Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0239946 (liver fibrosis)
 8,268 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Protein undernutrition, alterations of hormones such as IGF-1, testosterone and cortisol, and increased lipid peroxidation-which may be related with deranged metabolism of some elements such as iron (Fe), zinc (Zn), manganese (Mn), selenium (Se) or copper (Cu)-may contribute to muscle damage in non alcoholic cirrhosis. Here, we analyse the effect of protein deficiency on muscle Cu, Fe, Zn, Mn and Se in carbon-tetrachloride (CCl(4)) induced liver cirrhosis. We also study the association between protein undernutrition and these trace elements with the activity of glutathione peroxidase (GPX), superoxide dismutase (SOD) and lipid peroxidation products, and how all these are related with muscle morphological changes in 40 male adult Sprague-Dawley rats. Liver cirrhosis was induced by intraperitoneal injection of CCl(4) to 10 rats fed a 2% protein diet, and to another 10 fed a 18% protein control diet. Two further groups included rats without cirrhosis fed the 2% protein and the 18% protein diets. After sacrifice (6 weeks later), we found type IIa fibre atrophy in the cirrhotic animals, especially in the low-protein fed ones and this was due to protein deficiency. Muscle Fe increased in low protein fed cirrhotic rats. No relationship was found between muscle changes and any of the hormones, enzymes and trace elements analysed, or with liver fibrosis. These results suggest that muscle atrophy observed in CCl(4)-induced cirrhosis is related with protein deficiency, but not with cirrhosis itself.
 ...
PMID:Protein deficiency and muscle damage in carbon tetrachloride induced liver cirrhosis. 1456 4

Hepatitis C virus infection is often associated with an elevation of iron parameters. Free liver iron causes liver damage and liver fibrosis preferentially through induction of reactive oxygen species. With an allele frequency of 5-10% for the C282Y mutation and 6-30% for the H63D mutation, there is a frequent coincidence of hemochromatosis (HFE) mutations and chronic hepatitis C. There is increasing evidence that HFE homozygosity and even HFE heterozygosity are associated with an increased liver iron concentration and liver fibrosis progression in chronic hepatitis C. In addition, present data suggest an impact of iron on the outcome of interferon therapy. Thus, HFE mutations and liver iron stores seem to be important comorbid factors in chronic hepatitis C. Screening for iron parameters and HFE mutations should be considered in patients with hepatitis C.
 ...
PMID:[Iron as comorbid factor in chronic hepatitis C]. 1468 69

The mechanism(s) determining the progression from fatty liver to steatohepatitis is currently unknown. Our goal was to define the relative impact of iron overload, genetic mutations of HFE, and insulin resistance on the severity of liver fibrosis in a population of subjects with nonalcoholic fatty liver disease (NAFLD) who had low prevalence of obesity and no overt symptoms of diabetes. In a cohort of 263 prospectively enrolled patients with NAFLD, 7.4% of patients had signs of peripheral iron overload and 9% had signs of hepatic iron overload, but 21.1% had hyperferritinemia. The prevalence of C282Y and H63D HFE mutations was similar to the general population and mutations were not associated with iron overload. Although subjects were on average only moderately overweight, insulin sensitivity, measured both in the fasting state and in response to oral glucose, was lower. Univariate analysis demonstrated that the presence of severe fibrosis was independently associated with older age, female sex, overweight, aspartate/alanine aminotransferase ratio, serum ferritin level, fasting glucose and insulin levels, decreased insulin sensitivity, and with histologic features (degree of necroinflammation and steatosis). After adjustment for body mass index (BMI), age, sex, and degree of steatosis, ferritin levels (odds ratio [OR] = 1.77; 95% CI = 1.21- 2.58; P =.0032) and the oral glucose insulin sensitivity (OR = 0.53; CI = 0.33-0.87; P =.0113) were independent predictors of severe fibrosis. In conclusion, the current study indicates that insulin resistance is a major, independent risk factor for advanced fibrosis in patients with NAFLD. Increased ferritin levels are markers of severe histologic damage, but not of iron overload. Iron burden and HFE mutations do not contribute significantly to hepatic fibrosis in the majority of patients with NAFLD.
 ...
PMID:Relative contribution of iron burden, HFE mutations, and insulin resistance to fibrosis in nonalcoholic fatty liver. 1518 21

