|
1
|
Alharthi J, Pan Z, Gloss BS, McLeod D, Weltman M, George J, Eslam M. Loss of metabolic adaptation in lean MAFLD is driven by endotoxemia leading to epigenetic reprogramming. Metabolism 2023; 144:155583. [PMID: 37146900 DOI: 10.1016/j.metabol.2023.155583] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2023] [Revised: 04/24/2023] [Accepted: 04/28/2023] [Indexed: 05/07/2023] [Imported: 08/29/2023]
Abstract
Lean patients with MAFLD have an initial adaptive metabolic response characterised by increased serum bile acids and Farnesoid X Receptor (FXR) activity. How this adaptive response wanes resulting in an equal or perhaps worse long-term adverse outcome compared to patients with obese MAFLD is not known. We show that patients with lean MAFLD have endotoxemia while their macrophages demonstrate excess production of inflammatory cytokines in response to activation by Toll-like receptor (TLR) ligands when compared to healthy subjects. Alterations of the lean MAFLD macrophage epigenome drives this response and suppresses bile acids signalling to drive inflammation. Our data suggests that selectively restoring bile acids signalling might restore adaptive metabolic responses in patients with MAFLD who are lean.
Collapse
|
|
2
|
Pan Z, Alqahtani SA, Eslam M. MAFLD and chronic kidney disease: two sides of the same coin? Hepatol Int 2023; 17:519-521. [PMID: 37069420 DOI: 10.1007/s12072-023-10526-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Accepted: 03/16/2023] [Indexed: 04/19/2023] [Imported: 08/29/2023]
|
|
3
|
A metabolic associated fatty liver disease risk variant in MBOAT7 regulates toll like receptor induced outcomes. Nat Commun 2022; 13:7430. [PMID: 36473860 PMCID: PMC9726889 DOI: 10.1038/s41467-022-35158-9] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Accepted: 11/21/2022] [Indexed: 12/12/2022] [Imported: 08/29/2023] Open
Abstract
The breakdown of toll-like receptor (TLR) tolerance results in tissue damage, and hyperactivation of the TLRs and subsequent inflammatory consequences have been implicated as risk factors for more severe forms of disease and poor outcomes from various diseases including COVID-19 and metabolic (dysfunction) associated fatty liver disease (MAFLD). Here we provide evidence that membrane bound O-acyltransferase domain containing 7 (MBOAT7) is a negative regulator of TLR signalling. MBOAT7 deficiency in macrophages as observed in patients with MAFLD and in COVID-19, alters membrane phospholipid composition. We demonstrate that this is associated with a redistribution of arachidonic acid toward proinflammatory eicosanoids, induction of endoplasmic reticulum stress, mitochondrial dysfunction, and remodelling of the accessible inflammatory-related chromatin landscape culminating in macrophage inflammatory responses to TLRs. Activation of MBOAT7 reverses these effects. These outcomes are further modulated by the MBOAT7 rs8736 (T) MAFLD risk variant. Our findings suggest that MBOAT7 can potentially be explored as a therapeutic target for diseases associated with dysregulation of the TLR signalling cascade.
