UMLS:C0023890 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0023890 (cirrhosis)
42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The blood coagulation and fibrinolysis of 33 patients with compensated liver cirrhosis and 31 patients with hepatocellular carcinoma were examined using several markers, namely thrombin-antithrombin III complex (TAT), plasmin-alpha 2 plasmin inhibitor complex (PIC), antithrombin-III (AT-III) and prothrombin time, and the relationship between these markers, endotoxemia, and TNF-alpha was examined. These patients had no complications due to hepatic failure, such as infections, encephalopathy, ascites, G-I bleeding and clinical DIC. PIC was not elevated, but TAT tended to be elevated in LC and significantly elevated in HCC. AT-III was decreased in LC and HCC, and the blood endotoxin was partly positive in LC and HCC, but was not correlated with AT-III or PT. The TAT level in the blood-endotoxin-positive patients measured by endospecy methods was higher than that in the negative patients, and was significantly correlated with the blood endotoxin level in the LC and HCC patients (r = 0.57, r = 0.88, p < 0.01). No relationship was observed between TNF-alpha and blood endotoxin. In conclusion, (1) blood coagulability was activated already in compensated LC and HCC, but was not connected with fibrinolysis, (2) the activation of coagulability was closely related with endotoxemia, and (3) TNF-alpha was not correlated with blood endotoxin or TAT.
...
PMID:[Blood coagulation and fibrinolysis in relation to endotoxemia in liver cirrhosis and hepatocellular carcinoma]. 756 21

The purpose of the work was an assessment of TNF-alpha and Il-6 concentrations in 34 children with diagnosed chronic hepatitis. In all studied patients the values of TNF-alpha and Il-6 concentration were slightly increased. The correlations calculated between TNF-alpha and Il-6 concentrations calculated between TNF-alpha and Il-6 concentrations and laboratory parameters (laboratory indicators of hepatitis activity--AlAT; liver function indicators--prothrombin index, bilirubin concentration, bile acid concentration, alkaline phosphatase activity, anti-pyrin half-life) were non-significant in Spearman non-parametric test (p > 0.005) except for the correlation between albumin and TNF-alpha concentrations. No statistically significant differences of TNF-alpha and Il-6 concentrations were found between groups of patients with active and persistent hepatitis; groups with and without cirrhosis as well as between groups with and without portal hypertension. Normal or slightly increased TNF-alpha and Il-6 concentrations, observed in chronic hepatitis in children should be explained by compensated liver function in such patients.
...
PMID:[Can TNF-alpha and IL-6 be helpful in assessment of chronic hepatitis in children?]. 771 32

Cytokines constitute a complex network of molecules involved in the regulation of the inflammatory response and the homeostasis of organ functions. Cytokines coordinate physiologic and pathologic processes going on in the liver, such as liver growth and regeneration, inflammatory processes including viral liver disease, liver fibrosis and cirrhosis. Liver growth and regeneration are regulated by several cytokines. The platelet-derived hepatocyte growth factor, in particular, delivers a strong mitogenic stimulus for hepatocyte regeneration. The cell-mediated immune response plays a central role in hepatocellular necrosis and in the immunopathogenetic mechanisms involved in viral clearance and persistence in liver disease of viral etiology. In this context, cytokines modulate the immune system and exert direct antiviral activity by cytopathic and non-cytopathic mechanisms, as demonstrated in a transgenic mouse model. IL-6, TNF-alpha, IL-1 and IL-2 increase in acute fulminant viral hepatitis; in fact, they have pro-inflammatory and cytotoxic effects. Reduced IL-2 and IFN-alpha synthesis and increased serum levels of IL-1 and IL-2 soluble receptor (IL-2R) have been observed in HBV chronic liver disease. In HCV chronic hepatitis, IL-2R increases as well, while IFN-gamma and IL-2 decrease. In personal experimental observations, intra-hepatic messenger RNA expression of several cytokines was measured in liver specimens of patients with chronic HBV and HCV infections: patients with HCV chronic liver disease had higher levels of IL-2, IL-6, IL-10, and IFN-gamma. These data are in accordance with immunological studies showing a vigorous cell-mediated immune response in HCV chronic liver disease and a deficient immune response in HBV chronic hepatitis.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:[Cytokine mediators in acute inflammation and chronic course of viral hepatitis]. 772 1

