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Full-Text Articles in Hepatology
Alcohol And Hcv: Implications For Liver Cancer, Gyongyi Szabo, Banishree Saha, Terence Bukong
Alcohol And Hcv: Implications For Liver Cancer, Gyongyi Szabo, Banishree Saha, Terence Bukong
Gyongyi Szabo
Liver cancers are one of the deadliest known malignancies which are increasingly becoming a major public health problem in both developed and developing countries. Overwhelming evidence suggests a strong role of infection with hepatitis B and C virus (HBV and HCV), alcohol abuse, as well as metabolic diseases such as obesity and diabetes either individually or synergistically to cause or exacerbate the development of liver cancers. Although numerous etiologic mechanisms for liver cancer development have been advanced and well characterized, the lack of definite curative treatments means that gaps in knowledge still exist in identifying key molecular mechanisms and pathways …
Differences In Innate Immune Signaling Between Alcoholic And Non-Alcoholic Steatohepatitis, Jan Petrasek, Timea Csak, Michal Ganz, Gyongyi Szabo
Differences In Innate Immune Signaling Between Alcoholic And Non-Alcoholic Steatohepatitis, Jan Petrasek, Timea Csak, Michal Ganz, Gyongyi Szabo
Gyongyi Szabo
The similar histopathological characteristics of alcoholic steatohepatitis (ASH) and non-alcoholic steatohepatitis (NASH), and the crucial role of the innate immune response in both conditions may lead to the assumption that ASH and NASH represent the same pathophysiological entities caused by different risk factors. In this review paper, we elaborate on the pathophysiological differences between these two entities and highlight the disease-specific involvement of signaling molecules downstream of the Toll-like receptor 4, and the differential mechanism by which the inflammasome contributes to ASH versus NASH. Our findings emphasize that ASH and NASH have disease-specific mechanisms and therefore represent distinct biological entities. …
Toll-Like Receptors In Liver Disease, Jan Petrasek, Timea Csak, Gyongyi Szabo
Toll-Like Receptors In Liver Disease, Jan Petrasek, Timea Csak, Gyongyi Szabo
Gyongyi Szabo
Activation of inflammatory signaling pathways is of central importance in the pathogenesis of alcoholic liver disease (ALD) and nonalcoholic steatohepatitis (NASH). Recent studies demonstrated that Toll-like receptors, the sensors of microbial and endogenous danger signals, are expressed and activated in innate immune cells as well as in parenchymal cells in the liver and thereby contribute to ALD and NASH. In this review, we emphasize the importance of gut-derived endotoxin and its recognition by TLR4 in the liver. The significance of TLR-induced intracellular signaling pathways and cytokine production as well as the contribution of individual cell types to the inflammation is …
Hypoxia And Hypoxia Inducible Factors: Diverse Roles In Liver Diseases, Bharath Nath, Gyongyi Szabo
Hypoxia And Hypoxia Inducible Factors: Diverse Roles In Liver Diseases, Bharath Nath, Gyongyi Szabo
Gyongyi Szabo
Hypoxia has been shown to have a role in the pathogenesis of several forms of liver disease. The hypoxia inducible factors (HIFs) are a family of evolutionarily conserved transcriptional regulators that affect a homeostatic response to low oxygen tension and have been identified as key mediators of angiogenesis, inflammation, and metabolism. In this review we summarize the evidence for a role of HIFs across a range of hepatic pathophysiology. We describe regulation of the HIFs and review investigations that demonstrate a role for HIFs in the development of liver fibrosis, activation of innate immune pathways, hepatocellular carcinoma, as well as …
Innate Immune Response And Hepatic Inflammation, Gyongyi Szabo, Pranoti Mandrekar, Angela Dolganiuc
Innate Immune Response And Hepatic Inflammation, Gyongyi Szabo, Pranoti Mandrekar, Angela Dolganiuc
Gyongyi Szabo
Inflammation is a pathogenic component of various types of acute and chronic liver diseases, and it contributes to progressive liver damage and fibrosis. Cells of the innate immune system initiate and maintain hepatic inflammation though mediator production as a result of their activation by pathogen-derived products recognized by pattern recognition receptors. Innate immune cells, particularly dendritic cells, have a pivotal role in sensing pathogens and initiating adaptive immune responses by activation and regulation of T-lymphocyte responses. Although the liver provides a "tolerogenic" immune environment for antigen-specific T-cells, activation of Kupffer cells, recruited macrophages, and inflammatory cells results in production of …
Altered Innate Immunity In Chronic Hepatitis C Infection: Cause Or Effect, Gyongyi Szabo, Serena Chang, Angela Dolganiuc
Altered Innate Immunity In Chronic Hepatitis C Infection: Cause Or Effect, Gyongyi Szabo, Serena Chang, Angela Dolganiuc
Gyongyi Szabo
No abstract provided.
Alcohol-Induced Modulation Of Signaling Pathways In Liver Parenchymal And Nonparenchymal Cells: Implications For Immunity, Bharath Nath, Gyongyi Szabo
Alcohol-Induced Modulation Of Signaling Pathways In Liver Parenchymal And Nonparenchymal Cells: Implications For Immunity, Bharath Nath, Gyongyi Szabo
Gyongyi Szabo
Alcoholic liver injury involves a complex array of derangements in cellular signaling of hepatic parenchymal and nonparenchymal cells as well as cells of the immune system. In the hepatocyte, chronic ethanol abuse leads to lipid accumulation and liver steatosis. Multiple pathways are affected to promote lipid accumulation in the ethanol-exposed hepatocyte. Chronic ethanol renders Kupffer cells hyperresponsive to endotoxin, which results in production of inflammatory cytokines and the tumor necrosis factor-alpha via a toll-like receptor 4 dependent pathway, leading to inflammation and hepatic necrosis. Dysfunction of the innate and adaptive immune responses caused by ethanol contributes to impaired antiviral response, …
Pathogenic Interactions Between Alcohol And Hepatitis C, Gyongyi Szabo
Pathogenic Interactions Between Alcohol And Hepatitis C, Gyongyi Szabo
Gyongyi Szabo
Alcohol is the most commonly abused substance in the United States, and alcohol abuse leads to alcoholic liver disease, a long recognized major public health concern. The high prevalence of chronic hepatitis C virus (HCV) infection, along with the clinical observation that HCV infection is common in alcoholic patients presenting with liver disease, has directed attention to the interaction between alcohol and HCV infection. Clinical studies have identified alcohol use as an independent risk factor for progression of fibrosis in chronic HCV infection. Experimental evidence suggests additive inhibitory effects between HCV and alcohol on antiviral immune responses. In addition, specific …