Collapse
|
|
4
|
Pan Z, Eslam M. Metabolically healthy obese and MAFLD: does weight status alone matter? Hepatol Int 2022; 16:1253-1255. [PMID: 36253585 DOI: 10.1007/s12072-022-10433-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2022] [Accepted: 09/27/2022] [Indexed: 01/27/2023] [Imported: 08/29/2023]
|
|
5
|
Eslam M, El-Serag HB, Francque S, Sarin SK, Wei L, Bugianesi E, George J. Metabolic (dysfunction)-associated fatty liver disease in individuals of normal weight. Nat Rev Gastroenterol Hepatol 2022; 19:638-651. [PMID: 35710982 DOI: 10.1038/s41575-022-00635-5] [Citation(s) in RCA: 68] [Impact Index Per Article: 34.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/13/2022] [Indexed: 12/12/2022] [Imported: 08/29/2023]
Abstract
Metabolic (dysfunction)-associated fatty liver disease (MAFLD) affects up to a third of the global population; its burden has grown in parallel with rising rates of type 2 diabetes mellitus and obesity. MAFLD increases the risk of end-stage liver disease, hepatocellular carcinoma, death and liver transplantation and has extrahepatic consequences, including cardiometabolic disease and cancers. Although typically associated with obesity, there is accumulating evidence that not all people with overweight or obesity develop fatty liver disease. On the other hand, a considerable proportion of patients with MAFLD are of normal weight, indicating the importance of metabolic health in the pathogenesis of the disease regardless of body mass index. The clinical profile, natural history and pathophysiology of patients with so-called lean MAFLD are not well characterized. In this Review, we provide epidemiological data on this group of patients and consider overall metabolic health and metabolic adaptation as a framework to best explain the pathogenesis of MAFLD and its heterogeneity in individuals of normal weight and in those who are above normal weight. This framework provides a conceptual schema for interrogating the MAFLD phenotype in individuals of normal weight that can translate to novel approaches for diagnosis and patient care.
Collapse
|
|
6
|
Méndez-Sánchez N, Bugianesi E, Gish RG, Lammert F, Tilg H, Nguyen MH, Sarin SK, Fabrellas N, Zelber-Sagi S, Fan JG, Shiha G, Targher G, Zheng MH, Chan WK, Vinker S, Kawaguchi T, Castera L, Yilmaz Y, Korenjak M, Spearman CW, Ungan M, Palmer M, El-Shabrawi M, Gruss HJ, Dufour JF, Dhawan A, Wedemeyer H, George J, Valenti L, Fouad Y, Romero-Gomez M, Eslam M. Global multi-stakeholder endorsement of the MAFLD definition. Lancet Gastroenterol Hepatol 2022; 7:388-390. [PMID: 35248211 DOI: 10.1016/s2468-1253(22)00062-0] [Citation(s) in RCA: 125] [Impact Index Per Article: 62.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2022] [Revised: 02/21/2022] [Accepted: 02/22/2022] [Indexed: 02/07/2023] [Imported: 08/29/2023]
|
|
7
|
Alharthi J, Eslam M. Biomarkers of Metabolic (Dysfunction)-associated Fatty Liver Disease: An Update. J Clin Transl Hepatol 2022; 10:134-139. [PMID: 35233382 PMCID: PMC8845164 DOI: 10.14218/jcth.2021.00248] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2021] [Revised: 08/26/2021] [Accepted: 09/09/2021] [Indexed: 12/04/2022] [Imported: 08/29/2023] Open
Abstract
The prevalence of metabolic (dysfunction)-associated fatty liver disease (MAFLD) is rapidly increasing and affects up to two billion individuals globally, and this has also resulted in increased risks for cirrhosis, hepatocellular carcinoma, and liver transplants. In addition, it has also been linked to extrahepatic consequences, such as cardiovascular disease, diabetes, and various types of cancers. However, only a small proportion of patients with MAFLD develop these complications. Therefore, the identification of high-risk patients is paramount. Liver fibrosis is the major determinant in developing these complications. Although, liver biopsy is still considered the gold standard for the assessment of patients with MAFLD. Because of its invasive nature, among many other limitations, the search for noninvasive biomarkers for MAFLD remains an area of intensive research. In this review, we provide an update on the current and future biomarkers of MAFLD, including a discussion of the associated genetics, epigenetics, microbiota, and metabolomics. We also touch on the next wave of multiomic-based biomarkers.
