Molecular mechanisms in MASLD/MASH-related HCC

Hepatology, Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 13, 2024

Liver cancer is the third leading cause of cancer-related deaths and ranks as sixth most prevalent type globally. NAFLD or metabolic dysfunction-associated steatotic liver disease, its more severe manifestation, NASH steatohepatitis (MASH), pose a significant global health concern, affecting approximately 20%-25% population. The increased prevalence disease MASH parallel to increasing rates obesity-associated diseases, including 2 diabetes, insulin resistance, fatty diseases. can progress MASH-related HCC (MASH-HCC) in about 2% cases each year, influenced by various factors such genetic mutations, carcinogen exposure, immune microenvironment, microbiome. MASH-HCC exhibits distinct molecular characteristics compared other causes affects both men women equally. management early intermediate-stage typically involves surgery locoregional therapies, while advanced treated with systemic anti-angiogenic therapies checkpoint inhibitors. In this comprehensive review, we consolidate previous research findings also providing current insights into intricate processes underlying development. We delve MASH-HCC-associated variations somatic progression models, multiomics analysis, immunological microenvironmental impacts, discuss targeted/combined overcome evasion biomarkers recognize treatment responders. By furthering our comprehension mechanisms MASH-HCC, goal catalyze advancement potent strategies, ultimately enhanced patient outcomes.

Language: Английский

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Association of GLP-1 Receptor Agonists and Hepatocellular Carcinoma Incidence and Hepatic Decompensation in Patients With Type 2 Diabetes

Gastroenterology, Journal Year: 2024, Volume and Issue: 167(4), P. 689 - 703

Published: April 29, 2024

Hepatocellular carcinoma (HCC) is a leading cause of cancer death. HCC preventable with about 70% attributable to modifiable risk factors. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), Food and Drug Administration-approved medications for treating type 2 diabetes mellitus (T2DM), have pleiotropic effects on counteracting factors HCC. Here we evaluate the association GLP-1RAs incident in real-world population.

Language: Английский

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Safety and Efficacy of Efruxifermin in Combination With a GLP-1 Receptor Agonist in Patients With NASH/MASH and Type 2 Diabetes in a Randomized Phase 2 Study

Clinical Gastroenterology and Hepatology, Journal Year: 2024, Volume and Issue: unknown

Published: March 1, 2024

Background & AimsIn phase 2 studies, efruxifermin, an Fc–FGF21 analog, significantly reduced steatohepatitis and fibrosis in patients with non-alcoholic steatohepatitis, now called metabolic dysfunction-associated (MASH), for which there is no approved treatment. Type diabetes (T2D) obesity are prevalent among MASH increasingly treated glucagon-like peptide-1 receptor agonists (GLP-1RAs). This study evaluated the safety efficacy of efruxifermin MASH, fibrosis, T2D taking a GLP-1RA.MethodsCohort D was double-blind, placebo-controlled, 2b adults (F1–F3) on stable GLP-1RA therapy randomized (2:1) to receive 50 mg or placebo, once weekly 12 weeks. The primary endpoint tolerability added dose GLP-1RA. Secondary endpoints included changes hepatic fat fraction (HFF), markers liver injury parameters.ResultsAdults (N = 31) (semaglutide, 48.4%; dulaglutide, 45.2%; liraglutide, 6.5%) received (n 21) placebo 10) addition appeared safe well-tolerated. most frequent efruxifermin-related adverse events were mild moderate gastrointestinal events. One patient receiving discontinued due nausea, another withdrew consent. There treatment-related serious After weeks, HFF by 65% (P < .0001 vs placebo) compared 10% reduction (GLP-1RA alone). Efruxifermin also improved noninvasive injury, glucose, lipid metabolism while maintaining GLP-1RA–mediated weight loss.ConclusionsThe profile comparable that either drug alone, reducing T2D. Liver health already may be further efruxifermin. Clinicaltrials.gov, Number: NCT05039450.Graphical abstract

Language: Английский

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Organoid-guided precision hepatology for metabolic liver disease

Journal of Hepatology, Journal Year: 2024, Volume and Issue: 80(5), P. 805 - 821

Published: Jan. 17, 2024

Language: Английский

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Pharmacological therapy of metabolic dysfunction-associated steatotic liver disease-driven hepatocellular carcinoma

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 19, 2024

In light of a global rise in the number patients with type 2 diabetes mellitus (T2DM) and obesity, non-alcoholic fatty liver disease (NAFLD), now known as metabolic dysfunction-associated (MAFLD) or steatotic (MASLD), has become leading cause hepatocellular carcinoma (HCC), annual occurrence MASLD-driven HCC expected to increase by 45%–130% 2030. Although MASLD serious major public health threat globally, exact molecular mechanisms mediating remain an open problem, necessitating future investigation. Meanwhile, emerging studies are focusing on utility bioactive compounds halt progression HCC. this review, we first briefly review recent progress possible pathogenesis for We then discuss application mitigate through different modulatory encompassing anti-inflammatory, lipid metabolic, gut microbial pathways, providing valuable information treatment prevention Nonetheless, clinical research exploring effectiveness herbal medicines is still warranted.

