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)

Cytokines are a group of proteins with autocrine, paracrine and endocrine activities which provide communication among hepatic cells and other cells and tissues of the man. Active in minute quantities, the cytokines activate and regulate homeostasis and cellular repair through effects on cell growth, differentiation and receptor expression and cell-mediated immunity. Cytokines--IL-1, IL-2, IL-6, IL-8 IL-10, IL-12, TNF-alfa, PDGF and others, modulate liver metabolism in health and disease, physiological and pathologic liver functions and the evolution of liver inflammation and injury to hepatic fibrosis and liver cirrhosis. Data concerning the use of a recombinant form of Interleukin-10 and Interleukin-12 in the treatment of chronic liver disease (chronic viral hepatitis, fibrosis, cirrhosis, alcoholic liver disease) and cell-mediated immunity regulation are widely discussed in the review.
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PMID:[Cytokines and the liver in health and disease]. 1119 92

The mechanism by which Hepatitis C virus(HCV) infection promotes the development of hepatocellular carcinoma(HCC) is not known exactly. HCV related HCC occurs frequency in the patients with cirrhosis. There have been reports indicating that Th2-type cytokines down-regulated antitumor immunity, and the activation of type 1 T cell responses produced antitumor immunity. We thought Th1/Th2 imbalance in HCV-related liver cirrhosis might be closely related to the development of HCC. In this study, therefore, we investigated the Th1/Th2 balance at the single lymphocyte level of the patients with HCV-related liver cirrhosis and compared with normal controls by using flow cytometry. Th1-type cytokines(IFN-gamma, IL-2) production was significantly decreased in patients with cirrhosis, whereas Th2-type cytokine production(IL-10) was increased. These suggest Th1/Th2 imbalance in HCV-related cirrhosis would decrease the antitumor immunity and its improvement might present the protective effect from HCC.
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PMID:[Th1/Th2 imbalance in HCV-related liver cirrhosis]. 1149 34

The interleukin-12(IL-12), interleukin-10(IL-10), tumor necrosis factor(TNF) and nitric oxide (NO) levels in serum of 90 patients with hepatitis and cirrhosis were measured by the method of ELISA and colorimeter. The levels of IL-12, IL-10 and NO in serum of the patients with hepatitis were in close proximity to the level of healthy control, but the TNF level was significantly higher than that of healthy control. The IL-12, IL-10, TNF and NO levels in serum of the patients of hepatic cirrhosis were significantly higher than that of healthy control and patients with hepatitis. The results suggested that the NO level was not related with the hepatic damage of acute hepatitis. The dysfunction of immunology in the patients with cirrhosis was related with the increase of NO level.
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PMID:[Relationship of nitric oxide and immunal function of the patients with acute hepatitis and hepatic cirrhosis]. 1208 Jun 55

The liver plays an important physiological role in lipopolysaccharide (LPS) detoxification and, in particular, hepatocytes are involved in the clearance of endotoxin of intestinal derivation. In experimental shock models, tumor necrosis factor (TNF)-alpha induces hepatocyte apoptosis and lethal effects are due to secreted TNF-alpha and not to cell-associated TNF-alpha. An exaggerated production of TNF-alpha has been reported in murine viral infections, in which mice become sensitized to low amounts of LPS and both interferon (IFN)-gamma and IFN-alpha/beta are involved in the macrophage-induced release of TNF-alpha. The prominent role of LPS and TNF-alpha in liver injury is also supported by studies of ethanol-induced hepatic damage. In humans, evidence of LPS-induced hepatic injury has been reported in cirrhosis, autoimmune hepatitis, and primary biliary cirrhosis and a decreased phagocytic activity of the reticulo-endothelial system has been found in these diseases. The origin of endotoxemia in hepatitis C virus (HCV) infected patients seems to be multifactorial and LPS may be of exogenous or endogenous derivation. In endotoxemic HCV-positive patients responsive to a combined treatment with IFN-alpha/ribavirin (RIB), endotoxemia was no longer detected at the end of the therapeutic regimen. By contrast, 48% of the non-responders to this treatment were still endotoxemic and their monocytes displayed higher intracellular TNF-alpha and interleukin (IL)-1beta levels than responders. Moreover, in responders, an equilibrium between IFN-gamma and IL-10 serum levels was attained. In the non-responders, serum levels of IL-10 did not increase following treatment. This may imply that an imbalance between T helper (Th)1 and Th2 derived cytokines could be envisaged in the non-responders.
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PMID:The role of the liver in the response to LPS: experimental and clinical findings. 1253 90