Collapse
|
|
8
|
Pan Z, Chan WK, Eslam M. The role of B cells in metabolic (dysfunction)-associated fatty liver disease. Hepatobiliary Surg Nutr 2021; 10:875-877. [PMID: 35004959 PMCID: PMC8683912 DOI: 10.21037/hbsn-21-404] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Accepted: 10/18/2021] [Indexed: 08/29/2023] [Imported: 08/29/2023]
|
|
9
|
Alharthi J, Eslam M. Metabolic associated fatty liver disease (MAFLD): a milestone in the history of fatty liver disease. Hepatobiliary Surg Nutr 2021; 10:696-698. [PMID: 34760977 DOI: 10.21037/hbsn-21-269] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Accepted: 08/20/2021] [Indexed: 01/13/2023] [Imported: 08/29/2023]
|
|
10
|
Eslam M, Alkhouri N, Vajro P, Baumann U, Weiss R, Socha P, Marcus C, Lee WS, Kelly D, Porta G, El-Guindi MA, Alisi A, Mann JP, Mouane N, Baur LA, Dhawan A, George J. Defining paediatric metabolic (dysfunction)-associated fatty liver disease: an international expert consensus statement. Lancet Gastroenterol Hepatol 2021; 6:864-873. [PMID: 34364544 DOI: 10.1016/s2468-1253(21)00183-7] [Citation(s) in RCA: 124] [Impact Index Per Article: 41.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 05/17/2021] [Accepted: 05/18/2021] [Indexed: 12/11/2022] [Imported: 08/29/2023]
Abstract
The term non-alcoholic fatty liver disease (NAFLD), and its definition, have limitations for both adults and children. The definition is most problematic for children, for whom alcohol consumption is usually not a concern. This problematic definition has prompted a consensus to rename and redefine adult NAFLD associated with metabolic dysregulation to metabolic (dysfunction)-associated fatty liver disease (MAFLD). Similarities, distinctions, and differences exist in the causes, natural history, and prognosis of fatty liver diseases in children compared with adults. In this Viewpoint we, an international panel, propose an overarching framework for paediatric fatty liver diseases and an age-appropriate MAFLD definition based on sex and age percentiles. The framework recognises the possibility of other coexisting systemic fatty liver diseases in children. The new MAFLD diagnostic criteria provide paediatricians with a conceptual scaffold for disease diagnosis, risk stratification, and improved clinical and multidisciplinary care, and they align with a definition that is valid across the lifespan.
Collapse
|
|
11
|
Pan Z, Fan JG, Eslam M. An update on drug development for the treatment of metabolic (dysfunction) associated fatty liver disease: Progress and opportunities. Curr Opin Pharmacol 2021; 60:170-176. [PMID: 34455284 DOI: 10.1016/j.coph.2021.07.007] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 05/25/2021] [Accepted: 07/07/2021] [Indexed: 12/23/2022] [Imported: 08/29/2023]
Abstract
Despite the rising health burden of metabolic (dysfunction) associated fatty liver disease (MAFLD), there are no approved pharmacotherapies for MAFLD currently. This situation led to a significant escalation in drug development and randomized controlled trials for MAFLD, particularly as novel information about its molecular pathogenesis unfolds. Currently, there are numerous investigational candidate drugs for MAFLD in various stages of clinical development that act on different pathophysiological processes, such as metabolism/steatosis, inflammation or fibrosis. Here, we provide an update on drug development for the treatment of MAFLD and discuss the prospects and challenges for improving and accelerating the nonalcoholic fatty liver disease drug discovery pipeline.
