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

As part of a double-blind, randomized, controlled trial to evaluate the effect of colchicine on liver cirrhosis, 43 cirrhotic patients were assigned to either a placebo (20 patients) or a colchicine (23 patients) treatment group. Colchicine 1 mg and an indistinguishable placebo were administered orally on a daily dose 5 days a week. In the colchicine group, 12 were males and 11 females, while in the control group 13 were males and 7 females. The time elapsed between diagnosis and inclusion in the study was 14.1 mo for the controls and 14.5 mo for the patients on colchicine. Mortality related to the liver disease occurred in 4 patients on colchicine and 8 patients on placebo. Although the probability of surviving in the colchicine group was greater than that of the placebo, the difference did not reach statistically significant levels. Of the colchicine-treated patients, in three a remarkable decrease in liver fibrosis was observed in serial biopsies. In two other patients, carcinoma of the liver developed. Six of the survivors on colchicine have improved clinically, noticing disappearance of ascites and edema, as well as a decrease in the size of the spleen. All the survivors on placebo continue to show clinical deterioration. In contrast to the usual drop of serum albumin seen in the cirrhotic patients, those receiving colchicine increased and maintained their serum albumin levels throughout the study. Serum proline values were elevated only in the alcohol cirrhotic patients. Serum alkaline phosphatase increased only in those patients receiving colchicine. The results indicate that in some cases, liver fibrosis could be modified by treatment with antifibrotic drugs. The use of colchicine at present should remain within controlled studies.
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PMID:Treatment of cirrhosis with colchicine. A double-blind randomized trial. 37 54

The present study has been performed in order to establish the relative and combined roles of ethanol and malnutrition on liver Fe, Zn, Cu, and Mn alterations in alcoholic male adult Wistar rats, and also the relationships between these alterations and histomorphometrically determined hepatocyte and nuclear areas, perivenular fibrotic rim area, and total amount of fat present in the liver. Four groups of 8 animals each were fed: (1) a nutritionally adequate diet (C); (2) a 36% ethanol-containing (as percent of energy), isocaloric diet (A); (3) a 2% protein-containing, isocaloric diet (PD); and (4) a 36% ethanol, 2% protein-containing, isocaloric diet (A-PD), respectively, following the Lieber-DeCarli model. Ethanol-fed, protein-deficient animals showed the highest liver Fe, and the lowest Zn and Cu values, although differences in liver Zn, Mn, and Cu values were not significantly different between PD and A-PD groups. Statistically significant differences of these parameters were observed between the A and the A-PD groups, and between the A and PD groups, except for liver iron. Except for liver Mn, differences between C and A groups were statistically significant. These alterations correlated with liver fibrosis and steatosis, serum albumin, and weight loss, except for liver Mn, which was not correlated with fibrosis or steatosis. Thus, protein deficiency seems to enhance ethanol-induced liver Fe, Zn, and Cu alterations, whereas protein deficiency, but not ethanol, seems to play a major role on liver Mn alterations.
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PMID:Combined effects of ethanol and protein deficiency on hepatic iron, zinc, manganese, and copper contents. 141 56

