A weekly 4‐methylpyrazole treatment attenuates the development of non‐obese metabolic dysfunction‐associated steatotic liver disease (MASLD) in male mice: Role of JNK DOI Creative Commons

Katharina Burger,

Finn Jung,

Raphaela Staltner

и другие.

European Journal of Clinical Investigation, Год журнала: 2024, Номер unknown

Опубликована: Сен. 29, 2024

Abstract Background 4‐methylpyrazole (4MP, fomepizole) is a competitive inhibitor of alcohol dehydrogenase (ADH) preventing the metabolism ethylene glycol and methanol, respectively, into their toxic metabolites. 4MP seems also to possess potential in treatment intoxication from other substance, for example, acetaminophen, modulate JNK‐dependent signalling. Here, we determined if with once weekly affects development diet‐induced non‐obese metabolic dysfunction‐associated steatotic liver disease (MASLD) C57BL/6 mice. Methods Male mice (6–8 weeks old, n = 7‐8/group) were pair‐fed either liquid control diet (C) or sucrose‐, fat‐ cholesterol‐rich (SFC) 8 while being concomitantly treated (50 mg/kg bw i.p.) vehicle week. Liver damage, inflammatory markers glucose tolerance assessed. Moreover, endotoxin‐challenged J774A.1 cells pretreated 4MP, pro‐inflammatory Results The concomitant SFC‐fed attenuated increase JNK phosphorylation like IFNγ, IL‐6 3‐nitrotyrosine protein adducts tissue found vehicle‐treated mice, not affecting impairments portal endotoxin levels. pretreatment endotoxin‐stimulated significantly increases mediators Mcp1 . Conclusions Taken together, our results suggest that attenuates activation dampens MASLD

Язык: Английский

Insights into the results of Resmetirom trials: Can a thyroid hormone receptor agonist be the holy grail of MASH therapy? DOI Creative Commons
Konstantinos Arvanitakis, Theocharis Koufakis, Εvangelos Cholongitas

и другие.

Pharmacology & Therapeutics, Год журнала: 2025, Номер unknown, С. 108811 - 108811

Опубликована: Фев. 1, 2025

Despite the heavy individual patient and socioeconomic burden of metabolic dysfunction-associated steatohepatitis (MASH), until recently, no pharmacological therapy for MASH was approved, with available treatment options geared towards associated cardiometabolic risk factors. Accelerated approval resmetirom, a thyroid hormone receptor-β agonist to be used in conjunction diet exercise, marks significant step forward MASH, offering tempered optimism healthcare providers millions patients around world more effective management. Evidence from phase 2 3 clinical trials suggests that resmetirom has potential alleviate hepatic fibrosis inflammation significantly reduce liver lipid content. Notwithstanding this landmark event, implementation comes important challenges, example, ensuring access demonstrating effects on hard MASH-related outcomes, such as progression cirrhosis hepatocellular carcinoma. Additional considerations include evaluation co-administration other hepatoprotective treatments assessment efficacy specific sub-phenotypes. Furthermore, accumulation real-world data experience is expected help answer remaining questions about (long-term) effectiveness safety profile drug. The purpose article provide an updated critical review mechanisms action, efficacy, based latest trials, define its place within broader landscape management, highlight current knowledge gaps opportunities future research field.

Язык: Английский

Процитировано

0
Underrepresentation of Asians in diagnostic test development and drug trials in MASLD DOI
Lung‐Yi Mak, Terry Cheuk‐Fung Yip, Chi‐Ho Lee

и другие.

Journal of Hepatology, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0
Resmetirom: the first approved therapy for treating metabolic dysfunction associated steatohepatitis DOI
Sheena Bhushan, Aalam Sohal,

Mazen Noureddin

и другие.

