Effects of Pemafibrate on Serum Carnitine and Plasma Myostatin in Patients With Metabolic Dysfunction Associated Steatotic Liver Disease DOI Creative Commons
Ryohei Tanigawa, Atsushi Nakajima, Yuichiro Eguchi

et al.

Deleted Journal, Journal Year: 2025, Volume and Issue: 8(1)

Published: Jan. 1, 2025

ABSTRACT Background Pemafibrate, a selective peroxisome proliferator‐activated receptor alpha (PPARα) modulator (SPPARMα), has positive effects on liver‐related markers (e.g., liver stiffness determined by magnetic resonance elastography and alanine aminotransferase) in the PEMA‐FL study patients with metabolic dysfunction‐associated steatotic disease (MASLD). Patients MASLD reportedly have high rate of muscle mass loss; hence, prevention treatment sarcopenia is important for MASLD. PPARα may be involved expression carnitine myostatin, which are known muscle‐related markers. We conducted post‐hoc analysis to investigate pemafibrate myostatin levels. Methods The study, double‐blind, placebo‐controlled, randomized, multicenter, Phase 2 trial, randomized 118 either Pemafibrate 0.4 mg/day or placebo (1:1) group (orally, twice daily 72 weeks). This examined percentage change total carnitine, free acylcarnitine, compared those group. correlation between changes Results Pmafibrate significantly increased serum levels from baseline at Week 48 (treatment difference 24.2%; p < 0.001, 27.3%; respectively) similar trends acylcarnitine 10.7%). reduced plasma −11.0%; 0.01) baseline. Analysis significant subgroups showed almost all subgroups. percent 12 weeks demonstrated no obvious correlations ( r = 0.337, 0.358, 0.077, respectively). Conclusions decreased MASLD, potential application development progression sarcopenia, but there results effect mass. Further research warranted determine whether these physiology can lead clinical benefits Trial Registration: ClinicalTrials.gov identifier: NCT03350165.

Language: Английский

Semaglutide 2.4 mg in Participants With Metabolic Dysfunction‐Associated Steatohepatitis: Baseline Characteristics and Design of the Phase 3 ESSENCE Trial DOI Creative Commons
Philip N. Newsome, Arun J. Sanyal, Kristiane Aasen Engebretsen

et al.

Alimentary Pharmacology & Therapeutics, Journal Year: 2024, Volume and Issue: 60(11-12), P. 1525 - 1533

Published: Oct. 16, 2024

ABSTRACT Background Semaglutide, a glucagon‐like peptide‐1 receptor agonist, has demonstrated potential beneficial effects in metabolic dysfunction‐associated steatohepatitis (MASH). Aims To describe the trial design and baseline characteristics of ‘Effect Semaglutide Subjects with Non‐cirrhotic Non‐alcoholic Steatohepatitis’ (ESSENCE) (NCT04822181). Methods ESSENCE is two‐part, phase 3, randomised, multicentre evaluating effect subcutaneous semaglutide 2.4 mg participants biopsy‐proven MASH fibrosis stage 2 or 3. The primary objective Part 1 to demonstrate that improves liver histology compared placebo. two endpoints are: resolution no worsening fibrosis, improvement steatohepatitis. based on clinical outcomes. current work reports first 800 randomised which includes demographics, laboratory parameters, histology, non‐invasive tests presence steatotic disease (MASLD) cardiometabolic criteria. Results Of participants, 250 (31.3%) had 550 (68.8%) In overall population, mean (standard deviation [SD]) age was 56 (11.6) years, 57.1% were female, (SD) body mass index 34.6 (7.2) kg/m , 55.5% type diabetes > 99% at least one MASLD criterion according published definition. Conclusion population clinically significant stages Although criteria not requirement for study enrolment, almost all (> 99%) criterion. Trial Registration NCT04822181

