scholarly journals Bile acids, non-alcoholic fatty liver and pancreatic disease: chained by ursodeoxycholic acid?

2020 ◽  
Vol 49 (4) ◽  
pp. 42-50
Author(s):  
N. B. Gubergrits ◽  
N. V. Byelyayeva ◽  
T. L. Mozhyna
Keyword(s):  
Fatty Liver ◽  
Ursodeoxycholic Acid ◽  
Bile Acids ◽  
Carbohydrate Metabolism ◽  
Randomized Clinical Trials ◽  
Experimental Studies ◽  
Pancreatic Disease ◽  
Alcoholic Fatty Liver ◽  
Systemic Insulin Resistance ◽  
Stress Changes

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic fatty pancreatic disease (NAFPD) develop against the background of metabolic syndrome, systemic insulin resistance, oxidative stress, changes in lipid and carbohydrate metabolism. There are a number of similarities between NAFLD and NAFPD: the natural course of diseases proceeds from steatosis through inflammation to fibrosis and cancer, one of the etiopathogenetic factors is the disbalance of bile acids synthesis and low expression of farnesoid receptor X (FXR). One of the possible methods of treatment NAFLD and NAFPD is a correction of the biosynthesis of bile acids and increase FXR expression with FXR agonists. Ursodeoxycholic acid (UDCA) is a selective FXR agonist. It has a multipled spectrum of actions: anticholestatic, anti-apoptic, antioxidant, cytoprotective, antifibrotic, hypocholesterolemic, immunomodulatory, hepatoprotective. The ability of UDCA correct lipid and carbohydrate metabolism in combination with anti-inflammatory and antiapoptic effects may be of great importance for the treatment of NAFLD and NAFPD. The article reviews the results of clinical and experimental studies describing the efficacy of UDCA in NAFLD and some pancreatic diseases. It has been suggested that the therapy of UDCA can reduce the severity of NAFLD and NAFPDand improve the functional activity of hepatocytes and β cells. The need for randomized clinical trials was emphasized in order to make an informed decision on the expediency of including UDCA in the treatment of NAFLD and NAFPD.

From non-alcoholic fatty liver disease to COVID­19: the present and prospects for the use of ursodeoxycholic acid

2021 ◽  
Author(s):  
M. M. Dolzhenko ◽  
L. I. Konoplyanik
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Liver Disease ◽  
Epithelial Cells ◽  
Fatty Liver ◽  
Ursodeoxycholic Acid ◽  
Bile Acids ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

The clinical morphological manifestations of the course of non‑alcoholic fatty liver disease in patients, non‑alcohol drinkers, include steatohepatosis, non‑alcoholic steatohepatitis, liver cirrhosis, and hepatocellular carcinoma. There are four basic mechanisms in the pathogenesis of non‑alcoholic fatty liver disease: bile acid lipotoxicity, insulin resistance, systemic inflammation, increased oxidative stress and lipid peroxidation. Non‑alcoholic fatty liver disease increases the risk of onset, development and progression of the cardiovascular diseases independently from other predictors and manifestations of the metabolic syndrome. The complex treatment of patients with coronary heart disease, combined with the non‑alcoholic fatty liver disease includes diet, physical exercises, body mass reduction and drug therapy. The medications for this category of patients must be maximal safe and result in the improving of the clinical, laboratory and morphological parameters of liver. Ursodeoxycholic acid is one of the most effective medications with the mechanisms of action associated with the normalization of the hepatoenteric circulation of bile acids and a number of biologically active substances. It also possesses the cytoprotective and antiapoptotic action, affects the FXR­metabolic nuclear receptor, which plays an important role in the physiology of vascular pathology, is an important transcriptional regulator of bile acids, lipids and glucose metabolism. Ursodeoxycholic acid is able to suppress eosinophilic inflammation not only in the gastrointestinal tract. It improves histopathological changes in airway remodeling, that can be connected with the modulation of cytokines and inhibition of apoptosis of epithelial cells of the respiratory tract. Ursodeoxycholic acid can be potentially effective preparation for the reduction of fluid volume in pulmonary edema and prevention of lung damage caused by fat embolism syndrome. Moreover, its positive effects have been proved as regards the airway epithelial cells at cystic fibrosis. Taking into account that ursodeoxycholic acid inhibits pro‑inflammatory cytokines, has strong antioxidative properties and acts as a famous hepatoprotector, it can be effective in the treatment of coronavirus disease (COVID­19). In Ukraine Ursonost is available, it is one of the well‑known preparations containing ursodeoxycholic acid and advantageously distinguished by high quality and ease of dosing. It is bioequivalent to the reference drug due to the highest quality of the substance and modern production technology. The large evidence base on ursodeoxycholic acid allows the drug Ursonost to be considered as a drug with pronounced multipotent properties, thus it is indicated for the treatment of patients with non‑alcoholic and alcoholic fatty liver disease, especially in combination with the coronary heart disease, of conditions, associated with bile reflux (duodenogastric, duodenogastroesophageal reflux), biliary sludge, primary biliary cirrhosis, gallstone disease (for dissolving X‑ray negative stones) and other metabolic disorders. Ursonost preparation is available as 150 and 300 mg capsules, that facilitates the drug dosing depending on the body mass of a patient and a clinical situation.

