrasound, and dietary intake was assessed using a 147-item food frequency questionnaire (FFQ). Physical activity was evaluated using the Modifiable Activity Questionnaire (MAQ). Multivariable logistic regression models were applied to determine the associations. RESULTS After excluding 53 participants due to incomplete data, 325 were included in the final analysis. The mean age was 9.2 ± 1.7 years, and 35% had NAFLD. No significant association was found between fructose intake and NAFLD (OR: 0.67, 95% CI: 0.35-1.29, P = 0.221). However, higher intake of legume fiber (OR: 0.48, 95% CI: 0.26-0.90, P = 0.03) and nut fiber (OR: 0.52, 95% CI: 0.28-0.95, P = 0.04) was significantly associated with a reduced risk of NAFLD. Physical activity showed a trend towards reduced NAFLD risk but was not statistically significant after adjustments (OR: 0.53, 95% CI: 0.22-1.04, P = 0.07). CONCLUSIONS While fructose intake was not significantly linked to NAFLD in this population, fiber from legumes and nuts appeared protective. Further prospective studies are needed to confirm these findings and clarify the role of physical activity in NAFLD prevention.
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Affiliation(s)
- Camellia Akhgarjand
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Mahdieh Entezarian
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Simin Samavat
- Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Aryan Tavakoli
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Aliarash Anoushirvani
- Firoozabadi Clinical Research Development Unit (FACRDU), Department of Pediatrics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
- Hemato-Oncology Ward, Firoozgar Hospital, Iran University of Medical Science, Tehran, Iran
| | - Golaleh Asghari
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Emad Yusbashian
- Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Pooneh Dehghan
- Department of Imaging, Research Development Center, Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Parvin Mirmiran
- Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hossein Imani
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.
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Zhang LP, Wei HX, Lin SH, Qiu BW, Lin JL. Cotinine exposure enhances the association of blood manganese and non-alcoholic fatty liver disease in American children: a cross-sectional study. Sci Rep 2024; 14:24593. [PMID: 39426991 PMCID: PMC11490505 DOI: 10.1038/s41598-024-75298-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Accepted: 10/03/2024] [Indexed: 10/21/2024] Open
Abstract
This cross-sectional survey aims to determine whether cotinine exposure would enhance the relationship between blood manganese (Mn) and non-alcoholic fatty liver disease (NAFLD) in children using the NHANES database. Restricted cubic spline (RCS) and logistic regression analyses were adopted to determine the potential relationship. Besides, we tested the robustness of the results by performing trend tests and subgroup analyses. The study finally enrolled 866 children aged 18 years and below. Blood Mn was linearly linked to NAFLD and the risk of NAFLD was increased with the blood Mn elevation (P < 0.05). There was a notable relationship between blood Mn and NAFLD in crude model 1, which was still significant upon adjustment of all the identified covariates (all P < 0.05). Under Mn exposure, the cotinine-exposed group had a higher risk of NAFLD than the cotinine-unexposed group. In conclusion, blood Mn level is an independent risk factor for pediatric NAFLD, and cotinine exposure can enhance this relationship to some degree. Therefore, reducing cotinine exposure may alleviate detrimental consequences related to exposure to heavy metals in children.
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Affiliation(s)
- Li-Ping Zhang
- Pediatrics, Longyan First Affiliated Hospital of Fujian Medical University, No.105, Jiuyi North Road, Xinluo District, Longyan, 364000, Fujian, China
| | - Hua-Xing Wei
- Pediatrics, Longyan First Affiliated Hospital of Fujian Medical University, No.105, Jiuyi North Road, Xinluo District, Longyan, 364000, Fujian, China.
| | - Shi-Hui Lin
- Pediatrics, Longyan First Affiliated Hospital of Fujian Medical University, No.105, Jiuyi North Road, Xinluo District, Longyan, 364000, Fujian, China
| | - Bin-Wei Qiu
- Pediatrics, Longyan First Affiliated Hospital of Fujian Medical University, No.105, Jiuyi North Road, Xinluo District, Longyan, 364000, Fujian, China
| | - Jin-Liang Lin
- Pediatrics, Longyan First Affiliated Hospital of Fujian Medical University, No.105, Jiuyi North Road, Xinluo District, Longyan, 364000, Fujian, China
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Shin HJ, Song K, Hwang S, Han K, Ryu L. Impact of Respiratory Motion on the Quantification of Pediatric Hepatic Steatosis Using Two Different Ultrasonography Machines. Yonsei Med J 2024; 65:602-610. [PMID: 39313451 PMCID: PMC11427123 DOI: 10.3349/ymj.2023.0440] [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: 10/31/2023] [Revised: 03/26/2024] [Accepted: 04/03/2024] [Indexed: 09/25/2024] Open
Abstract
PURPOSE This study aimed to investigate the effect of respiratory motion on hepatic steatosis quantification using ultrasound attenuation imaging (ATI) or ultrasound-guided attenuation parameter (UGAP) in pediatric patients. MATERIALS AND METHODS Pediatric patients (aged ≤18 years) who underwent liver ultrasonography (US) with ATI or UGAP between May 2022 and February 2023 were included retrospectively. Median, interquartile range (IQR), and IQR/median values were calculated in both free-breathing (FB) and breath-holding (BH) states. Subjects were divided into normal and fatty liver groups according to grayscale US. Wilcoxon signed rank test, intraclass correlation coefficient (ICC), and linear regression test were used. RESULTS A total of 83 patients (M:F=46:37, median age 10 years, range 6-17 years) was included, with 55 patients in the ATI group and 28 patients in the UGAP group. The measured values of ATI and UGAP were not significantly different between FB and BH. The ICC values between FB and BH states were 0.950 [95% confidence interval (CI) 0.916-0.971] for median ATI and 0.786 (95% CI 0.591-0.894) for median UGAP. FB and BH status did not significantly affect the median ATI and UGAP (p=0.852, 0.531, respectively). The IQR/median value showed a significant association with age only in the FB status of the normal group using ATI (β= -0.014, p=0.042). CONCLUSION Respiratory motion does not significantly affect the measurement of ATI or UGAP. Median ATI value showed excellent agreement in FB and BH status, while UGAP showed good agreement. Younger age may affect measurement variability in FB status of the normal group using ATI.
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Affiliation(s)
- Hyun Joo Shin
- Department of Radiology, Research Institute of Radiological Science and Center for Clinical Imaging Data Science, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Korea.
| | - Kyungchul Song
- Department of Pediatrics, Severance Children's Hospital, Endocrine Research Institute, Yonsei University College of Medicine, Seoul, Korea
| | - Sinhye Hwang
- Department of Radiology, Research Institute of Radiological Science and Center for Clinical Imaging Data Science, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Korea
| | - Kyunghwa Han
- Department of Radiology, Research Institute of Radiological Science and Center for Clinical Imaging Data Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Leeha Ryu
- Department of Biostatistics and Computing, Yonsei University Graduate School, Seoul, Korea
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30
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Vimalesvaran S, Vajro P, Dhawan A. Pediatric metabolic (dysfunction)-associated fatty liver disease: current insights and future perspectives. Hepatol Int 2024; 18:873-883. [PMID: 38879851 PMCID: PMC11450008 DOI: 10.1007/s12072-024-10691-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Accepted: 04/24/2024] [Indexed: 10/05/2024]
Abstract
The historical use of the term non-alcoholic fatty liver disease (NAFLD) in obese/overweight children has been controversial as to the appropriateness of this terminology in children, and lately, in adults too. Newer game-changer terminology, metabolic (dysfunction)-associated fatty liver disease (MAFLD), for this condition signifies a positive step forward that addresses the limitations of the previous definition for both adults and children. The prevalence of MAFLD has surged in tandem with the global rise in obesity rates, establishing itself as a predominant cause of chronic liver disease in both adult and pediatric populations. The adoption of the recently proposed nomenclature reflects a more encompassing comprehension of the disease and its etiology compared to its predecessor, NAFLD. Notably, the revised terminology facilitates the recognition of MAFLD as an autonomous condition while acknowledging the potential coexistence of other systemic fatty liver disorders. Particularly in children, this includes various paediatric-onset genetic and inherited metabolic disorders, necessitating thorough exclusion, especially in cases where weight loss interventions yield no improvement or in the absence of obesity. MAFLD presents as a multifaceted disorder; evidence suggests its origins lie in a complex interplay of nutritional, genetic, hormonal, and environmental factors. Despite advancements, current non-invasive diagnostic biomarkers exhibit limitations in accuracy, often necessitating imaging and histological evaluations for definitive diagnosis. While dietary and lifestyle modifications stand as cornerstone measures for MAFLD prevention and management, ongoing evaluation of therapeutic agents continues. This article provides an overview of the latest developments and emerging therapies in the realm of paediatric MAFLD.
