Efficacy and safety of electroacupuncture for metabolic dysfunction-associated fatty liver disease: a study protocol for a multicentre, randomised, sham acupuncture-controlled, patient-blinded clinical trial DOI Creative Commons
Jingjie Zhao, Xinyu Zhao, Qianyi Wang

et al.

BMJ Open, Journal Year: 2024, Volume and Issue: 14(11), P. e084768 - e084768

Published: Nov. 1, 2024

Background Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most common chronic in world and carries an increased risk of liver-related events, but no approved medicine. Electroacupuncture has been used to treat non-alcoholic disease, its effect was uncertain because poor quality prior studies. We designed this trial evaluate efficacy safety electroacupuncture for MAFLD. Methods/design This a multicentre, randomised, sham acupuncture-controlled, patient-blinded clinical trial. Participants will take part total 20 weeks study, containing three phases: 4‐week run-in period, 12‐week treatment (36 sessions acupuncture) follow‐up. A 144 eligible patients diagnosed with MAFLD be randomly allocated or acupuncture groups. The primary outcome percentage relative fat reduction on MRI proton density fraction from baseline 12 weeks. Secondary outcomes include magnetic resonance elastography, metabolic biomarkers, anthropometry parameters, blinding assessment, credibility expectancy, adverse events. All who receive randomisation included intent-to-treat analysis. Discussion finding provide evidence results study published peer-reviewed journals. Trial registration number www.chictr.org.cn , ChiCTR2200060353. It registered 29 May 2022.

Language: Английский

Therapeutic Strategies for MASH: An Update on Drug Candidates Under Investigation in Late-Phase Clinical Trials DOI Creative Commons

Samuel Dinerman,

Yan Shu

International Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 5(1), P. 7 - 7

Published: Jan. 17, 2025

Metabolic dysfunction-associated steatohepatitis (MASH) is rapidly becoming a leading cause of hepatocellular carcinoma and end-stage liver transplantation. Characterized by hepatic steatosis, lobular inflammation, hepatocyte ballooning, there dire need to develop therapeutic strategies mitigate MASH alongside the subsequent fibrosis cirrhosis. For years, development for treatment had been considered graveyard, with various pharmacotherapies failing achieve clinical efficacy. However, recent Food Drug Administration (FDA) approval Madrigal Pharmaceuticals’ Resmetirom in United States provides positive step collective effort eradicate MASH. Granted, much about Resmetirom’s long-term efficacy safety still be determined multi-factorial nature pathogenesis, continuing evaluate alternative options remains best interest field. Currently, therapeutics previously approved other ailments, novel developed specifically MASH, are being evaluated late-phase trials. considering complex disease varying outcomes assess efficacy, achieving regulatory as continues rigorous endeavor. In this review, we summarize notable mechanistic backgrounds having achieved, or actively undergoing, trials offer our perspectives on anti-MASH development.

Language: Английский

Citations

0
Unlocking the potential of THR-β agonist therapies: resmetirom’s chemistry, biology, and patent insights DOI

K. K. Dahiya,

Mahesh B. Palkar,

Sanjay Sharma

et al.

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: March 11, 2025

Language: Английский

Citations

0
A Markov Model Unveiling the Impact of Resmetirom on the Natural History of MASLD Patients: A Sistematic Review and Meta‐Analysis DOI Creative Commons
Grazia Pennisi, Gabriele Di Maria, Marco Enea

et al.

Liver International, Journal Year: 2025, Volume and Issue: 45(4)

Published: March 11, 2025

ABSTRACT Background and Aim The MAESTRO‐NASH phase 3 trial reported that a 52‐week treatment of Resmetirom is effective in improving fibrosis metabolic dysfunction‐associated steatohepatitis (MASH) patients with MASH F2 or F3 fibrosis, while data on the impact 5‐year long‐term clinical outcomes are still lacking. We simulated transition probabilities disease progression MASLD effect outcomes. Methods A meta‐analysis literature formed matrices for stages complications, defined as compensated (CC) decompensated cirrhosis (DC), hepatocellular carcinoma (HCC) mortality—liver‐related mortality (LR‐M), cardiovascular (CV‐M) extra‐hepatic cancer (EHC‐M). Markov model was developed to depict stage towards complications evaluate natural history MASLD. Results estimated probability Resmetirom‐treated untreated baseline developing CC (5.16% vs. 6.82%, respectively), DC (0.25% 0.3%, HCC 0.32%, respectively) (0.15% 0.16% LR‐M; 1.02% 1.1% CV‐M; 1.07% 1.2% EHC‐M, respectively). Similarly, we five‐year (17.12% 21.34%, DC(1.1% 1.47%, (1.21% 1.73%, (0.59% 0.91% LR‐M, 1.92% 2.14% CV‐M 1.04% 1.14% Life Years Gained (LYG) were 0.45 0.63 respectively, sensitive changes efficacy probabilities. Conclusions decreases lifetime Markov‐model risk CC, DC, liver‐related fibrosis.

