NAFLD: Mechanisms, Treatments, and Biomarkers

Biomolecules, Journal Year: 2022, Volume and Issue: 12(6), P. 824 - 824

Published: June 13, 2022

Nonalcoholic fatty liver disease (NAFLD), recently renamed metabolic-associated (MAFLD), is one of the most common causes diseases worldwide. NAFLD growing in parallel with obesity epidemic. No pharmacological treatment available to treat NAFLD, specifically. The reason might be that a multi-factorial an incomplete understanding mechanisms involved, absence accurate and inexpensive imaging tools, lack adequate non-invasive biomarkers. consists accumulation excess lipids liver, causing lipotoxicity progress steatohepatitis (NASH), fibrosis, hepatocellular carcinoma. for pathogenesis current interventions management disease, role sirtuins as potential targets are discussed here. In addition, diagnostic non-coding RNAs emerging biomarkers summarized. availability biomarkers, diagnosis tools crucial detection early signs progression NAFLD. This will expedite clinical trials validation therapeutic treatments.

Language: Английский

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Targeted therapeutics and novel signaling pathways in non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH)

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Aug. 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

Language: Английский

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Current treatment of non‐alcoholic fatty liver disease

Journal of Internal Medicine, Journal Year: 2022, Volume and Issue: 292(2), P. 190 - 204

Published: July 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.

Language: Английский

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Insights into the molecular targets and emerging pharmacotherapeutic interventions for nonalcoholic fatty liver disease

Metabolism, Journal Year: 2021, Volume and Issue: 126, P. 154925 - 154925

Published: Nov. 3, 2021

Language: Английский

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Current therapies and new developments in NASH

Gut, Journal Year: 2022, Volume and Issue: 71(10), P. 2123 - 2134

Published: June 16, 2022

Non-alcoholic steatohepatitis is becoming the most important aetiology for advanced liver disease. There has been progress in field recent years and complexity of pathophysiology NASH better understood. Multiple non-invasive circulating imaging biomarkers have tested. The importance lifestyle recognised several drugs are being tested clinical trials. This review addresses challenges that healthcare professionals face management patients.

Language: Английский

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Novel therapeutic targets for cholestatic and fatty liver disease

Gut, Journal Year: 2021, Volume and Issue: 71(1), P. 194 - 209

Published: Oct. 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.

Language: Английский

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Pathogenesis and treatment of non-alcoholic steatohepatitis and its fibrosis

Clinical and Molecular Hepatology, Journal Year: 2022, Volume and Issue: 29(1), P. 77 - 98

Published: Oct. 13, 2022

The initial presentation of non-alcoholic steatohepatitis (NASH) is hepatic steatosis. dysfunction lipid metabolism within hepatocytes caused by genetic factors, diet, and insulin resistance causes accumulation. Lipotoxicity, oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress would further contribute to hepatocyte injury death, leading inflammation immune in the liver. During healing process, accumulation an excessive amount fibrosis might occur while healing. development NASH liver fibrosis, gut-liver axis, adipose-liver renin-angiotensin system (RAS) may be dysregulated impaired. Translocation bacteria or its end-products entering could activate hepatocytes, Kupffer cells, stellate exacerbating steatosis, inflammation, fibrosis. Bile acids regulate glucose through Farnesoid X receptors intestine. Increased adipose tissue-derived non-esterified fatty aggravate leptin also plays a role fibrogenesis, decreased adiponectin resistance. Moreover, dysregulation peroxisome proliferator-activated liver, adipose, muscle tissues impair metabolism. In addition, RAS acid metabolism, treatment includes lifestyle modification, pharmacological therapy, non-pharmacological therapy. Currently, weight reduction modification surgery most effective However, vitamin E, pioglitazone, obeticholic have been suggested. this review, we will introduce some new clinical trials experimental therapies for related

Language: Английский

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Breakthroughs in therapies for NASH and remaining challenges

Journal of Hepatology, Journal Year: 2022, Volume and Issue: 76(6), P. 1263 - 1278

Published: May 16, 2022

Language: Английский

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An adipocentric perspective on the development and progression of non-alcoholic fatty liver disease

Journal of Hepatology, Journal Year: 2023, Volume and Issue: 78(5), P. 1048 - 1062

Published: Feb. 3, 2023

Alongside the liver, white adipose tissue (WAT) is critical in regulating systemic energy homeostasis. Although each organ has its specialised functions, they must work coordinately to regulate whole-body metabolism. Adipose tissues and liver are relatively resilient can adapt an surplus by facilitating triglyceride (TG) storage up a certain threshold level without significant metabolic disturbances. However, lipid WAT beyond "personalised" adiposity becomes dysfunctional, leading inflexibility, progressive inflammation, aberrant adipokine secretion. Moreover, failure of store mobilise lipids results knock-on overload, particularly liver. Factors contributing hepatic overload include released from WAT, dietary fat intake, enhanced de novo lipogenesis. In contrast, extrahepatic mechanisms counteracting toxic entail coordinated compensation through oxidation fatty acids brown as TGs WAT. Failure these integrated homeostatic leads quantitative increases qualitative alterations lipidome Initially, hepatocytes preferentially accumulate TG species "benign" non-alcoholic with time, inflammatory responses ensue, progressing into more severe conditions such steatohepatitis, cirrhosis, hepatocellular carcinoma, some individuals (often early prognostic clue). Herein, we highlight pathogenic importance obesity-induced "adipose failure", resulting decreased functionality (i.e. capacity flexibility), development progression NAFL/NASH.

Language: Английский

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Using genetic association data to guide drug discovery and development: Review of methods and applications

The American Journal of Human Genetics, Journal Year: 2023, Volume and Issue: 110(2), P. 195 - 214

Published: Feb. 1, 2023

Language: Английский

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