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Affiliation(s)
- Sunitha Vimalesvaran
- Paediatric Liver, Gastroenterology and Nutrition Centres, King's College Hospital NHS Trust, London, UK
| | - Pietro Vajro
- Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", Section of Pediatrics, Baronissi, Salerno, Italy
| | - Anil Dhawan
- Paediatric Liver, Gastroenterology and Nutrition Centres, King's College Hospital NHS Trust, London, UK.
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31
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Zhao Q, Li Y, Zhang M, Ban B. Nonlinear relationship between the triglyceride-glucose index and alanine aminotransferase in children with short stature. Sci Rep 2024; 14:20588. [PMID: 39232127 PMCID: PMC11374982 DOI: 10.1038/s41598-024-71608-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2024] [Accepted: 08/29/2024] [Indexed: 09/06/2024] Open
Abstract
Metabolic dysfunction associated fatty liver disease (MAFLD) is a common cause of liver disease in children and adolescents. The relationship between insulin resistance (IR) and MAFLD in children with short stature remains largely unknown. The present study was to investigate the relationship between the triglyceride-glucose (TyG) index and alanine aminotransferase (ALT) levels in children with short stature. A total of 1754 children with short stature were enrolled. Anthropometric, biochemical and hormonal indexes were collected through physical measurement examinations and laboratory tests. A nonlinear association was found between the TyG index and ALT. The inflection point of the curve was at a TyG index of 8.24. In multivariate piecewise linear regression, only when the TyG index was greater than 8.24 was there a significant positive association between the TyG index and ALT (β 5.75, 95% CI 3.30, 8.19; P < 0.001). However, when the TyG index was less than 8.24, there was no significant association between the TyG index and ALT (β -0.57, 95% CI -1.84, 0.71; P = 0.382). This study demonstrated a nonlinear relationship between TyG index and ALT in children with short stature. This finding suggests that a high TyG index is associated with elevated ALT in children with short stature.
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Affiliation(s)
- Qianqian Zhao
- Department of Endocrinology, Affiliated Hospital of Jining Medical University, Jining Medical University, 89 Guhuai Road, Jining, 272029, Shandong, People's Republic of China
- Chinese Research Center for Behavior Medicine in Growth and Development, 89 Guhuai Road, Jining, 272029, Shandong, People's Republic of China
| | - Youqian Li
- Department of Cardiovasology, Affiliated Hospital of Jining Medical University, Jining Medical University, 89 Guhuai Road, Jining, 272029, Shandong, People's Republic of China
| | - Mei Zhang
- Department of Endocrinology, Affiliated Hospital of Jining Medical University, Jining Medical University, 89 Guhuai Road, Jining, 272029, Shandong, People's Republic of China
- Chinese Research Center for Behavior Medicine in Growth and Development, 89 Guhuai Road, Jining, 272029, Shandong, People's Republic of China
| | - Bo Ban
- Department of Endocrinology, Affiliated Hospital of Jining Medical University, Jining Medical University, 89 Guhuai Road, Jining, 272029, Shandong, People's Republic of China.
- Chinese Research Center for Behavior Medicine in Growth and Development, 89 Guhuai Road, Jining, 272029, Shandong, People's Republic of China.
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Wu ZY, Chi SW, Ouyang LJ, Xu XQ, Chen JN, Jin BH, Ullah R, Zhou XL, Huang K, Dong GP, Li ZM, Shen Y, Shao J, Ni Y, Fu JF, Shu Q, Wu W. Continuous age- and sex-specific reference ranges of liver enzymes in Chinese children and application in pediatric non-alcoholic fatty liver disease. World J Pediatr 2024; 20:949-956. [PMID: 38388968 DOI: 10.1007/s12519-023-00789-5] [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: 07/14/2023] [Accepted: 12/13/2023] [Indexed: 02/24/2024]
Abstract
BACKGROUND Alanine aminotransferase (ALT) is widely used to screen patients with hepatic diseases. However, the current reference ranges (< 50 U/L) were developed by laboratories and have not been validated in populations with a large number of healthy individuals. METHODS This study collected venous blood and anthropometric data from a total of 13,287 healthy children aged 3 months to 18 years who underwent routine physical examinations in the Department of Pediatric Healthcare. We applied the least mean square algorithm to establish age- and sex-related reference percentiles of serum levels of transaminases. For validation, we recruited 4276 children and adolescents with obesity/overweight who underwent evaluation and metabolic tests in the hospital. Using receiver operating characteristic curves, we determined age- and sex-specific upper limit percentiles of liver enzymes for fatty liver diseases. RESULTS This study revealed a significant correlation between serum transaminase levels and age and sex (P < 0.01). These transaminase levels exhibited age- and sex-specific patterns. Among individuals in the non-alcoholic fatty liver disease (NAFLD) cohort, elevated ALT levels displayed a positive association with clinical markers of disease severity, including homeostatic model assessment of insulin resistance, waist-hip ratio, and serum uric acid levels (P < 0.01). According to the receiver operating characteristic curves, ALT levels at the 92.58th percentile for boys and the 92.07th percentile for girls yielded the highest accuracy and specificity. CONCLUSIONS This study provides age- and sex-specific reference ranges for ALT, aspartate aminotransferase, and γ-glutamyltransferase in Chinese children and adolescents, making it the largest population study to date. Furthermore, the study establishes a precise upper limit for ALT levels, facilitating their use in NAFLD screening. Video Abstract.
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Affiliation(s)
- Zhao-Yuan Wu
- Department of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, 3333 Binsheng Road, Hangzhou, 310051, China
| | - Si-Wei Chi
- Department of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, 3333 Binsheng Road, Hangzhou, 310051, China
| | - Liu-Jian Ouyang
- Department of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, 3333 Binsheng Road, Hangzhou, 310051, China
| | - Xiao-Qin Xu
- Department of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, 3333 Binsheng Road, Hangzhou, 310051, China
| | - Jing-Nan Chen
- Department of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, 3333 Binsheng Road, Hangzhou, 310051, China
| | - Bing-Han Jin
- Department of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, 3333 Binsheng Road, Hangzhou, 310051, China
| | - Rahim Ullah
- Department of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, 3333 Binsheng Road, Hangzhou, 310051, China
| | - Xue-Lian Zhou
- Department of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, 3333 Binsheng Road, Hangzhou, 310051, China
| | - Ke Huang
- Department of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, 3333 Binsheng Road, Hangzhou, 310051, China
| | - Guan-Ping Dong
- Department of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, 3333 Binsheng Road, Hangzhou, 310051, China
| | - Zhe-Ming Li
- Department of Data and Information, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Ying Shen
- Department of Child Health Care, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
| | - Jie Shao
- Department of Child Health Care, 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, 3333 Binsheng Road, Hangzhou, 310051, China
| | - Jun-Fen Fu
- Department of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, 3333 Binsheng Road, Hangzhou, 310051, China.
| | - Qiang Shu
- Department of Thoracic & Cardiovascular Surgery, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children's Regional Medical Center, 3333 Binsheng Road, Hangzhou, 310051, China.
| | - Wei Wu
- Department of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, 3333 Binsheng Road, Hangzhou, 310051, China.
