The first MASH drug therapy on the horizon: Current perspectives of resmetirom

Liver International, Journal Year: 2024, Volume and Issue: 44(7), P. 1526 - 1536

Published: April 5, 2024

Abstract The rising prevalence of metabolic dysfunction‐associated steatotic liver disease (MASLD) poses a significant global health challenge, affecting over 30% adults worldwide. MASLD is linked to increased mortality rates and substantial healthcare costs, primarily driven by its progression steatohepatitis (MASH), which can lead severe complications including cirrhosis hepatocellular carcinoma. Despite growing burden, effective pharmacotherapy for MASLD/MASH has been lacking until the recent conditional approval resmetirom FDA. Resmetirom, liver‐targeted thyroid hormone receptor‐β selective drug, shown promise in clinical trials treating non‐cirrhotic MASH with moderate advanced fibrosis. It demonstrated efficacy reducing hepatic fat content, improving histology (both resolution fibrosis improvement), ameliorating biomarkers damage without effects on body weight or glucose metabolism. Notably, also exhibits favourable circulating lipids, potentially cardiovascular risk patients. safety profile appears acceptable, gastrointestinal adverse events being most common, though generally mild moderate. However, long‐term surveillance warranted monitor potential risks related thyroid, gonadal, bone diseases. Clinical implementation faces challenges patient selection monitoring treatment response, will heavily rely non‐invasive tests assessment. Nonetheless, represents landmark breakthrough treatment, paving way future therapeutic strategies aiming mitigate multifaceted associated this complex disease.

Language: Английский

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Epidemiology of Metabolic Dysfunction Associated Steatotic Liver Disease

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

Published: Aug. 19, 2024

As the rates of obesity and type 2 diabetes (T2D) continue to increase globally, so does prevalence metabolic dysfunction associated steatotic liver disease (MASLD). Currently, 38% all adults 7-14% children adolescents have MASLD. By 2040, MASLD rate for is projected over 55%. Although many with will not develop progressive disease, given vast number patients MASLD, it has now become top indication transplant in United States those hepatocellular carcinoma (HCC) women. However, most common cause mortality among remains death cardiovascular diseases. In addition outcomes (cirrhosis HCC), increased risk developing de-novo T2D, chronic kidney sarcopenia extrahepatic cancers. Furthermore, decreased health related quality life, work productivity, fatigue healthcare resource utilization substantial economic burden. Similar other lifestyle interventions heathy diet physical activity remain cornerstone managing these patients. a T2D drugs are available treat co-morbid Resmetirom only MASH-targeted medication that was recently approved by Federal Drug Administration use stage 2-3 fibrosis. The following review provides an overview epidemiology, its factors demonstrates without further global initiatives, may increase.

Language: Английский

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Systemic impacts of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) on heart, muscle, and kidney related diseases

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: July 16, 2024

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty (NAFLD), is the most common disorder worldwide, with an estimated global prevalence of more than 31%. steatohepatitis (MASH), formerly (NASH), a progressive form MASLD characterized by hepatic steatosis, inflammation, and fibrosis. This review aims to provide comprehensive analysis extrahepatic manifestations MASH, focusing on chronic diseases related cardiovascular, muscular, renal systems. A systematic published studies literature was conducted summarize findings systemic impacts MASH. The focused association MASH metabolic comorbidities, cardiovascular mortality, sarcopenia, kidney disease. Mechanistic insights into concept lipotoxic inflammatory "spill over" from MASH-affected were also explored. are highly associated (50%-80%) other comorbidities such impaired insulin response, type 2 diabetes, dyslipidemia, hypertriglyceridemia, hypertension. Furthermore, 90% obese patients diabetes have Data suggest that in middle-aged individuals (especially those aged 45-54), independent risk factor for plays crucial role mediating pathological effects observed. Understanding multifaceted impact heart, muscle, early detection stratification. knowledge timely implementing management strategies addressing multi-organ involvement pathogenesis.

