scholarly journals Molecular Mechanisms of Alcoholic Liver Disease: Innate Immunity and Cytokines

2011 ◽  
Vol 35 (5) ◽  
pp. 787-793 ◽  
Author(s):  
Andrew M. Miller ◽  
Norio Horiguchi ◽  
Won-IL Jeong ◽  
Svetlana Radaeva ◽  
Bin Gao
Keyword(s):  
Innate Immunity ◽  
Liver Disease ◽  
Alcoholic Liver Disease ◽  
Molecular Mechanisms

High resolution metabolomics technology reveals widespread pathway changes of alcoholic liver disease

2016 ◽  
Vol 12 (1) ◽  
pp. 262-273 ◽  
Author(s):  
Aihua Zhang ◽  
Guangli Yan ◽  
Xiaohang Zhou ◽  
Yangyang Wang ◽  
Ying Han ◽  
...  
Keyword(s):  
Liver Disease ◽  
High Resolution ◽  
Alcoholic Liver Disease ◽  
Molecular Mechanisms ◽  
High Resolution Metabolomics

The current study provides insights into the molecular mechanisms of ALD from widespread pathway changes.

scholarly journals The Crosstalk between Hypoxia and Innate Immunity in the Development of Obesity-Related Nonalcoholic Fatty Liver Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
María Teresa Arias-Loste ◽  
Emilio Fábrega ◽  
Marcos López-Hoyos ◽  
Javier Crespo
Keyword(s):  
Innate Immunity ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Molecular Mechanisms ◽  
Nonalcoholic Fatty Liver ◽  
Obstructive Sleep ◽  
Prevalence Of Obesity ◽  
Hypopnea Syndrome

Nonalcoholic fatty liver disease (NAFLD) has become a major health issue in western countries in parallel with the dramatic increase in the prevalence of obesity and all obesity related conditions, including respiratory diseases as obstructive sleep apnea-hypopnea syndrome (OSAHS). Interestingly, the severity of the liver damage in obesity-related NAFLD has been associated with the concomitant presence of OSAHS. In the presence of obesity, the proinflammatory state in these patients together with intermittent episodes of hypoxia, characteristic of OSAHS pathogenesis, may lead to an enhanced inflammatory response mediated by a positive feedback loop mechanism that implicates HIF-1 and NFκB. Thus, the severity of liver involvement in obese NAFLD patients with a concomitant diagnosis of OSAHS could be explained. In this review, we focus on the molecular mechanisms underlying the hepatic response to chronic intermittent hypoxia and its interaction with innate immunity in obesity-related NAFLD.

Molecular mechanisms of stem cell therapy in alcoholic liver disease

2014 ◽  
Vol 46 (5) ◽  
pp. 391-397 ◽  
Author(s):  
Phillip Levine ◽  
Kelly McDaniel ◽  
Heather Francis ◽  
Lindsey Kennedy ◽  
Gianfranco Alpini ◽  
...  
Keyword(s):  
Stem Cell ◽  
Liver Disease ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Alcoholic Liver Disease ◽  
Molecular Mechanisms

scholarly journals Epidemiological Realities of Alcoholic Liver Disease: Global Burden, Research Trends, and Therapeutic Promise

2020 ◽  
Vol 20 (2) ◽  
pp. 105-118
Author(s):  
Jia Xiao ◽  
Fei Wang ◽  
Nai-Kei Wong ◽  
Yi Lv ◽  
Yingxia Liu ◽  
...  
Keyword(s):  
Liver Disease ◽  
Alcohol Consumption ◽  
Alcoholic Liver Disease ◽  
Behavioral Interventions ◽  
Molecular Mechanisms ◽  
Management Strategies ◽  
National Income ◽  
Research Trends ◽  
World Health ◽  
Nonalcoholic Fatty Liver

Globally, alcohol consumption contributes to more than 3 million deaths each year. While much of its ramifications is preventable, a coherent public health discourse on how to limit alcohol-related harm has been overdue. By synthesizing information from national and global databases, we show in this analysis that alcohol consumption level and alcohol-attributable burden of diseases, particularly alcoholic liver disease (ALD), are intimately linked to national income distribution, cultural norms, religion, sex, age, and health status. Prevalence and burden of ALD are positively associated with economic standing in most countries, which necessitate active governmental control via cost-effective policies, such as the best buys proposed by the World Health Organization. To date, a number of critical questions remain unanswered over the molecular mechanisms underlying ALD pathophysiology; the insights gained thereof should provide new opportunities for the advancement of novel diagnostic and management strategies. In comparison with other prevailing liver diseases (e.g., viral hepatitis and nonalcoholic fatty liver disease), governmental support to ALD investigation has been sluggish in most Western countries and China, resulting in a dearth of breakthroughs on both the basic and clinical research fronts in the past decades. Emerging foci of clinical trials for ALD therapy include empirical use of probiotics, antioxidants, growth factors, monoclonal antibodies against key inflammatory mediators, and technology-enhanced behavioral interventions. In this article, we seek to provide a comprehensive analysis on the progress and challenges in tackling ALD as a global health problem, with particular emphasis on global disease burden, socioeconomic influences, research trends, government roles, and future therapies.

scholarly journals Alcoholic Liver Disease: Alcohol Metabolism, Cascade of Molecular Mechanisms, Cellular Targets, and Clinical Aspects

