Metabolic dysfunction-associated steatotic liver disease: heterogeneous pathomechanisms and effectiveness of metabolism-based treatment

The Lancet Diabetes & Endocrinology, Год журнала: 2024, Номер unknown

Опубликована: Дек. 1, 2024

Язык: Английский

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Advancements in pharmacological treatment of NAFLD/MASLD: a focus on metabolic and liver-targeted interventions

Gastroenterology report, Год журнала: 2023, Номер 12

Опубликована: Дек. 22, 2023

Abstract In the present narrative review, we have summarized evidence on pharmacological treatment of non-alcoholic fatty liver disease (NAFLD)/metabolic dysfunction-associated steatotic (MASLD). We start by reviewing epidemiology condition and its close association with obesity type 2 diabetes. then discuss how randomized–controlled trials are performed following guidance from regulatory agencies, including differences similarities between requirements US Food Drug Administration European Medicine Agency. Difficulties hurdles related to limitations biopsy, a large number screening failures in recruiting patients, as well unpredictable response rates placebo group evaluated. Finally, recapitulate strategies employed for potential drug treatments this orphan condition. The first is repurpose drugs that originally targeted T2DM and/or obesity, such pioglitazone, glucagon-like peptide 1 receptor agonists (liraglutide semaglutide), multi-agonists (tirzepatide retatrutide), sodium-glucose transporter inhibitors. second develop specifically targeting NAFLD/MASLD. Among those, focused resmetirom, fibroblast growth factor 21 analogs, lanifibranor, they currently Phase 3 their clinical trial development. While many characterized field NAFLD/MASLD past, it likely approval near. As occurs chronic conditions, combination therapy might lead better outcomes. case steatohepatitis, speculate treating underlying metabolic co-morbidities play bigger role earlier stages disease, while liver-targeting molecules will become vital patients more advanced terms inflammation fibrosis.

Язык: Английский

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Irisin alleviates hepatic steatosis by activating the autophagic SIRT3 pathway

Chinese Medical Journal, Год журнала: 2025, Номер unknown

Опубликована: Фев. 18, 2025

Abstract Background: Disruption of hepatic lipid homeostasis leads to excessive triglyceride accumulation and the development metabolic dysfunction-associated steatotic liver disease (MASLD). Autophagy, a critical process in metabolism, is impaired MASLD pathogenesis. Irisin, skeletal muscle-driven myokine, regulates but its impact on metabolism not well understood. Here, we aimed explore role irisin steatosis underlying mechanisms involved. Methods: A high-fat diet (HFD)-induced mouse model was used, recombinant protein, herein referred as “Irisin”, intraperitoneally administered for 4 weeks evaluate effects accumulation. Liver tissues were stained with Oil red O (ORO), (TG) total cholesterol (TC) contents measured serum homogenates. The expression autophagosome marker microtubule-associated protein 1 light chain 3 (LC3), autophagy receptor sequestosome-1 (SQSTM1/p62), initiation complex unc-51-like kinase (ULK1) lysosomal functional cathepsin B via Western blotting, transcription factor EB (TFEB) analyzed immunofluorescence autophagic changes. effect flux further evaluated palmitic acid-induced HepG2 cells by measuring degradation chloroquine (CQ), analyzing colocalization LC3 lysosome-associated (LAMP1). possible mechanism examined sirtuin (SIRT3) pathway validated using overexpression SIRT3 plasmid transfection or siRNA-mediated knockdown. Student’s t -test utilized statistical analysis. Results: Irisin significantly reduces mice fed HFD, accompanied enhanced hepatocyte upregulation pathway. In cells, attenuated accumulation, which partially dependent levels. Mechanistically, treatment upregulated phosphorylated AMP-activated (AMPK), inhibited mammalian target rapamycin (mTOR) activity, promoted TFEB nucleus translocation, increased expression, degradation, alleviated steatosis. No significant changes phosphorylation ULK1 hepatocytes observed. However, when siRNA used knock down , those reversed, exacerbated. Conclusions: Our findings highlight potential therapeutic modulating potentially providing novel management MASLD. Further research needed elucidate clinical applications this approach

Язык: Английский

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Liver fibrosis: More than meets the eye

Annals of Hepatology, Год журнала: 2024, Номер 29(4), С. 101479 - 101479

Опубликована: Фев. 10, 2024

Язык: Английский

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Alanine aminotransferase predicts incident steatotic liver disease of metabolic etiology: Long life to the old biomarker!

