scholarly journals Novel therapeutic targets for cholestatic and fatty liver disease

Gut ◽  
2021 ◽  
pp. gutjnl-2021-324305
Author(s):  
Michael Trauner ◽  
Claudia Daniela Fuchs
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Thyroid Hormone Receptor ◽  
Enterohepatic Circulation ◽  
Farnesoid X Receptor ◽  
Therapeutic Approaches ◽  
Alcoholic Fatty Liver ◽  
Therapeutic Concepts ◽  
Novel Therapeutic

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

scholarly journals The New Therapeutic Approaches in the Treatment of Non-Alcoholic Fatty Liver Disease

2021 ◽  
Vol 22 (24) ◽  
pp. 13219
Author(s):  
Branka Filipovic ◽  
Snezana Lukic ◽  
Dragana Mijac ◽  
Marija Marjanovic-Haljilji ◽  
Marko Vojnovic ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Farnesoid X Receptor ◽  
Peroxisome Proliferator ◽  
Biomedical Sciences ◽  
Therapeutic Approaches ◽  
Alcoholic Fatty Liver ◽  
New Therapeutic Approaches ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease which is characterized by extremely complex pathogenetic mechanisms and multifactorial etiology. Some of the many pathophysiological mechanisms involved in the development of NAFLD include oxidative stress, impaired mitochondrial metabolism, inflammation, gut microbiota, and interaction between the brain-liver-axis and the regulation of hepatic lipid metabolism. The new therapeutic approaches in the treatment of NAFLD are targeting some of these milestones along the pathophysiological pathway and include drugs like agonists of peroxisome proliferator-activated receptors (PPARs), glucagon-like peptide-1 (GLP-1) agonists, sodium/glucose transport protein 2 (SGLT2) inhibitors, farnesoid X receptor (FXR) agonists, probiotics, and symbiotics. Further efforts in biomedical sciences should focus on the investigation of the relationship between the microbiome, liver metabolism, and response to inflammation, systemic consequences of metabolic syndrome.

scholarly journals A look at new therapeutic opportunities in patients with non-alcoholic fatty liver disease

2019 ◽  
Vol 16 (3) ◽  
pp. 37-45
Author(s):  
Ekaterina E. Mishina ◽  
Alexander Y. Mayorov ◽  
Apollinariya V. Bogolyubova ◽  
Pavel O. Bogomolov ◽  
Maria V. Matsievich ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Farnesoid X Receptor ◽  
Bile Acid Metabolism ◽  
Alcoholic Fatty Liver ◽  
Inflammatory Processes ◽  
Active Research ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, and is considered to be the liver manifestation of metabolic syndrome. Currently, there is no etiotropic treatment of NAFLD, so an active research for new methods of treatment is underway. In the meantime, drugs are used to treat comorbid conditions, such as dyslipidemia, arterial hypertension, obesity, type 2 diabetes, which are present in varying degrees in patients. This review considers medications that are used in patients with NAFLD and related concomitant features, and also describes new strategies for regressing changes in liver tissue in NAFLD. In our opinion, one of the promising groups of drugs are agonists of the farnesoid X receptor (FXR). FXR belongs to the group of nuclear receptors, which are ligand-activated transcription factors that regulate the genes involved in metabolism. FXR agonists can claim to be a new promising drug for the treatment of NAFLD and related diseases influencing carbohydrate metabolism, fat metabolism, bile acid metabolism, as well as inflammatory processes in the liver to ensure metabolic homeostasis.

scholarly journals Why Bile Acids Are So Important in Non-Alcoholic Fatty Liver Disease (NAFLD) Progression

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1358 ◽  
Author(s):  
Aline Gottlieb ◽  
Ali Canbay
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Bile Acids ◽  
Fatty Liver Disease ◽  
The Body ◽  
Farnesoid X Receptor ◽  
Bile Acid Metabolism ◽  
Primary Biliary Cholangitis ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is a complex disease, affecting not just the liver, but also all other organs in the body. Despite an increasing amount of people worldwide developing NAFLD and having it progress to non-alcoholic steatohepatitis (NASH) and potentially cirrhosis, there is still no approved therapy. Therefore, huge efforts are being made to find and develop a successful treatment. One of the special interests is understanding the liver–gut axis and especially the role of bile acids in the progression of NAFLD. Farnesoid X receptor (FXR)-agonists have been approved und used in other liver diseases, such as primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), and have shown signs of being able to decrease inflammation and potentially steatosis. This review will mainly focus on targets/ligands that play an important role in bile acid metabolism and give an overview of ongoing clinical as well as pre-clinical trials. With the complexity of the issue, we did not aim at giving a complete review, rather highlighting important targets and potential treatments that could be approved for NAFLD/NASH treatment within the next few years.

