scholarly journals The Emerging Relevance of AIM2 in Liver Disease

2020 ◽  
Vol 21 (18) ◽  
pp. 6535
Author(s):  
Beatriz Lozano-Ruiz ◽  
José M. González-Navajas
Keyword(s):  
Liver Disease ◽  
Inflammatory Diseases ◽  
Research Area ◽  
Cellular Damage ◽  
Inflammasome Activation ◽  
Immune Recognition ◽  
Alcoholic Fatty Liver ◽  
Hepatic Diseases ◽  
Life Threatening ◽  
New Research

Absent in melanoma 2 (AIM2) is a cytosolic receptor that recognizes double-stranded DNA (dsDNA) and triggers the activation of the inflammasome cascade. Activation of the inflammasome results in the maturation of inflammatory cytokines, such as interleukin (IL)-1 β and IL-18, and a form of cell death known as pyroptosis. Owing to the conserved nature of its ligand, AIM2 is important during immune recognition of multiple pathogens. Additionally, AIM2 is also capable of recognizing host DNA during cellular damage or stress, thereby contributing to sterile inflammatory diseases. Inflammation, either in response to pathogens or due to sterile cellular damage, is at the center of the most prevalent and life-threatening liver diseases. Therefore, during the last 15 years, the study of inflammasome activation in the liver has emerged as a new research area in hepatology. Here, we discuss the known functions of AIM2 in the pathogenesis of different hepatic diseases, including non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), hepatitis B, liver fibrosis, and hepatocellular carcinoma (HCC).

The Relevance of Noninvasive Tools To Assess Fibrosis in Non-Alcoholic Fatty Liver Disease

2020 ◽  
Vol 26 (32) ◽  
pp. 3928-3938
Author(s):  
Grazia Pennisi ◽  
Ciro Celsa ◽  
Antonina Giammanco ◽  
Federica Spatola ◽  
Salvatore Petta
Keyword(s):  
Liver Disease ◽  
Liver Biopsy ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Assessment Tools ◽  
Hepatic Decompensation ◽  
Alcoholic Fatty Liver ◽  
Simple Steatosis ◽  
Life Threatening ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is a growing cause of chronic liver diseases worldwide, involving about 25% of people. NAFLD incorporates a large spectrum of pathological conditions, from simple steatosis to non-alcoholic steatohepatitis (NASH), cirrhosis and its complications include hepatic decompensation and hepatocellular carcinoma (HCC). This progression occurs, over many years, in an asymptomatic way, until advanced fibrosis appears. Thus, the differentiation of NASH from simple steatosis and identification of advanced hepatic fibrosis are key issues. To date, the histological assessment of fibrosis with liver biopsy is the gold standard, but obviously, invasiveness is the greater threshold. In addition, rare but potentially life-threatening complications, poor acceptability, sampling variability and cost maybe restrict its use. Furthermore, due to the epidemic of NAFLD worldwide and several limitations of liver biopsy evaluation, noninvasive assessment tools to detect fibrosis in NAFLD patients are needed.

scholarly journals Depression and Cognitive Impairment—Extrahepatic Manifestations of NAFLD and NASH

Biomedicines ◽  
2020 ◽  
Vol 8 (7) ◽  
pp. 229 ◽  
Author(s):  
Martina Colognesi ◽  
Daniela Gabbia ◽  
Sara De Martin
Keyword(s):  
Cognitive Impairment ◽  
Liver Disease ◽  
Depression And Anxiety ◽  
Extrahepatic Manifestations ◽  
Alcoholic Fatty Liver ◽  
Hepatic Diseases ◽  
Pharmacological Targets ◽  
Number Of Patients ◽  
Brain Insulin Resistance ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) and its complication non-alcoholic steatohepatitis (NASH) are important causes of liver disease worldwide. Recently, a significant association between these hepatic diseases and different central nervous system (CNS) disorders has been observed in an increasing number of patients. NAFLD-related CNS dysfunctions include cognitive impairment, hippocampal-dependent memory impairment, and mood imbalances (in particular, depression and anxiety). This review aims at summarizing the main correlations observed between NAFLD development and these CNS dysfunctions, focusing on the studies investigating the mechanism(s) involved in this association. Growing evidences point at cerebrovascular alteration, neuroinflammation, and brain insulin resistance as NAFLD/NASH-related CNS manifestations. Since the pharmacological options available for the management of these conditions are still limited, further studies are needed to unravel the mechanism(s) of NAFLD/NASH and their central manifestations and identify effective pharmacological targets.

scholarly journals Chemical Effect of Bisphenol A on Non-Alcoholic Fatty Liver Disease