Abnormal cytokine levels have been described in patients with chronic liver disease, but studies correlating cytokine homeostasis with abnormalities in coagulation and fibrinolysis are lacking. In order to establish a link between cytokines and the hemostatic changes the following parameters were determined in 44 patients with cirrhosis (alcoholic = 15, postnecrotic = 22, others = 7): TNF-alpha, IL-6, thrombin-antithrombin (TAT) complexes, prothrombin fragment 1 + 2 (F1 + 2) and t-PA by using enzyme-linked immunosorbent assays, and PAI-1, plasminogen and alpha 2-antiplasmin (alpha 2-AP) by using chromogenic substrates. All patients were at stages B and C of Child's classification when entering the study. Mean cytokine concentrations were significantly higher in cirrhotic patients as compared to age- and sex-matched controls (p < 0.009). There was a significant increase of TAT (p < 0.02) and F1 + 2 (p < 0.001) in the patients groups, suggesting a grade of intravascular coagulation. A hyperfibrinolytic state as demonstrated by an increase of t-PA and decrease of plasminogen and alpha 2-AP was also observed (p < 0.001). We could define a subgroup of patients with cytokine values higher than 20 pg/ml. Interestingly, in this group there was a significant increase of TAT (p < 0.04) and t-PA (p < 0.02) levels and a decrease of plasminogen and alpha 2-AP (p < 0.02) as compared to values observed in patients with cytokines lower than 20 pg/ml. We conclude that high levels of TNF-alpha and IL-6 may contribute to hyperfibrinolysis and intravascular coagulation in patients with liver cirrhosis, as assessed by the increase of TAT and t-PA levels and the reduction of plasminogen and alpha 2-AP.
...
PMID:Increased concentrations of tumor necrosis factor and interleukin-6 contribute to the hemostatic abnormalities in advanced liver disease. 858 22

We previously reported that the number of TNF-alpha-producing cells was increased in the liver of patients with type C chronic liver disease. To understand further the pathophysiology of this change, we examined serum levels of two soluble TNF receptors, TNF-alphaRI (p55) and -alphaRII (p75), and IL-10, all of which act as TNF-alpha buffer, and IL-15, a novel cytokine sharing many immunological activities with IL-2, using ELISA methods. We studied control individuals and patients with type C chronic liver disease, including asymptomatic hepatitis C virus (HCV) carriers with persistently normal serum ALT values, and those with chronic hepatitis (CH), liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Both types of sTNF-alphaR closely correlated with disease progression. Patients with LC and HCC had significantly elevated levels for sTNF-alphaRII compared with the other patient groups and controls. Serum IL-10 levels were significantly greater in all chronic liver disease groups than in controls. With respect to IL-15, the values were high in CH, LC and HCC compared with those of controls. Notably, HCC patients showed highest values for both IL-10 and IL-15, with significant differences from the other patient groups. Serial determinations revealed that interferon (IFN) treatment for CH patients resulted in the suppression of circulating IL-10 and IL-15 levels along with decrease in serum aminotransferase values. Both cytokines remained at decreased levels after cessation of therapy in patients who went into clinical and virological remission. On the other hand, treatment did not affect serum levels of sTNF-alphaRs. These findings indicate that serum levels of these molecules correlated with disease progress in chronic HCV infection, and that IL-10 and IL-15 may reflect the degree of inflammation in the liver. It is also suggested that both cytokines may be related to the development of HCC.
...
PMID:Serum levels of IL-10, IL-15 and soluble tumour necrosis factor-alpha (TNF-alpha) receptors in type C chronic liver disease. 932 22