Collapse
|
|
12
|
Metwally M, Bayoumi A, Khan A, Adams LA, Aller R, García-Monzón C, Arias-Loste MT, Bugianesi E, Miele L, Anna A, Latchoumanin O, Han S, Alenizi S, Sharkawy RE, Elattar A, Gallego-Durán R, Fischer J, Berg T, Liddle C, Romero-Gomez M, George J, Eslam M. Copy number variation and expression of exportin-4 associates with severity of fibrosis in metabolic associated fatty liver disease. EBioMedicine 2021; 70:103521. [PMID: 34388518 PMCID: PMC8365315 DOI: 10.1016/j.ebiom.2021.103521] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2021] [Revised: 07/23/2021] [Accepted: 07/26/2021] [Indexed: 01/11/2023] [Imported: 08/29/2023] Open
Abstract
Background Liver fibrosis risk is a heritable trait, the outcome of which is the net deposition of extracellular matrix by hepatic stellate cell-derived myofibroblasts. Whereas nucleotide sequence variations have been extensively studied in liver fibrosis, the role of copy number variations (CNV) in which genes exist in abnormal numbers of copies (mostly due to duplication or deletion) has had limited exploration. Methods The impact of the XPO4 CNV on histological liver damage was examined in a cohort comprised 646 Caucasian patients with biopsy-proven MAFLD and 170 healthy controls. XPO4 expression was modulated and function was examined in human and animal models. Findings Here we demonstrate in a cohort of 816 subjects, 646 with biopsy-proven metabolic associated liver disease (MAFLD) and 170 controls, that duplication in the exportin 4 (XPO4) CNV is associated with the severity of liver fibrosis. Functionally, this occurs via reduced expression of hepatic XPO4 that maintains sustained activation of SMAD3/SMAD4 and promotes TGF-β1-mediated HSC activation and fibrosis. This effect was mediated through termination of nuclear SMAD3 signalling. XPO4 demonstrated preferential binding to SMAD3 compared to other SMADs and led to reduced SMAD3-mediated responses as shown by attenuation of TGFβ1 induced SMAD transcriptional activity, reductions in the recruitment of SMAD3 to target gene promoters following TGF-β1, as well as attenuation of SMAD3 phosphorylation and disturbed SMAD3/SMAD4 complex formation. Interpretation We conclude that a CNV in XPO4 is a critical mediator of fibrosis severity and can be exploited as a therapeutic target for liver fibrosis. Funding ME and JG are supported by the Robert W. Storr Bequest to the Sydney Medical Foundation, University of Sydney; a National Health and Medical Research Council of Australia (NHMRC) Program Grant (APP1053206) and Project and ideas grants (APP2001692, APP1107178 and APP1108422). AB is supported by an Australian Government Research Training Program (RTP) scholarship. EB is supported by Horizon 2020 under grant 634413 for the project EPoS.
Collapse
|
|
13
|
Bayoumi A, Elsayed A, Han S, Petta S, Adams LA, Aller R, Khan A, García‐Monzón C, Arias‐Loste MT, Miele L, Latchoumanin O, Alenizi S, Gallego‐Durán R, Fischer J, Berg T, Craxì A, Metwally M, Qiao L, Liddle C, Yki‐Järvinen H, Bugianesi E, Romero‐Gomez M, George J, Eslam M. Mistranslation Drives Alterations in Protein Levels and the Effects of a Synonymous Variant at the Fibroblast Growth Factor 21 Locus. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2021; 8:2004168. [PMID: 34141520 PMCID: PMC8188187 DOI: 10.1002/advs.202004168] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Revised: 02/09/2021] [Indexed: 05/08/2023] [Imported: 08/29/2023]
Abstract
Fibroblast growth factor 21 (FGF21) is a liver-derived hormone with pleiotropic beneficial effects on metabolism. Paradoxically, FGF21 levels are elevated in metabolic diseases. Interventions that restore metabolic homeostasis reduce FGF21. Whether abnormalities in FGF21 secretion or resistance in peripheral tissues is the initiating factor in altering FGF21 levels and function in humans is unknown. A genetic approach is used to help resolve this paradox. The authors demonstrate that the primary event in dysmetabolic phenotypes is the elevation of FGF21 secretion. The latter is regulated by translational reprogramming in a genotype- and context-dependent manner. To relate the findings to tissues outcomes, the minor (A) allele of rs838133 is shown to be associated with increased hepatic inflammation in patients with metabolic associated fatty liver disease. The results here highlight a dominant role for translation of the FGF21 protein to explain variations in blood levels that is at least partially inherited. These results provide a framework for translational reprogramming of FGF21 to treat metabolic diseases.