We report the identification of a novel mutation in ferroportin1 in an Australian family with autosomal dominant iron overload. The phenotype of iron overload in one member of this family is associated with high serum ferritin concentration and elevated transferrin saturation. The pattern of iron overload in the liver shows accumulation predominantly in parenchymal cells with some Kupffer cell iron loading. Although some cases of type 4 haemochromatosis have been associated with the development of liver fibrosis this is the first report of a patient with fully established cirrhosis at a relatively young age (32 years). The coexistence of sarcoidosis in this patient may contribute to the more severe phenotype. This report highlights the phenotypic variability that can occur in type 4 haemochromatosis. Some patients have predominant reticuloendothelial iron loading and normal transferrin saturation whereas others have predominant parenchymal iron loading and elevated transferrin saturation. The reasons for this variability remain to be determined. Interestingly this is the third mutation to affect asparagine 144, reinforcing the important role for this amino acid in the function of ferroportin1.
 ...
PMID:Autosomal dominant iron overload due to a novel mutation of ferroportin1 associated with parenchymal iron loading and cirrhosis. 1503 Sep 91

Splenomegaly is a common finding in beta-thalassemia; however, its hemodynamic features and its potential correlations with high output state and hepatic disorders, both also frequent in thalassemia, have not yet been assessed in these patients. Eight beta-thalassemia patients with the indication for splenectomy and no symptoms or signs of heart disease, aged 25.6+/-5.5 years, were studied. Preoperative assessment included hematological profile, liver biology, hepatitis virus serology, and echocardiography. During splenectomy, splenic artery blood flow and splenic vein pressure were directly measured and liver biopsies were taken. Preoperative echocardiographic data were compared with those of 34 healthy controls. The preoperative cardiac index was significantly elevated in patients (4.8+/-1.3 vs 3.4+/-1.1 l/min per m2 in controls, p<0.001). Splenic blood flow, although increased, was not particularly high, being 285+/-56 ml/min or 0.13+/-0.04 ml/min per g of splenic mass, representing 4.1+/-0.9% of total cardiac output (CO). Splenic vein pressure was considerably elevated (29.7+/-5.5 cmH2O). Hepatic fibrosis, iron deposition, and extramedullary foci were found in all eight biopsies. Serology was positive in five of eight cases. beta-thalassemia patients with extensive splenomegaly requiring splenectomy are characterized by high output state, increased splenic blood flow, which probably makes a limited contribution to CO elevation, and portal hypertension, manifest by increased splenic vein pressure and hepatic histopathological abnormalities.
 ...
PMID:Hemodynamic assessment of splenomegaly in beta-thalassemia patients undergoing splenectomy. 1533 97

Alcohol abuse and hepatitis C virus (HCV) infection coexist with chronic liver disease in many patients. The mechanism of injury in these patients is probably multifactorial and involves, but is not limited to, a combination of diminished immune clearance of HCV, oxidative stress, emergence of HCV quasi-species, hepatic steatosis, increased iron stores, and increased rate of hepatocyte apoptosis. In patients with HCV infection, alcohol consumption is known to cause accelerated progression of liver fibrosis, higher frequency of cirrhosis, and increased incidence of hepatocellular carcinoma (HCC). These patients also have decreased survival as compared with patients with either alcohol abuse or HCV liver injury alone. Alcohol abuse causes decreased response to interferon treatment in HCV patients. It is therefore necessary for patients with HCV infection to abstain from alcohol consumption.
 ...
PMID:Alcohol and hepatitis C. 1534 7

Although cardiac complications remain the main causes of death in thalassemic patients, right heart dysfunction has been little studied and the mechanism is still unclear. Echocardiography was performed in 39 patients with beta-thalassemia major and 35 aged-matched controls. The gender, age, heart rate, blood pressure, left ventricular ejection fraction (LVEF), acceleration time (AcT) of right ventricular outflow and right ventricular ejection time (RVET), AcT/RVET, and the presence of tricuspid regurgitation (TR) were compared between the two groups. We also compared the gender, age, age at first blood transfusion, serum ferritin level, alanine aminotransferase (ALT), the presence of antibodies to hepatitis C virus, liver fibrosis, splenectomy, platelet counts, diabetes mellitus, arrhythmia, cardiomegaly, LVEF, AcT, RVET, AcT/RVET, and signal intensity ratio (SIR) of myocardial magnetic resonance imaging (MRI) between thalassemic patients with and without TR. The incidence of TR in thalassemic patients was significantly higher than that in the control group (30.8 vs 11.4%, p=0.03). The incidences of splenectomy (p=0.03), platelet counts (p=0.01), and SIR of myocardial MRI (p=0.03) in thalassemic patients with TR were significantly higher than in those without TR. The AcT was shorter and the AcT/RVET ratio was smaller, suggesting higher pulmonary pressure in the thalassemic patients with TR. Occurrence of TR in patients with beta-thalassemia major may be a consequence of cardiac iron deposit, thrombocytosis, splenectomy, or pulmonary hypertension.
 ...
PMID:Tricuspid regurgitation in patients with beta-thalassemia major. 1544 31

