الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Hepatitis C virus (HCV) infection is characterized by a chronic inflammatory state in the liver and increased production of pro-inflammatory cytokines and chemokines with activation of hepatic stellate cells (HSCs) and progressive accumulation of extracellular matrix that contributes to liver fibrosis. A major aspect of the inflammatory pathway is the activation of the inflammasome. Inflammasomes are multiprotein complexes present in the cytosol, which act as receptors of the innate immune system that can sense pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs) and evoke key inflammatory cascades. The NLR pyrin domain containing 3 (NLRP3) inflammasome is currently the most characterized inflammasome. It is composed of NLRP3 as the sensor, the adaptor protein ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain) and the inflammatory procaspase-1 (pro cysteine-dependent aspartate-directed protease-1). Assembly and activation of NLRP3 inflammasome require two steps/signals: priming step (signal 1) and activation step (signal 2). Once primed, NLRP3 recognizes PAMPs or DAMPs resulting in the assembly and activation of NLRP3 inflammasome complex. This yields to autocleavage of procaspase-1 into active caspase-1, which becomes capable of processing the interleukin (IL) precursors pro-IL-1β and pro-IL-18 into their mature and secreted forms leading to initiation of inflammation. Caspase-1 is also involved in the induction of a specialized form of cell death called ”pyroptosis” (inflammatory cell death), which is associated with rapid disruption of cell membrane integrity creating pores and the release of intracellular contents such as the proinflammatory cytokines and cell damage markers, which further enhance inflammation. Inflammasomes play a central role in the immune response to virus infection by promoting the secretion of proinflammatory cytokines and lysis of virus-infected cells, thus, facilitating the clearance of infections. In the liver, inflammasomes exist in both hepatocytes and nonparenchymal cells (liver sinusoidal endothelial cells, HSCs and macrophages). During liver injury, inflammasome activation is implicated in initiating and maintaining hepatic inflammation and subsequent hepatic fibrosis. In fact, there is an evidence that inflammasomes play an important role in the pathogenesis of various liver diseases.
Therefore, the present work was designed to study the role of NLRP3 inflammasome activation in patients with chronic HCV infection in relation to hepatic inflammation and fibrosis.
Forty nine treatment-naïve patients with chronic HCV infection [28 patients with chronic hepatitis C