World Journal of Gastroenterology, Год журнала: 2024, Номер 30(24), С. 3016 - 3021

Опубликована: Июнь 25, 2024

Alanine aminotransferase (ALT) serum levels increase because of hepatocellular damage. Metabolic dysfunction-associated fatty liver disease (MAFLD), which identifies steatotic (SLD) associated with ≥ 2 metabolic abnormalities, has prominent sexual differences. The Syndrome defines a cluster comprising abdominal obesity, altered glucose metabolism, dyslipidemia, and hypertension. Male sex, body mass index, glucose, lipids, ferritin, hypertension, age independently predict ALT among blood donors. Over the last few decades, reference range been animatedly debated owing to attempts update sex-specific ranges. With this backset, Chen

Язык: Английский

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Representation of Sex, Race and Ethnicity in MASH Randomised Controlled Trials: A Systematic Review and Meta‐Analysis

Liver International, Год журнала: 2025, Номер 45(4)

Опубликована: Март 3, 2025

ABSTRACT Background and Aims Randomised controlled trials (RCTs) have historically underrepresented female, racial ethnic minorities across various fields. This systematic review meta‐analysis aims to examine the global distribution, reporting participation of diverse groups based on sex, race ethnicity in focused metabolic dysfunction‐associated steatohepatitis (MASH). Methods PubMed Cochrane Library databases were systematically searched for MASH RCTs (through December 13, 2024) that included any pharmacotherapy as an intervention arm. qualitatively reviewed assess their distribution populations. A proportions was performed using a generalised linear mixed model. Results One hudred nine studies identified, data from 112 19 516 participants. Of 49 countries conducted trials, 34 high‐income (69.4%). Sex, reported 111 (99.1%), 69 (61.6%) 56 (50.0%) RCTs, respectively, with improving recent years. We found no sexual gender minorities. The pooled White, Asian, Black Hispanic/Latino 54.23% (95% confidence interval [CI]: 51.31–57.12), 87.63% CI: 85.37–89.58), 4.95% 3.42–7.10), 2.27% 1.89–2.71) 31.42% 26.61–36.66), respectively. Meta‐regressions showed trend toward more White participants over time. Conclusions Although female representation has increased time, are trials. These provide overview participant call collaborative efforts among researchers, sponsors, regulators other relevant stakeholders improve diversity these

Язык: Английский

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Hallazgos por imagen de las enfermedades hepáticas por depósito

Radiología, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

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MAFLD vs. MASLD: a year in review

Expert Review of Endocrinology & Metabolism, Год журнала: 2025, Номер unknown, С. 1 - 12

Опубликована: Апрель 12, 2025

In 2023, metabolic dysfunction-associated steatotic liver disease (MASLD) was introduced following fatty (MAFLD). Both aim to address the limitations of nonalcoholic (NAFLD). This review analyzes similarities and differences between MAFLD MASLD, focusing on their impacts epidemiology, diagnosis, stigma, related diseases. Current evidence suggests that criteria effectively identify individuals at higher risk through a good balance sensitivity specificity. Moreover, is more generalizable term easily understood globally. The transition from NAFLD MASLD marks significant advance in understanding within hepatology. identifies homogeneous cohort patients with due dysfunction provides valuable framework for holistic, patient-centered management strategies consider various contributing factors improve health outcomes.

Язык: Английский

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Resmetirom: Finally, the Light at the End of the NASH Tunnel?

Livers, Год журнала: 2024, Номер 4(1), С. 138 - 141

Опубликована: Фев. 26, 2024

Nonalcoholic steatohepatitis (NASH) is a double composite word that was first coined in 1980 by Ludwig and Colleagues [...]

Язык: Английский

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Red cell distribution width/platelet ratio predicts decompensation of metabolic dysfunction-associated steatotic liver disease-related compensated advanced chronic liver disease

World Journal of Gastroenterology, Год журнала: 2024, Номер 31(3)

Опубликована: Дек. 17, 2024

Prognostication of compensated advanced chronic liver disease (cACLD) is paramount importance for the physician-and-patient communication and rational clinical decisions. The paper published by Dallio et al reports on red cell distribution width (RDW)/platelet ratio (RPR) as a non-invasive biomarker in predicting decompensation metabolic dysfunction-associated steatotic (MASLD)-related cACLD. Differently from other biomarkers algorithms, RPR inexpensive widely available, based parameters which are included complete blood count. computed grounds two different items, one which, RDW, mirrors host's response to variety stimuli non-specific. second parameter involved RPR, platelet count, more specific has been used hepatological clinic discriminate cirrhotic non-cirrhotic decades. Cardiovascular primary cause mortality among MASLD subjects, followed extra-hepatic cancers liver-related mortality. Therefore, should be validated not only terms events but also prediction major adverse cardiovascular cancers. Adequately sized multi-ethnic confirmatory investigation required define role significance stratification MASLD-cACLD.

Язык: Английский

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