Recent Insights Into the Role of Immune Cells in Alcoholic Liver Disease

Li, Sha; Tan, Hor‐Yue; Wang, Ning; Feng, Yuqian; Wang, Xuanbin; Feng, Yibin

doi:10.3389/fimmu.2019.01328

Cited by 64 publications

(61 citation statements)

References 140 publications

(155 reference statements)

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“…Recent clinical and experimental research has shown that both innate and adaptive immunity plays a large role in the pathogenesis of ALD [68]. Alcohol activates innate immunity; whereas oxidative modification of hepatic constituents induces adaptive immunity [69]. Immune responses trigger the inflammation and drive the progression of ALD.…”

Section: Biomarkers Of Immune Responsementioning

confidence: 99%

Emerging Noninvasive Biomarkers, and Medical Management Strategies for Alcoholic Hepatitis: Present Understanding and Scope

Gala

Vatsalya

2020

Cells

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Alcohol use disorder is associated with a wide array of hepatic pathologies ranging from steatosis to alcoholic-related cirrhosis (AC), alcoholic hepatitis (AH), or hepatocellular carcinoma (HCC). Biomarkers are categorized into two main categories: biomarkers associated with alcohol consumption and biomarkers of alcoholic liver disease (ALD). No ideal biomarker has been identified to quantify the degree of hepatocyte death or severity of AH, even though numerous biomarkers have been associated with AH. This review provides information of some of the novel and latest biomarkers that are being investigated and have shown a substantial association with the degree and severity of liver injury and inflammation. Importantly, they can be measured noninvasively. In this manuscript, we consolidate the present understanding and prospects of these biomarkers; and their application in assessing the severity and progression of the alcoholic liver disease (ALD). We also review current and upcoming management options for AH.

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Section: Biomarkers Of Immune Responsementioning

confidence: 99%

Emerging Noninvasive Biomarkers, and Medical Management Strategies for Alcoholic Hepatitis: Present Understanding and Scope

Gala

Vatsalya

2020

Cells

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“…One of the first reports of dysregulated cAMP homeostasis in alcohol-associated hepatitis (AH) patients demonstrated decreased cAMP levels in peripheral blood mononuclear cells, suggesting that these patients had an immune dysfunction [ 128 ]. Later, it was also shown that lymphocytes from ALD patients had lower basal and adenosine-induced cAMP levels [ 129 ]. Bacterial dysbiosis and intestinal barrier damage due to chronic alcohol consumption leads to the leakage of harmful bacteria and bacterial products from the gut into the liver via the portal vein.…”

Section: Camp Signaling In Aldmentioning

confidence: 99%

cAMP Signaling in Pathobiology of Alcohol Associated Liver Disease

et al. 2020

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The importance of cyclic adenosine monophosphate (cAMP) in cellular responses to extracellular signals is well established. Many years after discovery, our understanding of the intricacy of cAMP signaling has improved dramatically. Multiple layers of regulation exist to ensure the specificity of cellular cAMP signaling. Hence, disturbances in cAMP homeostasis could arise at multiple levels, from changes in G protein coupled receptors and production of cAMP to the rate of degradation by phosphodiesterases. cAMP signaling plays critical roles in metabolism, inflammation and development of fibrosis in several tissues. Alcohol-associated liver disease (ALD) is a multifactorial condition ranging from a simple steatosis to steatohepatitis and fibrosis and ultimately cirrhosis, which might lead to hepatocellular cancer. To date, there is no FDA-approved therapy for ALD. Hence, identifying the targets for the treatment of ALD is an important undertaking. Several human studies have reported the changes in cAMP homeostasis in relation to alcohol use disorders. cAMP signaling has also been extensively studied in in vitro and in vivo models of ALD. This review focuses on the role of cAMP in the pathobiology of ALD with emphasis on the therapeutic potential of targeting cAMP signaling for the treatment of various stages of ALD.

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“…In a vicious loop, inflammatory agents are DAMP generators, and DAMPs create a pro-inflammatory state. These conditions are closely associated with immune mechanisms of both innate and acquired immunity triggering perpetuation of ALD [82].…”

Section: Hepatic Active Mediators and Signaling Pathways In Aldmentioning

confidence: 99%

Alcoholic Liver Disease: Current Mechanistic Aspects with Focus on Their Clinical Relevance

Teschke

2019

Biomedicines

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The spectrum of alcoholic liver disease (ALD) is broad and includes alcoholic fatty liver, alcoholic steatohepatitis, alcoholic hepatitis, alcoholic fibrosis, alcoholic cirrhosis, and alcoholic hepatocellular carcinoma, best explained as a five-hit sequelae of injurious steps. ALD is not primarily the result of malnutrition as assumed for many decades but due to the ingested alcohol and its metabolic consequences although malnutrition may marginally contribute to disease aggravation. Ethanol is metabolized in the liver to the heavily reactive acetaldehyde via the alcohol dehydrogenase (ADH) and the cytochrome P450 isoform 2E1 of the microsomal ethanol-oxidizing system (MEOS). The resulting disturbances modify not only the liver parenchymal cells but also non-parenchymal cells such as Kupffer cells (KCs), hepatic stellate cells (HSCs), and liver sinusoidal endothelial cells (LSECs). These are activated by acetaldehyde, reactive oxygen species (ROS), and endotoxins, which are produced from bacteria in the gut and reach the liver due to gut leakage. A variety of intrahepatic signaling pathways and innate or acquired immune reactions are under discussion contributing to the pathogenesis of ALD via the five injurious hits responsible for disease aggravation. As some of the mechanistic steps are based on studies with in vitro cell systems or animal models, respective proposals for humans may be considered as tentative. However, sufficient evidence is provided for clinical risk factors that include the amount of alcohol used daily for more than a decade, gender differences with higher susceptibility of women, genetic predisposition, and preexisting liver disease. In essence, efforts within the last years were devoted to shed more light in the pathogenesis of ALD, much has been achieved but issues remain to what extent results obtained from experimental studies can be transferred to humans.

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Recent Insights Into the Role of Immune Cells in Alcoholic Liver Disease

Cited by 64 publications

References 140 publications

Emerging Noninvasive Biomarkers, and Medical Management Strategies for Alcoholic Hepatitis: Present Understanding and Scope

Emerging Noninvasive Biomarkers, and Medical Management Strategies for Alcoholic Hepatitis: Present Understanding and Scope

cAMP Signaling in Pathobiology of Alcohol Associated Liver Disease

Alcoholic Liver Disease: Current Mechanistic Aspects with Focus on Their Clinical Relevance

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