Current status and future trends of the global burden of MASLD

Trends in Endocrinology and Metabolism, Journal Year: 2024, Volume and Issue: 35(8), P. 697 - 707

Published: Feb. 29, 2024

Language: Английский

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Insights into the molecular targets and emerging pharmacotherapeutic interventions for nonalcoholic fatty liver disease

Metabolism, Journal Year: 2021, Volume and Issue: 126, P. 154925 - 154925

Published: Nov. 3, 2021

Language: Английский

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Engineered human hepatocyte organoids enable CRISPR-based target discovery and drug screening for steatosis

Nature Biotechnology, Journal Year: 2023, Volume and Issue: 41(11), P. 1567 - 1581

Published: Feb. 23, 2023

Abstract The lack of registered drugs for nonalcoholic fatty liver disease (NAFLD) is partly due to the paucity human-relevant models target discovery and compound screening. Here we use human fetal hepatocyte organoids model first stage NAFLD, steatosis, representing three different triggers: free acid loading, interindividual genetic variability (PNPLA3 I148M) monogenic lipid disorders ( APOB MTTP mutations). Screening drug candidates revealed compounds effective at resolving steatosis. Mechanistic evaluation uncovered repression de novo lipogenesis as convergent molecular pathway. We present FatTracer, a CRISPR screening platform identify steatosis modulators putative targets using −/− organoids. From screen targeting 35 genes implicated in metabolism and/or NAFLD risk, FADS2 (fatty desaturase 2) emerged an important determinant hepatic Enhancement expression increases polyunsaturated abundancy which, turn, reduces lipogenesis. These organoid facilitate study etiology targets.

Language: Английский

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The Asian Pacific association for the study of the liver clinical practice guidelines for the diagnosis and management of metabolic dysfunction-associated fatty liver disease

Hepatology International, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 27, 2025

Language: Английский

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Insights into Nonalcoholic Fatty-Liver Disease Heterogeneity

Seminars in Liver Disease, Journal Year: 2021, Volume and Issue: 41(04), P. 421 - 434

Published: July 7, 2021

The acronym nonalcoholic fatty-liver disease (NAFLD) groups a heterogeneous patient population. Although in many patients the primary driver is metabolic dysfunction, complex and dynamic interaction of different factors (i.e., sex, presence one or more genetic variants, coexistence comorbidities, diverse microbiota composition, various degrees alcohol consumption among others) takes place to determine subphenotypes with distinct natural history prognosis and, eventually, response therapy. This review aims address this topic through analysis existing data on differential contribution known pathogenesis clinical expression NAFLD, thus determining observed practice. To improve our understanding NAFLD heterogeneity dominant drivers subgroups would predictably impact development precision-targeted therapies for NAFLD.

Language: Английский

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Endoplasmic reticulum stress in nonalcoholic (metabolic associated) fatty liver disease (NAFLD/MAFLD)

Journal of Cellular Biochemistry, Journal Year: 2022, Volume and Issue: 123(10), P. 1585 - 1606

Published: May 1, 2022

Abstract Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic fat accumulation in the absence of excessive alcohol consumption and strongly associated with obesity, type 2 diabetes (T2DM) other metabolic syndrome features. NAFLD becoming increasingly prevalent currently constitutes leading cause hepatocellular carcinoma (HCC). Recently, term (dysfunction) (MAFLD) has been proposed reflecting more accurately underlying pathogenesis cardiometabolic disorders to NAFLD/MAFLD. Given vital functions maintain body homeostasis, an extended endoplasmic reticulum (ER) network mandatory hepatocytes retain its capacity adapt multiple extracellular intracellular signals mediating changes. Dysfunction hepatocyte ER homeostasis disturbance interaction mitochondria have recognized be involved pathophysiology. Apart from hepatocytes, stellate cells, Kupffer cells shown play important role occurrence progression nonalcoholic steatohepatitis (NASH) possibly different roles stages spectrum. Furthermore, excess lipid causes lipotoxicity which interacts stress culminates inflammation damage, mechanisms crucially implicated NASH pathogenesis. Finally, circadian clock machinery regulates stress‐related pathways vice versa, thus controlling metabolism being progression. This review presents a comprehensive overview current knowledge supporting impact signaling on NAFLD, whilst summarizing potential therapeutic interventions targeting this process.