Language: Английский

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Economic evaluation of non-invasive test pathways for high-risk metabolic dysfunction-associated steatotic liver disease (MASLD) in the United Kingdom (UK)

Annals of Hepatology, Journal Year: 2025, Volume and Issue: unknown, P. 101789 - 101789

Published: Feb. 1, 2025

Non-invasive tests (NITs) identifying high-risk MASLD in primary care is suggested but, these strategies cost-effectiveness remain uncertain the United Kingdom (UK). A cost-utility/budget impact model was developed for evaluation of two screening (1) FIB-4 followed by Enhanced Liver Fibrosis (ELF) (FIB-4/ELF); (2) Transient Elastography (FIB-4/TE) compared to standard (SoC). cohort patients with an advanced fibrosis prevalence 4.20% simulated. decision tree classified as true positives, false negatives, or negatives based on NIT diagnostic accuracy, a 3-year Markov estimate costs and quality-adjusted life years (QALYs). The included 11 health states: MASLD, stages (F0-F3), cirrhosis, decompensated liver transplant, death. Costs came from National Tariff, Schedule Personal Social Services Research Unit. SoC had diagnosis rate 36.26%, while ELF TE reduced positive rates 23.20% 20.91%, respectively. Compared 112,807 unnecessary hepatology referrals under SoC, FIB-4/ELF FIB-4/TE 38,031 (33.71%) 45,767 (40.57%), Both demonstrated relative total cost per patient GBP 983.37 FIB-4/TE, 993.15 1,014.15. Sequential strategies, combining TE, are cost-saving, reduce referrals, offer efficient (improve outcomes healthcare costs) approach managing UK care.

Language: Английский

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Global Epidemiological Impact of PNPLA3 I148M on Liver Disease

Liver International, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 7, 2024

ABSTRACT The prevalence of metabolic dysfunction‐associated steatotic liver disease (MASLD) has increased exponentially over the past three decades, in parallel with global rise obesity and type 2 diabetes. It is currently most common cause liver‐related morbidity mortality. Although been identified as a key factor MASLD, individual differences susceptibility are significantly influenced by genetic factors. PNPLA3 I148M (rs738409 C>G) variant greatest impact on risk developing progressive MASLD likely other forms disease. This prevalent across globe, allele (G) frequency exhibiting considerable variation. Here, we review contribution to burden regional prevalence, focusing recent evidence emerging from population‐based sequencing studies assessments. We calculated population attributable fraction (PAF) means quantifying MASLD. Furthermore, employ quantitative trait locus (QTL) analysis ascertain associations between rs738409 range phenotypic traits. suggests that these QTLs may underpin pleiotropic effects extrahepatic Finally, outline potential avenues for further research identify areas investigation future studies.

Language: Английский

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A Precision Medicine Guided Approach to the Utilization of Biomarkers in MASLD

Seminars in Liver Disease, Journal Year: 2024, Volume and Issue: 44(03), P. 273 - 286

Published: July 11, 2024

The new nomenclature of metabolic dysfunction-associated steatotic liver disease (MASLD) emphasizes a positive diagnosis based on cardiometabolic risk factors. This definition is not only less stigmatizing but also allows for subclassification and stratification, thereby addressing the heterogeneity what was historically referred to as nonalcoholic fatty disease. within this spectrum influenced by several factors which include are limited demographic/dietary factors, amount alcohol use drinking patterns, status, gut microbiome, genetic predisposition together with epigenetic net effect dynamic intricate system-level interaction reflected in phenotypic presentation MASLD. Therefore, application precision medicine scenario aims at complex phenotyping consequent individual prediction, development individualized preventive strategies, improvements clinical trial designs. In review, we aim highlight importance approaches MASLD, including novel biomarkers disease, its subsequent utilization future study

Language: Английский

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Establishing of a risk prediction model for metabolic dysfunction-associated steatotic liver disease: a retrospective cohort study

BMC Gastroenterology, Journal Year: 2025, Volume and Issue: 25(1)

Published: Jan. 28, 2025

Over 30% of people worldwide suffer from metabolic dysfunction-associated steatotic liver disease (MASLD), a significant global health issue. Identifying and preventing high-risk individuals for MASLD early is crucial. The purpose our study to investigate the factors related development develop risk prediction model its occurrence. included 5107 subjects, divided into training validation groups in 7:3 ratio using random number table method. Collinearity diagnosis Cox regression were used identify associated with incidence, was created. model's accuracy, reliability, clinical applicability assessed. Our indicated that male, body mass index (BMI), low-density lipoprotein cholesterol (LDL-C), high-density (HDL-C), fasting plasma glucose (FPG), serum uric acid creatinine (SUA/Cr) white blood cell (WBC) incidence. elements determined be crucial creating model. showed strong discriminative potential C-index 0.783 time-dependent AUCs 0.781, 0.789, 0.814 0.796 1–4 years group, 0.788 0.798, 0.782, 0.787 0.825 validation. Calibration curves confirmed decision curve analysis (DCA) validated utility. may provide physicians reliable method identifying populations serve as guide developing models other diseases.