Expert Opinion on Pharmacotherapy, Год журнала: 2025, Номер unknown

Опубликована: Март 18, 2025

Metabolic dysfunction associated steatohepatitis (MASH), previously referred to as nonalcoholic (NASH), has emerged one of the leading indications for liver transplantation in United States. The disease is with increased cardiovascular mortality patients early-stage fibrosis and a heightened risk hepatic complications those advanced fibrosis. Despite its growing prevalence significant healthcare burden, there were no approved drugs treat this chronic disease. In March 2024, Resmetirom, selective thyroid hormone receptor-beta agonist, became first drug receive FDA approval treatment MASH stages F2/F3. This accelerated was granted based on significantly higher rates resolution review summarizes current literature mechanism action, preclinical data, pharmacokinetics, clinical efficacy, indications, contraindications resmetirom management MASH. moderate major advance recent positive results ESSENCE trial semaglutide, if conditional approval, may offer clinicians two options

Язык: Английский

Процитировано

0
Clinical Insights on Resmetirom DOI
Eda Kaya, Yusuf Yılmaz,

Naim Alkhouri

и другие.

Journal of Clinical Gastroenterology, Год журнала: 2025, Номер 59(5), С. 412 - 419

Опубликована: Фев. 13, 2025

The recent conditional approval by the Food and Drug Administration of resmetirom for treating metabolic dysfunction-associated steatohepatitis (MASH) with significant or advanced fibrosis represents a pivotal milestone in history steatotic liver disease (MASLD) treatment. As first liver-directed pharmacological therapy option MASLD, offers novel approach that specifically targets pathology, marking transformative step forward managing this widespread challenging condition. For initiating resmetirom, biopsy is not required. Consequently, accurately excluding patients less severe histology cirrhosis using noninvasive tests (NITs) essential. In addition, monitoring response should be conducted NITs. Given approval, our current clinical understanding primarily informed phase 3 trials. long-term effects drug evaluated further studies encouraging use eligible patients. This review highlights key aspects use, including identifying target population, therapeutic response, determining appropriate discontinuation criteria, strategies to prevent unnecessary treatment interruptions.

Язык: Английский

Процитировано

0
Effect of high-intensity interval training on clinical parameters in patients with metabolic dysfunction–associated steatotic liver disease: a systematic review and meta-analysis of randomized controlled trials DOI
Jie Fu, Chunlan Liu, Luping Yang

и другие.

European Journal of Gastroenterology & Hepatology, Год журнала: 2025, Номер unknown

Опубликована: Март 7, 2025

High-intensity interval training (HIIT) has potential health benefits in the treatment of many chronic diseases. However, efficacy HIIT patients with metabolic dysfunction–associated steatotic liver disease (MASLD) remains unclear. This systematic review and meta-analysis aimed to assess impact on intrahepatic lipids (IHLs) , enzymes, profiles individuals MASLD. All randomized-controlled trials (RCT) that evaluated compared effects clinical parameters MASLD were searched using PubMed, EMBASE, WOS, Cochrane databases. Data analysis integration performed RevMan 5.3 (Cochrane Collaboration, Copenhagen, Denmark) Stata version 18 software (StataCorp LLC, College Station, Texas, USA), outcomes assessed standardized mean difference (SMD). Our results showed other types exercise or no exercise, could reduce levels IHL [SMD: −0.56%, 95% confidence (CI): −0.99 −0.13, P = 0.01], BMI (SMD: −0.31, CI: −0.62 −0.01, 0.04), alanine aminotransferase (ALT) −0.61, −0.95 −0.26, 0.0006), aspartate aminotransaminase (AST) −0.43, −0.81 −0.05, 0.03) In addition, subgroup analyses had a positive indicators an intervention duration less than equal 8 weeks. study supports idea can significantly IHL, BMI, ALT, AST levels, further studies are needed long-term adherence HIIT.

Язык: Английский

Процитировано

0
A New Classification System for Fatty Liver—What Sonographers Should Know DOI Creative Commons

Elspeth L. Keys,

Katie L. McMahon, Elizabeth E. Powell

и другие.