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Wu Z, Xia F, Wang W, Zhang K, Fan M, Lin R. Worldwide burden of liver cancer across childhood and adolescence, 2000-2021: a systematic analysis of the Global Burden of Disease Study 2021. EClinicalMedicine 2024; 75:102765. [PMID: 39170941 PMCID: PMC11338123 DOI: 10.1016/j.eclinm.2024.102765] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Revised: 07/13/2024] [Accepted: 07/15/2024] [Indexed: 08/23/2024] Open
Abstract
Background Liver cancer is a significant contributor to the global disease burden, of which hepatoblastomas are the most common liver tumors in children, with 90% of cases occurring within the first 5 years of life. It is important for pediatricians and subspecialists in pediatric gastroenterology and hepatology to have knowledge of the epidemiology and incidence trends of pediatric hepatic cancer, despite its rarity. In the present study, we first provide estimates of the incidence and mortality burden of hepatoblastoma and liver cancer from 2000 to 2021 in the childhood and adolescence. Methods Liver cancer burden and its attributable risk factors were estimated using data from the Global Burden of Disease Study (GBD) 2021. Percentage change was estimated to show the trend of liver cancer estimates from 2000 to 2021. The age-standardized rate (ASR) and estimated annual percentage change (EAPC) were utilized for measuring hepatoblastomas incidence and deaths rate trends. In accordance with the GBD framework, 95% uncertainty intervals (UIs) for all estimates by averaging the data from 1000 draws, with the lower and upper bounds of the 95% UIs. Findings Globally, from 2000 to 2021 in the age 5-19 years group, the incidence cases and deaths cases due to liver cancer decreased from 2449.2 (95% UI: 2235.9-2689.8) to 1692.9 (95% UI: 1482.0-1992.5) and 2248.5 (95% UI: 2053.7-2474.9) to 1516.6 (95% UI: 1322.1-1797.9), respectively. Meanwhile, from 2000 to 2021 in the age 20-24 years group, the incidence cases and deaths cases due to liver cancer decreased from 1453.5 (95% UI: 1327.8-1609.4) to 1285.1 (95% UI: 1159.2-1447.2) and 1432.3 (95% UI: 1307.6-1585.7) to 1195.5 (95% UI: 1066.1-1355.2), respectively. In addition, the prevalence of liver cancer decreased from 41.9% (95% UI: 18.7%-64.7%) to 26.4% (95% UI: 14.2%-39.1%) in the age 5-19 years group, and 46.6% (95% UI: 42.8%-51.5%) to 36.5% (95% UI: 33.1%-40.9%) in the age 20-24 years. From 2000 to 2021, in the age group of 5-19 years, the proportion of liver cancer incidence due to hepatitis B has decreased from 42.2% to 37.9%, while the proportion due to hepatitis C has increased from 1.1% to 1.6%. Additionally, there has been an increase in the proportion of NASH-induced liver cancer incidence from 5.2% to 9.4%, and alcohol use induced liver cancer incidence has also increased from 0.5% to 0.7% over the same period. Globally, from 2000 to 2021, the incidence cases and deaths cases due to hepatoblastoma decreased from 6131.8 (95% UI: 5234.8-6961.9) to 4045.6 (95% UI: 3250-4995.8) and 4059.2 (95% UI: 3494.5-4621.2) to 2416 (95% UI: 1940.2-3022.5), respectively. There was some variation in age-related sex-specific patterns, the highest number of hepatoblastoma incidence cases occurred in children between 2 and 4 years old and females in the age range of 12 months to 9 years had a higher number of new cases. Importantly, the incidence of hepatoblastoma was started to increase sharply after the age of 1 month. Interpretation The results of the present study are significant for liver health policy and practice in childhood and adolescence. Differentiated intervention and outreach strategies based on age and gender would be necessary to reduce the impact of liver cancer. Early screening and interventions for hepatoblastoma is important especially in the population of under 9 years old. Funding This study was supported by the National Key R&D Program of China (grant numbers 2023YFC2307000), National Natural Science Foundation of China [grant numbers 82170571 and 81974068], China Postdoctoral Science Foundation (grant numbers 2023M741283).
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Affiliation(s)
- Zenghong Wu
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Fangnan Xia
- Biomedical Materials Engineering Research Center, Hubei Key Laboratory of Polymer Materials, Ministry-of-Education Key Laboratory for the Green Preparation and Application of Functional Materials, School of Materials Science & Engineering, State Key Laboratory of Biocatalysis and Enzyme Engineering, Hubei University, Wuhan, China
| | - Weijun Wang
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Kun Zhang
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Mengke Fan
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Rong Lin
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Liu L, Li M, Qin Y, Liu L, Xiao Y. Serum follistatin like 1 in children with obesity and metabolic-associated fatty liver disease. BMC Endocr Disord 2024; 24:165. [PMID: 39210310 PMCID: PMC11360849 DOI: 10.1186/s12902-024-01702-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2024] [Accepted: 08/23/2024] [Indexed: 09/04/2024] Open
Abstract
BACKGROUND Follistatin-like protein 1 (FSTL1) has been identified as a secreted glycoprotein that plays an important role in obesity. However, its role in children with metabolic-associated fatty liver disease (MAFLD) has not been investigated. This study aimed at characterizing the relationship between serum FSTL1 concentration and MAFLD in children with obesity. METHODS A total of 121 subjects were recruited from the Second Affiliated Hospital of Xi'an Jiaotong University, including 45 obese children with MAFLD, 31 obese children without MAFLD, and 45 healthy controls. Anthropometric parameters, biochemical data were measured and circulating FSTL1 levels were detected by ELISA. RESULTS The levels of FSTL1 in obese children with MAFLD were higher than that in obese children without MAFLD: 1.31 (0.35-2.29) ng/mL vs. 0.55 (0.36-1.38) ng/mL. Correlation analysis illustrated that FSTL1 was associated with nonesterified free fatty acid and leptin (r = 0.278, P < 0.05 and r = 0.572, P < 0.05, respectively). Binary logistic regression suggested that increased FSTL1 was a risk factor for MAFLD in children (OR = 1.105, 95% CI: 1.066-1.269, P < 0.05). CONCLUSIONS Serum FSTL1 concentrations increase in obese children with MAFLD and may have the potential to be a risk factor for MAFLD in children with obesity.
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Affiliation(s)
- Lujie Liu
- Department of Pediatrics, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 Xiwu Road, Xi'an, 710061, Shaanxi, China
| | - Meng Li
- Department of Pediatrics, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 Xiwu Road, Xi'an, 710061, Shaanxi, China
| | - Yujie Qin
- Department of Pediatrics, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 Xiwu Road, Xi'an, 710061, Shaanxi, China
| | - Luyang Liu
- School of Public Health, Xi'an Jiaotong University, Xi'an, China
| | - Yanfeng Xiao
- Department of Pediatrics, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 Xiwu Road, Xi'an, 710061, Shaanxi, China.
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Peng T, Yi X, Lin Y, Dong X, Zhang P, Qiao Z, Li L. Controlled attenuation parameter (CAP): the clinical value based on MRI-PDFF in children with obesity. J Pediatr Endocrinol Metab 2024; 37:605-612. [PMID: 38723170 DOI: 10.1515/jpem-2023-0566] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2023] [Accepted: 04/29/2024] [Indexed: 07/14/2024]
Abstract
OBJECTIVES Controlled attenuation parameter (CAP) is a noninvasive and quantitative method to evaluate hepatic steatosis, which is not well evaluated in children. The aim of this study was to examine the diagnostic value of CAP for hepatic steatosis in children with obesity based on MR proton density fat fraction (PDFF). METHODS About 108 pediatric patients with nonalcoholic fatty liver disease (NAFLD) who were assessed for PDFF, CAP, and other laboratory results were enrolled. In this study, pediatric patients were separated for the obese group (n=80) and the severe obese group (n=28). Hepatic steatosis grades (0-3) were classified according to PDFF using cutoff values of 6.4 , 17.4, and 22.1 %. RESULTS There are significant differences in CAP between the obese and severe obese groups (p<0.05). CAP showed a good correlation with PDFF in pediatric patients with NAFLD for diagnosing hepatic steatosis using a cutoff value of 265 dB/m (p<0.001). Meanwhile, ALT significantly outperforms CAP in receiver-operating curve (ROC) analysis for diagnosing hepatic steatosis grades. The diagnostic accuracy of CAP for steatosis is 77.8 %, and the diagnostic accuracy of ALT for steatosis is 83.3 %. CONCLUSIONS While CAP holds promise as a diagnostic tool for pediatric NAFLD, its diagnostic performance warrants some caution. The potential of CAP is evident; however, ALT emerges as a simpler and more accurate measure for detecting hepatic steatosis in children. Further research is essential to determine the optimal role of CAP in pediatric NAFLD diagnosis and management.