Therapeutic Mechanisms of Bile Acids and Nor-Ursodeoxycholic Acid in Non-Alcoholic Fatty Liver Disease

2017 ◽  
Vol 35 (3) ◽  
pp. 282-287 ◽  
Author(s):  
Daniel Steinacher ◽  
Thierry Claudel ◽  
Michael Trauner
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Ursodeoxycholic Acid ◽  
Bile Acids ◽  
Fatty Liver Disease ◽  
Liver Diseases ◽  
Hepatic Metabolism ◽  
Alcoholic Fatty Liver ◽  
New Class ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease is one of the most rapidly rising clinical problems in the 21st century. So far no effective drug treatment has been established to cure this disease. Bile acids (BAs) have a variety of signaling properties, which can be used therapeutically for modulating hepatic metabolism and inflammation. A side-chain shorted derivative of ursodeoxycholic acid (UDCA) is 24 nor-ursodeoxycholic acid (NorUDCA) and it represents a new class of drugs for treatment of liver diseases. NorUDCA has unique biochemical and therapeutic properties, since it is relatively resistant to conjugation with glycine or taurine compared to UDCA. NorUDCA undergoes cholehepatic shunting, resulting in ductular targeting, bicarbonate-rich hypercholeresis, and cholangiocyte protection. Furthermore, it showed anti-fibrotic, anti-inflammatory, and anti-lipotoxic properties in several animal models. As such, NorUDCA is a promising new approach in the treatment of cholestatic and metabolic liver diseases. This review is a summary of current BA-based therapeutic approaches in the treatment of the fatty liver disease.

scholarly journals Parallels between non-alcoholic fatty liver disease and non-alcoholic fatty pancreatic disease: looking for points of contact or regard through the lens of metabolic syndrome

2020 ◽  
Vol 183 (11) ◽  
pp. 80-101
Author(s):  
N. B. Gubergrits ◽  
N. V. Byelyayeva ◽  
T. L. Mozhyna
Keyword(s):  
Metabolic Syndrome ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Pancreatic Insufficiency ◽  
Pancreatic Disease ◽  
Alcoholic Fatty Liver ◽  
Enzyme Replacement ◽  
Stress Changes ◽  
Alcoholic Fatty Liver Disease

The aim. The aim of our study was to analyze the available data from literature sources concerning the issues of etiology, pathogenesis, clinic, diagnosis and features of treatment of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic fatty pancreatic disease (NAFPD).Materials and methods. We conducted a retrospective analysis of foreign literature sources that contain up-to-date information about the state of the problem of NAFLD and NAFPD.Results. NAFLD and NAFPD develop against the background of metabolic syndrome (MS), systemic insulin resistance, oxidative stress, changes in lipid metabolism. The natural course of NAFPD is associated with high risk of MS progression, occurrence of NAFLD, arterial hypertension, type 2 diabetes mellitus, exocrine pancreatic insufficiency, acute and chronic pancreatitis, pancreas cancer. Correction of the components of MS can reduce the severity of NAFLD and NAFPD; enzyme replacement therapy can improve the function of β-cells in pancreas steatosis.Conclusion. The alternatives of the pharmacological treatment of NAFLD and NAFPD continue to be actively explored. We emphasize the need of including medications containing pancreatic enzymes in the treatment of NAFLD.

