Steatotic Liver Disease: Pathophysiology and Emerging Pharmacotherapies DOI Open Access
Michail Kokkorakis, Emir Muzurović, Špela Volčanšek

и другие.

Pharmacological Reviews, Год журнала: 2024, Номер 76(3), С. 454 - 499

Опубликована: Янв. 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.

Язык: Английский

Aging and aging-related diseases: from molecular mechanisms to interventions and treatments DOI Creative Commons
Jun Guo, Xiuqing Huang, Lin Dou

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)

Опубликована: Дек. 16, 2022

Aging is a gradual and irreversible pathophysiological process. It presents with declines in tissue cell functions significant increases the risks of various aging-related diseases, including neurodegenerative cardiovascular metabolic musculoskeletal immune system diseases. Although development modern medicine has promoted human health greatly extended life expectancy, aging society, variety chronic diseases have gradually become most important causes disability death elderly individuals. Current research on focuses elucidating how endogenous exogenous stresses (such as genomic instability, telomere dysfunction, epigenetic alterations, loss proteostasis, compromise autophagy, mitochondrial cellular senescence, stem exhaustion, altered intercellular communication, deregulated nutrient sensing) participate regulation aging. Furthermore, thorough pathogenesis to identify interventions that promote longevity caloric restriction, microbiota transplantation, nutritional intervention) clinical treatment methods for (depletion senescent cells, therapy, antioxidative anti-inflammatory treatments, hormone replacement therapy) could decrease incidence turn healthy longevity.

Язык: Английский

Процитировано

773

EASL–EASD–EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD) DOI Creative Commons
Frank Tacke, Paul Horn, Vincent Wai‐Sun Wong

и другие.

Journal of Hepatology, Год журнала: 2024, Номер 81(3), С. 492 - 542

Опубликована: Июнь 7, 2024

Язык: Английский

Процитировано

409

Targeting fibrosis: mechanisms and clinical trials DOI Creative Commons

Manyu Zhao,

Liqun Wang, Mengzhu Wang

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)

Опубликована: Июнь 30, 2022

Fibrosis is characterized by the excessive extracellular matrix deposition due to dysregulated wound and connective tissue repair response. Multiple organs can develop fibrosis, including liver, kidney, heart, lung. such as liver cirrhosis, idiopathic pulmonary cystic fibrosis caused substantial disease burden. Persistent abnormal activation of myofibroblasts mediated various signals, transforming growth factor, platelet-derived fibroblast growh has been recongized a major event in occurrence progression fibrosis. Although mechanisms driving organ-specific have not fully elucidated, drugs targeting these identified aberrant signals achieved potent anti-fibrotic efficacy clinical trials. In this review, we briefly introduce aetiology epidemiology several diseases, kidney cardiac Then, summarise cells (epithelial cells, endothelial immune fibroblasts) their interactions addition, also focus on signaling pathways therapeutic targets that regulate myofibroblast activation, cross-linking, metabolism, inflammation Finally, discuss based This review provides reference for further research mechanism, drug development,

Язык: Английский

Процитировано

272

Targeted therapeutics and novel signaling pathways in non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH) DOI Creative Commons
Xiaohan Xu, Kyle L. Poulsen, Lijuan Wu

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)

Опубликована: Авг. 13, 2022

Non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH) has become the leading cause of liver disease worldwide. NASH, an advanced form NAFL, can be progressive and more susceptible to developing cirrhosis hepatocellular carcinoma. Currently, lifestyle interventions are most essential effective strategies for preventing controlling NAFL without development fibrosis. While there still limited appropriate drugs specifically treat NAFL/NASH, growing progress is being seen in elucidating pathogenesis identifying therapeutic targets. In this review, we discussed recent developments etiology prospective targets, as well pharmacological candidates pre/clinical trials patents, with a focus on diabetes, hepatic lipid metabolism, inflammation, Importantly, evidence elucidates that disruption gut-liver axis microbe-derived metabolites drive NAFL/NASH. Extracellular vesicles (EVs) act signaling mediator, resulting accumulation, macrophage stellate cell activation, further promoting inflammation fibrosis progression during Targeting gut microbiota or EVs may serve new treatment Finally, other mechanisms, such therapy genetic approaches, also have enormous potential. Incorporating different mechanisms personalized medicine improve efficacy better benefit patients

Язык: Английский

Процитировано

214

Current treatment of non‐alcoholic fatty liver disease DOI
Rafael Paternostro, Michael Trauner