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Affiliation(s)
- Tianfang Peng
- 26494 Affiliated Hospital of Hangzhou Normal University , Hangzhou, Zhejiang, China
| | - Xiaolian Yi
- 26494 Affiliated Hospital of Hangzhou Normal University , Hangzhou, Zhejiang, China
| | - Yan Lin
- 26494 Affiliated Hospital of Hangzhou Normal University , Hangzhou, Zhejiang, China
| | - Xianhui Dong
- 26494 Affiliated Hospital of Hangzhou Normal University , Hangzhou, Zhejiang, China
| | - Pengwei Zhang
- 26494 Affiliated Hospital of Hangzhou Normal University , Hangzhou, Zhejiang, China
| | - Zhihui Qiao
- 117836 Women's Hospital Zhejiang University School of Medicine , Hangzhou, Zhejiang, China
| | - Li Li
- Department of Clinical Medics, 26494 Hangzhou Normal University , Hangzhou, Zhejiang, China
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Fu DF, Chen B. The relationship between the systemic immune inflammation index and the nonalcoholic fatty liver disease in American adolescents. BMC Gastroenterol 2024; 24:233. [PMID: 39044158 PMCID: PMC11267776 DOI: 10.1186/s12876-024-03324-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Accepted: 07/15/2024] [Indexed: 07/25/2024] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is a growing health crisis in the general population of the United States (U.S.), but the relationship between systemic immune-inflammation (SII) index and NAFLD is not known. METHODS We collected data from the National Health and Nutrition Examination Survey 2017-2018. Next, propensity score matching (PSM), collinearity analysis, restricted cubic spline (RCS) plot, logistic regression, quantile regression analysis, subgroup analysis, mediation analysis, and population attributable fraction were used to explore the association of the SII with risk of NAFLD. RESULTS A total of 665 participants including the 532 Non-NAFLD and 133 NAFLD were enrolled for further analysis after PSM analysis. The RCS results indicated that there was a linear relationship between the SII and controlled attenuation parameter (p for nonlinear = 0.468), the relationship also existed after adjustment for covariates (p for nonlinear = 0.769). The logistic regression results indicated that a high SII level was an independent risk factor for NAFLD (OR = 3.505, 95% CI: 1.092-11.249, P < 0.05). The quantile regression indicated that at higher quantiles (0.90, and 0.95) the SII was significantly associated with NAFLD (p < 0.05). Mediation analysis indicated that alanine aminotransferase (ALT), triglycerides, and blood urea nitrogen (BUN) were partially contribute to the relationship between SII and NAFLD. The population attributable fractions indicated that 23.19% (95% CI: 8.22%, 38.17%) of NAFLD cases could be attributed to SII corresponding to 133 NAFLD cases. CONCLUSION There was a positive linear relationship between the SII and the risk of NAFLD. The ALT, triglycerides, and BUN had a partial mediating effect on the relationship between the SII and NAFLD.
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Affiliation(s)
- Dong-Fang Fu
- Department of Ultrasound, Hangzhou Xiaoshan First People's Hospital, No.199, Shixin South Road, Xiaoshan District, Hangzhou, Zhejiang, 311201, China
| | - Bin Chen
- Department of Ultrasound, Hangzhou Xiaoshan First People's Hospital, No.199, Shixin South Road, Xiaoshan District, Hangzhou, Zhejiang, 311201, China.
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Biao Y, Li D, Zhang Y, Gao J, Xiao Y, Yu Z, Li L. Wulingsan Alleviates MAFLD by Activating Autophagy via Regulating the AMPK/mTOR/ULK1 Signaling Pathway. Can J Gastroenterol Hepatol 2024; 2024:9777866. [PMID: 39035827 PMCID: PMC11260214 DOI: 10.1155/2024/9777866] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2023] [Revised: 04/19/2024] [Accepted: 06/24/2024] [Indexed: 07/23/2024] Open
Abstract
Here, we presented the study of the molecular mechanisms underlying the action of Wulingsan (WLS) in rats with metabolic-associated fatty liver disease (MAFLD) induced by a high-fat diet (HFD). High-performance liquid chromatography was employed to identify the chemical components of WLS. After 2 weeks of HFD induction, MAFLD rats were treated with WLS in three different doses for 6 weeks, a positive control treatment or with a vehicle. Lipid metabolism, liver function, oxidative stress, and inflammatory factors as well as pathomorphological changes in liver parenchyma were assessed in all groups. Finally, the expressions of autophagy-related markers, adenosine monophosphate-activated protein kinase (AMPK)/mechanistic target of rapamycin (mTOR)/unc-51-like kinase-1 (ULK1) signaling pathway-related genes, and proteins in liver were detected. The results revealed that WLS significantly ameliorated liver injury, the dysfunction of the lipid metabolism, the oxidative stress, and overall inflammatory status. Furthermore, WLS increased the expressions of LC3B-II, Beclin1, p-AMPK, and ULK1, along with decreased p62, p-mTOR, and sterol regulatory element-binding protein-1c levels. In conclusion, we showed that WLS is capable of alleviating HFD-induced MAFLD by improving lipid accumulation, suppressing oxidative stress and inflammation, and promoting autophagy.
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Affiliation(s)
- Yaning Biao
- School of Basic MedicineHebei University of Chinese Medicine, Shijiazhuang, Hebei, China
| | - Dantong Li
- School of PharmacyHebei University of Chinese Medicine, Shijiazhuang, Hebei, China
| | - Yixin Zhang
- School of PharmacyHebei University of Chinese Medicine, Shijiazhuang, Hebei, China
| | - Jingmiao Gao
- School of PharmacyHebei University of Chinese Medicine, Shijiazhuang, Hebei, China
| | - Yi Xiao
- School of PharmacyHebei University of Chinese Medicine, Shijiazhuang, Hebei, China
| | - Zehe Yu
- School of PharmacyHebei University of Chinese Medicine, Shijiazhuang, Hebei, China
| | - Li Li
- School of PharmacyHebei Medical University, Shijiazhuang, Hebei, China
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Mahmoudi A, Jalili A, Butler AE, Aghaee-Bakhtiari SH, Jamialahmadi T, Sahebkar A. Exploration of the Key Genes Involved in Non-alcoholic Fatty Liver Disease and Possible MicroRNA Therapeutic Targets. J Clin Exp Hepatol 2024; 14:101365. [PMID: 38433957 PMCID: PMC10904918 DOI: 10.1016/j.jceh.2024.101365] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2023] [Accepted: 02/11/2024] [Indexed: 03/05/2024] Open
Abstract
Background MicroRNAs (miRNAs) are promising therapeutic agents for non-alcoholic fatty liver disease (NAFLD). This study aimed to identify key genes/proteins involved in NAFLD pathogenesis and progression and to evaluate miRNAs influencing their expression. Methods Gene expression profiles from datasets GSE151158, GSE163211, GSE135251, GSE167523, GSE46300, and online databases were analyzed to identify significant NAFLD-related genes. Then, protein-protein interaction networks and module analysis identified hub genes/proteins, which were validated using real-time PCR in oleic acid-treated HepG2 cells. Functional enrichment analysis evaluated signaling pathways and biological processes. Gene-miRNA interaction networks identified miRNAs targeting critical NAFLD genes. Results The most critical overexpressed hub genes/proteins included: TNF, VEGFA, TLR4, CYP2E1, ACE, SCD, FASN, SREBF2, and TGFB1 based on PPI network analysis, of which TNF, TLR4, SCD, FASN, SREBF2, and TGFB1 were up-regulated in oleic acid-treated HepG2 cells. Functional enrichment analysis for biological processes highlighted programmed necrotic cell death, lipid metabolic process response to reactive oxygen species, and inflammation. In the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, the highest adjusted P-value signaling pathways encompassed AGE-RAGE in diabetic complications, TNF, and HIF-1 signaling pathways. In gene-miRNA network analysis, miR-16 and miR-124 were highlighted as the miRNAs exerting the most influence on important NAFLD-related genes. Conclusion In silico analyses identified NAFLD therapeutic targets and miRNA candidates to guide further experimental investigation.
