Persistent Deficiency of Mucosa-associated Invariant T (MAIT) cells During Alcohol-related Liver Disease

2021 ◽  
Author(s):  
Yujue Zhang ◽  
Yuanyuan Fan ◽  
Wei He ◽  
Yi Han ◽  
Huarui Bao ◽  
...  
Keyword(s):  
Liver Disease ◽  
Inflammatory Diseases ◽  
Alcoholic Cirrhosis ◽  
Cell Loss ◽  
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, and the inflammatory response is a basic pathological feature of ALD. Immunity throughout different stages of ALD has not yet been elucidated. The mucosal-associated invariant T(MAIT) cells are a novel population of innate immune cells, which may be depleted in various inflammatory diseases. However, the mechanism of MAIT cell loss in ALD remains unclear.Results: In this study, we found that MAIT cells were depleted in patients with alcoholic fatty liver disease, alcoholic cirrhosis, and mixed cirrhosis (alcoholic + viral). Furthermore, the reduction in circulating MAIT cells was correlated with liver function in patients with cirrhosis. We detected 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 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.

Liver disorders

2021 ◽  
pp. 208-258
Author(s):  
Thomas Marjot
Keyword(s):  
Liver Transplantation ◽  
Liver Disease ◽  
Core Curriculum ◽  
Chronic Viral Hepatitis ◽  
Alcoholic Fatty Liver ◽  
Liver Disorders ◽  
Bacterial Peritonitis ◽  
Complications Of Cirrhosis ◽  
Related Liver Disease ◽  
Curriculum Topics

This chapter covers core curriculum topics relating to liver disorders including the anatomy, physiology, and biochemistry of the liver as it relates to disease processes. There is a focus on the investigation and management of acute hepatitis including viral, drug- and toxin-induced, and the risk stratification of patients with acute liver failure. All major chronic liver diseases are discussed including non-alcoholic fatty liver disease, autoimmune liver disease, alcohol related liver disease and chronic viral hepatitis. There is also education on managing the complications of cirrhosis including renal dysfunction, hepatic encephalopathy, variceal haemorrhage, and spontaneous bacterial peritonitis. Additional important topics covered include nutrition in liver disease, hepatocellular carcinoma, liver transplantation indications and assessment, and complications following liver transplantation. Additional curriculum material regarding liver disorders will also be covered in the mock examination chapter.

scholarly journals Alkoholos májbetegség: a genetikai-epigenetikai tényezők szerepe és az absztinencia hatása

2019 ◽  
Vol 160 (14) ◽  
pp. 524-532 ◽  
Author(s):  
Alajos Pár ◽  
Gabriella Pár
Keyword(s):  
Risk Factors ◽  
Liver Disease ◽  
Environmental Factors ◽  
Alcoholic Liver Disease ◽  
Liver Toxicity ◽  
Hepatitis Virus ◽  
Alcoholic Cirrhosis ◽  
Protective Role ◽  
Micro Rna ◽  
Alcoholic Fatty Liver

Abstract: The pathogenesis of alcoholic liver disease depends not only on the toxic effects of alcohol, but also on the complex interaction of host’s and environmental factors. Thus, the genetic pre-disposition, co-morbidities and behavioral factors all play a role in the individual variations in the disease outcomes. On the other hand, the essential part of the therapeutic strategy is the complete withdrawal of the harmful etiological agent. The present paper is devoted to overview the genetics, the environmental factors and the effects of abstinence in alcoholic liver disease. Genetic variants in two enzymes involved in the metabolism of ethanol, alcohol-dehydrogenase ADH1B *2 and aldehyde-dehydrogenase ALDH2 *2 through increasing the blood level of acetaldehyde, may play a “protective” role against alcoholism. The P450 CYP2E1 *5 c2, an inducible microsomal oxidase, upregulated by ethanol and by formation of acetaldehyde and reactive oxygen species, increases liver toxicity. Three novel gene polymorphisms – such as the patatin-like phospholipase domain-containing 3 (PNPLA3 I148M C>G), the transmembrane 6 superfamily member 2 (TM6SF2 E167K), and the membrane-bound O-acyltransferase domain-containing 7 (MB0AT7 rs641738 C>T) – have been proven as risk factors of steatosis, fibrosis and even hepatocellular carcinoma in both alcoholic and non-alcoholic fatty liver disease patients. Alcohol-induced epigenetic effects, reversible but inheritable gene expression alterations – as histon modulations, DNA methylation and micro-RNA-s – are of importance in the pathogenesis as well, and in the future, they may serve as diagnostic markers and therapeutic targets. Women are at greater risk of developing alcoholic cirrhosis, furthermore, malnutrition, obesity, diabetes, smoking, and hepatitis virus infections are also risk factors. Alcoholic liver disease should be regarded as a preventable disease. Several clinical studies revealed that abstinence may result in the regression of steatohepatitis and fibrosis, compensation of cirrhosis, improving disease outcome and increasing survival even in patients with advanced stages. Early diagnosis and multidisciplinary interventions are highly required to achieve long-term abstinence and to prevent alcoholic cirrhosis. Orv Hetil. 2019; 160(14): 524–532.

