Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatitis C virus-related liver failure is the single leading indication for liver transplantation, and the study of HCV in the transplant setting has enhanced the understanding of the natural history of disease and putative mechanisms by which HCV causes liver injury. In a subset of patients, allograft cirrhosis develops within a few years after transplantation, and recent findings suggest these individuals are immunologically impaired compared with individuals with mild HCV recurrence at long-term follow-up. Fig. 9 shows a conceptual paradigm of mechanisms potentially involved in shaping HCV outcome after transplantation. It is possible that relative antiviral control by innate and adaptive immune responses (to maintain HCV replication below a certain threshold) prevents direct cytopathic injury and induction of oxidative stress and apoptosis of cells. Additional phenomena that may contribute to induction of apoptosis (eg, genetic polymorphisms within the donor organ. CMV coinfection, and ischemic-preservation injury) may augment the initial cascade of liver injury. Recruitment to the allograft of nonspecific cells may decrease viral replication by way of noncytolytic mechanisms or augment viral replication (eg, Th2 phenotype) and direct cytopathic injury. The immune response is likely insufficiently vigorous to keep viral replication under control, but may maintain chronic liver injury. The liver transplant model is unique in that distinct phenotypic outcomes can be observed over a short period of time. A consideration of the temporal evolution of different mechanisms is also important, because mechanisms that initially predominate may become less important over time, and conversely, as suggested with the inverse correlation between viral load at 5 years and allograft fibrosis, new immune responses may emerge that modify the host-virus interaction. Prospective characterization of the immunoregulatory and virologic mechanisms involved in the liver transplantation model hopefully will help unravel the causal basis of reported associations, lead to the development of highly specific therapeutic strategies, and ultimately diminish the rate of graft loss from recurrent disease.
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PMID:Hepatitis C virus in the human liver transplantation model. 1269 61

Chronic consumption of ethanol induces hepatic steatosis and inflammation, which can eventually lead to more severe liver injury, characterized by fibrosis and cirrhosis. Recruitment of neutrophils to the liver, as well as activation of Kupffer cells, mediates the inflammatory responses observed after chronic ethanol exposure. Kupffer cells, the resident macrophages of the liver, are critical to the onset of ethanol-induced liver injury. Activation of Kupffer cells leads to an increased production of proinflammatory cytokines, such as tumor necrosis factor-alpha and also reactive oxygen species, a process mediated in part by changes in lipopolysaccharide-induced TLR4-dependent signal transduction. The isolation and culture of Kupffer cells is an important technique with which one can elucidate the mechanisms that contribute to alcoholic liver injury.
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PMID:Isolation of Kupffer cells from rats fed chronic ethanol. 1836 21

Leucocyte infiltration into human liver tissue is a common process in all adult inflammatory liver diseases. Chronic infiltration can drive the development of fibrosis and progression to cirrhosis. Understanding the molecular mechanisms that mediate leucocyte recruitment to the liver could identify important therapeutic targets for liver disease. The key interaction during leucocyte recruitment is that of inflammatory cells with endothelium under conditions of shear stress. Recruitment to the liver occurs within the low shear channels of the hepatic sinusoids which are lined by hepatic sinusoidal endothelial cells (HSEC). The conditions within the hepatic sinusoids can be recapitulated by perfusing leucocytes through channels lined by human HSEC monolayers at specific flow rates. In these conditions leucocytes undergo a brief tethering step followed by activation and firm adhesion, followed by a crawling step and subsequent transmigration across the endothelial layer. Using phase contrast microscopy, each step of this 'adhesion cascade' can be visualized and recorded followed by offline analysis. Endothelial cells or leucocytes can be pretreated with inhibitors to determine the role of specific molecules during this process.
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PMID:A flow adhesion assay to study leucocyte recruitment to human hepatic sinusoidal endothelium under conditions of shear stress. 2468 18

The progression of liver fibrosis and cirrhosis is associated with the persistence of an injury causing agent, leading to changes in the extracellular environment and a disruption of the cellular homeostasis of liver resident cells. Recruitment of inflammatory cells, apoptosis of hepatocytes, and changes in liver microvasculature are some examples of changing cellular environment that lead to the induction of stress responses in nearby cells. During liver fibrosis, the major stresses include hypoxia, oxidative stress, and endoplasmic reticulum stress. When hepatic stellate cells (HSCs) are subjected to such stress, they modulate fibrosis progression by induction of their activation toward a myofibroblastic phenotype, or by undergoing apoptosis, and thus helping fibrosis resolution. It is widely accepted that microRNAs are import regulators of gene expression, both during normal cellular homeostasis, as well as in pathologic conditions. MicroRNAs are short RNA sequences that regulate the gene expression by mRNA destabilization and inhibition of mRNA translation. Specific microRNAs have been identified to play a role in the activation process of HSCs on the one hand and in stress-responsive pathways on the other hand in other cell types (Table 2). However, so far there are no reports for the involvement of miRNAs in the different stress responses linked to HSC activation. Here, we review briefly the major stress response pathways and propose several miRNAs to be regulated by these stress responsive pathways in activating HSCs, and discuss their potential specific pro-or anti-fibrotic characteristics.
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PMID:The role of miRNAs in stress-responsive hepatic stellate cells during liver fibrosis. 2628 69