scholarly journals Gut-Pancreas-Liver Axis as a Target for Treatment of NAFLD/NASH

2020 ◽  
Vol 21 (16) ◽  
pp. 5820
Author(s):  
Gianluca Svegliati-Baroni ◽  
Bárbara Patrício ◽  
Gessica Lioci ◽  
Maria Paula Macedo ◽  
Amalia Gastaldelli
Keyword(s):  
Liver Transplantation ◽  
Liver Disease ◽  
Fatty Liver Disease ◽  
Incretin Hormones ◽  
Portal Circulation ◽  
Therapeutic Approaches ◽  
Alcoholic Fatty Liver ◽  
Obesity And Diabetes ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) represents the most common form of chronic liver disease worldwide. Due to its association with obesity and diabetes and the fall in hepatitis C virus morbidity, cirrhosis in NAFLD is becoming the most frequent indication to liver transplantation, but the pathogenetic mechanisms are still not completely understood. The so-called gut-liver axis has gained enormous interest when data showed that its alteration can lead to NAFLD development and might favor the occurrence of non-alcoholic steatohepatitis (NASH). Moreover, several therapeutic approaches targeting the gut-pancreas-liver axis, e.g., incretins, showed promising results in NASH treatment. In this review, we describe the role of incretin hormones in NAFLD/NASH pathogenesis and treatment and how metagenomic/metabolomic alterations in the gut microbiota can lead to NASH in the presence of gut barrier modifications favoring the passage of bacteria or bacterial products in the portal circulation, i.e., bacterial translocation.

scholarly journals Cardiovascular involvement after liver transplantation: role of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis

2021 ◽  
Author(s):  
Rosa Lombardi ◽  
Giuseppina Pisano ◽  
Silvia Fargion ◽  
Anna Ludovica Fracanzani
Keyword(s):  
Metabolic Syndrome ◽  
Liver Transplantation ◽  
Liver Disease ◽  
High Risk ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Patients submitted to liver transplantation (LT) are exposed to high risk of cardiovascular (CV) complications which are the main determinants of both short-term and long-term morbidity and mortality in LT. Non-alcoholic fatty liver disease (NAFLD) is a very frequent condition in general population and is associated with a high risk of cardiovascular disease (CVD) which represents the first cause of death of these patients. NAFLD is predicted to become the first indication to LT and nowadays is also frequently detected in patients submitted to LT for other indications. Thus, the risk of CVD in patients submitted to LT is forecasted to increase in the next years. In this review the extent of CV involvement in patients submitted to LT and the role of NAFLD, either recurring after transplantation or as de novo presentation, in increasing CV risk is analysed. The risk of developing metabolic alterations, including diabetes, hypertension, dyslipidemia and weight gain, all manifestations of metabolic syndrome, occurring in the first months after LT, is depicted. The different presentations of cardiac involvement, represented by early atherosclerosis, coronary artery disease, heart failure and arrhythmias in patients with NAFLD submitted to LT is described. In addition, the tools to detect cardiac alterations either before or after LT is reported providing the possibility for an early diagnosis of CVD and an early therapy able to reduce morbidity and mortality for these diseases. The need for long-term concerted multidisciplinary activity with dietary counseling and exercise combined with drug treatment of all manifestations of metabolic syndrome is emphasized.

scholarly journals NONINVASIVE METHODS IN THE DIAGNOSIS OF NON-ALCOHOLIC FATTY LIVER DISEASE

2017 ◽  
Vol 20 (2) ◽  
pp. 107-112
Author(s):  
Igor G. Bakulin ◽  
M. P Abatsieva
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Diagnostic Methods ◽  
Noninvasive Methods ◽  
Alcoholic Fatty Liver ◽  
Obesity And Diabetes ◽  
Inflammatory Processes ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) being increasingly diagnosed worldwide is considered as the most common liver disease in Western countries. The incidence is growing rapidly due to the continuing epidemic of the obesity and diabetes mellitus type 2. There is the extremely topical question of the affordable, effective and early diagnosis of NAFLD. Over the past few years, significant progress has been made in the understanding of its risk factors, pathogenesis, clinical course, methods of diagnosis and treatment of NAFLD. The article gives an overview of modern and promising methods for diagnosing NAFLD, useful for physicians of various specialties who have to deal with NAFLD patients. Key problems of diagnostics are formulated and directions for further research are determined. There is discussed the role of biomarkers as promising noninvasive diagnostic methods, that provides to assess the severity of necrotic inflammatory processes and liver fibrosis in NAFLD patients.