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Affiliation(s)
- Ali Mahmoudi
- Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Iran
| | - Amin Jalili
- Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Iran
| | | | - Seyed H. Aghaee-Bakhtiari
- Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Iran
- Bioinformatics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Tannaz Jamialahmadi
- Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
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Gao XY, Yang YF, Li L, Xing YF, Wang YX, Li XY, Yang SH, Wang MY, Fan JG, Wang H. Survey of physicians' knowledge about pediatric nonalcoholic fatty liver disease in China. J Dig Dis 2024; 25:380-393. [PMID: 38992957 DOI: 10.1111/1751-2980.13297] [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: 01/11/2024] [Revised: 05/26/2024] [Accepted: 06/11/2024] [Indexed: 07/13/2024]
Abstract
OBJECTIVES To evaluate physicians' awareness and knowledge towards pediatric nonalcoholic fatty liver disease (NAFLD) and their attitude toward change in nomenclature from NAFLD to metabolic dysfunction-associated fatty liver disease (MAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD) in China. METHODS The questionnaire survey contained five parts (characteristics of the participants, epidemiology, diagnosis, management of NAFLD, and attitudes toward the nomenclature of MAFLD/MASLD). The participants included 53 hepatologists, 88 gastroenterologists (GEs), 74 endocrinologists (ENDOs), 61 primary care physicians (PCPs), and 157 pediatricians across 31 municipalities, provinces and autonomous regions of China's mainland. RESULTS Hepatologists saw the largest number of pediatric NAFLD patients annually (median 9 [range 1-20]), with the lowest number by PCPs (even notwithstanding one patient annually). The primary sources of pediatric NAFLD knowledge were acquired via guidelines. Hepatologists had the highest total knowledge score among all five types of physicians. Approximately one-third of nonspecialists (ENDOs and PCPs) considered liver biopsy necessary for pediatric NAFLD patients, and this percentage increased to half in specialists (hepatologists and GEs). For nonspecialists, the major barriers to the management of pediatric NAFLD were poor patient adherence to lifestyle modifications and lacking confidence in managing NAFLD. Above 90% physicians agreed to change the nomenclature NAFLD to MAFLD; however, they were not sure whether it could reduce the economic burden. CONCLUSIONS Despite the epidemic of pediatric NAFLD in China, a significant knowledge gap remains in the identification, diagnosis, and treatment of pediatric NAFLD, particularly among frontline workers such as pediatricians and PCPs. More education programs should be carried out in the future.
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Affiliation(s)
- Xiang Yang Gao
- Health Management Institute, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China
| | - Yi Fan Yang
- Department of Maternal and Child Health, School of Public Health, Peking University, Beijing, China
| | - Li Li
- Department of Endocrinology and Metabolism, Ningbo First Hospital, Ningbo, Zhejiang Province, China
| | - Yun Fei Xing
- Department of Maternal and Child Health, School of Public Health, Peking University, Beijing, China
| | - You Xin Wang
- Department of Maternal and Child Health, School of Public Health, Peking University, Beijing, China
| | - Xue Ying Li
- Department of Maternal and Child Health, School of Public Health, Peking University, Beijing, China
| | - Shu Han Yang
- Department of Maternal and Child Health, School of Public Health, Peking University, Beijing, China
| | - Ming Yue Wang
- Department of Maternal and Child Health, School of Public Health, Peking University, Beijing, China
| | - Jian Gao Fan
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Lab of Pediatric Gastroenterology and Nutrition, Shanghai, China
| | - Hui Wang
- Department of Maternal and Child Health, School of Public Health, Peking University, Beijing, China
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Lee EJ, Choi M, Ahn SB, Yoo JJ, Kang SH, Cho Y, Song DS, Koh H, Jun DW, Lee HW. Prevalence of nonalcoholic fatty liver disease in pediatrics and adolescents: a systematic review and meta-analysis. World J Pediatr 2024; 20:569-580. [PMID: 38771552 DOI: 10.1007/s12519-024-00814-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Accepted: 04/23/2024] [Indexed: 05/22/2024]
Abstract
BACKGROUND As childhood obesity escalates worldwide, the prevalence of nonalcoholic fatty liver disease (NAFLD) in pediatric and adolescent populations is also increasing. However, systematic studies and meta-analyses evaluating the prevalence of pediatric NAFLD remain limited. METHODS The MEDLINE, Korean Medical Database (KMBASE), Embase, Global Health, and Cochrane Library databases were searched from January 1997 to April 2023. Search terms included NAFLD or steatosis; nonalcoholic or steatohepatitis; child(ren), adolescent, or teenager; and prevalence, incidence, or epidemiology. A random-effects meta-analysis model was used to estimate the prevalence of pediatric NAFLD. RESULTS A total of 2116 publications were found, of which 62 were included in the meta-analysis. Among them, 27 reported the prevalence in the general population and 39 in the obese population. The worldwide pooled prevalence of pediatric NAFLD was 13% [95% confidence interval (CI) 9-18%] in the general population and 47% (95% CI 41%-53%) in the obese population. Among 16 studies in the general population and 18 in the obese population, NAFLD prevalence varied by gender. In the general population, the prevalence of NAFLD was 15% (95% CI 8%-23%) in males and 10% (95% CI 6%-15%) in females. In the obese population, it was 54% (95% CI 46%-61%) in males and 39% (95% CI 30%-49%) in females. CONCLUSIONS The global prevalence of pediatric NAFLD is rising in both the general and obese populations. Given the increasing rates of childhood obesity, epidemiological studies on the prevalence and incidence of NAFLD are needed.
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Affiliation(s)
- Eun Joo Lee
- Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea
| | - Miyoung Choi
- Clinical Evidence Research, National Evidence-Based Healthcare Collaborating Agency (NECA), Seoul, Korea
| | - Sang Bong Ahn
- Department of Internal Medicine, Nowon Eulji Medical Center, Eulji University College of Medicine, Seoul, Korea
| | - Jeong-Ju Yoo
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Seong Hee Kang
- Department of Internal Medicine, Sangkye Paek Hospital, Inje University College of Medicine, Seoul, Korea
| | - Yuri Cho
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea
| | - Do Seon Song
- Department of Internal Medicine, College of Medicine, St. Vincent's Hospital, The Catholic University of Korea, Suwon, Korea
| | - Hong Koh
- Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea
| | - Dae Won Jun
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea.
| | - Hye Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
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Hegazy MA, Elshafei A, Salem MR, Ashoush O, Abdelghani A. Non-alcoholic fatty liver disease related knowledge among a sample of Egyptians: an exploratory cross-sectional study. Front Public Health 2024; 11:1290842. [PMID: 38872989 PMCID: PMC11173582 DOI: 10.3389/fpubh.2023.1290842] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Accepted: 12/29/2023] [Indexed: 06/15/2024] Open
Abstract
Introduction The global prevalence of Non-alcoholic fatty liver disease (NAFLD) is about 25% worldwide making it an actual health disaster. This study aimed to assess non-alcoholic fatty liver disease (NAFLD)-related knowledge in a sample of Egyptians. Materials and methods This exploratory cross-sectional study was conducted on 3,124 individuals using 2000 online and 1,124 printed questionnaire forms. These questionnaires, covering sociodemographic characteristics and fatty liver-related knowledge, comprised 30 items. These items include ten questions on definition, symptoms, and complications: 14 about risk factors, and six about prevention and therapy. The data were analyzed using SPSS. Categorical variables were expressed in proportions and percentages. Chi-square and Fisher's exact tests were applied as appropriate. For quantitative variables, the t-test, Mann-Whitney U test, Kruskal-Wallis test, and ANOVA test were used for comparisons. Results A total of 3,124 respondents were enrolled in the current study. More than half (57%) were females, and 25% ranged in age from 18 to 29. 10.8% of the participants believed that fatty liver patients were asymptomatic, and 34% knew that fatty liver disease was caused by fat accumulation. Regarding predisposing factors, hypercholesterolemia, increased fat in the diet, and obesity had the highest proportion of accurate responses (60, 54, and 46.6%, respectively). On the other hand, 89.3% believed it could be prevented, and 81.4% of the respondents knew that weight reduction could prevent the condition. All respondents (100%) stated wrongly that it was a familial disease related to aging, and most participants (97.3%) did not believe that fatty liver could be treated. Females demonstrated a significantly higher score in preventive measures, while the employed participants scored significantly higher in general knowledge of fatty liver, risk factors, and preventive measures. Conclusion Despite the increasing NAFLD prevalence, the current study indicated that Egyptians had fair to moderate knowledge about fatty liver and its risk factors, preventive measures, and therapy. However, a false belief was documented by all respondents that it is a disease that runs in families and occurs only in old age. A fundamental shift in healthcare management with a prioritization of prevention, proactive measures, and early detection of NAFLD should be emphasized.