Resveratrol Supplementation in Patients with Non-Alcoholic Fatty Liver Disease: Systematic Review and Meta-analysis

2017 ◽  
Vol 26 (1) ◽  
pp. 59-67 ◽  
Author(s):  
Ahmed Elgebaly ◽  
Ibrahim A. I. Radwan ◽  
Mohamed M. AboElnas ◽  
Hamza H. Ibrahim ◽  
Moutaz F. M. Eltoomy ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Randomized Clinical Trials ◽  
Controlled Trial ◽  
Antioxidant Properties ◽  
Density Lipoprotein ◽  
Current Evidence ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Background: Resveratrol is a potential treatment option for management of non-alcoholic fatty liver disease (NAFLD) due to its anti-inflammatory, antioxidant properties, and calorie restriction-like effects. We aimed to synthesise evidence from published randomized clinical trials (RCTs) about the efficacy of resveratrol in the management of NAFLD.Methods: A computer literature search of PubMed, Scopus, Web of Science, and Cochrane Central was conducted using relevant keywords. Records were screened for eligible studies and data were extracted and synthesized using Review Manager Version 5.3 for windows. Subgroup analysis and sensitivity analysis were conducted.Results: Four RCTs (n=158 patients) were included in the final analysis. The overall effect estimates did not favor resveratrol group in terms of: serum ALT (MD -2.89, 95%CI [-15.66, 9.88], p=0.66), serum AST (MD -3.59, 95%CI [-13.82, 6.63], p=0.49), weight (MD -0.18, 95%CI [-0.92, 0.55], p=0.63), BMI (MD -0.10, 95 %CI [-0.43, 0.24], p=0.57), blood glucose level (MD -0.27, 95%CI [-0.55, 0.01], p=0.05), insulin level (MD -0.12, 95%CI [-0.69, 0.46], p=0.69), triglyceride level (MD 0.04, 95%CI [-0.45, 0.53], p=0.87), and LDL level (MD 0.21, 95%CI [-0.41, 0.83], p=0.51). Pooled studies were heterogeneous.Conclusion: Current evidence is insufficient to support the efficacy of resveratrol in the management of NAFLD. Resveratrol does not attenuate the degree of liver fibrosis or show a significant decrease in any of its parameters.Abbreviations: ALT: Alanine aminotransferase; AMPK: AMP-activated protein kinase; AST: Aspartate aminotransferase; BMI: Body mass index; CK-18: Cytokeratin-18; CRP: C-reactive protein; HC: Head circumference; HDL: High density lipoprotein; IL-6: Interleukin-6; LDL: Low density lipoprotein; MD: Mean difference; NAFLD: Non-alcoholic fatty liver disease; NASH: Non-alcoholic steatohepatitis; RCT: Randomized Controlled Trial; RR: Relative risk; SIRT1: Silent information regulation 2 homologue 1; TNF-α: Tumor necrosis factor α; WC: Waist circumference; WHR: Waist hip ratio.

miR-34a/SIRT1/p53 is suppressed by ursodeoxycholic acid in the rat liver and activated by disease severity in human non-alcoholic fatty liver disease

2013 ◽  
Vol 58 (1) ◽  
pp. 119-125 ◽  
Author(s):  
Rui E. Castro ◽  
Duarte M.S. Ferreira ◽  
Marta B. Afonso ◽  
Pedro M. Borralho ◽  
Mariana V. Machado ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Ursodeoxycholic Acid ◽  
Disease Severity ◽  
Rat Liver ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

scholarly journals Effect of Combination Therapy with Atorvastatin and Ursodeoxycholic Acid on the Course of Ischemic Heart Disease with Co-Existent Non-Alcoholic Fatty Liver Disease and Obesity

