MASLD/MASH Learning Center
Noninvasive identification of metabolic dysfunction-associated steatohepatitis (INFORM MASH): a retrospective cohort and disease modeling study
CONCLUSION: The composite likelihood score could potentially be a tool for early MASH screening.
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A Markov Model Unveiling the Impact of Resmetirom on the Natural History of MASLD Patients: A Sistematic Review and Meta-Analysis
CONCLUSIONS: Resmetirom decreases the 5-year and lifetime Markov-model estimated risk of CC, DC, HCC and liver-related mortality in patients with MASLD and F2 or F3 fibrosis.
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Emerging insights into the gut microbiota as a key regulator of immunity and response to immunotherapy in hepatocellular carcinoma
The gut microbiota, a complex microbial ecosystem closely connected to the liver via the portal vein, has emerged as a critical regulator of liver health and disease. Numerous studies have underscored its role in the onset and progression of liver disorders, including alcoholic liver disease, metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction-associated steatohepatitis (MASH), liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). This review provides...
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Hormone correction of dysfunctional metabolic gene expression in stem cell-derived liver tissue
The increase in metabolic dysfunction-associated steatotic liver disease (MASLD) and its progression to metabolic dysfunction-associated steatohepatitis (MASH) is a worldwide healthcare challenge. Heterogeneity between men and women in the prevalence and mechanisms of MASLD and MASH is related to differential sex hormone signalling within the liver, and declining hormone levels during aging. In this study we used biochemically characterised pluripotent stem cell derived 3D liver spheres to model...
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Induction of MASH-like pathogenesis in the Nwd1(-/-) mouse liver
Endoplasmic reticulum (ER) stores Ca^(2+) and plays crucial roles in protein folding, lipid transfer, and it's perturbations trigger an ER stress. In the liver, chronic ER stress is involved in the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH). Dysfunction of sarco/endoplasmic reticulum calcium ATPase (SERCA2), a key regulator of Ca^(2+) transport from the cytosol to ER, is associated with the...
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Unlocking the potential of THR-β agonist therapies: resmetirom's chemistry, biology, and patent insights
Non-alcoholic steatohepatitis (NASH) is a severe manifestation of non-alcoholic fatty liver disease (NAFLD), which is characterized by hepatic steatosis, inflammation, and hepatocyte destruction. Newly adopted nomenclature, metabolic dysfunction-associated fatty liver disease (MAFLD), allows to signify the importance of metabolic dysfunction. For which the current treatment options are limited and often associated with adverse effects, creating a need for targeted therapies. This manuscript...
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Pentraxin-3 as a poor marker of fibrosis in metabolic dysfunction-associated steatotic liver disease among older adults: findings from the PolSenior2 substudy
CONCLUSION: Our study suggests that plasma PTX-3 levels are not sensitive enough to be used as a non-specific marker of liver fibrosis in older adults.
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Carabrone Attenuates Metabolic Dysfunction-Associated Steatohepatitis by Targeting STAT3 in Mice
Metabolic dysfunction-associated steatohepatitis (MASH) has become one of the most common progressive liver diseases worldwide, but effective treatment options are severely unmet. Carabrone, a sesquiterpene lactone from the traditional Chinese herb Carpesium abrotanoides L., shows various pharmacological properties, whereas its effect on the improvement of MASH and the underlying mechanisms have not yet been reported. In this work, we revealed for the first time the beneficial effect of...
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Cinnabarinic acid protects against metabolic dysfunction-associated steatohepatitis by activating Aryl hydrocarbon Receptor-dependent AMPK signaling
Metabolic dysfunction-associated steatohepatitis (MASH) is an advanced form of metabolic dysfunction-associated steatotic liver disease (MASLD) characterized by accumulation of fats in liver, chronic inflammation, hepatocytic ballooning, and fibrosis. This study investigates the significance of hepatic Aryl hydrocarbon Receptor (AhR) signaling in cinnabarinic acid (CA)-mediated protection against MASH. Here, we report that livers of high-fat, high-fructose, high-cholesterol diet-fed...
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In vivo anti-FAP CAR T therapy reduces fibrosis and restores liver homeostasis in metabolic dysfunction-associated steatohepatitis
In this study, we aimed to determine the efficacy of in vivo chimeric antigen receptor (CAR) T cell therapy, generated by targeted lipid nanoparticles (t-LNPs), as an anti-fibrotic in metabolic dysfunction-associated steatotic liver disease. Hepatic fibrosis is a key predictor of mortality in liver disease, driven by fibrogenic hepatic stellate cells (HSCs). In heart, chimeric antigen receptor (CAR) T cells targeting fibroblast activation protein alpha (FAP) reduce murine cardiac fibrosis....
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Liver lipid droplet cholesterol content is a key determinant of metabolic dysfunction-associated steatohepatitis
Metabolic dysfunction-associated steatohepatitis (MASH) represents a progressive form of steatotic liver disease which increases the risk for fibrosis and advanced liver disease. The accumulation of discrete species of bioactive lipids has been postulated to activate signaling pathways that promote inflammation and fibrosis. However, the key pathogenic lipid species is a matter of debate. We explored candidates using various dietary, molecular, and genetic models. Mice fed a choline-deficient...
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Transcriptomics, lipidomics, and single-nucleus RNA sequencing integration: exploring sphingolipids in MASH-HCC progression
CONCLUSION: Our findings provided valuable insights into the role of sphingolipids in the progression of MASH to HCC. Specific serum and liver sphingolipid profiles may serve as valuable biomarkers for diagnosis and prognosis in MASH-HCC.
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