2019 ◽  
Vol 16 (17) ◽  
pp. 3134 ◽  
Author(s):  
Marcello Dallio ◽  
Nadia Diano ◽  
Mario Masarone ◽  
Antonietta Gerarda Gravina ◽  
Vittorio Patanè ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Liver Disease ◽  
Bisphenol A ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Scientific Evidence ◽  
Research Area ◽  
Chemical Effect ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is considered a predominant chronic liver disease worldwide and a component of metabolic syndrome. Due to its relationship with multiple organs, it is extremely complex to precisely define its pathogenesis as well as to set appropriate therapeutic and preventive strategies. Endocrine disruptors (EDCs) in general, and bisphenol A (BPA) in particular, are a heterogeneous group of substances, largely distributed in daily use items, able to interfere with the normal signaling of several hormones that seem to be related to type 2 diabetes mellitus (T2DM), obesity, and other metabolic disorders. It is reasonable to hypothesize a BPA involvement in the pathogenesis and evolution of NAFLD. However, its mechanisms of action as well as its burden in the vicious circle that connects obesity, T2DM, metabolic syndrome, and NAFLD still remain to be completely defined. In this review we analyzed the scientific evidence on this promising research area, in order to provide an overview of the harmful effects linked to the exposure to EDCs as well as to frame the role that BPA would have in all phases of NAFLD evolution.

scholarly journals Persistent deficiency of mucosa-associated invariant T (MAIT) cells during alcohol-related liver disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yujue Zhang ◽  
Yuanyuan Fan ◽  
Wei He ◽  
Yi Han ◽  
Huarui Bao ◽  
...  
Keyword(s):  
Liver Disease ◽  
Inflammatory Diseases ◽  
Alcoholic Cirrhosis ◽  
Serum Levels ◽  
Pathological Feature ◽  
Alcoholic Fatty Liver ◽  
Functional Changes ◽  
Mait Cells ◽  
Related Liver Disease ◽  
Mait Cell

Abstract Background Alcohol-related liver disease (ALD) is a major cause of chronic liver diseases. Inflammatory response is a basic pathological feature of ALD. Mucosal-associated invariant T(MAIT) cells are a novel population of innate immune cells, which may be depleted in various inflammatory diseases. However, the changes of MAIT cell in ALD remains unclear. Results In this study, the levels of MAIT cell were significantly decreased in patients with alcoholic fatty liver disease, alcoholic cirrhosis, and mixed cirrhosis (alcoholic + viral). Furthermore, the reduction of circulating MAIT cells was correlated with liver function in patients with cirrhosis. Functional changes among circulating MAIT cells in patients with alcoholic cirrhosis, including increased production of IL-17A and perforin, and reduced production of TNF-α. Plasma cytokine and chemokine levels were quantified using multiple immunoassays and ELISA. Serum levels of chemokine IL-8 were correlated with MAIT cell frequency in patients with alcoholic cirrhosis. Moreover, no differences were observed in the expression of CCR6, CXCR6, and PD-1 in circulating MAIT cells of patients with alcoholic cirrhosis. The MAIT cells in patients with alcoholic cirrhosis were prone to apoptosis, which was promoted by IL-12, IL-18, and IL-8. Conclusions Our findings indicate persistent MAIT cell loss during alcohol-related liver disease and suggest that MAIT cells can be promising indicator and therapeutic targets in ALD.

scholarly journals Molecular and Cellular Mediators of the Gut-Liver Axis in the Progression of Liver Diseases

2021 ◽  
Vol 8 ◽  
Author(s):  
Alix Bruneau ◽  
Jana Hundertmark ◽  
Adrien Guillot ◽  
Frank Tacke
Keyword(s):  
Liver Disease ◽  
Bile Acids ◽  
Intracellular Signaling ◽  
Liver Diseases ◽  
Immune Cell ◽  
Chronic Liver ◽  
Inflammasome Activation ◽  
Liver Inflammation ◽  
Alcoholic Fatty Liver ◽  
Liver Disease Progression

The gut-liver axis covers the bidirectional communication between the gut and the liver, and thus includes signals from liver-to-gut (e.g., bile acids, immunoglobulins) and from gut-to-liver (e.g., nutrients, microbiota-derived products, and recirculating bile acids). In a healthy individual, liver homeostasis is tightly controlled by the mostly tolerogenic liver resident macrophages, the Kupffer cells, capturing the gut-derived antigens from the blood circulation. However, disturbances of the gut-liver axis have been associated to the progression of varying chronic liver diseases, such as non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, and primary sclerosing cholangitis. Notably, changes of the gut microbiome, or intestinal dysbiosis, combined with increased intestinal permeability, leads to the translocation of gut-derived bacteria or their metabolites into the portal vein. In the context of concomitant or subsequent liver inflammation, the liver is then infiltrated by responsive immune cells (e.g., monocytes, neutrophils, lymphoid, or dendritic cells), and microbiota-derived products may provoke or exacerbate innate immune responses, hence perpetuating liver inflammation and fibrosis, and potentiating the risks of developing cirrhosis. Similarly, food derived antigens, bile acids, danger-, and pathogen-associated molecular patterns are able to reshape the liver immune microenvironment. Immune cell intracellular signaling components, such as inflammasome activation, toll-like receptor or nucleotide-binding oligomerization domain-like receptors signaling, are potent targets of interest for the modulation of the immune response. This review describes the current understanding of the cellular landscape and molecular pathways involved in the gut-liver axis and implicated in chronic liver disease progression. We also provide an overview of innovative therapeutic approaches and current clinical trials aiming at targeting the gut-liver axis for the treatment of patients with chronic liver and/or intestinal diseases.

