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Di Sessa A, Zarrilli S, Forcina G, Frattolillo V, Camponesco O, Migliaccio C, Ferrara S, Umano GR, Cirillo G, Miraglia Del Giudice E, Marzuillo P. Role of metabolic dysfunction-associated steatotic liver disease and of its genetics on kidney function in childhood obesity. Int J Obes (Lond) 2025; 49:605-611. [PMID: 39521922 DOI: 10.1038/s41366-024-01674-5] [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: 07/18/2024] [Revised: 10/29/2024] [Accepted: 10/31/2024] [Indexed: 11/16/2024]
Abstract
OBJECTIVES Evidence linked metabolic associated steatotic liver disease (MASLD) to kidney damage with the potential contribution of the I148M variant of the Patatin-like phospholipase containing domain 3 (PNPLA3) gene. We aimed at investigating the relationship of MASLD and of its genetics with kidney function in children with obesity. METHODS A comprehensive evaluation including genotyping for the I148M PNPLA3 polymorphism was performed in 1037 children with obesity. Fatty liver (FL) was assessed by liver ultrasound. According to MASLD criteria, subjects with obesity but without FL were included in group 1, while patients with obesity and FL (encompassing one MASLD criterion) were clustered into group 2. Group 3 included patients with obesity, FL, and metabolic dysregulation (encompassing >1 MASLD criterion). RESULTS Alanine transaminase levels significantly increased while estimated glomerular filtration rate (eGFR) significantly reduced from group 1 to 3. Group 3 showed a higher percentage of carriers of the I148M allele of the PNPLA3 gene compared to other groups (p < 0.0001). Carriers of group 2 and of group 3 showed reduced eGFR levels than noncarriers of group 2 (p = 0.04) and of group 3 (p = 0.02), respectively. A general linear model for eGFR variance in the study population showed an inverse association of eGFR with both MASLD and PNPLA3 genotypes (p = 0.011 and p = 0.02, respectively). An inverse association of eGFR with MASLD was also confirmed only in carriers (p = 0.006). CONCLUSIONS The coexistence of more than 1 MASLD criterion in children with obesity seems to adversely affect kidney function. The PNPLA3 I148M allele further impacts on this association.
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Affiliation(s)
- Anna Di Sessa
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy.
| | - Sarah Zarrilli
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Gianmario Forcina
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Vittoria Frattolillo
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Ornella Camponesco
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Claudia Migliaccio
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Serena Ferrara
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Giuseppina Rosaria Umano
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Grazia Cirillo
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Emanuele Miraglia Del Giudice
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Pierluigi Marzuillo
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
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Méndez-Sánchez N, Brouwer WP, Lammert F, Yilmaz Y. Metabolic dysfunction associated fatty liver disease in healthy weight individuals. Hepatol Int 2024; 18:884-896. [PMID: 39052203 PMCID: PMC11449956 DOI: 10.1007/s12072-024-10662-w] [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: 12/20/2023] [Accepted: 02/13/2024] [Indexed: 07/27/2024]
Abstract
Metabolic dysfunction associated fatty liver disease (MAFLD) is an increasing public health problem, affecting one third of the global population. Contrary to conventional wisdom, MAFLD is not exclusive to obese or overweight individuals. Epidemiological studies have revealed a remarkable prevalence among healthy weight individuals, leading investigations into the genetic, lifestyle, and dietary factors that contribute to the development of MAFLD in this population. This shift in perspective requires reconsideration of preventive strategies, diagnostic criteria and therapeutic approaches tailored to address the unique characteristics of MAFLD healthy weight individuals. It also underscores the importance of widespread awareness and education, within the medical community and among the general population, to promote a more inclusive understanding of liver metabolic disorders. With this review, we aim to provide a comprehensive exploration of MAFLD in healthy weight individuals, encompassing epidemiological, pathophysiological, and clinical aspects.
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Affiliation(s)
- Nahum Méndez-Sánchez
- Liver Research Unit, Medica Sur Clinic and Foundation, Mexico City, Mexico
- Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico
| | - Willem Pieter Brouwer
- Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, The Netherlands.