Sonography, Год журнала: 2025, Номер unknown

Опубликована: Апрель 23, 2025

ABSTRACT Hepatic steatosis or fatty liver disease is a rapidly emerging health issue and closely linked to an increase in cardiometabolic conditions such as obesity type 2 diabetes. The nomenclature surrounding has recently undergone multiple reviews better reflect its underlying causes. This article recent guidelines changes will explore the various ultrasound technologies that are available for fat quantification, emphasising ultrasound's importance diagnosing monitoring steatosis. Sonographers must remain informed of classification criteria they directly impact their role detecting assessing

Язык: Английский

Процитировано

0
NAFLD No More: A Review of Current Guidelines in the Diagnosis and Evaluation of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) DOI
Kerim B. Kaylan, Sonali Paul

Current Diabetes Reports, Год журнала: 2024, Номер 25(1)

Опубликована: Ноя. 13, 2024

Язык: Английский

Процитировано

3
Hepatic thyroid hormone receptor‐β signalling: Mechanisms and recent advancements in the treatment of metabolic dysfunction‐associated steatohepatitis DOI
Stergios A. Pοlyzos, Giovanni Targher

Diabetes Obesity and Metabolism, Год журнала: 2024, Номер unknown

Опубликована: Дек. 10, 2024

The pharmacotherapy of metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form, the steatohepatitis (MASH), remains a hot topic in research largely unmet need clinical practice. As first approval disease-specific drug, resmetirom, was regarded as milestone for management this common disease, comprehensive updated review aimed to highlight importance hepatic thyroid hormone (TH) receptor (THR)-β signalling treatment MASH, with special focus on resmetirom. First, genomic non-genomic actions liver-directed THR-β mediated mechanisms are summarized. has key role lipid carbohydrate metabolism; disruption leads dysmetabolism, thus promoting MASLD possibly progression MASH cirrhosis. In setting, is translated into significant association between primary hypothyroidism MASLD, confirmed by recent meta-analyses. An subclinical intrahepatic (i.e. state relatively low triiodothyronine concentrations, circulating TH concentrations within normal range) also emerging under investigation. line this, favourable results phase 3 placebo-controlled MAESTRO trials led conditional resmetirom US FDA treating adults moderate-to-advanced fibrosis. This opened new window burdensome bringing global scientific community front perspectives challenges.

Язык: Английский

Процитировано

2
Effectiveness of Resmetirom in Reducing Cholesterol Levels in Patients With Nonalcoholic Steatohepatitis: A Systematic Review and Meta-Analysis DOI Open Access

Estifanos Bejitual,

Muhammad Awais, Dhruvi Modi

и другие.

Cureus, Год журнала: 2024, Номер unknown

Опубликована: Окт. 4, 2024

Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease (NAFLD) associated with metabolic syndrome and increased cardiovascular risk. Resmetirom, novel liver-directed selective thyroid hormone receptor-β (THR-β) agonist, has shown promise in addressing both hepatic systemic lipid metabolism. This systematic review meta-analysis aimed to evaluate the efficacy resmetirom improving cholesterol levels NASH patients. A literature search was conducted across multiple databases including PubMed, Embase, Cochrane Library, ClinicalTrials.gov, identifying three randomized controlled trials for inclusion. The revealed that significantly reduced low-density lipoprotein (LDL-C) compared placebo (MD: -23.62; 95% CI: -37.32 -9.93; p < 0.001). Similarly, triglyceride (TG) showed significant reduction group -33.86; -47.79 -19.92; Importantly, there no difference risk serious adverse events between groups (RR: 1.09; 0.73 1.63; = 0.67). These findings suggest effectively improves profiles patients without compromising safety. However, analysis limited by small number studies, all from same research group, high heterogeneity results. Future should include more diverse longer follow-up periods, cost-effectiveness evaluations. Despite these limitations, shows as potential treatment managing dyslipidemia patients, potentially influencing future guidelines health this population.

Язык: Английский

Процитировано

1
Identification of Candidates for MASLD Treatment with Indeterminate Vibration-Controlled Transient Elastography DOI Creative Commons
David Martí‐Aguado, José Miguel Carot Sierra,

Aida Villalba-Ortiz

и другие.

Clinical Gastroenterology and Hepatology, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 1, 2024

A noteworthy proportion of patients with metabolic dysfunction-associated steatotic liver disease (MASLD) have an indeterminate vibration-controlled transient elastography (VCTE). Among these patients, we aimed to identify candidates for MASLD treatment by diagnosing significant fibrosis.

Язык: Английский

Процитировано

1