scholarly journals Inflammation and Fibrogenesis in MAFLD: Role of the Hepatic Immune System

2021 ◽  
Vol 8 ◽  
Author(s):  
Pietro Torre ◽  
Benedetta Maria Motta ◽  
Roberta Sciorio ◽  
Mario Masarone ◽  
Marcello Persico
Keyword(s):  
Immune System ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Liver Diseases ◽  
Metabolic Dysfunction ◽  
Therapeutic Approaches ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Metabolic (dysfunction)-associated fatty liver disease (MAFLD) is the definition recently proposed to better circumscribe the spectrum of conditions long known as non-alcoholic fatty liver disease (NAFLD) that range from simple steatosis without inflammation to more advanced liver diseases. The progression of MAFLD, as well as other chronic liver diseases, toward cirrhosis, is driven by hepatic inflammation and fibrogenesis. The latter, result of a “chronic wound healing reaction,” is a dynamic process, and the understanding of its underlying pathophysiological events has increased in recent years. Fibrosis progresses in a microenvironment where it takes part an interplay between fibrogenic cells and many other elements, including some cells of the immune system with an underexplored or still unclear role in liver diseases. Some therapeutic approaches, also acting on the immune system, have been probed over time to evaluate their ability to improve inflammation and fibrosis in NAFLD, but to date no drug has been approved to treat this condition. In this review, we will focus on the contribution of the liver immune system in the progression of NAFLD, and on therapies under study that aim to counter the immune substrate of the disease.

scholarly journals The Role of the Transsulfuration Pathway in Non-Alcoholic Fatty Liver Disease

2021 ◽  
Vol 10 (5) ◽  
pp. 1081
Author(s):  
Mikkel Parsberg Werge ◽  
Adrian McCann ◽  
Elisabeth Douglas Galsgaard ◽  
Dorte Holst ◽  
Anne Bugge ◽  
...  
Keyword(s):  
Liver Disease ◽  
Animal Models ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
Precise Control ◽  
Transsulfuration Pathway ◽  
Global Population ◽  
Alcoholic Fatty Liver Disease

The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing and approximately 25% of the global population may have NAFLD. NAFLD is associated with obesity and metabolic syndrome, but its pathophysiology is complex and only partly understood. The transsulfuration pathway (TSP) is a metabolic pathway regulating homocysteine and cysteine metabolism and is vital in controlling sulfur balance in the organism. Precise control of this pathway is critical for maintenance of optimal cellular function. The TSP is closely linked to other pathways such as the folate and methionine cycles, hydrogen sulfide (H2S) and glutathione (GSH) production. Impaired activity of the TSP will cause an increase in homocysteine and a decrease in cysteine levels. Homocysteine will also be increased due to impairment of the folate and methionine cycles. The key enzymes of the TSP, cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE), are highly expressed in the liver and deficient CBS and CSE expression causes hepatic steatosis, inflammation, and fibrosis in animal models. A causative link between the TSP and NAFLD has not been established. However, dysfunctions in the TSP and related pathways, in terms of enzyme expression and the plasma levels of the metabolites (e.g., homocysteine, cystathionine, and cysteine), have been reported in NAFLD and liver cirrhosis in both animal models and humans. Further investigation of the TSP in relation to NAFLD may reveal mechanisms involved in the development and progression of NAFLD.

scholarly journals Target Therapies for NASH/NAFLD: From the Molecular Aspect to the Pharmacological and Surgical Alternatives