Language: Английский

Citations

26
Integrated Management of Cardiovascular–Renal–Hepatic–Metabolic Syndrome: Expanding Roles of SGLT2is, GLP-1RAs, and GIP/GLP-1-RAs DOI Creative Commons
Nikolaos Theodorakis, Maria Nikolaou

Biomedicines, Journal Year: 2025, Volume and Issue: 13(1), P. 135 - 135

Published: Jan. 8, 2025

Cardiovascular-Kidney-Metabolic syndrome, introduced by the American Heart Association in 2023, represents a complex and interconnected spectrum of diseases driven shared pathophysiological mechanisms. However, this framework notably excludes liver-an organ fundamental to metabolic regulation. Building on concept, Cardiovascular-Renal-Hepatic-Metabolic (CRHM) syndrome incorporates liver's pivotal role disease spectrum, particularly through its involvement via dysfunction-associated steatotic liver (MASLD). Despite increasing prevalence CRHM unified management strategies remain insufficiently explored. This review addresses following critical question: How can novel anti-diabetic agents, including sodium-glucose cotransporter-2 inhibitors (SGLT2is), glucagon-like peptide-1 receptor agonists (GLP-1RAs), dual gastric inhibitory polypeptide (GIP)/GLP-1RA, offer an integrated approach managing beyond boundaries traditional specialties? By synthesizing evidence from landmark clinical trials, we highlight paradigm-shifting potential these therapies. SGLT2is, such as dapagliflozin empagliflozin, have emerged cornerstone guideline-directed treatments for heart failure (HF) chronic kidney (CKD), providing benefits that extend glycemic control are independent diabetes status. GLP-1RAs, e.g., semaglutide, transformed obesity enabling weight reductions exceeding 15% improving outcomes atherosclerotic cardiovascular (ASCVD), diabetic CKD, HF, MASLD. Additionally, tirzepatide, GIP/GLP-1RA, enables unprecedented loss (>20%), reduces risk over 90%, improves HF with preserved ejection fraction (HFpEF), MASLD, obstructive sleep apnea. moving organ-specific approach, propose integrates agents into holistic syndrome. paradigm shift moves away fragmented, organ-centric toward more fostering collaboration across specialties marking progress precision cardiometabolic medicine.

Language: Английский

Citations

10
From Cardiovascular-Kidney-Metabolic Syndrome to Cardiovascular-Renal-Hepatic-Metabolic Syndrome: Proposing an Expanded Framework DOI Creative Commons
Nikolaos Theodorakis, Maria Nikolaou

Biomolecules, Journal Year: 2025, Volume and Issue: 15(2), P. 213 - 213

Published: Feb. 2, 2025

Cardiometabolic diseases represent an escalating global health crisis, slowing or even reversing earlier declines in cardiovascular disease (CVD) mortality. Traditionally, conditions such as obesity, type 2 diabetes mellitus (T2DM), atherosclerotic CVD, heart failure (HF), chronic kidney (CKD), and metabolic dysfunction-associated steatotic liver (MASLD) were managed isolation. However, emerging evidence reveals that these disorders share overlapping pathophysiological mechanisms treatment strategies. In 2023, the American Heart Association proposed Cardiovascular-Kidney-Metabolic (CKM) syndrome, recognizing interconnected roles of heart, kidneys, system. Yet, this model omits liver—a critical organ impacted by dysfunction. MASLD, which can progress to steatohepatitis (MASH), is closely tied insulin resistance contributing directly renal impairment. Notably, MASLD bidirectionally associated with development progression CKM syndrome. As a result, we introduce expanded framework—the Cardiovascular-Renal-Hepatic-Metabolic (CRHM) syndrome—to more comprehensively capture broader inter-organ dynamics. We provide guidance for integrated diagnostic approach aimed at halting advanced stages preventing further damage. addition, highlight advances medical management target shared pathways, offering benefits across multiple systems. Viewing whole, rather than discrete entities, incorporating into framework fosters holistic strategy offers promising path addressing cardiometabolic pandemic.