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).

Abnormal liver function tests

2019 ◽  
Vol 12 (9) ◽  
pp. 507-515
Author(s):  
Ceen-Ming Tang
Keyword(s):  
Primary Care ◽  
Liver Disease ◽  
Liver Function ◽  
Liver Function Tests ◽  
Alcoholic Fatty Liver ◽  
Premature Deaths ◽  
Function Tests ◽  
Medication Reviews ◽  
Related Liver Disease ◽  
The Uk

Liver disease is a clinical priority area identified by the RCGP, due to increasing levels of morbidity and mortality. Liver disease causes an estimated 8500 premature deaths in the UK annually, predominantly from a rise in non-alcoholic fatty liver disease, alcohol-related liver disease, and viral hepatitis. There has been a corresponding increase in liver function tests (LFTs) ordered from primary care, often as part of medication reviews or monitoring of chronic disease. GPs will therefore encounter an increasing number of abnormal LFTs in patients asymptomatic of liver disease. This article outlines a framework for investigating abnormal LFTs in primary care.

scholarly journals Fungi–Bacteria Correlation in Alcoholic Hepatitis Patients

Toxins ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 143
Author(s):  
Bei Gao ◽  
Xinlian Zhang ◽  
Bernd Schnabl
Keyword(s):  
Liver Disease ◽  
Alcoholic Hepatitis ◽  
Predictive Power ◽  
Positive Association ◽  
Shotgun Metagenomics ◽  
Functional Changes ◽  
Compositional Changes ◽  
Bacteria And Fungi ◽  
Related Liver Disease ◽  
Better Than

Alcohol-related liver disease is one of the most prevalent types of chronic liver diseases globally. Alcohol-related liver disease begins with fatty liver, which further develops into hepatic inflammation, hepatocyte injury, and progresses to fibrosis and cirrhosis. Compositional changes of gut bacteria and fungi were found in patients with alcohol-related liver disease. However, the functional changes of fungi and correlations between fungi and bacteria have not been investigated. In this study, we first examined the functional capacity of fungi in patients with alcohol-related liver disease using shotgun metagenomics. Among 24 MetaCyc pathways contributed by fungi, superpathway of allantoin degradation in yeast was enriched in patients with alcoholic hepatitis. Furthermore, we compared the predictive power of bacteria versus fungi and found that bacteria performed better than fungi to separate patients with alcoholic hepatitis from non-alcoholic controls and patients with alcohol use disorder. Finally, we investigated the associations between the intestinal fungi and bacteria in alcoholic hepatitis patients. Positive association between fungi and bacteria was found between Cladosporium and Gemmiger, meanwhile negative association was found between Cryptococcus and Pseudomonas in alcoholic hepatitis patients.

scholarly journals Impact of Sarcopenia and Myosteatosis in Non-Cirrhotic Stages of Liver Diseases: Similarities and Differences across Aetiologies and Possible Therapeutic Strategies

Biomedicines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 182
Author(s):  
Annalisa Cespiati ◽  
Marica Meroni ◽  
Rosa Lombardi ◽  
Giovanna Oberti ◽  
Paola Dongiovanni ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Diseases ◽  
Early Stage ◽  
Alcoholic Fatty Liver ◽  
Early Stages ◽  
Advanced Stages ◽  
Related Liver Disease ◽  
And Function ◽  
The Relationship