2021 ◽  
Vol 11 (6) ◽  
pp. 499
Author(s):  
Michele Finotti ◽  
Maurizio Romano ◽  
Pasquale Auricchio ◽  
Michele Scopelliti ◽  
Marco Brizzolari ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Fatty Liver Disease ◽  
Hepatic Disease ◽  
Lifestyle Modifications ◽  
Alcoholic Fatty Liver ◽  
Target Therapies ◽  
Chronic Hepatic Disease ◽  
The Impact ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease represents an increasing cause of chronic hepatic disease in recent years. This condition usually arises in patients with multiple comorbidities, the so-called metabolic syndrome. The therapeutic options are multiple, ranging from lifestyle modifications, pharmacological options, to liver transplantation in selected cases. The choice of the most beneficial one and their interactions can be challenging. It is mandatory to stratify the patients according to the severity of their disease to tailor the available treatments. In our contribution, we review the most recent pharmacological target therapies, the role of bariatric surgery, and the impact of liver transplantation on the NAFLD outcome.

scholarly journals The Role of Oxidative Stress in NAFLD–NASH–HCC Transition—Focus on NADPH Oxidases

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 687
Author(s):  
Daniela Gabbia ◽  
Luana Cannella ◽  
Sara De De Martin
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Current Knowledge ◽  
Mechanisms Of Action ◽  
Nadph Oxidases ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

A peculiar role for oxidative stress in non-alcoholic fatty liver disease (NAFLD) and its transition to the inflammatory complication non-alcoholic steatohepatitis (NASH), as well as in its threatening evolution to hepatocellular carcinoma (HCC), is supported by numerous experimental and clinical studies. NADPH oxidases (NOXs) are enzymes producing reactive oxygen species (ROS), whose abundance in liver cells is closely related to inflammation and immune responses. Here, we reviewed recent findings regarding this topic, focusing on the role of NOXs in the different stages of fatty liver disease and describing the current knowledge about their mechanisms of action. We conclude that, although there is a consensus that NOX-produced ROS are toxic in non-neoplastic conditions due to their role in the inflammatory vicious cycle sustaining the transition of NAFLD to NASH, their effect is controversial in the neoplastic transition towards HCC. In this regard, there are indications of a differential effect of NOX isoforms, since NOX1 and NOX2 play a detrimental role, whereas increased NOX4 expression appears to be correlated with better HCC prognosis in some studies. Further studies are needed to fully unravel the mechanisms of action of NOXs and their relationships with the signaling pathways modulating steatosis and liver cancer development.

scholarly journals Role of illness perception and self-efficacy in lifestyle modification among non-alcoholic fatty liver disease patients

2017 ◽  
Vol 23 (10) ◽  
pp. 1881 ◽  
Author(s):  
Shira Zelber-Sagi ◽  
Shiran Bord ◽  
Gali Dror-Lavi ◽  
Matthew Lee Smith ◽  
Samuel D Towne Jr ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Self Efficacy ◽  
Fatty Liver Disease ◽  
Lifestyle Modification ◽  
Illness Perception ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

scholarly journals A Narrative Review on the Role of AMPK on De Novo Lipogenesis in Non-Alcoholic Fatty Liver Disease: Evidence from Human Studies

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1822
Author(s):  
Christian von Loeffelholz ◽  
Sina M. Coldewey ◽  
Andreas L. Birkenfeld
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Mammalian Cells ◽  
De Novo ◽  
Adenosine Monophosphate ◽  
De Novo Lipogenesis ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

5′AMP-activated protein kinase (AMPK) is known as metabolic sensor in mammalian cells that becomes activated by an increasing adenosine monophosphate (AMP)/adenosine triphosphate (ATP) ratio. The heterotrimeric AMPK protein comprises three subunits, each of which has multiple phosphorylation sites, playing an important role in the regulation of essential molecular pathways. By phosphorylation of downstream proteins and modulation of gene transcription AMPK functions as a master switch of energy homeostasis in tissues with high metabolic turnover, such as the liver, skeletal muscle, and adipose tissue. Regulation of AMPK under conditions of chronic caloric oversupply emerged as substantial research target to get deeper insight into the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Evidence supporting the role of AMPK in NAFLD is mainly derived from preclinical cell culture and animal studies. Dysbalanced de novo lipogenesis has been identified as one of the key processes in NAFLD pathogenesis. Thus, the scope of this review is to provide an integrative overview of evidence, in particular from clinical studies and human samples, on the role of AMPK in the regulation of primarily de novo lipogenesis in human NAFLD.

Sign in / Sign up

Export Citation Format

Share Document