Randomised clinical trial: Pemafibrate, a novel selective peroxisome proliferator‐activated receptor α modulator (SPPARMα), versus placebo in patients with non‐alcoholic fatty liver disease DOI Creative Commons
Atsushi Nakajima, Yuichiro Eguchi, Masato Yoneda

и другие.

Alimentary Pharmacology & Therapeutics, Год журнала: 2021, Номер 54(10), С. 1263 - 1277

Опубликована: Сен. 16, 2021

Summary Background Pemafibrate is a novel, selective peroxisome proliferator‐activated receptor α modulator (SPPARMα). In mice, improved the histological features of non‐alcoholic steatohepatitis (NASH). patients with dyslipidaemia, it serum alanine aminotransferase (ALT). Aims To evaluate efficacy and safety in high‐risk, fatty liver disease (NAFLD). Methods This double‐blind, placebo‐controlled, randomised multicentre, phase 2 trial 118 (1:1) to either 0.2 mg or placebo, orally, twice daily for 72 weeks. The key inclusion criteria included fat content ≥10% by magnetic resonance imaging‐estimated proton density fraction (MRI‐PDFF); stiffness ≥2.5 kPa, elastography (MRE); elevated ALT levels. primary endpoint was percentage change MRI‐PDFF from baseline week 24. secondary endpoints MRE‐based stiffness, ALT, fibrosis markers lipid parameters. Results There no significant difference between groups (−5.3% vs −4.2%; treatment −1.0%, P = 0.85). However, significantly decreased compared placebo at 48 (treatment −5.7%, 0.036), maintained −6.2%, 0.024), reduction LDL‐C. Adverse events were comparable therapy well tolerated. Conclusions did not decrease but had stiffness. may be promising therapeutic agent NAFLD/NASH, also candidate combination agents that reduce content. ClinicalTrials.gov, number: NCT03350165.

Язык: Английский

Nonalcoholic fatty liver disease increases risk of incident chronic kidney disease: A systematic review and meta-analysis DOI
Alessandro Mantovani, Gianluigi Zaza, Christopher D. Byrne

и другие.

Metabolism, Год журнала: 2017, Номер 79, С. 64 - 76

Опубликована: Ноя. 11, 2017

Язык: Английский

Процитировано

296
Genetic contributions to NAFLD: leveraging shared genetics to uncover systems biology DOI
Mohammed Eslam, Jacob George

Nature Reviews Gastroenterology & Hepatology, Год журнала: 2019, Номер 17(1), С. 40 - 52

Опубликована: Окт. 22, 2019

Язык: Английский

Процитировано

270
Macrophages in obesity and non-alcoholic fatty liver disease: Crosstalk with metabolism DOI Creative Commons
Sander Lefere, Frank Tacke

JHEP Reports, Год журнала: 2019, Номер 1(1), С. 30 - 43

Опубликована: Март 27, 2019

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent worldwide, and a major cause of cirrhosis hepatocellular carcinoma. NAFLD intimately linked with other metabolic disorders characterized by insulin resistance. Metabolic diseases are driven chronic inflammatory processes, in which macrophages perform essential roles. The polarization status itself influenced stimuli such as acids, turn affect progression dysfunction at multiple stages various tissues. For instance, adipose tissue respond to obesity, adipocyte stress dietary factors specific programme that stimulates locally liver. Kupffer cells monocyte-derived represent ontologically distinct hepatic macrophage populations range functions. These integrate signals from gut-liver axis (related dysbiosis, reduced intestinal barrier integrity, endotoxemia), overnutrition, systemic low-grade inflammation local environment steatotic This makes them central players steatohepatitis (non-alcoholic or NASH) fibrosis. Moreover, particular involvement lipid metabolism, well activation macrophages, may pathogenically link NAFLD/NASH cardiovascular disease. In this review, we highlight polarization, classification function subsets their interaction cues pathophysiology obesity NAFLD. Evidence animal clinical studies suggests targeting improve course related disorders.

Язык: Английский

Процитировано

236
KASL clinical practice guidelines: Management of nonalcoholic fatty liver disease DOI Creative Commons
Seong Hee Kang, Hye Won Lee, Jeong‐Ju Yoo

и другие.

Clinical and Molecular Hepatology, Год журнала: 2021, Номер 27(3), С. 363 - 401

Опубликована: Июнь 22, 2021

Evidence collectionThe committee systematically collected and reviewed the international domestic literature published in PubMed, MEDLINE, KoreaMed, other databases.The was limited to research papers English Korean languages.The keywords used were 'nonalcoholic fatty liver disease,' liver,' steatohepatitis,' 'fatty 'hepatic steatosis,' 'steatohepatitis.'In addition, related specific clinical questions included. Levels of evidence grades recommendationsThe gathered for data collection analyzed a systematic review, quality classified based on modified Grading Recommendations, Assessment, Development Evaluation (GRADE) system (Table 1).According types studies, randomized, controlled studies approached from high level evidence, while observational low evidence.Subsequently, basis sets corresponding stud-

Язык: Английский

Процитировано

225
The crucial role and mechanism of insulin resistance in metabolic disease DOI Creative Commons
Xuefei Zhao, Xuedong An,

Cunqing Yang

и другие.