Sarcopenia is defined as a loss of muscle strength, mass and function and it is a predictor of mortality. Sarcopenia is not only a geriatric disease, but it is related to several chronic conditions, including liver diseases in both its early and advanced stages. Despite the increasing number of studies exploring the role of sarcopenia in the early stages of chronic liver disease (CLD), its prevalence and the relationship between these two clinical entities are still controversial. Myosteatosis is characterized by fat accumulation in the muscles and it is related to advanced liver disease, although its role in the early stages is still under researched. Therefore, in this narrative review, we firstly aimed to evaluate the prevalence and the pathogenetic mechanisms underlying sarcopenia and myosteatosis in the early stage of CLD across different aetiologies (mainly non-alcoholic fatty liver disease, alcohol-related liver disease and viral hepatitis). Secondly, due to the increasing prevalence of sarcopenia worldwide, we aimed to revise the current and the future therapeutic approaches for the management of sarcopenia in CLD.

scholarly journals Functional and Activation Profiles of Mucosal-Associated Invariant T Cells in Patients With Tuberculosis and HIV in a High Endemic Setting

2021 ◽  
Vol 12 ◽  
Author(s):  
Avuyonke Balfour ◽  
Charlotte Schutz ◽  
Rene Goliath ◽  
Katalin A. Wilkinson ◽  
Sumaya Sayed ◽  
...  
Keyword(s):  
T Cells ◽  
Hiv Infection ◽  
Functional Impairment ◽  
Functional Profile ◽  
Functional Changes ◽  
Mait Cells ◽  
Endemic Setting ◽  
Tb Treatment ◽  
Hla Dr ◽  
Mait Cell

Background: MAIT cells are non-classically restricted T lymphocytes that recognize and rapidly respond to microbial metabolites or cytokines and have the capacity to kill bacteria-infected cells. Circulating MAIT cell numbers generally decrease in patients with active TB and HIV infection, but findings regarding functional changes differ.Methods: We conducted a cross-sectional study on the effect of HIV, TB, and HIV-associated TB (HIV-TB) on MAIT cell frequencies, activation and functional profile in a high TB endemic setting in South Africa. Blood was collected from (i) healthy controls (HC, n = 26), 24 of whom had LTBI, (ii) individuals with active TB (aTB, n = 36), (iii) individuals with HIV infection (HIV, n = 50), 37 of whom had LTBI, and (iv) individuals with HIV-associated TB (HIV-TB, n = 26). All TB participants were newly diagnosed and sampled before treatment, additional samples were also collected from 18 participants in the aTB group after 10 weeks of TB treatment. Peripheral blood mononuclear cells (PBMC) stimulated with BCG-expressing GFP (BCG-GFP) and heat-killed (HK) Mycobacterium tuberculosis (M.tb) were analyzed using flow cytometry. MAIT cells were defined as CD3+ CD161+ Vα7.2+ T cells.Results: Circulating MAIT cell frequencies were depleted in individuals with HIV infection (p = 0.009). MAIT cells showed reduced CD107a expression in aTB (p = 0.006), and reduced IFNγ expression in aTB (p < 0.001) and in HIV-TB (p < 0.001) in response to BCG-GFP stimulation. This functional impairment was coupled with a significant increase in activation (defined by HLA-DR expression) in resting MAIT cells from HIV (p < 0.001), aTB (p = 0.019), and HIV-TB (p = 0.005) patients, and higher HLA-DR expression in MAIT cells expressing IFNγ in aTB (p = 0.009) and HIV-TB (p = 0.002) after stimulation with BCG-GFP and HK-M.tb. After 10 weeks of TB treatment, there was reversion in the observed functional impairment in total MAIT cells, with increases in CD107a (p = 0.020) and IFNγ (p = 0.010) expression.Conclusions: Frequencies and functional profile of MAIT cells in response to mycobacterial stimulation are significantly decreased in HIV infected persons, active TB and HIV-associated TB, with a concomitant increase in MAIT cell activation. These alterations may reduce the capacity of MAIT cells to play a protective role in the immune response to these two pathogens.

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