scholarly journals Mitochondrial Mutations and Genetic Factors Determining NAFLD Risk

2021 ◽  
Vol 22 (9) ◽  
pp. 4459
Author(s):  
Siarhei A. Dabravolski ◽  
Evgeny E. Bezsonov ◽  
Mirza S. Baig ◽  
Tatyana V. Popkova ◽  
Ludmila V. Nedosugova ◽  
...  
Keyword(s):  
Liver Disease ◽  
Causative Role ◽  
Nucleotide Polymorphisms ◽  
Mitochondrial Mutations ◽  
Single Nucleotide ◽  
Alcoholic Fatty Liver ◽  
Dna Mutations ◽  
Life Threatening ◽  
Mitochondria Dna

NAFLD (non-alcoholic fatty liver disease) is a widespread liver disease that is often linked with other life-threatening ailments (metabolic syndrome, insulin resistance, diabetes, cardiovascular disease, atherosclerosis, obesity, and others) and canprogress to more severe forms, such as NASH (non-alcoholic steatohepatitis), cirrhosis, and HCC (hepatocellular carcinoma). In this review, we summarized and analyzed data about single nucleotide polymorphism sites, identified in genes related to NAFLD development and progression. Additionally, the causative role of mitochondrial mutations and mitophagy malfunctions in NAFLD is discussed. The role of mitochondria-related metabolites of the urea cycle as a new non-invasive NAFLD biomarker is discussed. While mitochondria DNA mutations and SNPs (single nucleotide polymorphisms) canbe used as effective diagnostic markers and target for treatments, age and ethnic specificity should be taken into account.

scholarly journals Oxidation-Specific Epitopes in Non-Alcoholic Fatty Liver Disease

2020 ◽  
Vol 11 ◽  
Author(s):  
Tim Hendrikx ◽  
Christoph J. Binder
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Inflammatory Diseases ◽  
Normal Function ◽  
Peroxidation Of Lipids ◽  
Oxygen Species ◽  
Alcoholic Fatty Liver ◽  
Dying Cells ◽  
Alcoholic Fatty Liver Disease

An improper balance between the production and elimination of intracellular reactive oxygen species causes increased oxidative stress. Consequently, DNA, RNA, proteins, and lipids are irreversibly damaged, leading to molecular modifications that disrupt normal function. In particular, the peroxidation of lipids in membranes or lipoproteins alters lipid function and promotes formation of neo-epitopes, such as oxidation-specific epitopes (OSEs), which are found to be present on (lipo)proteins, dying cells, and extracellular vesicles. Accumulation of OSEs and recognition of OSEs by designated pattern recognition receptors on immune cells or soluble effectors can contribute to the development of chronic inflammatory diseases. In line, recent studies highlight the involvement of modified lipids and OSEs in different stages of the spectrum of non-alcoholic fatty liver disease (NAFLD), including inflammatory non-alcoholic steatohepatitis (NASH), fibrosis, and hepatocellular carcinoma. Targeting lipid peroxidation products shows high potential in the search for novel, better therapeutic strategies for NASH.

scholarly journals Analysis of Common Pathways and Markers From Non-Alcoholic Fatty Liver Disease to Immune-Mediated Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Rocío Gallego-Durán ◽  
Rocío Montero-Vallejo ◽  
Douglas Maya-Miles ◽  
Ana Lucena ◽  
Franz Martin ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Loss Of Function ◽  
Alcoholic Fatty Liver ◽  
Mortality And Morbidity ◽  
Immunological Markers ◽  
Hepatic Diseases ◽  
Immune Mediated ◽  
Immune Changes

Metabolic associated fatty liver disease (MAFLD) is the most prevalent form of liver disease worldwide, accounting for a high liver-related mortality and morbidity with extensive multi-organ involvement. This entity has displaced viral hepatitis as the main cause of severe forms of hepatic diseases, although the onset and transition of MAFLD stages still remains unclear. Nevertheless, innate and adaptive immune responses seem to play an essential role in the establishment and further progression of this disease. The immune system is responsible of safeguard and preserves organs and systems function, and might be altered under different stimuli. Thus, the liver suffers from metabolic and immune changes leading to different injuries and loss of function. It has been stablished that cell-cell crosstalk is a key process in the hepatic homeostasis maintenance. There is mounting evidence suggesting that MAFLD pathogenesis is determined by a complex interaction of environmental, genetic and host factors that leads to a full plethora of outcomes. Therefore, herein we will revisit and discuss the interplay between immune mechanisms and MAFLD, highlighting the potential role of immunological markers in an attempt to clarify its relationship.

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