Resmetirom, the first approved drug for the management of metabolic dysfunction-associated steatohepatitis: Trials, opportunities, and challenges

Metabolism, Journal Year: 2024, Volume and Issue: 154, P. 155835 - 155835

Published: March 19, 2024

Language: Английский

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Steatotic Liver Disease: Pathophysiology and Emerging Pharmacotherapies

Pharmacological Reviews, Journal Year: 2024, Volume and Issue: 76(3), P. 454 - 499

Published: Jan. 30, 2024

Steatotic liver disease (SLD) displays a dynamic and complex phenotype. Consequently, the metabolic dysfunction-associated steatotic (MASLD)/metabolic steatohepatitis (MASH) therapeutic pipeline is expanding rapidly in multiple directions. In parallel, non-invasive tools for diagnosing monitoring responses to interventions are being studied, clinically feasible findings explored as primary outcomes interventional trials. The realization that distinct subgroups exist under umbrella of SLD should guide more precise personalized treatment recommendations facilitate advancements pharmacotherapeutics. This review summarizes recent updates pathophysiology-based nomenclature outlines both effective pharmacotherapeutics those MASLD/MASH, detailing their mode action current status phase 2 3 clinical Of extensive arsenal MASLD/MASH pipeline, several have been rejected, whereas other, mainly monotherapy options, shown only marginal benefits now tested part combination therapies, yet others still development monotherapies. Although successful drug candidate (or combinations) remains elusive, such approaches will ideally target MASH fibrosis while improving cardiometabolic risk factors. Due urgent need novel strategies potential availability safety tolerability data, repurposing existing approved drugs an appealing option. Finally, it essential highlight and, by extension, MASLD be recognized approached systemic affecting organs, with vigorous implementation interdisciplinary coordinated plans. Significance Statement SLD, including, among others, MASH, considered most prevalent chronic condition than one-fourth global population. aims provide information regarding pathophysiology, diagnosis, management line guidelines Collectively, hoped provided furthers understanding state direct implications stimulates additional research initiatives.

Language: Английский

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MAFLD: Exploring the Systemic Effects Beyond Liver.

Journal of Community Hospital Internal Medicine Perspectives, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 4, 2025

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a growing global health concern which driven by the increasing prevalence of diabetes and obesity. MAFLD characterized excessive fat accumulation in liver, encompasses range conditions, from simple hepatic steatosis to more severe forms. This condition associated with various complications, including chronic kidney (CKD), Cardiovascular Disease (CVD), cirrhosis, even malignancy. Recent research has highlighted potential connection between gut dysbiosis MAFLD, particularly relation CKD. underscored significance gut-liver-kidney axis understanding MAFLD's pathogenesis. Inflammation triggered increases risk CVD through multiple mechanisms linked metabolic dysfunction. These include heightened oxidative stress, systemic insulin resistance, low-grade inflammation, endothelial Hepatic dysfunction are major diagnostic criteria for often coexisting other ailments. prospective review emphasizes intricate associations cardiovascular renal issues, diseases. Understanding underlying pathophysiological pathways crucial comprehending increased CKD, CVD, complications individuals MAFLD.

Language: Английский

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Prediction of MASLD using different screening indexes in Chinese type 2 diabetes mellitus

Diabetology & Metabolic Syndrome, Journal Year: 2025, Volume and Issue: 17(1)

Published: Jan. 9, 2025

Formerly known as non-alcoholic fatty liver disease (NAFLD), metabolic dysfunction-associated steatotic (MASLD) has now become the most widespread chronic worldwide. The primary goal of this study is to assess ability different indexes (including VAI, TyG, HOMA-IR, BMI, LAP, WHtR, TyG-BMI, TyG-WC, and TyG-WHtR) predict MASLD in individuals diagnosed with type 2 diabetes mellitus (T2DM), particularly within Chinese population. This cross-sectional involved 1,742 patients T2DM, recruited from Metabolic Management Centers (MMC) at Suzhou Municipal Hospital. Abdominal ultrasonography was employed for diagnosis T2DM. predictive accuracy various screening T2DM population evaluated using logistic regression receiver operating characteristic (ROC) curve analyses. Among participants, 996 were MASLD. After adjusting potential confounding factors, positive associations risk found all nine indexes. lipid accumulation product (LAP) exhibited greatest value detecting MASLD, an area under (AUC) 0.786(95%CI 0.764,0.807), followed by BMI(AUC = 0.785), VAI(AUC 0.744), TyG(AUC 0.720), WHtR(AUC 0.710) HOMA-IR(AUC 0.676). composite Indexes (TyG-BMI, also showed considerable AUCs 0.765, 0.752 0.748, respectively. Our results indicated that have favorable correlations them a good performance predicting According our study, LAP reliable index among patients. exploration non-invasive screenings will provide significant support early detection

Language: Английский

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Metabolic dysfunction-associated steatotic liver disease: Evolution of the final terminology

European Journal of Internal Medicine, Journal Year: 2024, Volume and Issue: 124, P. 35 - 39

Published: April 22, 2024

The medical term nonalcoholic fatty liver disease (NAFLD) was coined in 1986 for a condition that has since become the most prevalent disorder worldwide. In last 3 years, global professional community launched 2 consecutive efforts to purge NAFLD from dictionary and recommended new terms based on pathophysiology rather than distinction similar conditions featuring steatosis. A consensus by renowned clinical scholars primarily residing Asian-Pacific region introduced metabolic dysfunction-associated (MAFLD) as name replace 2020. 2023, nomenclature classification resulting steatotic (MASLD) developed large expert panel under auspices of leading societies Europe Americas. These marked rapid shifts have garnered attention many researchers clinicians across globe due multilevel impact frequent potentially progressive chronic both adult pediatric populations. proposed terminologies differ several ways but they more common differences. They capture key features associated with cardiometabolic risk factors significant all-cause liver-related mortality. framework MASLD incorporated innovative aspects MAFLD while conceptual disparities remain work progress, should focus insights into pathogenesis, outcome trajectories, prevention, treatment. Here, some these challenges are discussed facilitate this process.