Collapse
|
|
14
|
Eslam M, George J. MAFLD: Now is the time to capitalize on the momentum. J Hepatol 2021; 74:1262-1263. [PMID: 33587953 DOI: 10.1016/j.jhep.2021.02.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Accepted: 02/03/2021] [Indexed: 12/17/2022] [Imported: 08/29/2023]
|
|
15
|
Eslam M, Ratziu V, George J. Yet more evidence that MAFLD is more than a name change. J Hepatol 2021; 74:977-979. [PMID: 33453331 DOI: 10.1016/j.jhep.2020.12.025] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Accepted: 12/23/2020] [Indexed: 12/19/2022] [Imported: 08/29/2023]
|
|
16
|
Eslam M, George J. MAFLD: A holistic view to redefining fatty liver disease. J Hepatol 2021; 74:983-985. [PMID: 33453330 DOI: 10.1016/j.jhep.2020.12.027] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Accepted: 12/22/2020] [Indexed: 02/08/2023] [Imported: 08/29/2023]
|
|
17
|
Eslam M, George J. MAFLD: A game changer redefining fatty liver disease for adults and children. J Hepatol 2021; 74:992-994. [PMID: 33453327 DOI: 10.1016/j.jhep.2021.01.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Accepted: 01/07/2021] [Indexed: 12/24/2022] [Imported: 08/29/2023]
|
|
18
|
Eslam M, Chen F, George J. NAFLD in Lean Asians. Clin Liver Dis (Hoboken) 2021; 16:240-243. [PMID: 33489095 PMCID: PMC7805295 DOI: 10.1002/cld.930] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2019] [Accepted: 12/28/2019] [Indexed: 02/04/2023] [Imported: 08/29/2023] Open
|
|
19
|
Bayoumi A, Jalil I, Metwally M, Adams LA, Aller R, García-Monzón C, Arias-Loste MT, Miele L, Petta S, Craxì A, Gallego-Durán R, Fischer J, Berg T, Qiao L, Liddle C, Bugianesi E, Romero-Gomez M, George J, Eslam M. Genetic variation in the TLL1 gene is not associated with fibrosis in patients with metabolic associated fatty liver disease. PLoS One 2020; 15:e0243590. [PMID: 33306709 PMCID: PMC7732106 DOI: 10.1371/journal.pone.0243590] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2020] [Accepted: 11/24/2020] [Indexed: 12/27/2022] [Imported: 08/29/2023] Open
Abstract
Metabolic associated fatty liver disease (MAFLD) is the most prevalent liver disease in Western nations, with high heritability. A recent study of Japanese patients with the disease suggested that TLL1 rs17047200 is associated with fibrosis; whether a similar association is observed in Caucasian patients with MAFLD is unknown. We investigated the association of the TLL1 rs17047200 polymorphism with liver fibrosis in a cohort of Caucasian patients with MAFLD (n = 728). We also investigated whether TLL1 expression is altered during liver injury in humans, in murine models of fibrosis, and in in-vitro. While TLL1 expression is upregulated in the liver of humans with MAFLD and in mice, the rs17047200 variant was not associated with fibrosis or any other histological features, or with hepatic TLL1 expression. In conclusion, the TLL1 rs17047200 variant is not a risk variant for fibrosis in Caucasian patients with MAFLD. However, TLL1 could be involved in the pathogenesis of liver fibrosis.