2016 ◽  
Vol 23 (4) ◽  
pp. 2016420
Author(s):  
Nataliya Karpyshyn
Keyword(s):  
Heart Disease ◽  
Liver Disease ◽  
Ischemic Heart Disease ◽  
Fatty Liver ◽  
Ursodeoxycholic Acid ◽  
Functional Status ◽  
Fatty Liver Disease ◽  
Ischemic Heart ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease is considered as an independent predictor of cardiovascular diseases which plays an important role in the development of ischemic heart disease. The drug most frequently used for treating this comorbidity is atorvastatin which favours better survival outcomes and is essential in the primary and secondary prevention of cardiovascular diseases. Ursodeoxycholic acid is prescribed as an alternative therapy for ischemic heart disease with co-existent non-alcoholic fatty liver disease and obesity to eliminate statin side effects. The use of ursodeoxycholic acid as a hepatoprotector in comprehensive basic treatment contributes to the improvement of the cardiovascular system in patients with ischemic heart disease as well as the increase in treatment efficacy; it improves the functional status of the liver affecting the major pathogenic mechanisms of the disease.The objective of the research was to study the effect of combined hypolipidemic therapy with atorvastatin and ursodeoxycholic acid on the indices of blood lipids, liver transaminase levels, functional status of the liver and the course of non-alcoholic fatty liver disease in patients with ischemic heart disease and obesity.Materials and methods. 20 patients with ischemic heart disease, co-existent non-alcoholic fatty liver disease and obesity were examined. They received ursodeoxycholic acid in addition to atorvastatin for four weeks. All the patients underwent clinical tests, visceral ultrasonography, blood lipid test, liver transaminase test and 13C-methacetin breath test.Results. The study revealed a significant decrease in the level of the pro-atherogenic fractions of blood lipids (р<0.01) as well as an improved functional status of the liver due to a significant increase in metabolic capacity of the liver and cumulative dose on the 40th and 120th minutes after ursodeoxycholic acid administration (р<0.01).Conclusions. The use of ursodeoxycholic acid in addition to atorvastatin in patients with ischemic heart disease, co-existent non-alcoholic fatty liver disease and obesity makes it possible to avoid the adverse effect of hypolipidemic therapy on the functional status of the liver.

scholarly journals Association of insulin resistance and non-alcoholic fatty liver disease

2021 ◽  
Vol 23 (5) ◽  
pp. 412-423
Author(s):  
Ekaterina E. Mishina ◽  
Alexander Y. Mayorov ◽  
Pavel O. Bogomolov ◽  
Ekaterina O. Liusina ◽  
Alexey O. Bueverov
Keyword(s):  
Insulin Resistance ◽  
Mathematical Model ◽  
Liver Disease ◽  
Fatty Liver ◽  
Carbohydrate Metabolism ◽  
Gold Standard ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
The Mathematical Model ◽  
Alcoholic Fatty Liver Disease

BACKGROUND: The number of patients with chronic metabolic disorders such as obesity, type 2 diabetes mellitus (T2D) and non-alcoholic fatty liver disease (NAFLD) is growing at an alarming rate worldwide in both developed and developing countries. In the world, the prevalence of NAFLD is approaching 25%. Among patients with T2D, 70–80% are diagnosed with NAFLD. Insulin resistance (IR) is recognized as one of the main pathogenetic factors in the development of the most common chronic liver disease — NAFLD.AIM: Our search work was aimed at determining the contribution of the degree of IR to the progression of NAFLD; compare the gold standard for the determination of IR (clamp) and the mathematical model (HOMA-IR).METHODS: An observational one-stage open comparative study was conducted on the basis of the case-control principle. The objects of the study were overweight and obese patients who had not previously been diagnosed carbohydrate metabolism disorders, without secondary causes of fat accumulation in the liver. During the examination, clinical and laboratory studies were carried out, IR indices (M-index, HOMA-IR index) were obtained, a diagnosis of carbohydrate metabolism disturbance (or its absence) was made, a liver biopsy was made, morphological and clinical diagnoses were made.RESULTS: The analysis included information about 60 patients, they are divided into 3 groups: without NAFLD (7 people), with steatosis (18 people), with non-alcoholic steatohepatitis (NASH) (35 people), groups are comparable by age, gender, and body mass index (BMI), glycated hemoglobin. When assessing the degree of IR using the hyperinsulinemic euglycemic clamp test, 19 showed a severe degree of IR, 28 had a moderate degree, 8 had a mild degree, and 5 had no IR. In the three studied groups, the median IR corresponded to an average degree and did not significantly differ. When comparing the gold standard for determining IR and the mathematical model (HOMA-IR) in the studied groups, an negative significant correlation was revealed (p = 0,0001).CONCLUSIONS: In the course of our study, no correlation was found between the degree of IR and the severity of NAFLD. This result allows us to think about other pathogenetic factors that affect the progression of NAFLD.

scholarly journals Bile Acids and Nonalcoholic Fatty Liver and Pancreas Disease: Going Together?