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Affiliation(s)
- Mona A. Hegazy
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Arwa Elshafei
- Public Health and Community Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
- Public Health and Community Medicine Department, Armed Forces College of Medicine, Cairo, Egypt
| | - Marwa Rashad Salem
- Public Health and Community Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Omar Ashoush
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ahmed Abdelghani
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
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Jin Y, Shangguan Z, Pang J, Chen Y, Lin S, Liu H. Pin1 Exacerbates Non-Alcoholic Fatty Liver Disease by Enhancing Its Activity through Binding to ACC1. Int J Mol Sci 2024; 25:5822. [PMID: 38892011 PMCID: PMC11171836 DOI: 10.3390/ijms25115822] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Revised: 05/17/2024] [Accepted: 05/19/2024] [Indexed: 06/21/2024] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterized by diffuse hepatocellular steatosis due to fatty deposits in hepatocytes, excluding alcohol and other known liver injury factors. However, there are no specific drugs for the clinical treatment of NAFLD. Therefore, research on the pathogenesis of NAFLD at the cellular and molecular levels is a promising approach to finding therapeutic targets and developing targeted drugs for NAFLD. Pin1 is highly expressed during adipogenesis and contributes to adipose differentiation, but its specific mechanism of action in NAFLD is unclear. In this study, we investigated the role of Pin1 in promoting the development of NAFLD and its potential mechanisms in vitro and in vivo. First, Pin1 was verified in the NAFLD model in vitro using MCD diet-fed mice by Western Blot, RT-qPCR and immunohistochemistry (IHC) assays. In the in vitro study, we used the oleic acid (OA) stimulation-induced lipid accumulation model and examined the lipid accumulation in each group of cells by oil red O staining as well as BODIPY staining. The results showed that knockdown of Pin1 inhibited lipid accumulation in hepatocytes in an in vitro lipid accumulation model and improved lipid indices and liver injury levels. Moreover, in vivo, WT and Pin1-KO mice were fed a methionine-choline deficient (MCD) diet for 4 weeks to induce the NAFLD model. The effects of Pin1 on lipid accumulation, hepatic fibrosis, and oxidative stress were evaluated by biochemical analysis, glucose and insulin tolerance tests, histological analysis, IHC, RT-qPCR and Western blot assays. The results indicate that Pin1 knockdown significantly alleviated hepatic steatosis, fibrosis and inflammation in MCD-induced NAFLD mice, improved glucose tolerance and alleviated insulin resistance in mice. Further studies showed that the AMPK/ACC1 signalling pathway might take part in the process by which Pin1 regulates NAFLD, as evidenced by the inhibition of the AMPK/ACC1 pathway. In addition, immunofluorescence (IF), coimmunoprecipitation (Co-IP) and GST pull-down experiments also showed that Pin1 interacts directly with ACC1 and inhibits ACC1 phosphorylation levels. Our study suggests that Pin1 promotes NAFLD progression by inhibiting the activation of the AMPK/ACC1 signalling pathway, and it is possible that this effect is achieved by Pin1 interacting with ACC1 and inhibiting the phosphorylation of ACC1.
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Affiliation(s)
| | | | | | | | | | - Hekun Liu
- Fujian Key Laboratory of Translational Research in Cancer and Neurodegenerative Diseases, The School of Basic Medical Sciences, Fujian Medical University, No. 1, Xuefu North Road, Fuzhou 350122, China; (Y.J.); (Z.S.); (J.P.); (Y.C.); (S.L.)
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Samanta A, Sen Sarma M. Metabolic dysfunction-associated steatotic liver disease: A silent pandemic. World J Hepatol 2024; 16:511-516. [PMID: 38689742 PMCID: PMC11056897 DOI: 10.4254/wjh.v16.i4.511] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Revised: 03/05/2024] [Accepted: 04/07/2024] [Indexed: 04/24/2024] Open
Abstract
The worldwide epidemiology of non-alcoholic fatty liver disease (NAFLD) is showing an upward trend, parallel to the rising trend of metabolic syndrome, owing to lifestyle changes. The pathogenesis of NAFLD has not been fully understood yet. Therefore, NAFLD has emerged as a public health concern in the field of hepatology and metabolisms worldwide. Recent changes in the nomenclature from NAFLD to metabolic dysfunction-associated steatotic liver disease have brought a positive outlook changes in the understanding of the disease process and doctor-patient communication. Lifestyle changes are the main treatment modality. Recently, clinical trial using drugs that target 'insulin resistance' which is the driving force behind NAFLD, have shown promising results. Further translational research is needed to better understand the underlying pathophysiological mechanism of NAFLD which may open newer avenues of therapeutic targets. The role of gut dysbiosis in etiopathogenesis and use of fecal microbiota modification in the treatment should be studied extensively. Prevention of this silent epidemic by spreading awareness and early intervention should be our priority.
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Affiliation(s)
- Arghya Samanta
- Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India
| | - Moinak Sen Sarma
- Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India.
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Qin ZW, Ren QN, Zhang HX, Liu YR, Huang K, Wu W, Dong GP, Ni Y, Fu JF. Development and validation of a novel non-invasive test for diagnosing nonalcoholic fatty liver disease in Chinese children. World J Pediatr 2024; 20:413-421. [PMID: 37004681 DOI: 10.1007/s12519-023-00704-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2022] [Accepted: 02/07/2023] [Indexed: 04/04/2023]
Abstract
BACKGROUND With the exploding prevalence of obesity, many children are at risk of developing nonalcoholic fatty liver disease. Using anthropometric and laboratory parameters, our study aimed to develop a model to quantitatively evaluate liver fat content (LFC) in children with obesity. METHODS A well-characterized cohort of 181 children between 5 and 16 years of age were recruited to the study in the Endocrinology Department as the derivation cohort. The external validation cohort comprised 77 children. The assessment of liver fat content was performed using proton magnetic resonance spectroscopy. Anthropometry and laboratory metrics were measured in all subjects. B-ultrasound examination was carried out in the external validation cohort. The Kruskal-Wallis test, Spearman bivariate correlation analyses, univariable linear regressions and multivariable linear regression were used to build the optimal predictive model. RESULTS The model was based on indicators including alanine aminotransferase, homeostasis model assessment of insulin resistance, triglycerides, waist circumference and Tanner stage. The adjusted R2 of the model was 0.589, which presented high sensitivity and specificity both in internal [sensitivity of 0.824, specificity of 0.900, area under curve (AUC) of 0.900 with a 95% confidence interval: 0.783-1.000] and external validation (sensitivity of 0.918 and specificity of 0.821, AUC of 0.901 with a 95% confidence interval: 0.818-0.984). CONCLUSIONS Our model based on five clinical indicators was simple, non-invasive, and inexpensive; it had high sensitivity and specificity in predicting LFC in children. Thus, it may be useful for identifying children with obesity who are at risk for developing nonalcoholic fatty liver disease.
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Affiliation(s)
- Zhe-Wen Qin
- Division of Endocrinology, National Clinical Research Center for Child Health, National Children's Regional Medical Center, The Children's HospitalDepartment of Endocrinology, National Clinical Research Center for Child Health, National Children's Regional Medical Center, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310052, China
| | - Qian-Nan Ren
- Division of Endocrinology, National Clinical Research Center for Child Health, National Children's Regional Medical Center, The Children's HospitalDepartment of Endocrinology, National Clinical Research Center for Child Health, National Children's Regional Medical Center, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310052, China
| | - Hong-Xi Zhang
- Department of Radiology, National Clinical Research Center for Child Health, National Children's Regional Medical Center, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310052, China
| | - Ya-Ru Liu
- Division of Endocrinology, National Clinical Research Center for Child Health, National Children's Regional Medical Center, The Children's HospitalDepartment of Endocrinology, National Clinical Research Center for Child Health, National Children's Regional Medical Center, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310052, China
| | - Ke Huang
- Division of Endocrinology, National Clinical Research Center for Child Health, National Children's Regional Medical Center, The Children's HospitalDepartment of Endocrinology, National Clinical Research Center for Child Health, National Children's Regional Medical Center, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310052, China
| | - Wei Wu
- Division of Endocrinology, National Clinical Research Center for Child Health, National Children's Regional Medical Center, The Children's HospitalDepartment of Endocrinology, National Clinical Research Center for Child Health, National Children's Regional Medical Center, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310052, China
| | - Guan-Ping Dong
- Division of Endocrinology, National Clinical Research Center for Child Health, National Children's Regional Medical Center, The Children's HospitalDepartment of Endocrinology, National Clinical Research Center for Child Health, National Children's Regional Medical Center, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310052, China
| | - Yan Ni
- Division of Endocrinology, National Clinical Research Center for Child Health, National Children's Regional Medical Center, The Children's HospitalDepartment of Endocrinology, National Clinical Research Center for Child Health, National Children's Regional Medical Center, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310052, China
| | - Jun-Fen Fu
- Division of Endocrinology, National Clinical Research Center for Child Health, National Children's Regional Medical Center, The Children's HospitalDepartment of Endocrinology, National Clinical Research Center for Child Health, National Children's Regional Medical Center, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310052, China.