Changes in the salivary glands, liver and pancreas in rats with experimentally induced liver injuries were examined. The injuries (experimental group) were induced by subcutaneous injections of carbon tetrachloride (0.01ml/kg body weight) in a 50% olive-oil solution. The injections were administered twice weekly for 10,20 and 40 weeks. Control animals received the same doses of olive oil during the same periods. 1. In the experimental group, serum glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) increased remarkably, whereas serum albumin decreased. 2. Swelling of the liver and multiple nodular formations occurred in the experimental group. Liver fibrosis with the formation of pseudolobules indicated a form of liver cirrhosis. 3. No significant histological changes were observed in the pancreases of animals in the 10- and 20-week experimental groups. Vacuolation in the acinar cells was observable in 3 of 8 cases in the 40-week experimental group. 4. In connection with histological findings of parotid glands, vacuolation of the acinar cells occurred in 7 of 12 cases in the 10-week experimental group, in 7 of 8 cases in the 20-week experimental group, and in all 8 cases in the 40-week experimental group. Vacuole numbers and sizes increased as the experimental period was prolonged. 5. Immunohistochemical investigation showed strong positive reactions to the anti-amylase antibody around vacuoles in acinar cells of parotid glands. In unvacuolated acinar cells, on the other hand, only slight positive reaction was observed. 6. Electronmicroscopic observation of the acini revealed greatly enlarged lumina and dilated intercellular canaliculi connected to the lumina. Small vacuoles were observed on the basement of the acini. 7. No such significant changes as fibrosis, vacuolation, and atrophy of acinar cells were observed in the submandibular and sublingual glands of the experimental animals. 8. Serum amylase activity increased more in the experimental than in the control rats. Electrophoretic patterns suggested that in the control group 95 percent of serum amylase was parotid type, and also in the experimental group 95 percent of serum amylase was parotid type. 9. Amylase activity in the parotid glands also increased more in the experimental than in the control animals.
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PMID:[A study on changes of liver and salivary glands in rats with experimentally induced liver injuries. Pathological and biochemical observations]. 172 65

Synthesis of 99Tcm-galactosyl-neoglycoalbumin (99Tcm-NGA), a recently described new radioligand with high specificity for hepatic binding protein (HBP), a galactose-residue specific receptor on hepatocytes, was carried out by covalent coupling of 2-imino-2-methoxyethyl-1-thio-beta-D-galactopyranoside to the primary amino groups of human serum albumin. NGA was purified by ultrafiltration and size exclusion high-pressure liquid chromatography (HPLC). Using a computer-based simulation program, time-activity data for the liver and precordium, blood radioactivity 2 min after i.v. injection of the radioligand, the association constant of 99Tcm-NGA-binding to HBP measured on human liver biopsies in vitro, and other patient-related parameters were put into a five-state non-linear model describing the pharmacokinetics of 99Tcm-NGA. By fitting the parameters of the model iteratively to the experimental data, an estimate of HBP concentration in the liver and of total liver blood flow was obtained. Using this model we studied 32 patients (53 +/- 11 years) with different clinical stages of alcoholic liver cirrhosis. Child B and Child C stage cirrhotic patients had a lower HBP concentration in the liver compared to control individuals (0.96 +/- 0.21 mumol l-1). The group with the most advanced cirrhosis (Child C stage) had a significantly lower HBP concentration (0.27 +/- 0.15 mumol l-1) than Child A patients (0.66 +/- 0.21 mumol l-1; P less than 0.01) and Child B patients (0.53 +/- 0.18 mumol l-1; P less than 0.05). In four patients with biopsy-proven liver fibrosis (0.84 +/- 0.20 mumol l-1) no difference in receptor concentration from normal individuals was estimated. Changes in liver blood flow were not significant between the groups. A direct comparison of HBP concentration estimated in vivo by 99Tcm-NGA functional imaging and HBP concentration measured in vitro on a surgically removed liver biopsy specimen from the same patient with a normal liver and liver cirrhosis showed good matching of these two values. The results suggest that in vivo estimation of HBP concentration in the liver by 99Tcm-NGA functional imaging might be a suitable method for determining liver cell mass.
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PMID:Functional liver imaging with 99Tcm-galactosyl-neoglycoalbumin (NGA) in alcoholic liver cirrhosis and liver fibrosis. 186 4