Language: Английский

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Burden of five major types of gastrointestinal cancer in the Eastern Mediterranean Region

BMJ Open Gastroenterology, Journal Year: 2025, Volume and Issue: 12(1), P. e001577 - e001577

Published: Feb. 1, 2025

Objective We provide an overview of the latest estimates five gastrointestinal (GI) cancers in Eastern Mediterranean Region (EMR) countries to guide cancer control policy. Methods extracted number cases and deaths for oesophageal, gastric, liver, colorectal pancreatic from GLOBOCAN database produced as estimated by International Agency Research on Cancer year 2022. Age-standardised incidence mortality rates (ASR) per 100 000 person-years were 22 EMR countries, site sex. Results The 173 new 139 GI corresponded 22.2% 28.7% burden EMR. Across all (for both sexes combined), ranked third (6.9%; ASR 8.9), followed liver (6.2%; 8.4) terms incidence, while (9.6%; 8.1) gastric (6.4%; 5.5) fourth leading causes cancer-related region, respectively. Marked differences observed between particularly 10-fold variations seen incidence. Conclusion currently account important fraction EMR; present analysis seeks inform tailored decision-making according country-specific profiles.

Language: Английский

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Artificial Intelligence‐Based Diets: A Role in the Nutritional Treatment of Metabolic Dysfunction‐Associated Steatotic Liver Disease?

Journal of Human Nutrition and Dietetics, Journal Year: 2025, Volume and Issue: 38(2)

Published: Feb. 27, 2025

ABSTRACT Background Metabolic dysfunction‐associated steatotic liver disease (MASLD) is a growing global health concern. Effective management of this condition relies heavily on lifestyle modifications and dietary interventions. In study, we sought to evaluate the plans for MASLD generated by ChatGPT (GPT‐4o) according current guideline recommendations. Methods was used create single‐day meal 48 simulated patients with MASLD, tailored individual characteristics such as age, gender, height, weight transient elastography parameters. The were assessed appropriateness disease‐specific guidelines. Results mean energy content menus planned 1596.9 ± 141.5 kcal accuracy 91.3 11.0%, fibre 22.0 0.6 g 88.1 2.5%. However, they exhibited elevated levels protein, fat saturated acids. Conversely, carbohydrate lower. recommended loss obese but did not extend advice normal‐weight overweight individuals. Notably, recommendations Mediterranean diet physical activity absent. Conclusions shows potential in developing management. discrepancies macronutrient distributions omission key evidence‐based highlight need further refinement. To enhance effectiveness AI tools recommendations, alignment established guidelines must be improved.

Language: Английский

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A bibliometric analysis of a decade’s research on metabolic dysfunction-associated steatotic liver disease in the Arab world

Saudi Journal of Gastroenterology, Journal Year: 2025, Volume and Issue: unknown

Published: March 3, 2025

Abstract Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) presents a significant global health challenge, with the Arab region exhibiting markedly higher prevalence. We aim to evaluate MASLD research output, collaboration patterns, and funding impact in over last decade. Methods: conducted bibliometric analysis of 22 countries (2014–2023) using Clarivate Analytics’ InCites. Data on prevalence were extracted from Global Burden Disease, while population economic data World Bank. assessed MASLD-related publications, prevalence, citation impact. Results: Between 2014 2023, contributed 844 publications (3.3% research). identified positive correlations between gross domestic product (GDP) ( r s = 0.825, P < 0.001), age-standardized 0.627, 0.002), size 0.509, 0.016). International collaborations accounted for 48.7% these 15.7 compared average 23.7. Arab-funded constituted 19.4% world versus 42.3% globally funded. Citation impacts similar (30.6) funded (30.3). Of top 10 highest GDP, 47.8% received funding, yielding 33.5. Conclusion: Despite high exhibit lower impact, levels. Increased regional investment are critical addressing this disparity.

Language: Английский

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