Biomedicines ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 106 ◽  
Author(s):  
Rolf Teschke
Keyword(s):  
Liver Disease ◽  
Liver Injury ◽  
Alcoholic Liver Disease ◽  
Molecular Mechanisms ◽  
Lipid Peroxides ◽  
Sirtuin 1 ◽  
Clinical Aspects ◽  
Alkoxyl Radical ◽  
Alcoholic Fatty Liver ◽  
Cyp 2E1

Alcoholic liver disease is the result of cascade events, which clinically first lead to alcoholic fatty liver, and then mostly via alcoholic steatohepatitis or alcoholic hepatitis potentially to cirrhosis and hepatocellular carcinoma. Pathogenetic events are linked to the metabolism of ethanol and acetaldehyde as its first oxidation product generated via hepatic alcohol dehydrogenase (ADH) and the microsomal ethanol-oxidizing system (MEOS), which depends on cytochrome P450 2E1 (CYP 2E1), and is inducible by chronic alcohol use. MEOS induction accelerates the metabolism of ethanol to acetaldehyde that facilitates organ injury including the liver, and it produces via CYP 2E1 many reactive oxygen species (ROS) such as ethoxy radical, hydroxyethyl radical, acetyl radical, singlet radical, superoxide radical, hydrogen peroxide, hydroxyl radical, alkoxyl radical, and peroxyl radical. These attack hepatocytes, Kupffer cells, stellate cells, and liver sinusoidal endothelial cells, and their signaling mediators such as interleukins, interferons, and growth factors, help to initiate liver injury including fibrosis and cirrhosis in susceptible individuals with specific risk factors. Through CYP 2E1-dependent ROS, more evidence is emerging that alcohol generates lipid peroxides and modifies the intestinal microbiome, thereby stimulating actions of endotoxins produced by intestinal bacteria; lipid peroxides and endotoxins are potential causes that are involved in alcoholic liver injury. Alcohol modifies SIRT1 (Sirtuin-1; derived from Silent mating type Information Regulation) and SIRT2, and most importantly, the innate and adapted immune systems, which may explain the individual differences of injury susceptibility. Metabolic pathways are also influenced by circadian rhythms, specific conditions known from living organisms including plants. Open for discussion is a 5-hit working hypothesis, attempting to define key elements involved in injury progression. In essence, although abundant biochemical mechanisms are proposed for the initiation and perpetuation of liver injury, patients with an alcohol problem benefit from permanent alcohol abstinence alone.

scholarly journals Innate immunity in alcoholic liver disease

2011 ◽  
Vol 300 (4) ◽  
pp. G516-G525 ◽  
Author(s):  
Bin Gao ◽  
Ekihiro Seki ◽  
David A. Brenner ◽  
Scott Friedman ◽  
Jessica I. Cohen ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Liver Disease ◽  
Alcohol Consumption ◽  
Liver Fibrosis ◽  
Alcoholic Liver Disease ◽  
Chronic Viral Hepatitis ◽  
Western World ◽  
Excessive Alcohol Consumption ◽  
Alcoholic Steatohepatitis

Excessive alcohol consumption is a leading cause of chronic liver disease in the Western world. Alcohol-induced hepatotoxicity and oxidative stress are important mechanisms contributing to the pathogenesis of alcoholic liver disease. However, emerging evidence suggests that activation of innate immunity involving TLR4 and complement also plays an important role in initiating alcoholic steatohepatitis and fibrosis, but the role of adaptive immunity in the pathogenesis of alcoholic liver disease remains obscure. Activation of a TLR4-mediated MyD88-independent (TRIF/IRF-3) signaling pathway in Kupffer cells contributes to alcoholic steatohepatitis, whereas activation of TLR4 signaling in hepatic stellate cells promotes liver fibrosis. Alcohol consumption activates the complement system in the liver by yet unidentified mechanisms, leading to alcoholic steatohepatitis. In contrast to activation of TLR4 and complement, alcohol consumption can inhibit natural killer cells, another important innate immunity component, contributing to alcohol-mediated acceleration of viral infection and liver fibrosis in patients with chronic viral hepatitis. Understanding of the role of innate immunity in the pathogenesis of alcoholic liver disease may help us identify novel therapeutic targets to treat this disease.

scholarly journals Autophagy in HCV Infection: Keeping Fat and Inflammation at Bay

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Tiziana Vescovo ◽  
Giulia Refolo ◽  
Alessandra Romagnoli ◽  
Fabiola Ciccosanti ◽  
Marco Corazzari ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Life Cycle ◽  
Liver Disease ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Viral Persistence ◽  
Hcv Infection ◽  
Lipid Homeostasis ◽  
Specific Host

Hepatitis C virus (HCV) infection is one of the main causes of chronic liver disease. Viral persistence and pathogenesis rely mainly on the ability of HCV to deregulate specific host processes, including lipid metabolism and innate immunity. Recently, autophagy has emerged as a cellular pathway, playing a role in several aspects of HCV infection. This review summarizes current knowledge on the molecular mechanisms that link the HCV life cycle with autophagy machinery. In particular, we discuss the role of HCV/autophagy interaction in dysregulating inflammation and lipid homeostasis and its potential for translational applications in the treatment of HCV-infected patients.

Sign in / Sign up

Export Citation Format

Share Document