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Fernandez CJ, Nagendra L, Pappachan JM. Metabolic Dysfunction-associated Fatty Liver Disease: An Urgent Call for Global Action. TOUCHREVIEWS IN ENDOCRINOLOGY 2024; 20:5-9. [PMID: 38812662 PMCID: PMC11132654 DOI: 10.17925/ee.2023.20.1.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Accepted: 07/13/2023] [Indexed: 05/31/2024]
Abstract
There has been an exponential increase in the global prevalence of fatty liver disease in recent years in association with the obesity pandemic worldwide. 'Metabolic dysfunction-associated fatty liver disease', the new terminology adopted by an international panel of experts in 2020 to largely replace the old term 'non-alcoholic fatty liver disease', has now been accepted by most hepatologists and diabetologists across the globe. The term metabolic dysfunction-associated fatty liver disease was created to better reflect the metabolicand liver-specific manifestations and complications of fatty liver disease. It is important to disseminate our current understanding of this enigmatic disease among the global scientific fraternity. Recent publications, including articles from the latest issue of Endocrinology & Metabolism Clinics of North America, are attempting to fill this knowledge gap.
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Affiliation(s)
- Cornelius J Fernandez
- Department of Endocrinology & Metabolism, Pilgrim Hospital, United Lincolnshire Hospitals NHS Trust, Boston, UK
| | - Lakshmi Nagendra
- Department of Endocrinology, JSS Medical College, JSS Academy of Higher Education and Research, Mysore, India
| | - Joseph M Pappachan
- Department of Endocrinology & Metabolism, Lancashire Teaching Hospitals NHS Trust, Preston, UK
- Faculty of Science, Manchester Metropolitan University, Manchester, UK
- Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK
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Perazza F, Leoni L, Colosimo S, Musio A, Bocedi G, D’Avino M, Agnelli G, Nicastri A, Rossetti C, Sacilotto F, Marchesini G, Petroni ML, Ravaioli F. Metformin and the Liver: Unlocking the Full Therapeutic Potential. Metabolites 2024; 14:186. [PMID: 38668314 PMCID: PMC11052067 DOI: 10.3390/metabo14040186] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Revised: 03/20/2024] [Accepted: 03/22/2024] [Indexed: 04/28/2024] Open
Abstract
Metformin is a highly effective medication for managing type 2 diabetes mellitus. Recent studies have shown that it has significant therapeutic benefits in various organ systems, particularly the liver. Although the effects of metformin on metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction-associated steatohepatitis are still being debated, it has positive effects on cirrhosis and anti-tumoral properties, which can help prevent the development of hepatocellular carcinoma. Furthermore, it has been proven to improve insulin resistance and dyslipidaemia, commonly associated with liver diseases. While more studies are needed to fully determine the safety and effectiveness of metformin use in liver diseases, the results are highly promising. Indeed, metformin has a terrific potential for extending its full therapeutic properties beyond its traditional use in managing diabetes.
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Affiliation(s)
- Federica Perazza
- Department of Medical and Surgical Sciences, IRCCS Azienda Ospedaliero, Universitaria di Bologna, 40138 Bologna, Italy; (F.P.); (L.L.); (G.A.); (A.N.); (C.R.); (F.S.); (G.M.); (M.L.P.)
| | - Laura Leoni
- Department of Medical and Surgical Sciences, IRCCS Azienda Ospedaliero, Universitaria di Bologna, 40138 Bologna, Italy; (F.P.); (L.L.); (G.A.); (A.N.); (C.R.); (F.S.); (G.M.); (M.L.P.)
| | - Santo Colosimo
- Doctorate School of Nutrition Science, University of Milan, 20122 Milan, Italy;
| | | | - Giulia Bocedi
- U.O. Diabetologia, Ospedale C. Magati, Scandiano, 42019 Reggio Emilia, Italy;
| | - Michela D’Avino
- S.C. Endocrinologia Arcispedale Santa Maria Nuova, 42123 Reggio Emilia, Italy;
| | - Giulio Agnelli
- Department of Medical and Surgical Sciences, IRCCS Azienda Ospedaliero, Universitaria di Bologna, 40138 Bologna, Italy; (F.P.); (L.L.); (G.A.); (A.N.); (C.R.); (F.S.); (G.M.); (M.L.P.)
| | - Alba Nicastri
- Department of Medical and Surgical Sciences, IRCCS Azienda Ospedaliero, Universitaria di Bologna, 40138 Bologna, Italy; (F.P.); (L.L.); (G.A.); (A.N.); (C.R.); (F.S.); (G.M.); (M.L.P.)
| | - Chiara Rossetti
- Department of Medical and Surgical Sciences, IRCCS Azienda Ospedaliero, Universitaria di Bologna, 40138 Bologna, Italy; (F.P.); (L.L.); (G.A.); (A.N.); (C.R.); (F.S.); (G.M.); (M.L.P.)
| | - Federica Sacilotto
- Department of Medical and Surgical Sciences, IRCCS Azienda Ospedaliero, Universitaria di Bologna, 40138 Bologna, Italy; (F.P.); (L.L.); (G.A.); (A.N.); (C.R.); (F.S.); (G.M.); (M.L.P.)
| | - Giulio Marchesini
- Department of Medical and Surgical Sciences, IRCCS Azienda Ospedaliero, Universitaria di Bologna, 40138 Bologna, Italy; (F.P.); (L.L.); (G.A.); (A.N.); (C.R.); (F.S.); (G.M.); (M.L.P.)
| | - Maria Letizia Petroni
- Department of Medical and Surgical Sciences, IRCCS Azienda Ospedaliero, Universitaria di Bologna, 40138 Bologna, Italy; (F.P.); (L.L.); (G.A.); (A.N.); (C.R.); (F.S.); (G.M.); (M.L.P.)
| | - Federico Ravaioli
- Department of Medical and Surgical Sciences, IRCCS Azienda Ospedaliero, Universitaria di Bologna, 40138 Bologna, Italy; (F.P.); (L.L.); (G.A.); (A.N.); (C.R.); (F.S.); (G.M.); (M.L.P.)
- Division of Hepatobiliary and Immunoallergic Diseases, Department of Internal Medicine, IRCCS Azienda Ospedaliero, Universitaria di Bologna, 40138 Bologna, Italy
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Xiao XP, Dai YJ, Zhang Y, Yang M, Xie J, Chen G, Yang ZJ. Investigating the causal associations between five anthropometric indicators and nonalcoholic fatty liver disease: Mendelian randomization study. World J Clin Cases 2024; 12:1215-1226. [PMID: 38524522 PMCID: PMC10955530 DOI: 10.12998/wjcc.v12.i7.1215] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Revised: 01/14/2024] [Accepted: 02/06/2024] [Indexed: 02/29/2024] Open
Abstract
BACKGROUND Although the etiology of nonalcoholic fatty liver disease (NAFLD) has not been thoroughly understood, the emerging roles of anthropometric indicators in assessing and predicting the risk of NAFLD have been highlighted by accumulating evidence. AIM To evaluate the causal relationships between five anthropometric indicators and NAFLD employing Mendelian randomization (MR) design. METHODS The Anthropometric Consortium provided genetic exposure data for five anthropometric indicators, including hip circumference (HC), waist circumference (WC), waist-to-hip ratio (WHR), body mass index (BMI), and body fat percentage (BF). Genetic outcome data for NAFLD were obtained from the United Kingdom Biobank and FinnGen Consortium. Genome-wide significant single nucleotide polymorphisms were chosen as instrumental variables. Univariable MR (UVMR) and multivariable MR (MVMR) designs with analytical approaches, including inverse variance weighted (IVW), MR-Egger, weighted median (WM), and weighted mode methods, were used to assess the causal relationships between anthropometric indicators and NAFLD. RESULTS Causal relationships were revealed by UVMR, indicating that a higher risk of NAFLD was associated with a per-unit increase in WC [IVW: odds ratio (OR) = 2.67, 95%CI: 1.42-5.02, P = 2.25 × 10-3], and BF was causally associated with an increased risk of NAFLD (WM: OR = 2.23, 95%CI: 1.07-4.66, P = 0.033). The presence of causal effects of WC on the decreased risk of NAFLD was supported by MVMR after adjusting for BMI and smoking. However, no causal association between BF and NAFLD was observed. In addition, other causal relationships of HC, WHR (BMI adjusted), and BMI with the risk of NAFLD were not retained after FDR correction. CONCLUSION This study establishes a causal relationship, indicating that an increase in WC is associated with a higher risk of NAFLD. This demonstrates that a suitable decrease in WC is advantageous for preventing NAFLD.