Recent data from animal studies suggest that induced hypothyroidism prevents the hyperdynamic circulation in portal vein ligated rats, liver cirrhosis in rats chronically treated with thioacetamide (TAA), and immune-mediated acute liver injury induced in mice by concanavalin A. Therefore, the aim of this present study is to determine whether hypothyroidism would likewise prevent fulminant hepatic failure (FHF) in rats. FHF was induced by 3 consecutive ip injections of TAA (400 mg/kg) at 24-hour intervals. Hypothyroidism was induced in rats by either methimazole (MMI) or propylthiouracil (PTU) and surgical thyroidectomy and was confirmed by elevated serum thyroid stimulating hormone levels. Serum levels of liver enzymes, blood ammonia, and prothrombin time were significantly lower in all 3 groups of hypothyroid rats. The stage of hepatic encephalopathy (HE) and the survival rates were significantly improved in the hypothyroid rats (P < .01); the histologic examination of their livers showed less necrosis and inflammation (P < .01). In the hypothyroid rats, the serum levels of malondialdehyde 48 hours after thioacetamide (TAA) administration were lower than in control rats (P < .01). Exogenous supplementation of hypothyroid rats with L-thyroxine started 48 hours before TAA administration abrogated the protective effects of hypothyroidism. The serum levels of tumor necrosis factor alfa (TNF-alpha), interleukin (IL) 2 and IL-6 after 24 hours were slightly lower in the hypothyroid rats, but the administration of soluble receptor of TNF (10-1,000 microg/rat) did not prevent the induction of fulminant liver failure by TAA. Oxygen extraction, studied in isolated perfused liver preparation, was significantly lower in livers of hypothyroid rats (P < .01). These results suggest that induced hypothyroidism decreases the development of liver injury in a rat model of FHF. The mechanism may involve diminished oxidative cell injury caused by decreased oxygen utilization and hypometabolism associated with hypothyroidism.
...
PMID:Hypothyroidism minimizes liver damage and improves survival in rats with thioacetamide induced fulminant hepatic failure. 953 41

In chronic viral hepatitis, autoimmune hepatitis, and some chronic cholestatic liver diseases, T-lymphocytes serve as effector cells of the immunostimulatory processes. Cellular interactions of immune cells with extracellular matrix (ECM) components are regulated primarily via the beta 1 subfamily of integrin receptors. The target epitope of several such integrin receptors is the Arg-Gly-Asp (RGD) sequence, a cell adhesion motif shared by several matrix-associated adhesive glycoproteins. We review the use of synthetic nonpeptidic analogues of RGD and of soluble receptor of tumor necrosis factor (TNF)-alpha in the prevention of immune-mediated, concanavalin A-induced liver damage in mice and of RGD analogues in inhibiting the development of liver cirrhosis in rats. The concanavalin A-induced elevation of serum transaminases and TNF-alpha, and the infiltration of liver tissue by inflammatory cells, were inhibited by pretreatment of the mice with the synthetic RGD mimetics and soluble TNF receptor. In rats, the progression of thioacetamide-induced liver cirrhosis was markedly inhibited by the coadministration of the RGD mimetic SF-6,5. The compounds described here may be examined therapeutically for pathological conditions in the liver, manifested as necroinflammation, cholestasis and fibrosis.
...
PMID:The use of synthetic analogues of Arg-Gly-Asp (RGD) and soluble receptor of tumor necrosis factor to prevent acute and chronic experimental liver injury. 962 59

The inducible nitric oxide synthase (iNOS) gene is expressed by hepatocytes in a number of physiologic and pathophysiologic conditions affecting the liver including septic and hemorrhagic shock. The molecular regulation of iNOS expression is complex and occurs at multiple levels in the gene expression pathway. The cytokines TNF-alpha, IL-1beta, and INF-gamma synergistically activate iNOS expression in the liver, and the human iNOS gene was first cloned from cytokine-stimulated hepatocytes. iNOS expression requires the transcription factor NF-kappaB and is down-regulated by steroids, TGF-beta, the heat shock response, p53, and nitric oxide (NO) itself. In vivo, hepatic iNOS induction is differentially regulated from the typical acute-phase reactants and is not expressed as a mandatory component of the acute phase response. Thus, numerous mechanisms have evolved to regulate iNOS expression during hepatocellular injury. Studies of the effects of NO in the liver demonstrate that induced NO synthesis plays an important role in hepatocyte function and protects the liver during sepsis and ischemia reperfusion. Its cytoprotective role is best exemplified in a rodent model of endotoxemia. Here the addition of the nonspecific NOS inhibitors significantly increased hepatic damage. NO exerts a protective effect through its ability to prevent intravascular thrombosis by inhibiting platelet adhesion and neutralizing toxic oxygen radicals. NO also exerts a protective effects both in vivo and in vitro by blocking TNF-alpha-induced apoptosis and hepatotoxicity, in part by a thiol-dependent inhibition of caspase-3-like protease activity. These studies demonstrate the cytoprotective effects of NO in the liver and suggest hepatic iNOS expression functions as an adaptive response to minimize inflammatory injury. In addition, NO has anti-tumor effects as well as known mutagenic effects, is involved in the systemic vasodilatation of cirrhosis, and has potent antimicrobial properties.
...
PMID:Inducible nitric oxide synthase in the liver: regulation and function. 972 29