99mTc-galactosyl-neoglycoalbumin (99mTc-NGA) was synthesized by covalent coupling of 2-imino-2-methoxyethyl-1-thio-beta-D-galactopyranoside to the primary amino groups of human serum albumin. Injection of 99mTc-NGA (150 MBq; 3.5 mg (= 50 nmol)/ml demonstrated the liver to be the exclusive site of tracer-uptake. Simulation of 99mTc-NGA-kinetics allowed quantification of binding to the hepatic binding protein (HBP). Using this model we studied 250 patients with various liver disease. In alcoholic liver cirrhosis such patients with Child B and Child C stage cirrhosis had a lower HBP-concentration in the liver compared to control individuals (0.85-1.2 mumol/l). The group with the most advanced cirrhosis (Child C stage) had a significantly lower HBP-concentration (0.20-0.45 mumol/l) than Child A patients (0.60-0.85 mumol/l; p less than 0.01) and Child B patients (0.45-0.60 mumol/l; p less than 0.05). In patients with biopsy proven liver fibrosis (0.80-1.22 mumol/l) no difference in receptor concentration to normal individuals was estimated. Patients with recently diagnosed acute viral hepatitis underwent repeated 99mTc-galactosyl-neoglycoalbumin (NGA) scanning of the liver during the course of the disease. Return of liver function tests to normal values was associated with an increased hepatic imaging size as well as increase in HBP-concentration (up to a 3-fold of initial concentration). In patients exhibiting a prolonged course of the disease changes in NGA-kinetic data were borderline and the hepatic image size unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Quantification of human hepatic binding protein (HBP) via 99mTc-galactosyl-neoglycoalbumin (NGA) liver scintigraphy. 192 72

The aim of this study was to assess the specific correlation of apolipoprotein-AI to hepatic fibrosis in alcoholic patients. Four hundred eighty two patients were prospectively included with serum measurement of apolipoprotein-AI within 10 days before liver biopsy. Pathologic features were semiquantitatively assessed by two observers. In 28 patients liver biopsy was used for histomorphometric assessment of fibrosis and immunohistochemical labeling of apolipoprotein-AI. Serum apolipoprotein-AI was negatively correlated to semiquantitative score of fibrosis (r = -0.50; p less than 0.001), independently of the scores of steatosis and alcoholic hepatitis (r = -0.44; p less than 0.001) and of the value of serum albumin, bilirubin, and prothrombin time (r = -0.22; p less than 0.001) and independently of the nutritional parameters (r = -0.29; p less than 0.009). The mean value of apolipoprotein-AI decreased according to the grade of fibrosis from 220 +/- 6 mg/dl (mean +/- SEM) to 110 +/- 8 mg/dl. Serum apolipoprotein-AI was negatively correlated to the percentage of fibrosis (r = -0.70; p less than 0.001) in the biopsies morphometrically assessed. The labeling was superimposed to the extracellular matrix. In conclusion, this study shows that decrease of apolipoprotein-AI is a serum and tissue marker of liver fibrosis independently of steatosis, alcoholic hepatitis, liver function tests, and nutritional parameters.
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PMID:Apolipoprotein AI is a serum and tissue marker of liver fibrosis in alcoholic patients. 251 36

It has been suggested that glycosaminoglycans are involved in the pathogenesis of liver fibrosis. Furthermore, recent studies have reported that one of them, hyaluronate, was mainly taken up and degraded by the liver. Using an enzymoimmunological assay, based on hyaluronate-hyaluronectin interaction, serum levels of hyaluronate were measured in 113 patients with various liver diseases. Patients were divided into six groups according to clinical, biological and histological data: Group 1-alcoholic cirrhosis (n = 47) including alcoholic cirrhosis with alcoholic hepatitis (n = 24); Group 2-primary biliary cirrhosis (n = 21); Group 3-cirrhosis related to viral hepatitis (n = 10); Group 4-idiopathic hemochromatosis (n = 17); Group 5-alcoholic fatty liver (n = 8); and Group 6-viral or drug acute hepatitis (n = 10). Ninety-four blood donors were studied as controls. Levels of hyaluronate were found to be strikingly elevated in Group 1 (1,225 +/- 1,137 micrograms per liter), Group 2 (792 +/- 739 micrograms per liter), Group 3 (649 +/- 373 micrograms per liter), and Group 4 (246 +/- 242 micrograms per liter), whereas patients in Group 5 (94 +/- 63 micrograms per liter) and Group 6 (73 +/- 57 micrograms per liter) had values close to controls (23 +/- 17 micrograms per liter). There was a significant correlation between serum hyaluronate and serum albumin, prothrombin time, factor V concentration and serum gamma-globulins. It is suggested that hyaluronate levels reflect both active fibrosis and hepatic failure and may be a quantitative marker of severity of hepatic injury.
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PMID:Serum hyaluronate in liver diseases: study by enzymoimmunological assay. 371 Apr 27