scholarly journals Variables associated with increased incidence of non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes

2021 ◽  
Vol 9 (1) ◽  
pp. e002243
Author(s):  
Sven H Loosen ◽  
Münevver Demir ◽  
Anselm Kunstein ◽  
Markus Jördens ◽  
Natalia Qvarskhava ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Large Population ◽  
Alcoholic Fatty Liver ◽  
Therapeutic Concepts ◽  
The Impact ◽  
Alcoholic Fatty Liver Disease

IntroductionType 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD) show a rapidly increasing incidence worldwide. Although both diseases often occur in the same patient population, their mutual influence is not fully understood. We therefore aimed at analyzing the impact of T2D on the incidence of NAFLD in a large cohort of outpatients in Germany.Research design and methods32 201 patients with T2D diagnosed between 2012 and 2018 were identified in the IQVIA Disease Analyzer database. Probability of NAFLD was analyzed using Cox regression models.ResultsThe cumulative incidence of NAFLD within the 7-year observation period was 4.3%. The probability of NAFLD was significantly higher among patients with T2D with increased body mass index but not hemoglobin A1c. Prescriptions of sodium-glucose cotransporter-2 inhibitors (HR: 0.54, 95% CI 0.45 to 0.64), glucagon-like peptide-1 receptor antagonists (HR: 0.65, 95% CI 0.52 to 0.81), and insulin (HR: 0.72, 95% CI 0.62 to 0.8) were significantly associated with lower incidence of NAFLD.ConclusionOur data from a large population-based cohort of patients with T2D identified sociodemographic and therapeutic parameters associated with NAFLD incidence in patients with T2D which should be taken into account for novel therapeutic concepts.

scholarly journals Modern view of the importance of cholecystectomy in the prognosis of a patient with non-alcoholic fatty liver disease: follow-up algorithm and therapeutic approaches

2021 ◽  
Vol 5 (6) ◽  
pp. 438-445
Author(s):  
S.N. Mekhtiev ◽  
◽  
O.A. Mekhtieva ◽  
M.V. Ukhova ◽  
Z.M. Ibragimova ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Therapeutic Approaches ◽  
Alcoholic Fatty Liver ◽  
Strict Adherence ◽  
Modern View ◽  
Alcoholic Fatty Liver Disease

The gallbladder is an organ that plays an important role in maintaining effective enterohepatic circulation (EHC) of bile and preserving the metabolic homeostasis of lipids and bile acids. Despite modern ideas about the role of the gallbladder in the human body, especially in subjects with metabolic syndrome and non-alcoholic fatty liver disease (NAFLD), cholecystectomy (CE) remains one of the most common surgeries, including in this patient category. The review examines the following in patients with NAFLD: the gallbladder role, the association between NAFLD and cholelithiasis (C), indications for CE, as well as the consequences of this intervention. The authors discuss the issues of patient management with NAFLD after CE. Patients with C and NAFLD who have undergone CE need a number of diagnostic measures aimed at identifying and timely correction of disorders, as well as complex treatment, which includes the risk factors elimination, strict adherence to diet, exercise regime, the use of drugs improving the EHC state, lipid and carbohydrate metabolism, the metabolic function of hepatocytes and inhibiting the liver fibrogenesis. KEYWORDS: cholecystectomy, non-alcoholic fatty liver disease, cholelithiasis, ursodeoxycholic acid, metabolic syndrome, insulin resistance. FOR CITATION: Mekhtiev S.N., Mekhtieva O.A., Ukhova M.V., Ibragimova Z.M. Modern view of the importance of cholecystectomy in the prognosis of a patient with non-alcoholic fatty liver disease: follow-up algorithm and therapeutic approaches. Russian Medical Inquiry. 2021;5(6):438–445 (in Russ.). DOI: 10.32364/2587-6821-2021-5-6-438-445.

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