Language: Английский

Citations

4
Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) in Children with Obesity: An Obesity Medicine Association (OMA) and Expert Joint Perspective 2025 DOI Creative Commons

Jennifer Panganiban,

Mohit Kehar, Samar H. Ibrahim

et al.

Obesity Pillars, Journal Year: 2025, Volume and Issue: 14, P. 100164 - 100164

Published: Feb. 1, 2025

This Obesity Medicine Association (OMA) Expert Joint Perspective examines steatotic liver disease (SLD), which is composed of metabolic dysfunction-associated (MASLD), and steatohepatitis (MASH) in children with obesity. The prevalence obesity increasing, rates have tripled since 1963 from 5 % to now 19 US affected 2018. MASLD, the most common seen children, can be a precursor development Type 2 Diabetes (T2DM) primary reason for transplant listing young adults. We must vigilant prevention treatment MASLD childhood prevent further progression. joint clinical perspective based upon scientific evidence, peer expertise. medical literature was reviewed via PubMed search appropriate articles were included this review. work formulated collaboration eight hepatologists/gastroenterologists expertise two physicians OMA. authors who are experts field, determined sentinel questions often asked by clinicians regarding They created consensus guideline on screening, diagnosis, associated children. comorbidity increasing problem that needs addressed urgently. It well known chronic continue these diseases as adults, leads reduced life expectancy, quality life, healthcare financial burden. paper recommend healthy weight reduction not only through lifestyle modification but pharmacotherapy bariatric surgery. Therefore, guidance reviews available therapies achieve reverse progressive fibrosis, disease.

Language: Английский

Citations

2
Lipid Metabolism in MASLD and MASH: from mechanism to the clinic DOI Creative Commons
Fabrizia Carli, Giuseppe Della Pepa, Silvia Sabatini

et al.

JHEP Reports, Journal Year: 2024, Volume and Issue: 6(12), P. 101185 - 101185

Published: Aug. 9, 2024

Metabolic dysfunction-associated steatotic liver disease/steatohepatitis (MASLD/MASH) is recognised as a metabolic disease characterised by excess intrahepatic lipid accumulation due to overflow and synthesis, alongside impaired oxidation and/or export of these lipids. But where do lipids come from? The main pathways related hepatic are

Language: Английский

Citations

8
Arterial stiffness as a complication of metabolic dysfunction-associated steatotic liver disease: a systematic review and meta-analysis DOI
Alexios Giannakodimos,

Evangelos Oikonomou,

Panteleimon Pantelidis

et al.

Expert Review of Gastroenterology & Hepatology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 23, 2025

Introduction The purpose of this systematic review and meta-analysis is to investigate the association metabolic dysfunction-associated steatotic liver disease (MASLD) with arterial stiffness enlighten on potential cardiometabolic co-factors.

Language: Английский

Citations

1
Mortality outcomes in individuals with MASLD versus MASLD and increased alcohol intake DOI
Majd B. Aboona, Pojsakorn Danpanichkul, Vincent Chen

et al.

Journal of Gastroenterology and Hepatology, Journal Year: 2024, Volume and Issue: 39(11), P. 2456 - 2463

Published: Aug. 22, 2024

Abstract Background and Aim Metabolic dysfunction‐associated steatotic liver disease (MASLD) has become a leading cause of chronic worldwide. A new entity termed MetALD also been described is defined as individuals with MASLD increased alcohol intake. However, the natural history compared unknown. We aimed to compare longitudinal outcomes in patients versus MetALD. Methods This study was performed using data from National Health Nutrition Examination Survey 2011 2018. (defined by United States Fatty Liver Index > 30) who met cardiometabolic criteria including body mass index (BMI) 25 (BMI 23 Asians), hypertension, diabetes mellitus, dyslipidemia, hypertriglyceridemia were included. intake (3–6 standard drinks per day males; 2–5 females). comparison overall, cardiovascular, cancer‐related, other causes mortality performed. Results total 2838 2557 included median follow‐up time 56 months. at risk cancer‐related (hazard ratio 1.32; 95% confidence interval 1.14–1.53; P < 0.01). there no significant difference mortality. Conclusions Patients higher for than MASLD. Close attention regular cancer surveillance accurate classification consumption diagnosed warranted help improve patient care outcome.