- Erasmus MC Transplant Institute, Erasmus Medical Center, Rotterdam, The Netherlands.
| | - Frank Lammert
- Health Sciences, Hannover Medical School, Hannover, Germany
| | - Yusuf Yilmaz
- Department of Gastroenterology, School of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey
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Zhang R, Zhang H, Wang Y, Tang LJ, Li G, Huang OY, Chen SD, Targher G, Byrne CD, Gu BB, Zheng MH. Higher consumption of animal organ meat is associated with a lower prevalence of nonalcoholic steatohepatitis. Hepatobiliary Surg Nutr 2023; 12:645-657. [PMID: 37886189 PMCID: PMC10598295 DOI: 10.21037/hbsn-21-468] [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: 11/08/2021] [Accepted: 03/23/2022] [Indexed: 10/28/2023]
Abstract
Background Animal organ meat (offal) is a food with high nutrient density that is popular in different parts of the world, but its relationship with nonalcoholic steatohepatitis (NASH) is unclear. We aimed to examine whether daily animal organ meat consumption is associated with the presence of NASH in individuals with nonalcoholic fatty liver disease (NAFLD). Methods A total of 136 Chinese adults with biopsy-proven NAFLD were included. Definite NASH was defined as NAFLD activity score ≥4 and at least one point for steatosis, ballooning, and lobular inflammation. Daily animal organ meat consumption was estimated using a self-administered validated food frequency questionnaire. Logistic regression analysis was performed to assess the association between animal organ meat intake and liver disease severity. Results The 136 participants (80.9% men) of the study had a mean ± standard deviation (SD) age of 39.0±12.5 years and body mass index of 27.4±3.6 kg/m2. Prevalence of definite NASH was 65.4%. Daily median organ meat consumption was 1.30 g/1,000 kcal. Animal organ meat consumption was inversely associated with the presence of NASH even after adjustment of demographics, lifestyle variables, metabolic and dietary factors, as well as liver fibrosis stage; adjusted-odds ratios (95% confidence intervals) for NASH were 0.15 (0.03, 0.69) for the highest tertile and 0.18 (0.05, 0.70) for the medium tertile, compared to the lowest (reference) tertile of animal organ meat intake (P value for trend =0.024). Conclusions Our results suggest for the first time that higher animal organ meat consumption is associated with a lower prevalence of NASH in Chinese individuals with biopsy-proven NAFLD.
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Affiliation(s)
- Rui Zhang
- Department of Nutrition, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Huai Zhang
- Biostatistics and Medical Quality Management Office, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Yi Wang
- Department of Nutrition, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Liang-Jie Tang
- MAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Gang Li
- MAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Ou-Yang Huang
- MAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Sui-Dan Chen
- Department of Pathology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Giovanni Targher
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Christopher D. Byrne
- Southampton National Institute for Health Research Biomedical Research Centre, University Hospital Southampton, Southampton General Hospital, Southampton, UK
| | - Bin-Bin Gu
- Department of Nutrition, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Ming-Hua Zheng
- MAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Institute of Hepatology, Wenzhou Medical University, Wenzhou, China
- Key Laboratory of Diagnosis and Treatment for The Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, China
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Shi F, Zhao M, Zheng S, Zheng L, Wang H. Advances in genetic variation in metabolism-related fatty liver disease. Front Genet 2023; 14:1213916. [PMID: 37753315 PMCID: PMC10518415 DOI: 10.3389/fgene.2023.1213916] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Accepted: 08/30/2023] [Indexed: 09/28/2023] Open
Abstract
Metabolism-related fatty liver disease (MAFLD) is the most common form of chronic liver disease in the world. Its pathogenesis is influenced by both environmental and genetic factors. With the upgrading of gene screening methods and the development of human genome project, whole genome scanning has been widely used to screen genes related to MAFLD, and more and more genetic variation factors related to MAFLD susceptibility have been discovered. There are genetic variants that are highly correlated with the occurrence and development of MAFLD, and there are genetic variants that are protective of MAFLD. These genetic variants affect the development of MAFLD by influencing lipid metabolism and insulin resistance. Therefore, in-depth analysis of different mechanisms of genetic variation and targeting of specific genetic variation genes may provide a new idea for the early prediction and diagnosis of diseases and individualized precision therapy, which may be a promising strategy for the treatment of MAFLD.