Language: Английский

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Emerging role of aging in the progression of NAFLD to HCC

Ageing Research Reviews, Journal Year: 2022, Volume and Issue: 84, P. 101833 - 101833

Published: Dec. 22, 2022

Language: Английский

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Effect of cofactors on NAFLD/NASH and MAFLD. A paradigm illustrating the pathomechanics of organ dysfunction

Metabolism and Target Organ Damage, Journal Year: 2022, Volume and Issue: 2, P. 12 - 12

Published: Jan. 1, 2022

Primary nonalcoholic fatty liver disease (NAFLD) is bi-directionally associated with the metabolic syndrome and its constitutive features ("factors": impaired glucose disposal, visceral obesity, arterial hypertension, dyslipidemia). Secondary NAFLD occurs due to endocrinologic disturbances or other cofactors. This nosography tends be outdated by novel definition of (MAFLD). Irrespective nomenclature, this condition exhibits a remarkable pathogenic heterogeneity unpredictable clinical outcomes which are heavily influenced histology changes. Genetics epigenetics, lifestyle habits [including diet physical (in)activity] immunity/infection appear major cofactors that modulate NAFLD/MAFLD outcomes, including organ dysfunction owing cirrhosis hepatocellular carcinoma, type 2 diabetes, chronic kidney disease, heart failure, sarcopenia. The identification for may help understand reliably support inherently personalized medicine approaches research priority, thus paving way innovative treatment strategies.

Language: Английский

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Liver fibrosis in nonalcoholic fatty liver disease patients: noninvasive evaluation and correlation with cardiovascular disease and mortality

Metabolism and Target Organ Damage, Journal Year: 2023, Volume and Issue: 3(1), P. 1 - 1

Published: Jan. 1, 2023

Liver fibrosis is critical for liver-related outcomes and mortality in chronic liver disease, irrespective of etiology, including nonalcoholic fatty disease (NAFLD). NAFLD has been viewed as an independent correlate cardiovascular risk. This review article briefly describes the cellular molecular pathomechanisms underlying hepatic fibrosis. We then address noninvasive assessment Finally, we discuss published evidence supporting biomarkers’ role assessing risk among patients with NAFLD. While histological diagnostic standard fibrosis, specifically techniques, equations based on anthropometric parameters, laboratory indices, elastometry obtained imaging techniques. The former group includes AST: ALT ratio, Forns Index, AST-to-platelet ratio index score, BARD (BMI, AAR, Diabetes) fibrosis-4 (FIB-4), gamma-glutamyl transferase-to-platelet Hepamet score. latter comprises elastographic techniques associated ultrasonography or magnetic resonance. Our literature identified numerous studies demonstrating that biomarkers (the most common being FIB-4) predict overall major events patients. mechanisms accounting this association are reviewed. In addition to at baseline, during follow-up, after therapeutic interventions patients, may these

Language: Английский

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FLAME: Training and Validating a Newly Conceived Model Incorporating Alpha-Glutathione-S-Transferase Serum Levels for Predicting Advanced Hepatic Fibrosis and Acute Cardiovascular Events in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 761 - 761

Published: Jan. 17, 2025

Alpha-Glutathione-S-transferase (alphaGST) is a liver enzyme whose serum levels increase with the worsening of fibrosis in alcoholic and viral chronic hepatitis. Its usefulness Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) remains unexplored. From January 2016 to December 2017, 200 patients MASLD 30 controls were enrolled. AlphaGST measured. Variables related advanced (AF) selected via Principal Component Analysis (PCA), best cut-off (BCO) was estimated using ROC analysis. stiffness measurement (LSM), NAFLD (NFS), Fibrosis-4 (FIB-4), BMI-AST/ALT Ratio-Diabetes (BARD) scores determined. The first acute cardiovascular events (ACE) ACE-naïve subjects recorded over five years. A validation cohort 60 enrolled from 2018 May 2019 followed for increased stage (p < 0.0001) both cohorts, showing high accuracy predicting AF (TrC: AUC 0.89, VlC: 0.89). PCA-selected variables HbA1c, HDL, alphaGST, forming "FLAME" model. FLAME showed superior predictive performance ACEs compared other models scores. represents novel tool that accurately predicts MASLD.

Language: Английский

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