Language: Английский

Citations

8
Protective Effect of Caffeine and Chlorogenic Acids of Coffee in Liver Disease DOI Creative Commons

Daniela Di Pietrantonio,

Valeria Pace Palitti,

Angelo Cichelli

et al.

Foods, Journal Year: 2024, Volume and Issue: 13(14), P. 2280 - 2280

Published: July 20, 2024

Coffee is one of the most widely consumed beverages in world due to its unique aroma and psychostimulant effects, mainly presence caffeine. In recent years, experimental evidence has shown that moderate consumption coffee (3/4 cups per day) safe beneficial human health, revealing protective effects against numerous chronic metabolic diseases such as diabetes, cardiovascular, neurodegenerative, hepatic diseases. This review focuses on two coffee's main bioactive compounds, i.e., caffeine chlorogenic acids, their progression liver diseases, demonstrating regular correlates with a lower risk development non-alcoholic steatohepatitis, viral hepatitis, cirrhosis, hepatocellular carcinoma. particular, this analyzes acid from pharmacological point view explores molecular mechanism through which these compounds are responsible for role coffee. Both therefore, have antifibrotic stellate cells hepatocytes, induce decrease connective tissue growth factor, stimulate increased apoptosis anti-cancer promote major inhibition focal adhesion kinase, actin, protocollagen synthesis. conclusion, shows many data favor patients encouraging, but further prospective studies needed demonstrate preventive therapeutic

Language: Английский

Citations

6
Transitioning from NAFLD to MAFLD and MASLD: the toxic relationship with alcohol consumption DOI Creative Commons
Mübin Özercan, Ahmed Tawheed, Mohamed El‐Kassas

et al.

Exploration of Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 13, 2025

Alcohol is a well-known toxic etiologic factor for liver injury. Metabolic substrates of alcohol (especially acetaldehyde) have major responsibility and genetic susceptibility, alterations in microbiota immune system are important co-factors this Major injury hepatocellular lipid accumulation. Therefore the relationship between non-alcoholic alcoholic fatty diseases should been defined clearly. Recently two committees adopted new terminologies such as metabolic-associated disease (MAFLD), metabolic dysfunction-associated steatotic (MASLD), dysfunction alcohol-related (MetALD), (ALD) instead (NAFLD). These were based on effects syndrome liver. consumption was differently according to these nomenclatures. MAFLD intake (regardless amount) “dual etiology disease” Delphi consensus MASLD, MetALD, or ALD daily amount.

Language: Английский

Citations

0
A Rare Case of Hepatocellular Carcinoma Presenting as Cervical Lymph Node Metastases and Review of the Literature DOI Creative Commons
Bryce Tkachuk, Igor Stukalin, Yinong Wang

et al.

ACG Case Reports Journal, Journal Year: 2025, Volume and Issue: 12(2), P. e01620 - e01620

Published: Feb. 1, 2025

ABSTRACT Hepatocellular carcinoma (HCC) is a leading cause of cancer morbidity and mortality worldwide. Common sites metastases include the lungs, regional lymph nodes, bone, adrenal glands. Although rare, distant to cervical nodes have been reported. With better therapies for viral hepatitis, there has shift in landscape chronic liver disease development HCC with rising prevalence attributable metabolic dysfunction-associated steatotic disease. In this study, we describe case metastatic presenting as lymphadenopathy patient absence cirrhosis.

Language: Английский

Citations

0