Thioacetamide (TAA) administration is an established technique for generating rat models of liver fibrosis and cirrhosis. Oxidative stress is believed to be involved as TAA-induced liver fibrosis is initiated by thioacetamide S-oxide, which is derived from the biotransformation of TAA by the microsomal flavine-adenine dinucleotide (FAD)-containing monooxygense (FMO) and cytochrome P450 systems. A two-dimensional gel electrophoresis-mass spectrometry approach was applied to analyze the protein profiles of livers of rats administered with sublethal doses of TAA for 3, 6 and 10 weeks respectively. With this approach, 59 protein spots whose expression levels changed significantly upon TAA administration were identified, including three novel proteins. These proteins were then sorted according to their common biochemical properties and functions, so that pathways involved in the pathogenesis of rat liver fibrosis due to TAA-induced toxicity could be elucidated. As a result, it was found that TAA-administration down-regulated the enzymes of the primary metabolic pathways such as fatty acid beta-oxidation, branched chain amino acids and methionine breakdown. This phenomenon is suggestive of the depletion of succinyl-CoA which affects heme and iron metabolism. Up-regulated proteins, on the other hand, are related to oxidative stress and lipid peroxidation. Finally, these proteomics data and the data obtained from the scientific literature were integrated into an "overview model" for TAA-induced liver cirrhosis. This model could now serve as a useful resource for researchers working in the same area.
 ...
PMID:A proteomic analysis of thioacetamide-induced hepatotoxicity and cirrhosis in rat livers. 1552 43

In untreated hepatitis virus (HCV)-positive renal transplant patients, the rate of liver fibrosis progression is low. In contrast, in those treated by ribavirin monotherapy, liver fibrosis score increased significantly after only 1 year of ribavirin monotherapy. The aim of this study was to identify the factors that might contribute to accelerate liver fibrosis progression in this population. Eleven patients were included in the study. Intrahepatic transforming growth factor (TGF)-beta, interferon (IFN)-gamma, and interleukin (IL)-10 mRNA quantification determined by real-time reverse transcription-polymerase chain reaction (RT-PCR) were similar before and after ribavirin therapy. The number of amino acid substitutions observed in the hypervariable region (HVR)-1 of the HCV genome between baseline and 1 year after ribavirin monotherapy was low, i.e., 3 (1-11) amino acid substitutions, suggesting the absence of a high selection pressure induced by ribavirin. In contrast, due to ribavirin-induced hemolysis, there was a significant increase in serum ferritin levels (P = 0.02) and in intrahepatic iron deposition (P = 0.04). Transferrin level and total iron-binding capacity decreased significantly during ribavirin monotherapy (P = 0.004). The increased liver fibrosis observed in renal transplant patients receiving ribavirin monotherapy could be related to ribavirin-induced anemia. Severe chronic hemolysis is responsible for iron overload, liver iron deposition, and an acceleration in the progression of liver fibrosis.
 ...
PMID:Factors accelerating liver fibrosis progression in renal transplant patients receiving ribavirin monotherapy for chronic hepatitis C. 1577 76

Hepatic fibrosis occurs after many years of iron overload in liver. An effective iron deposition model induced by ferric nitrilotriacetate (FeNTA) in cultured rat hepatocytes was assumed. It has been shown that treatment of rat hepatocytes with FeNTA lead to oxidative stress and hepatocyte apoptosis. Hepatocyte apoptosis can promote liver fibrosis. The mechanisms of hepatocyte apoptosis induced by FeNTA have not yet been fully elucidated. The present study demonstrated that FeNTA-induced hepatocyte apoptosis was related to Bax translocation, cytochrome c release, and caspase-3 activation.
 ...
PMID:Translocation of Bax in rat hepatocytes cultured with ferric nitrilotriacetate. 1580 78


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>