We have developed the methodology for evaluating the effects of pathophysiological conditions on the molecular mechanisms of hepatic protein synthesis and fibrogenesis in baboons and man. Total RNA was extracted from percutaneous liver biopsies of five baboons who were chronically fed an ethanol-rich liquid diet, their pair-fed controls and from humans with a variety of liver abnormalities. Chronic alcohol administration in baboons with liver fibrosis and normal serum albumin levels increased in vitro protein synthesis as measured by [35S]methionine incorporation, albumin mRNA content and Type I procollagen mRNA content. There was no difference in the beta-actin (a constitutive protein) mRNA content. In humans, serum albumin levels correlated with albumin mRNA content as indicated by the intensity of dot blot hybridization and Type I procollagen mRNA levels correlated with the activity of liver fibrosis. The use of RNA-DNA hybridization to investigate procollagen mRNA from human biopsies appears to be a valuable tool for evaluating the potential for collagen synthesis and the future course of liver disease. Besides the use of RNA-DNA hybridization, we describe other methodologies which are useful in delineating the levels of gene expression responsible for hepatic mRNA regulation in normal liver and disease states in man. The use of molecular techniques to evaluate human liver disease provides an opportunity to develop clinically relevant information while at the same time offering the additional advantage of providing fundamental knowledge about fibrogenesis.
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PMID:Development of molecular hybridization technology to evaluate albumin and procollagen mRNA content in baboons and man. 380 13

The distribution in the mouse of colchicine and of two colchicine derivatives, namely formylcolchicine/formylated serum albumin (FC/FTSA) and formylcolchicine/lactosaminated serum albumin (FC/LASA), was studied. The presence of radioactivity after the intravenous injection of labelled colchicine or of its derivatives was determined in liver, small intestine, kidney and blood. The radioactivity of the derivatives was better retained than that of colchicine. The derivatives accumulated in the liver to a much greater extent than colchicine, but were scarcely present in the gut. Tropism towards the liver might be important for the use of FC/LASA and FC/FTSA to control liver fibrosis.
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PMID:Derivatives of colchicine preferentially taken up by the liver: an approach to the treatment of liver fibrosis. 757 53

Liver fibrosis is a complex process characterized by two major events: fibroproliferation and increased collagen synthesis. The exact role of cytokines in the pathogenesis of hepatic fibrosis remains to be established, but platelet-derived growth factor clearly stimulates proliferation of fibroblasts and increases collagen synthesis. In in vitro studies, pentoxifylline, a methylxanthine, significantly reduced platelet-derived growth factor-driven proliferation of fibroblasts. Platelet-derived growth factor has also been identified as a fibroproliferative factor produced spontaneously by monocytes obtained from patients with liver disease. Long-term administration of pentoxifylline (16 mg/kg orally, 5 days/wk for 12 wk) in an animal model of liver fibrosis prevented elevations in gamma-glutamyl transpeptidase and alkaline phosphatase levels and prevented the reduction in serum albumin level normally observed in this animal model of liver disease. The animal model used was a long-term, low-dose yellow phosphorus--induced model in pigs that reproducibly results in extensive fibrosis after 10 to 12 wk of treatment. Long-term administration of pentoxifylline also prevented the histological changes characteristic of fibrosis in this animal model. Collagen concentration was significantly elevated in liver sections obtained from animals receiving yellow phosphorus, compared with controls. Long-term pentoxifylline treatment resulted in significantly lower collagen concentrations in liver sections from animals receiving yellow phosphorus than in sections from animals receiving yellow phosphorus alone; this was supported by histological observation. Therefore administration of pentoxifylline prevented the biochemical and histological changes associated with an animal model of liver disease. Pentoxifylline will likely have an important therapeutic role in liver fibrosis.
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PMID:Pentoxifylline prevents fibrosis in an animal model and inhibits platelet-derived growth factor-driven proliferation of fibroblasts. 809 47


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