Doctor Ru ◽  
2020 ◽  
Vol 19 (7) ◽  
pp. 21-30
Author(s):  
N.B. Gubergritz ◽  
◽  
N.V. Belyaeva ◽  
T.L. Mozhina ◽  
N.E. Monogarova ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Ursodeoxycholic Acid ◽  
Nonalcoholic Fatty Liver Disease ◽  
Bile Acids ◽  
Fatty Liver Disease ◽  
Farnesoid X Receptor ◽  
Pancreas Disease ◽  
Nonalcoholic Fatty Liver ◽  
Fatty Pancreas

Objective of the Review: to analyse changes in bile acids (BA) metabolism due to nonalcoholic fatty liver disease (NAFL), nonalcoholic fatty pancreas disease (NAFP); to assess the efficiency of ursodeoxycholic acid (UDCA) for their correction. Key Points. NAFL and NAFP have much in common, including BA synthesis imbalance and reduced farnesoid X receptor (FXR) expression. One possible therapy of NAFL and NAFP is BA synthesis correction and increase in FXR expression using FXR agonists. The article discusses clinical and experimental trials of the efficiency of selective FXR agonist — UDCA — in NAFL and NAFP. Conclusion. The multifactorial UDCA mechanism of action including anti-inflammatory, antioxidant, cytoprotective and antiapoptotic actions, can normalise carbohydrate, lipid metabolism and activate FXR; it can justify medicine inclusion into NAFL and NAFP therapeutic regimens. Keywords: nonalcoholic fatty liver disease, nonalcoholic fatty pancreas disease, ursodeoxycholic acid.

scholarly journals Bile Acid and Fibroblast Growth Factor 19 Regulation in Obese Diabetics, and Non-Alcoholic Fatty Liver Disease after Sleeve Gastrectomy

2019 ◽  
Vol 8 (6) ◽  
pp. 815 ◽  
Author(s):  
Hsien-Hao Huang ◽  
Wei-Jei Lee ◽  
Shu-Chun Chen ◽  
Tung-Fang Chen ◽  
Shou-Dong Lee ◽  
...  
Keyword(s):  
Bile Acid ◽  
Fatty Liver ◽  
Bile Acids ◽  
Fatty Liver Disease ◽  
Total Bile Acid ◽  
Alcoholic Fatty Liver ◽  
Liver Index ◽  
Fatty Liver Index ◽  
Total Bile Acids ◽  
Alcoholic Fatty Liver Disease

Background: Sleeve gastrectomy (SG) is an effective treatment for obesity and type 2 diabetes mellitus (T2DM), and non-alcoholic fatty liver disease (NAFLD); however, the mechanism is not completely understood. Bile acids and fibroblast growth factors (FGFs) are involved in the regulation of energy metabolism. Methods: We investigated the roles of total bile acid and FGF 19 in T2DM remission and NAFLD improvement in obese subjects undergoing SG. A total of 18 patients with obesity and T2DM undergoing laparoscopic SG were enrolled in this study. Serial plasma total bile acid and FGF 19 levels were measured, while the fatty liver index was calculated before and after surgery. Results: The FGF 19 level significantly increased, and the total bile acid level and fatty liver index decreased 1 year after surgery. The complete T2DM remission rate was 66.7% one year after surgery; the complete remitters had significantly lower FGF 19 levels and higher insulin levels than the non-complete remitters. The complete remitters also had significantly decreased total bile acid levels and increased FGF 19 levels 1 year after surgery compared with those before surgery. The fatty improvers had significantly decreased total bile acid levels and increased FGF 19 levels 1 year after surgery compared with those before surgery. Conclusion: The total bile acids level and fatty liver index decreased, and the FGF 19 levels increased 1 year after SG. Both T2DM complete remitters and NAFLD improvers showed significantly decreased total bile acid levels and increased FGF 19 levels 1 year after SG. Plasma total bile acids and FGF 19 might have roles in T2DM remission and NAFLD improvement. Low preoperative FGF 19 levels might be a predictor for NAFLD improvement after SG.

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