Chronic hepatitis B virus (HBV) infection can cause a broad spectrum diseases, including from asymptomatic HBV carriers or cryptic hepatitis, to acute hepatitis, chronic hepatitis, Liver cirrhosis and primary hepatocellular carcinoma. The variable pattern and clinical outcome of the infection were mainly determined by virological itself factors, host immunological factors and genetic factors as well as the experimental factors. Among the human genetic factors, major candidate or identified genes involved in the process of HBV infection fall into the following categories: (1) genes that mediate the processes of viral entry into hepatocytes, including genes involved in viral binding, fusion with cellular membrane and transportation in target cells; (2) genes that modulate or control the immune response to HBV infection; (3) genes that participate in the pathological alterations in liver tissue; (4) genes involved in the development of liver cirrhosis and hepatocellular carcinoma associated with chronic HBV infection, including genes related to mother-to-infant transmission of HBV infection; and (5) those that contribute to resistance to antiviral therapies. Most of the reports of human genes associated with HBV infection have currently focused on HLA associations. For example, some investigators reported the association of the HLA class II alleles such as DRB1*1302 or HLA-DR13 or DQA1*0501-DQB1*0301-DQB1*1102 haplotypes with acute and/or chronic hepatitis B virus infection, respectively. Several pro-inflammatory cytokines such as Th1 cytokines (including IL-2 and IFN-gamma) and TNF-alpha have been identified to participate the process of viral clearance and host immune response to HBV. In contrast, the Th2 cytokine IL-10 serves as a potent inhibitor of Th1 effector cells in HBV diseases. The MBP polymorphisms in its encoding region were found to be involved in chronic infection. Thus, reports from various laboratories have shown some inconsistencies with regard to the effects of host genetic factors on HBV clearance and persistence. Since genetic interactions are complex, it is unlikely that a single allelic variant is responsible for HBV resistance or susceptibility. However, the collective influence of several single nucleotide polymorphisms (SNPs) or haplotype (s) may underlie the natural combinational or synergistic protection against HBV. The future study including the multi-cohort collaboration will be needed to clarify these preliminary associations and identify other potential candidate genes. The ongoing study of the distributions and functions of the implicated allele polymorphisms will not only provide insight into the pathogenesis of HBV infection, but may also provide a novel rationale for new methods of diagnosis and therapeutic strategies.
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PMID:Current status and prospects of studies on human genetic alleles associated with hepatitis B virus infection. 1267 1

The current study was designed to investigate the immune status in hepatitis C virus (HCV) patients with persistently normal alanine transferase activity (ALT) (patients with normal alanine transferase). For this purpose, serum levels and lipopolysaccharide (LPS)-induced IFN-gamma, IL12 p70, IL12 p40 and IL-10 as well as NK cell activity were assayed in six patients with normal ALT, 22 HCV-infected individuals with chronic hepatitis (CH), 13 cases of liver cirrhosis (LC) and 26 age-matched controls. Cytokine production was assayed with the whole blood induction method. IFN-gamma levels were significantly lower in patients with HCV-infected chronic hepatitis and liver cirrhosis than in controls ( [Formula: see text], [Formula: see text] and [Formula: see text] pg/ml, respectively, [Formula: see text] ). However, IFN-gamma production in those individuals with normal ALT was not reduced ( [Formula: see text] pg/ml). Although variation was observed, four of the six patients showed moderate to strong IFN-gamma production. No intergroup differences were observed for IL12 p70, IL12 p40 and IL-10 production and NK cell activity. Our results suggest that preserved IFN-gamma production in patients with normal ALT, in contrast to the reduction in chronic hepatitis and liver cirrhosis, may be related to a slow rate of disease progression.
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PMID:Production of IFN-gamma and IL-12 by peripheral whole blood is maintained in hepatitis C virus patients with persistently normal alanine transferase activity; A preliminary report. 1516 29

Persons with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfection are at increased risk for progression to cirrhosis compared with persons with HCV alone, but the reasons for this are unclear. In chronic HCV, the mechanism of liver injury is presumed to be due to HCV-specific T cell destruction of hepatocytes, so it is paradoxical that immunosuppressed hosts have higher rates of fibrosis progression. We examined intrahepatic cellular immune responses to HCV antigens to determine whether there were qualitative or quantitative differences in subjects with and without HIV. Expanded, CD4-enriched, liver-infiltrating lymphocytes from 18 subjects with chronic HCV and 12 subjects with HIV/HCV were cultured in the presence of HCV core protein, nonstructural proteins NS3 and NS5, and recall antigens tetanus toxoid and Candida. Secretion of interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and interleukin (IL) 10 was determined using enzyme-linked immunosorbent spot assay. There were no significant differences in liver biopsy grade or stage for HIV/HCV versus HCV groups. There were no significant differences between groups in the secretion of IFN-gamma or TNF-alpha in response to HCV or recall antigens. However, there was a significant increase in IL-10 secretion in response to NS3 and NS5 in subjects with HCV compared with HIV and HCV coinfection. In conclusion, subjects with coinfection have an alteration of intrahepatic HCV-specific IL-10 cytokine response that may have implications for HCV-related disease progression.
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PMID:Comparison of HCV-specific intrahepatic CD4+ T cells in HIV/HCV versus HCV. 1523 95