Collapse
|
|
20
|
Bayoumi A, Shatat M, Eslam M. Metabolic associated fatty liver disease and cancer risk: causal role or epiphenomenon? Hepatobiliary Surg Nutr 2020; 9:774-776. [PMID: 33299832 DOI: 10.21037/hbsn.2020.03.05] [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: 12/24/2022] [Imported: 08/29/2023]
|
|
21
|
Reply to: correspondence regarding "A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement": Bringing evidence to the NAFLD-MAFLD debate. J Hepatol 2020; 73:1575. [PMID: 32933781 DOI: 10.1016/j.jhep.2020.07.045] [Citation(s) in RCA: 78] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2020] [Accepted: 07/31/2020] [Indexed: 12/23/2022] [Imported: 08/29/2023]
|
|
22
|
Zheng KI, Eslam M, George J, Zheng MH. When a new definition overhauls perceptions of MAFLD related cirrhosis care. Hepatobiliary Surg Nutr 2020; 9:801-804. [PMID: 33299840 DOI: 10.21037/hbsn-20-725] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] [Imported: 08/29/2023]
|
|
23
|
Eslam M, Sarin SK, Wong VWS, Fan JG, Kawaguchi T, Ahn SH, Zheng MH, Shiha G, Yilmaz Y, Gani R, Alam S, Dan YY, Kao JH, Hamid S, Cua IH, Chan WK, Payawal D, Tan SS, Tanwandee T, Adams LA, Kumar M, Omata M, George J. The Asian Pacific Association for the Study of the Liver clinical practice guidelines for the diagnosis and management of metabolic associated fatty liver disease. Hepatol Int 2020; 14:889-919. [PMID: 33006093 DOI: 10.1007/s12072-020-10094-2] [Citation(s) in RCA: 397] [Impact Index Per Article: 99.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Accepted: 09/06/2020] [Indexed: 02/06/2023] [Imported: 08/29/2023]
Abstract
Metabolic associated fatty liver disease (MAFLD) is the principal worldwide cause of liver disease and affects nearly a quarter of the global population. The objective of this work was to present the clinical practice guidelines of the Asian Pacific Association for the Study of the Liver (APASL) on MAFLD. The guidelines cover various aspects of MAFLD including its epidemiology, diagnosis, screening, assessment, and treatment. The document is intended for practical use and for setting the stage for advancing clinical practice, knowledge, and research of MAFLD in adults, with specific reference to special groups as necessary. The guidelines also seek to improve patient care and awareness of the disease and assist stakeholders in the decision-making process by providing evidence-based data. The guidelines take into consideration the burden of clinical management for the healthcare sector.
Collapse
|
|
24
|
Eslam M, George J. Reply to: Correspondence on "A new definition for metabolic associated fatty liver disease: an international expert consensus statement": MAFLD: Moving from a concept to practice. J Hepatol 2020; 73:1268-1269. [PMID: 32800588 DOI: 10.1016/j.jhep.2020.06.036] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Accepted: 06/24/2020] [Indexed: 12/18/2022] [Imported: 08/29/2023]
|
|
25
|
Shiha G, Korenjak M, Eskridge W, Casanovas T, Velez-Moller P, Högström S, Richardson B, Munoz C, Sigurðardóttir S, Coulibaly A, Milan M, Bautista F, Leung NWY, Mooney V, Obekpa S, Bech E, Polavarapu N, Hamed AE, Radiani T, Purwanto E, Bright B, Ali M, Dovia CK, McColaugh L, Koulla Y, Dufour JF, Soliman R, Eslam M. Redefining fatty liver disease: an international patient perspective. Lancet Gastroenterol Hepatol 2020; 6:73-79. [PMID: 33031758 DOI: 10.1016/s2468-1253(20)30294-6] [Citation(s) in RCA: 117] [Impact Index Per Article: 29.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2020] [Revised: 08/27/2020] [Accepted: 08/30/2020] [Indexed: 02/06/2023] [Imported: 08/29/2023]
Abstract
Despite its increased recognition as a major health threat, fatty liver disease associated with metabolic dysfunction remains largely underdiagnosed and undertreated. An international consensus panel has called for the disease to be renamed from non-alcoholic fatty liver disease (NAFLD) to metabolic-associated fatty liver disease (MAFLD) and has suggested how the disease should be diagnosed. This Viewpoint explores the call from the perspective of patient advocacy groups. Patients are well aware of the negative consequences of the NAFLD acronym. This advocacy group enthusiastically endorses the call to reframe the disease, which we believe will ultimately have a positive effect on patient care and quality of life and, through this effect, will reduce the burden on health-care systems. For patients, policy makers, health planners, donors, and non-hepatologists, the new acronym MAFLD is clear, squarely placing the disease as a manifestation of metabolic dysfunction and improving understanding at a public health and patient level. The authors from representative patient groups are supportive of this change, particularly as the new acronym is meaningful to all citizens as well as governments and policy makers, and, above all, is devoid of any stigma.
Collapse
|