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Affiliation(s)
- Fan Shi
- School of Heilongjiang University of Chinese Medicine, Harbin, China
| | - Mei Zhao
- School of Heilongjiang University of Chinese Medicine, Harbin, China
| | - Shudan Zheng
- School of Heilongjiang University of Chinese Medicine, Harbin, China
| | - Lihong Zheng
- Department of Internal Medicine, Fourth Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Haiqiang Wang
- Department of Internal Medicine, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China
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Lanzaro F, Guarino S, D'Addio E, Salvatori A, D'Anna JA, Marzuillo P, Miraglia del Giudice E, Di Sessa A. Metabolic-associated fatty liver disease from childhood to adulthood: State of art and future directions. World J Hepatol 2022; 14:1087-1098. [PMID: 35978659 PMCID: PMC9258256 DOI: 10.4254/wjh.v14.i6.1087] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 12/26/2021] [Accepted: 04/25/2022] [Indexed: 02/06/2023] Open
Abstract
In 2020, an international group of experts proposed to replace the term of nonalcoholic fatty liver disease with metabolic-associated fatty liver disease (MAFLD). This recent proposal reflects the close association of fatty liver with metabolic derangements, as demonstrated by previous robust data. Several factors [including genetics, inflammation, metabolic abnormalities, insulin resistance (IR), obesity, prenatal determinants, and gut–liver axis] have been found to be involved in MAFLD pathophysiology, but this tangled puzzle remains to be clearly understood. In particular, IR has been recognized as a key player in metabolic impairments development in children with fatty liver. On this ground, MAFLD definition focuses on the pathophysiological basis of the disease, by emphasizing the crucial role of metabolic impairments in this condition. Although primarily developed for adults, MAFLD diagnostic criteria have been recently updated with an age-appropriate definition for sex and age percentiles, because of the increasing attention to cardiometabolic risk in childhood. To date, accumulating evidence is available on the feasibility of MAFLD definition in clinical practice, but some data are still conflicting in highly selected populations. Considering the growing prevalence worldwide of fatty liver and its close relationship with metabolic dysfunction both in children and adults with subsequent increased cardiovascular risk, early strategies for MAFLD identification, treatment and prevention are needed. Novel therapeutic insights for MAFLD based on promising innovative biological techniques are also emerging. We aimed to summarize the most recent evidence in this intriguing research area both in children and adults.
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Affiliation(s)
- Francesca Lanzaro
- Department of Woman, Child, and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
| | - Stefano Guarino
- Department of Woman, Child, and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
| | - Elisabetta D'Addio
- Department of Woman, Child, and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
| | - Alessandra Salvatori
- Department of Woman, Child, and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
| | - Josè Alberto D'Anna
- Department of Woman, Child, and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
| | - Pierluigi Marzuillo
- Department of Woman, Child, and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
| | - Emanuele Miraglia del Giudice
- Department of Woman, Child, and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
| | - Anna Di Sessa
- Department of Woman, Child, and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
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Méndez-Sánchez N, Díaz-Orozco LE. Editorial: International Consensus Recommendations to Replace the Terminology of Non-Alcoholic Fatty Liver Disease (NAFLD) with Metabolic-Associated Fatty Liver Disease (MAFLD). Med Sci Monit 2021; 27:e933860. [PMID: 34248137 PMCID: PMC8284081 DOI: 10.12659/msm.933860] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2021] [Accepted: 07/04/2021] [Indexed: 12/14/2022] Open
Abstract
In 2020, international consensus guidelines recommended the renaming of non-alcoholic fatty liver disease (NAFLD) to metabolic-associated fatty liver disease (MAFLD), supported by diagnostic criteria. MAFLD affects up to 25% of the global population. However, the rates of MAFLD are likely to be underestimated due to the increasing prevalence of type 2 diabetes mellitus (T2DM) and obesity. Within the next decade, MAFLD has been projected to become a major cause of cirrhosis and hepatocellular carcinoma (HCC) worldwide, as well as the most common indication for liver transplantation in the US. This transition in terminology and clinical criteria may increase momentum and clinical evidence at multiple levels, including patient diagnosis, management, and care, and provide the basis for new research areas and clinical development for therapeutics. The diagnostic criteria for MAFLD are practical, simple, and superior to the existing NAFLD criteria for identifying patients at increased risk of developing progressive liver disease. This Editorial aims to present the historical evolution of the terminology for fatty liver disease and the advantages of diagnosis, patient management, and future research on MAFLD.
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Affiliation(s)
- Nahum Méndez-Sánchez
- Liver Research Unit, Médica Sur Clinic and Foundation and Faculty of Medicine, Mexico City, Mexico
- National Autonomous University of Mexico, Mexico City, Mexico
| | - Luis Enrique Díaz-Orozco
- Liver Research Unit, Médica Sur Clinic and Foundation and Faculty of Medicine, Mexico City, Mexico
- National Autonomous University of Mexico, Mexico City, Mexico
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