Language: Английский

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Metabolic dysfunction-associated steatotic liver disease: Recent turning points for its diagnosis and management

Metabolism, Journal Year: 2024, Volume and Issue: 157, P. 155936 - 155936

Published: May 17, 2024

Language: Английский

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New Nomenclature for Nonalcoholic Fatty Liver Disease: Understanding Metabolic Dysfunction-Associated Steatotic Liver Disease, Metabolic Dysfunction- and Alcohol-Associated Liver Disease, and Their Implications in Clinical Practice

Seminars in Liver Disease, Journal Year: 2024, Volume and Issue: 44(01), P. 035 - 042

Published: Feb. 1, 2024

In June 2023, under the patronage of American Association for Study Liver Disease, European Liver, and Asociación Latinoamericana para el Estudio del Hígado with involvement 236 participants from around world, a new nomenclature definition nonalcoholic fatty liver disease (NAFLD) has been proposed. Metabolic dysfunction-associated steatotic (MASLD) was defined as presence hepatic steatosis at least one cardiometabolic risk factors alcohol intake less than 140 g/wk women 210 men no other causes steatosis. A entity called combined metabolic dysfunction- alcohol-associated (MetALD) created outside pure MASLD patients dysfunction greater that allowed (i.e., 140–350 210–420 men). Recent studies have confirmed 95% overlap between NAFLD diagnostic criteria. Natural history, biomarkers, thresholds in MetALD group remains to be studied validated.

Language: Английский

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Emerging Pharmacotherapies for Obesity: A Systematic Review

Pharmacological Reviews, Journal Year: 2024, Volume and Issue: 77(1), P. 100002 - 100002

Published: Sept. 20, 2024

The history of anti-obesity pharmacotherapies is marked by disappointments, often entangled with societal pressure promoting weight loss and the conviction that excess body signifies a lack willpower. However, categories emerging generate hope to reduce obesity rates. This systematic review phase 2 3 trials in adults overweight/obesity investigates effect novel pharmacotherapies, compared placebo/control or Food Drug Administration-approved medication, through searching Medline, Embase, ClinicalTrials.gov (2012-2024). We identified 53 trials, 36 drugs combinations thereof four withdrawn terminated trials. Oral semaglutide 50 mg only medication has completed trial. There are 14 ongoing on glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) (ecnoglutide, orforglipron, TG103), GLP-1 RA/amylin agonist (CagriSema), GLP-1/glucagon RAs (mazdutide, survodutide), GLP-1/glucose-dependent insulinotropic polypeptide glucagon RA (retatrutide), dapagliflozin, combination sibutramine/topiramate. Completed incretin-based therapies showed mean percent 7.4-24.2%. Almost half undergoing were incretin analogs. drug pipeline expanding rapidly, most promising results reported Data mortality obesity-related complications, such as cardio-renal-metabolic events, needed. Moreover, long-term follow-up data safety efficacy maintenance along studies focused under-represented populations, cost-effectiveness assessments, availability, needed bridge care gap for patients obesity. Significance Statement Obesity epidemic 21st century. Except newer injectable medications, suboptimal have been available clinician's armamentarium. alternatives agents populate therapeutic pipeline. identifies state mechanism action having clinical information provided herein furthers understanding management, implying direct implications stimulating research initiatives.

Language: Английский

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The association of metabolic dysfunction-associated steatotic liver disease (MASLD) with the risk of myocardial infarction: a systematic review and meta-analysis

Annals of Medicine, Journal Year: 2024, Volume and Issue: 56(1)

Published: Jan. 22, 2024

Objective While studies have documented how metabolic dysfunction-associated steatotic liver disease (MASLD) can contribute to cardiovascular (CVD), whether MASLD is associated with myocardial infarction (MI) remains debateable. Herein, we systematically reviewed published articles and performed a meta-analysis determine the relationship between MI risk.

Language: Английский

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Executive summary of the Hellenic Atherosclerosis Society guidelines for the diagnosis and treatment of dyslipidemias - 2023

Atherosclerosis Plus, Journal Year: 2024, Volume and Issue: 55, P. 74 - 92

Published: Feb. 17, 2024

Atherosclerotic cardiovascular disease (ASCVD) remains the main cause of death worldwide, and thus its prevention, early diagnosis treatment is paramount importance. Dyslipidemia represents a major ASCVD risk factor that should be adequately managed at different clinical settings. 2023 guidelines Hellenic Atherosclerosis Society focus on assessment risk, laboratory evaluation dyslipidemias, new emerging lipid-lowering drugs, as well lipid disorders in women, elderly patients with familial hypercholesterolemia, acute coronary syndromes, heart failure, stroke, chronic kidney disease, diabetes, autoimmune diseases, non-alcoholic fatty liver disease. Statin intolerance also discussed.

Language: Английский

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