Journal of Internal Medicine, Год журнала: 2022, Номер 292(2), С. 190 - 204

Опубликована: Июль 7, 2022

Abstract Non‐alcoholic fatty liver disease (NAFLD) comprises a wide spectrum of pathologies ranging from non‐alcoholic (NAFL), characterized by simple steatosis without inflammation, to steatohepatitis (NASH), the accompanied inflammation and hepatocyte ballooning, which can lead advanced fibrosis, cirrhosis hepatocellular carcinoma. Apart lifestyle modifications such as weight loss, Mediterranean diet physical activity, only few NAFLD‐specific pharmacological treatment options Vitamin E Pioglitazone are considered current international guidelines. However, recently randomized controlled trials with GLP‐1 agonists, FXR PPAR ligands well other agents have been published may expand therapeutic armamentarium for NAFLD in near future. Finally, knowledge about treating complications end‐stage due NASH becomes an increasingly important cornerstone broad NAFLD. In this review, we summarize currently available future patients that help internal medicine specialists treat complete clinical highly prevalent disease.

Язык: Английский

Процитировано

182

Efficacy of peroxisome proliferator-activated receptor agonists, glucagon-like peptide-1 receptor agonists, or sodium-glucose cotransporter-2 inhibitors for treatment of non-alcoholic fatty liver disease: a systematic review DOI
Alessandro Mantovani, Christopher D. Byrne, Giovanni Targher

и другие.

˜The œLancet. Gastroenterology & hepatology, Год журнала: 2022, Номер 7(4), С. 367 - 378

Опубликована: Янв. 12, 2022

Язык: Английский

Процитировано

177

Advancements in the treatment of non-alcoholic fatty liver disease (NAFLD) DOI Creative Commons

Rong Li,

Junyan Zou,

Wei Ran

и другие.

Frontiers in Endocrinology, Год журнала: 2023, Номер 13

Опубликована: Янв. 16, 2023

Non-alcoholic fatty liver disease (NAFLD) is a series of diseases, involving excessive lipid deposition in the and often accompanied by obesity, diabetes, dyslipidemia, abnormal blood pressure, other metabolic disorders. In order to more accurately reflect its pathogenesis, an international consensus renamed NAFLD 2020 as (dysfunction) associated with (MAFLD). The changes diet lifestyle are recognized non-drug treatment strategies; however, due complex pathogenesis NAFLD, current drug therapies mainly focused on pathogenic factors, key links related disorders targets. There still lack specific drugs. clinical studies, common treatments include regulation glucose metabolism protect anti-inflammation. based enterohepatic axis, targeting gut microbiota, gradually emerging, various new metabolism-regulating drugs also under development. Therefore, this review article has comprehensively discussed research advancements recent years.

Язык: Английский

Процитировано

165

Insights into the molecular targets and emerging pharmacotherapeutic interventions for nonalcoholic fatty liver disease DOI Open Access
Chander K. Negi, Pavel Babica, Lola Bajard

и другие.

Metabolism, Год журнала: 2021, Номер 126, С. 154925 - 154925

Опубликована: Ноя. 3, 2021

Язык: Английский

Процитировано

163

Novel therapeutic targets for cholestatic and fatty liver disease DOI Creative Commons
Michael Trauner, Claudia Fuchs

Gut, Год журнала: 2021, Номер 71(1), С. 194 - 209

Опубликована: Окт. 6, 2021

Cholestatic and non-alcoholic fatty liver disease (NAFLD) share several key pathophysiological mechanisms which can be targeted by novel therapeutic concepts that are currently developed for both areas. Nuclear receptors (NRs) ligand-activated transcriptional regulators of metabolic processes including hepatic lipid glucose metabolism, energy expenditure bile acid (BA) homoeostasis, as well inflammation, fibrosis cellular proliferation. Dysregulation these contributes to the pathogenesis progression cholestatic disease, placing NRs at forefront approaches. This includes BA activated such farnesoid-X receptor (FXR) peroxisome proliferator-activated receptors, respectively, high affinity ligands targeting specific or multiple isoforms have been developed. Moreover, liver-specific thyroid hormone beta 1 complete spectrum available NR-targeted drugs. Apart from FXR ligands, signalling mimetics FXR-activated fibroblast growth factor 19, modulation their enterohepatic circulation through uptake inhibitors in hepatocytes enterocytes, derivatives undergoing cholehepatic shunting (instead circulation). Other approaches more directly target inflammation and/or critical events progression. Combination strategies synergistically disturbances, may ultimately necessary successful treatment complex multifactorial disorders.

Язык: Английский

Процитировано

136

PPAR-γ signaling in nonalcoholic fatty liver disease: Pathogenesis and therapeutic targets DOI
Hao Chen, Huabing Tan, Juan Wan

и другие.

Pharmacology & Therapeutics, Год журнала: 2023, Номер 245, С. 108391 - 108391

Опубликована: Март 22, 2023

Язык: Английский

Процитировано

131