Frontiers in Endocrinology, Год журнала: 2023, Номер 14

Опубликована: Март 28, 2023

Insulin resistance (IR) plays a crucial role in the development and progression of metabolism-related diseases such as diabetes, hypertension, tumors, nonalcoholic fatty liver disease, provides basis for common understanding these chronic diseases. In this study, we provide systematic review causes, mechanisms, treatments IR. The pathogenesis IR depends on genetics, obesity, age, drug effects. Mechanistically, any factor leading to abnormalities insulin signaling pathway leads host, including receptor abnormalities, disturbances internal environment (regarding inflammation, hypoxia, lipotoxicity, immunity), metabolic function organelles, other abnormalities. available therapeutic strategies are mainly exercise dietary habit improvement, chemotherapy based biguanides glucagon-like peptide-1, traditional Chinese medicine (e.g., herbs acupuncture) can also be helpful. Based current there still some vacancies follow up consider, is need define more precise biomarkers different lifestyle interventions, explore natural or synthetic drugs targeting treatment. This could enable treatment patients with multiple combined diseases, aim treating disease holistically reduce healthcare expenditures improve quality life extent.

Язык: Английский

Процитировано

222
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

207
Nonalcoholic Fatty Liver Disease DOI Open Access

Yan-Ci Zhao,

Guojun Zhao, Ze Chen

и другие.

Hypertension, Год журнала: 2019, Номер 75(2), С. 275 - 284

Опубликована: Дек. 23, 2019

Hypertension, a multifactorial disorder resulting from the interplay between genetic predisposition and environmental risk factors, affects ≈30% of adults. Emerging evidence has shown that nonalcoholic fatty liver disease (NAFLD), as an underestimated metabolic abnormality, is strongly associated with increased incident prehypertension hypertension. However, role NAFLD in development hypertension still obscure highly overlooked by general public. Herein, we highlight epidemiological putative mechanisms focusing on emerging roles hypertension, purpose reinforcing notion may serve independent factor important driving force progression Finally, also briefly summarize current potential treatments for might be beneficial approaches against

Язык: Английский

Процитировано

192
Molecular mechanisms of metabolic associated fatty liver disease (MAFLD): functional analysis of lipid metabolism pathways DOI Creative Commons
Olufunto O. Badmus,

Sarah A. Hillhouse,

Christopher D. Anderson

и другие.

Clinical Science, Год журнала: 2022, Номер 136(18), С. 1347 - 1366

Опубликована: Сен. 1, 2022

Abstract The metabolic-associated fatty liver disease (MAFLD) is a condition of fat accumulation in the combination with metabolic dysfunction form overweight or obesity and insulin resistance. It also associated an increased cardiovascular risk, including hypertension atherosclerosis. Hepatic lipid metabolism regulated by uptake export acids, de novo lipogenesis, utilization β-oxidation. When balance between these pathways altered, hepatic commences, long-term activation inflammatory fibrotic can progress to worsen disease. This review discusses details molecular mechanisms regulating lipids emerging therapies targeting as potential future treatments for MAFLD.

Язык: Английский

Процитировано

179
Pathophysiological, Molecular and Therapeutic Issues of Nonalcoholic Fatty Liver Disease: An Overview DOI Open Access
Simona Marchisello, Antonino Di Pino, Roberto Scicali

и другие.

International Journal of Molecular Sciences, Год журнала: 2019, Номер 20(8), С. 1948 - 1948

Опубликована: Апрель 20, 2019

Nonalcoholic Fatty Liver Disease (NAFLD) represents the leading cause of liver disease in developed countries but its diffusion is currently also emerging Asian countries, South America and other developing countries. It progressively becoming one main diseases responsible for hepatic insufficiency, hepatocarcinoma need orthotopic transplantation. NAFLD linked with metabolic syndrome a close bidirectional relationship. To date, diagnosis exclusion, biopsy gold standard diagnosis. pathogenesis complex multifactorial, mainly involving genetic, environmental factors. New concepts are constantly arising literature promising new diagnostic therapeutic tools. One challenges will be to better characterize not only development overall progression, order identify patients at higher risk metabolic, cardiovascular neoplastic complications. This review analyses epidemiology different prevalence distinct groups, particularly according sex, age, body mass index, type 2 diabetes dyslipidemia. Furthermore, work expands on pathophysiology NAFLD, examining multiple-hit role factors steatosis progression: genetics, insulin resistance, diet, adipose tissue, gut microbiota, iron deposits, bile acids circadian clock. In conclusion, current available therapies discussed.

Язык: Английский

Процитировано

171
Treatments for NAFLD: State of Art DOI Open Access
Alessandro Mantovani, Andrea Dalbeni

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(5), С. 2350 - 2350

Опубликована: Фев. 26, 2021

Non-alcoholic fatty liver disease (NAFLD) is to date the most common chronic in clinical practice and, consequently, a major health problem worldwide. It affects approximately 30% of adults general population and up 70% patients with type 2 diabetes (T2DM). Despite current knowledge epidemiology, pathogenesis, natural history NAFLD, no specific pharmacological therapies are until now approved for this strategies have been proposed manage it. They include: (a) lifestyle change order promote weight loss by diet physical activity, (b) control main cardiometabolic risk factors, (c) correction all modifiable factors leading development progression advanced forms (d) prevention hepatic extra-hepatic complications. In last decade, several potential agents widely investigated treatment NAFLD its forms—shedding some light but casting few shadows. include glucose-lowering drugs (such as pioglitazone, glucagon-like peptide-1 (GLP-1) receptor agonists, sodium-glucose co-transporter-2 (SGLT-2) inhibitors), antioxidants vitamin E), statins or other lipid lowering agents, bile non-bile acid farnesoid X activated (FXR) others. This narrative review discusses detail different available approaches prevent treat forms.

Язык: Английский

Процитировано

165