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Affiliation(s)
- Xian-Pei Xiao
- Department of Oncology, Luojiang District People's Hospital of Deyang City, Deyang 618000, Sichuan Province, China
| | - Yong-Jun Dai
- Department of Orthopaedics, Luojiang District People's Hospital of Deyang City, Deyang 618000, Sichuan Province, China
| | - Yu Zhang
- Department of Oncology, Luojiang District People's Hospital of Deyang City, Deyang 618000, Sichuan Province, China
| | - Meng Yang
- Department of Oncology, Luojiang District People's Hospital of Deyang City, Deyang 618000, Sichuan Province, China
| | - Jian Xie
- Department of Oncology, Luojiang District People's Hospital of Deyang City, Deyang 618000, Sichuan Province, China
| | - Guo Chen
- Department of Infectious Diseases, Hospital of Chengdu University of Traditional Chinese Medical, Chengdu 610500, Sichuan Province, China
| | - Zheng-Jun Yang
- Department of Oncology, Luojiang District People's Hospital of Deyang City, Deyang 618000, Sichuan Province, China
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Medyńska-Przęczek A, Stochel-Gaudyn A, Wędrychowicz A. Liver fibrosis assessment in pediatric population - can ultrasound elastography be an alternative method to liver biopsy? A systematic review. Adv Med Sci 2024; 69:8-20. [PMID: 38198895 DOI: 10.1016/j.advms.2023.12.001] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2023] [Revised: 09/17/2023] [Accepted: 12/19/2023] [Indexed: 01/12/2024]
Abstract
Liver diseases of various etiologies are becoming increasingly common in the pediatric population. So far, the gold diagnostic standard in these disorders is liver biopsy. This procedure is invasive, painful and requires general anesthesia in this group of patients. Due to the continuous development of new research techniques, such as liver elastography, it is necessary to evaluate them in the context of their diagnostic usefulness. Ultrasound elastography, as a quick and effective method, is being used more and more often in the assessment and monitoring of liver dysfunction in both adults and children. There are several techniques of liver elastography, such as transient elastography, shear wave elastography consisting of various subtypes such as two-dimensional shear wave elastography, acoustic radiation force impulse and point shear wave elastography, which differ in terms of the measurement technique and the achieved results. The purpose of our review was to determine whether techniques of liver elastography could replace liver biopsy. Although now, based on the analyzed papers, elastography cannot replace liver biopsy, in our opinion, the role of this tool in monitoring pediatric patients with liver diseases will grow in the coming years.
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Affiliation(s)
- Aleksandra Medyńska-Przęczek
- School of Medical and Health Sciences, Faculty of Medicine, Jagiellonian University Medical College, Krakow, 31-530, Poland.
| | - Anna Stochel-Gaudyn
- Department of Paediatrics, Gastroenterology and Nutrition, Pediatric Institute, Faculty of Medicine, Jagiellonian University Medical College, Krakow, 30-663, Poland
| | - Andrzej Wędrychowicz
- Department of Paediatrics, Gastroenterology and Nutrition, Pediatric Institute, Faculty of Medicine, Jagiellonian University Medical College, Krakow, 30-663, Poland
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Xu X, Zhang C, Tang G, Wang N, Feng Y. Updated Insights into Probiotics and Hepatobiliary Diseases. Biomedicines 2024; 12:515. [PMID: 38540128 PMCID: PMC10968574 DOI: 10.3390/biomedicines12030515] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Revised: 02/21/2024] [Accepted: 02/22/2024] [Indexed: 05/03/2025] Open
Abstract
Hepatobiliary diseases have a high prevalence worldwide, with a wide range of diseases involved in the liver and biliary system. Modifications in gut microbiota have been proven to have an association with unbalanced intestinal homeostasis and the dysfunction of host metabolism and the immune system, which can be the risk factors for many hepatobiliary diseases, such as nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), nonalcoholic fatty steatohepatitis (NASH), hepatitis, cirrhosis, hepatocellular carcinoma (HCC) and cholestasis, as well as infection due to liver transplantation. Probiotics are commonly used gut microbiota-targeted strategies to treat dysbiosis and intestinal dysfunction, as well as the gut-liver axis, which can enhance the effectiveness of probiotics in the management of liver diseases. Recent studies have explored more potential single or mixed strains of probiotics, and bioinformatics methods can be used to investigate the potential mechanisms of probiotics on liver diseases. In this review, we summarize the preclinical and clinical studies on the role of probiotics in hepatobiliary diseases from 2018 to 2023, revealing the possible mechanism of probiotics in the treatment of hepatobiliary diseases and discussing the limitations of probiotics in treating hepatobiliary diseases. This review provides updated evidence for the development of probiotic products, exploration of new probiotic strains, and support for clinical studies. Further studies should focus on the safety, viability, and stability of probiotics, as well as medication dosage and duration in clinical practice.
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Affiliation(s)
| | | | | | | | - Yibin Feng
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China; (X.X.); (C.Z.); (G.T.); (N.W.)
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50
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Li H, Liu Y, Meng F, Chen J, Han X. Adrenarche-accompanied rise of adrenal sex steroid precursors prevents NAFLD in Young Female rats by converting into active androgens and inactivating hepatic Srebf1 signaling. BMC Genomics 2024; 25:190. [PMID: 38369486 PMCID: PMC10875776 DOI: 10.1186/s12864-024-10107-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Accepted: 02/09/2024] [Indexed: 02/20/2024] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) has rapidly become the most common cause of chronic liver disease in children and adolescents, but its etiology remains largely unknown. Adrenarche is a critical phase for hormonal changes, and any disturbance during this period has been linked to metabolic disorders, including obesity and dyslipidemia. However, whether there is a causal linkage between adrenarche disturbance and the increasing prevalence of NAFLD in children remains unclear. RESULTS Using the young female rat as a model, we found that the liver undergoes a transient slowdown period of growth along with the rise of adrenal-derived sex steroid precursors during adrenarche. Specifically blocking androgen actions across adrenarche phase using androgen receptor antagonist flutamide largely increased liver weight by 47.97% and caused marked fat deposition in liver, thus leading to severe NAFLD in young female rats. Conversely, further administrating nonaromatic dihydrotestosterone (DHT) into young female rats across adrenarche phase could effectively reduce liver fat deposition. But, administration of the aromatase inhibitor, formestane across adrenarche had minimal effects on hepatic de novo fatty acid synthesis and liver fat deposition, suggesting adrenal-derived sex steroid precursors exert their anti-NAFLD effects in young females by converting into active androgens rather than into active estrogens. Mechanistically, transcriptomic profiling and integrated data analysis revealed that active androgens converted from the adrenal sex steroid precursors prevent NAFLD in young females primarily by inactivating hepatic sterol regulatory element-binding transcription factor 1 (Srebf1) signaling. CONCLUSIONS We firstly evidenced that adrenarche-accompanied rise of sex steroid precursors plays a predominant role in preventing the incidence of NAFLD in young females by converting into active androgens and inactivating hepatic Srebf1 signaling. Our novel finding provides new insights into the etiology of NAFLD and is crucial in developing effective prevention and management strategies for NAFLD in children.
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Affiliation(s)
- Haoqing Li
- College of Life Science, Sichuan Agricultural University, Ya'an, 625014, China
| | - Yingyu Liu
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, 611130, China
| | - Fengyan Meng
- College of Life Science, Sichuan Agricultural University, Ya'an, 625014, China
| | - Junan Chen
- College of Life Science, Sichuan Agricultural University, Ya'an, 625014, China
| | - Xingfa Han
- College of Life Science, Sichuan Agricultural University, Ya'an, 625014, China.
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