Language: Английский

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New and Old Key Players in Liver Cancer

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(24), P. 17152 - 17152

Published: Dec. 5, 2023

Liver cancer represents a major health problem worldwide with growing incidence and high mortality, hepatocellular carcinoma (HCC) being the most frequent. Hepatocytes are likely cellular origin of HCCs through accumulation genetic alterations, although hepatic progenitor cells (HPCs) might also be candidates in specific cases, as discussed here. HCC usually develops context chronic inflammation, fibrosis, cirrhosis, role fibrosis is controversial. The interplay between hepatocytes, immune stellate key issue. This review summarizes critical aspects liver tumor microenvironment paying special attention to platelets new players, which exert both pro- anti-tumor effects, determined by contexts tight regulation platelet signaling. Additionally, relevance signaling pathways, mainly HGF/MET, EGFR TGF-β discussed. HGF produced different regulate not only cell fate but HPCs, inflammation these players processes. C3G/RAPGEF1, required for proper function HGF/MET highlighted, due its ability promote growth and, HPC platelet-mediated actions on cancer.

Language: Английский

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Exploring Promising Therapies for Non-Alcoholic Fatty Liver Disease: A ClinicalTrials.gov Analysis

Diabetes Metabolic Syndrome and Obesity, Journal Year: 2024, Volume and Issue: Volume 17, P. 545 - 561

Published: Feb. 1, 2024

Background: Non-alcoholic fatty liver disease (NAFLD) is a common and has been increasing in recent years. To date, no FDA-approved drug specifically targets NAFLD. Methods: The terms "Non-alcoholic Fatty Liver Disease" "NAFLD" were used search of ClinicalTrials.gov on August 24, 2023. Two evaluators independently examined the trials using predetermined eligibility criteria. Studies had to be interventional, NAFLD focused, Phase IV, completed eligible for this review. Results: database was searched examining pharmacotherapeutics revealed 1364 trials, with 31 meeting inclusion Out these, 19 finalized evaluation. dominant intervention model Parallel. most prevalent studies Korea (26.3%) China (21.1%). metformin (12.1%), others like Exenatide Pioglitazone accounting 9.1%. Conclusion: Therapeutics manage are limited. However, various medications offer potential benefits. Further investigations definitely warranted. Keywords: NAFLD, hepatology, clinical therapeutics, metabolic disorder

Language: Английский

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Effects of Oat β-Glucan and Inulin on Alleviation of Nonalcoholic Steatohepatitis Aggravated by Circadian Disruption in C57BL/6J Mice

Journal of Agricultural and Food Chemistry, Journal Year: 2024, Volume and Issue: 72(7), P. 3520 - 3535

Published: Feb. 9, 2024

This was the first study that examined effects of oat β-glucan and inulin on diet-induced nonalcoholic steatohepatitis (NASH) in circadian-disrupted (CD)-male C57BL/6J mice. CD intensified NASH, significantly increasing alanine aminotransferase upregulating hepatic tumor necrosis factor α (TNFα) transforming growth β 1 (TGFβ1). However, these observations were alleviated by treatments. Compared to NASH mice, decreased liver index, aspartate (AST), insulin. In prebiotic-treated significant negative correlations found between enrichment Muribaculaceae bacterium Isolate-036 (Harlan), Isolate-001 (NCI), Bacteroides ovatus after supplementation with TNFα TGFβ1 levels; Isolate-110 (HZI) AST level. conclusion, exhibited similar antiliver injury, anti-inflammatory, antifibrotic activities but had no effect cecal short-chain fatty acids gut microbiota diversity

Language: Английский

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Precision targeting in hepatocellular carcinoma: Exploring ligand-receptor mediated nanotherapy

World Journal of Hepatology, Journal Year: 2024, Volume and Issue: 16(2), P. 164 - 176

Published: Feb. 27, 2024

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and poses a major challenge to global health due its high morbidity mortality. Conventional chemotherapy usually targeted patients with intermediate advanced stages, but it often ineffective suffers from problems such as multidrug resistance, rapid drug clearance, nonspecific targeting, side effects, low accumulation in tumor cells. In response these limitations, recent advances nanoparticle-mediated delivery technologies have emerged breakthrough approaches for treatment of HCC. This review focuses on nanoparticle-based systems, special attention various receptors overexpressed HCC These are key enhancing specificity efficacy nanoparticle represent new paradigm actively targeting combating We comprehensively summarize current understanding receptors, their role impact therapies By gaining deeper receptor-mediated mechanisms innovative therapies, more effective precise can be achieved.

Language: Английский

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Therapeutic potential of stem cell‐derived somatic cells to treat metabolic dysfunction‐associated steatotic liver disease and diabetes

Obesity Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 24, 2025

Summary Developments in basic stem cell biology have paved the way for technology translation human medicine. An exciting prospective use of cells is ex vivo generation hepatic and pancreatic endocrine biomedical applications. This includes creating novel models ‘in a dish’ developing therapeutic strategies complex diseases, such as metabolic dysfunction‐associated steatotic liver disease (MASLD) diabetes. In this review, we explore recent advances cell‐derived hepatocyte‐like insulin‐producing β‐like cells. We cover different differentiation strategies, new discoveries, caveats that still exist regarding their routine use. Finally, discuss challenges limitations therapies clinical strategy to manage diseases humans.

Language: Английский

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