Postoperative infection is one of the main factors that affect mortality after hepatic resection, especially in patients with liver cirrhosis. In the pathogenesis of postoperative organ failures complicating endotoxemia or other surgical injuries, inflammatory cytokine has proved to play an important role. We herein report the changes in tumor necrosis factor-alpha, interleukin-1 beta, and granulocyte colony-stimulating factor in production from macrophages/monocytes stimulated with lipopolysaccharide (LPS) after hepatic resection of cirrhotic livers. Seven hepatocellular carcinoma patients with liver cirrhosis who were undergoing limited resection or segmental resection of the liver were examined. Peripheral blood monocytes were separated and incubated with 10 microg/ml LPS, and cytokine release was measured by ELISA before surgery as well as on Postoperative Days (PODs) 1, 3, 7, and 14. Preoperative cytokine production in cirrhotic patients was greater than cytokine production in noncirrhotic controls. Cytokine productivity increased after hepatic resection. TNF-alpha production was 1,846.6 +/- 882.6 pg/ml, 1,947.3 +/- 221.9 pg/ml, 2,486.9 +/- 519.7 pg/ml, and 1,640.2 +/- 416.0 pg/ml on PODs 1, 3, 7, and 14, respectively. The values on all PODs were significantly greater than the healthy control value, and the value on POD 7 was significantly greater than the preoperative value. Interleukin-1 beta and granulocyte colony-stimulating factor production values corroborated this result in general. In conclusion, macrophages/monocytes are primed in cirrhotic patients preoperatively, and they are supposed to carry greater cytokine producing abilities after hepatic resection. When endotoxin spills over in the blood or in the liver after hepatic resection, postoperative hepatic failure could develop as a result of hypercytokinemia.
...
PMID:Inflammatory cytokine production enhancement in the presence of lipopolysaccharide after hepatic resection in cirrhotic patients. 1022 86

Nitric oxide (NO) has been implicated in the arterial vasodilation and associated vascular hyporesponsiveness to vasoconstrictors observed in liver cirrhosis. Bacteria, potent activators of NO and TNF-alpha synthesis, are found in the mesenteric lymph nodes (MLNs) of ascitic cirrhotic rats. Here, we investigated the impact of bacterial translocation (BT) to MLNs on TNF-alpha production, vascular NO release, and contractility in the mesenteric vasculature of ascitic cirrhotic rats. Vascular response to the alpha-adrenoagonist methoxamine, which is diminished in the superior mesenteric arterial beds of cirrhotic rats, is further blunted in the presence of BT. BT promoted vascular NO release in cirrhotic rats, an effect that depended on pressure-induced shear stress and was blocked by the NO inhibitor N(omega)-nitro-L-arginine. Removing the endothelium had the same effect. Endothelial NO synthase (eNOS), but not the inducible isoform (iNOS), was present in mesenteric vasculature of cirrhotic rats with and without BT, and its expression was enhanced compared with controls. TNF-alpha was induced in MLNs by BT and accumulated in parallel in the serum. This TNF-alpha production was associated with elevated levels of tetrahydrobiopterin (BH(4)), a TNF-alpha-stimulated cofactor and enhancer of eNOS-derived NO biosynthesis and NOS activity in mesenteric vasculature. These findings establish a link between BT to MLNs and increased TNF-alpha production and elevated BH(4) levels enhancing eNOS-derived NO overproduction, further impairing contractility in the cirrhotic mesenteric vasculature.
...
PMID:Bacterial translocation in cirrhotic rats stimulates eNOS-derived NO production and impairs mesenteric vascular contractility. 1054 21

1 2 3 4 5 6 7 Next >>