Language: Английский

Citations

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

Naim Alkhouri

et al.

Journal of Clinical Gastroenterology, Journal Year: 2025, Volume and Issue: 59(5), P. 412 - 419

Published: Feb. 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.

Language: Английский

Citations

0
Effects of Intermittent Fasting on Liver Steatosis and Fibrosis, Serum FGF-21 and Autophagy Markers in Metabolic Dysfunction-Associated Fatty Liver Disease: A Randomized Controlled Trial DOI Creative Commons
Tuğçe ÖZLÜ, Elvan Yılmaz Akyüz,

Demet Karadağ

et al.

Life, Journal Year: 2025, Volume and Issue: 15(5), P. 696 - 696

Published: April 25, 2025

Background: This randomized controlled study sought to determine the effect of intermittent fasting on anthropometric measurements, fibroblast growth factor (FGF)-21, and autophagy markers, as well hepatic steatosis fibrosis levels in overweight or obese patients with metabolic dysfunction-associated fatty liver disease (MAFLD). Methods: Patients were randomly assigned into two groups: received a dietary treatment involving 22–25 kcal/kg/day energy for 8 weeks followed same intervention 16:8 pattern. The extent was determined using transient elastography FibroScan® device. attenuation parameter (CAP) stiffness measurement (LSM), by elastography, reflect fibrosis, respectively. In duplicate, serum FGF-21, Beclin-1, ATG-5 enzyme-linked immunosorbent assay. Results: included 48 mean age 48.2 ± 1.4 years (27 female 21 male). Improvements CAP LSM decrease FGF-21 found both groups (p < 0.05). Changes higher + time-restricted diet group Autophagy-related protein (ATG)-5 increased only [(0.74 (0.46–1.29) ng/mL vs. 0.95 (0.73–1.32) ng/mL, p = 0.03]. Conclusions: Intermittent potentially practical management MAFLD. particular, changes indicate potential regulate processes autophagy. However, methodological limitations should be taken consideration when interpreting results.

Language: Английский

Citations

0
Targeting Metabolism: Innovative Therapies for MASLD Unveiled DOI Open Access
Weixin Wang, Xin Gao, Wei Niu

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(9), P. 4077 - 4077

Published: April 25, 2025

The recent introduction of the term metabolic-dysfunction-associated steatotic liver disease (MASLD) has highlighted critical role metabolism in disease’s pathophysiology. This innovative nomenclature signifies a shift from previous designation non-alcoholic fatty (NAFLD), emphasizing condition’s progressive nature. Simultaneously, MASLD become one most prevalent diseases worldwide, highlighting urgent need for research to elucidate its etiology and develop effective treatment strategies. review examines delineates revised definition MASLD, exploring epidemiology pathological changes occurring at various stages disease. Additionally, it identifies metabolically relevant targets within provides summary latest targeted drugs under development, including those clinical some preclinical stages. finishes with look ahead future therapy goal summarizing providing fresh ideas insights.

Language: Английский

Citations

0
Efficacy and safety of electroacupuncture for metabolic dysfunction-associated fatty liver disease: a study protocol for a multicentre, randomised, sham acupuncture-controlled, patient-blinded clinical trial DOI Creative Commons
Jingjie Zhao, Xinyu Zhao, Qianyi Wang

et al.

BMJ Open, Journal Year: 2024, Volume and Issue: 14(11), P. e084768 - e084768

Published: Nov. 1, 2024

Background Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most common chronic in world and carries an increased risk of liver-related events, but no approved medicine. Electroacupuncture has been used to treat non-alcoholic disease, its effect was uncertain because poor quality prior studies. We designed this trial evaluate efficacy safety electroacupuncture for MAFLD. Methods/design This a multicentre, randomised, sham acupuncture-controlled, patient-blinded clinical trial. Participants will take part total 20 weeks study, containing three phases: 4‐week run-in period, 12‐week treatment (36 sessions acupuncture) follow‐up. A 144 eligible patients diagnosed with MAFLD be randomly allocated or acupuncture groups. The primary outcome percentage relative fat reduction on MRI proton density fraction from baseline 12 weeks. Secondary outcomes include magnetic resonance elastography, metabolic biomarkers, anthropometry parameters, blinding assessment, credibility expectancy, adverse events. All who receive randomisation included intent-to-treat analysis. Discussion finding provide evidence results study published peer-reviewed journals. Trial registration number www.chictr.org.cn , ChiCTR2200060353. It registered 29 May 2022.

Language: Английский

Citations

1