Chronic liver disease and cirrhosis are two of the most important health problems according to current gastroenterology literature. Based on the recent developments in the field of immunology, advanced follow-up and treatment modalities have been introduced for these disorders. Immune defence against viral infections depends on effective cellular immune responses derived mainly from Th1-related cytokines. Th2 type immune responses can inhibit efficient immune function by secretion of several cytokines such as IL-10, TGF-beta1. In this particular study, we determined the serum levels of TGF-beta1, which plays a role in immune suppression and induction of tissue fibrosis. We evaluated the role of TGF-beta1 in the pathogenesis of chronic liver disease and cirrhosis. Fourteen chronic hepatitis B (CHB), 12 chronic hepatitis C (CHC) patients and 21 cirrhotic patients were enrolled in the study. The control group consisted of ten healthy people. Serum TGF-beta1 levels were higher in both cirrhosis and CHC group when compared to those in CHB and control groups (P < 0.05). Although serum TGF-beta1 levels in the cirrhosis group were higher than that in the CHC group, the difference was not statistically significant. In conclusion, elevated TGF-beta1 levels in patients with CHC and cirrhosis may have a role in the pathogenesis and chronicity of these diseases.
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PMID:Serum transforming growth factor-beta1(TGF-beta1) in patients with cirrhosis, chronic hepatitis B and chronic hepatitis C [corrected]. 1531 69

Alterations of cytokine responses are thought to favor the establishment of persistent hepatitis C virus (HCV) infections, enhancing the risk of liver cirrhosis and hepatocellular carcinoma. Here we demonstrate that the expression of the HCV core (C) protein in stably transfected T cells correlates with a selective reduction of interleukin-2 (IL-2) promoter activity and IL-2 production in response to T-cell receptor triggering, whereas the activation of IL-4, IL-10, gamma interferon, and tumor necrosis factor alpha was moderately increased. This altered cytokine expression profile was associated with a perturbation of mitogen-activated protein (MAP) kinase responses. Extracellular regulated kinase and p38 were constitutively phosphorylated in C-expressing cells, while triggering of the costimulatory c-Jun N-terminal kinase (JNK) signaling cascade and activation of the CD28 response element within the IL-2 promoter appeared to be impaired. The perturbations of MAP kinase phosphorylation could be eliminated by cyclosporine A-mediated inhibition of nuclear factor of activated T cells, suggesting that the inactivation of JNK signaling and hyporesponsiveness to IL-2 induction were downstream consequences of C-induced Ca(2+) flux in a manner that mimics the induction of clonal anergy.
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PMID:Hepatitis C virus core protein induces an anergic state characterized by decreased interleukin-2 production and perturbation of mitogen-activated protein kinase responses. 1568 25

Hepatitis C virus (HCV) is the leading cause of chronic liver disease worldwide with a prevalence of approximately 14% in Egypt. IL-10 is a cytokine produced by Th2 cells. It down-regulates the proinflammatory response and modulates hepatic fibrogenesis. IL-12 is produced by antigen presenting cells. It promotes Th1 cell response and has many antiviral properties. Data concerning the Th-1/Th-2 balance in chronic hepatitis C (CH-C) are rather conflicting. Using ELISA, we assessed serum IL-10 and IL-12p40 levels in 66 Egyptian patients with HCV-related liver illness (CH-C, cirrhosis, and HCC), and their relationship to disease activity. Our results showed that spontaneous IL-10 was undetectable in patients with CH-C, HCC or controls. Only 5/22 (23%) of patients with cirrhosis showed detectable levels of IL-10. IL-12p40 was elevated in the patient groups compared to controls (p= 0.01, p= 0.01, p= 0.05 in CH-C, cirrhosis and HCC, respectively). The presence of IL-12p40 was associated with HCV level of viremia and serum AST. Serum ALT level was significantly associated with the level of IL-12p40. IL-12p40 was unrelated to liver histology or fibrosis. We concluded that in the Egyptian patients an augmentation of IL-12p40 and a suppression of IL-10 are both found. Whether this pattern is related to HCV genotype 4, or to the presence of schistosomiasis would need to be further investigated.
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PMID:IL-10 and IL-12p40 in Egyptian patients with HCV-related chronic liver disease. 1571 17


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