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Query: UMLS:C0239946 (liver fibrosis)
 8,268 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous experiments showed that the presence of high levels of acute phase reactants (APR) enhance CCl4-induced liver fibrosis in the rat. A high correlation was found between the degree of fibrosis and alpha 2-macroglobulin of the rat (alpha 2-macrofetoprotein, alpha M-FP) used for monitoring the acute phase response. This acute phase reaction was provoked by epinephrine just before CCl4 treatment was started. In the present study we analyzed the effect of APR by repeating these experiments and estimating liver neutral collagenase with a synthetic substrate and endogenous collagen as a substrate, and liver prolyl-4-hydroxylase. A strong depression of liver collagenase activity was found in rats with a preceding acute phase reaction contrary to the rats that underwent CCl4 treatment only. A high level of alpha M-FP correlated negatively with collagenase activity. Also in vitro alpha M-FP proved to inhibit collagenase activity. Prolyl-4-hydroxylase was increased in the rats during acute phase reaction and correlated highly and positively with alpha M-FP, haptoglobin, and ceruloplasmin. Thus high levels of APR promote development of CCl4-induced fibrosis, partly by anticollagenase activity and partly because of enhancement of prolyl-4-hydroxylase activity. The latter phenomenon can also be explained by the presence of APR, but this has to be proved.
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PMID:Mechanisms by which acute phase proteins enhance development of liver fibrosis: effects on collagenase and prolyl-4-hydroxylase activity in the rat liver. 242 60

A liver fibrosis index was recently prospectively validated in a cross-sectional study where patients infected by hepatitis C virus (HCV) had only one biopsy and no longitudinal follow-up. The aim of this study was to retrospectively assess the diagnostic value of this index in patients included in a randomized trial of interferon (IFN) using repeated measurements, two biopsies and hyaluronic acid as a comparative reference. One-hundred and sixty-five patients who had had two interpretable liver biopsies and at least one stored serum sample before IFN treatment were selected. Seventy-eight patients received 3 MU of IFN-alpha thrice weekly for 24 weeks and 87 followed a reinforced regimen for 48 weeks. A fibrosis index combining five biochemical markers (alpha2-macroglobulin, haptoglobin, apolipoprotein A1, gamma-glutamyl transpeptidase (GGT) and total bilirubin adjusted for gender and age) as well as hyaluronic acid was assessed on 461 samples available at baseline, at the end of treatment and at the end of follow-up (72 weeks). There was a significant decrease of the fibrosis index score among the 17 sustained virologic responders, from 0.33 +/- 0.06 (mean +/- SE) at baseline to 0.18 +/- 0.06 at 72 weeks in comparison with 92 nonresponders (from 0.41 +/- 0.03 at baseline to 0.44 +/- 0.03 at 72 weeks; P < 0.001) and in comparison with 56 relapsers (from 0.36 +/- 0.03 at baseline to 0.32 +/- 0.03 at 72 weeks; P=0.05). No significant differences were observed for hyaluronic acid.Hence, this fibrosis index could be used as a surrogate marker of the antifibrotic effect of treatments in patients with chronic hepatitis C.
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PMID:Biochemical markers of liver fibrosis in patients infected by hepatitis C virus: longitudinal validation in a randomized trial. 1187 95

Intravascular hemolysis is associated with several pathologic conditions that include hemoglobinopathies, trauma, malaria, and bacterial infections. Among plasma-protective proteins against oxidative damage caused by red blood cell rupture, haptoglobin and hemopexin are thought to play a crucial role. Haptoglobin and hemopexin, by binding with high-affinity hemoglobin and heme, respectively, exert an antioxidant action by preventing heme-catalyzed free radical production. Moreover, these proteins prevent iron loss by inhibiting glomerular filtration of hemoglobin and heme diffusion through plasma membranes. Analysis of single-null mice demonstrated the antioxidant action of haptoglobin and hemopexin in vivo and suggests that the 2 proteins cooperate in the resolution of hemolytic stress. To evaluate the physiological relevance of the haptoglobin-hemopexin system and the principal targets of its action, we generated haptoglobin-hemopexin double-knockout mice and analyzed them under basal conditions and after acute hemolysis. Whereas haptoglobin-hemopexin double-null mice displayed no obvious alteration in phenotype under basal conditions, nonlethal hemolytic stress in these animals led to pronounced splenomegaly as well as liver inflammation and fibrosis. These data demonstrate that haptoglobin and hemopexin together are essential for protection from splenomegaly and liver fibrosis resulting from intravascular hemolysis.
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PMID:Enhanced splenomegaly and severe liver inflammation in haptoglobin/hemopexin double-null mice after acute hemolysis. 1239 71

BACKGROUND: Biochemical markers for liver fibrosis (FibroTest) and necroinflammatory features (ActiTest) are an alternative to liver biopsy in patients with chronic hepatitis C. Our aim was to assess the inter-laboratory variability of these tests, and their 6 components (gamma-glutamyl transpeptidase, alanine aminotransferase, alpha2-macroglobulin, haptoglobin, apolipoprotein A1, and total bilirubin) and to identify factors associated with this variability. RESULTS: Serum of 24 patients with chronic hepatitis C or severe alcoholic liver disease were prospectively recorded and analyzed in one reference center and in 8 additional laboratories. When gamma-glutamyl transpeptidase and alanine aminotransferase were expressed in international units, there was no significant difference between laboratories in the results of FibroTest or ActiTest; kappa statistics were greater than 0.50 with only 0.8% of cases (3/384) with a discordance of more than one stage. The main factor significantly associated with variability was the expression of gamma-glutamyl transpeptidase and alanine aminotransferase, as multiples of upper limit of reference values. The use of standardized method with pyridoxal phosphate reduced the variability of alanine aminotransferase expression, and standardized original Szasz method reduced the variability of gamma-glutamyl transpeptidase expression. CONCLUSIONS: The variability of FibroTest and ActiTest was acceptable without clinical consequences for the prediction of the stage of liver fibrosis and grade of activity. Standardized methods and assay calibration should be used and expression of alanine aminotransferase and gamma-glutamyl transpeptidase in multiples of the upper limit of reference values should not be employed.
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PMID:A prospective assessment of the inter-laboratory variability of biochemical markers of fibrosis (FibroTest) and activity (ActiTest) in patients with chronic liver disease. 1253 83

The follow up of patients with chronic liver diseases and the data from multicentric clinical studies are affected by the variability of assay results for the same parameter between the different laboratories. Today, the main objective in clinical chemistry throughout the world is to harmonise the assay results between the laboratories after the confirmation of their traceability, in relation to defined reference systems. In this context, the purpose of our study was to verify the homogeneity of haptoglobin, apolipoprotein A1, total bilirubin, GGT activity, ALAT activity results, which are combined in Fibrotest and Actitest, between Dimension Analysers RXL, ARX and X-PAND (Dade Behring Society). Moreover, we verified the transferability of Fibrotest and Actitest results between the RXL, and either the BN2 (haptoglobin and apolipoprotein A1) or the Modular DP (total bilirubin, GGT and ALAT activity concentrations). The serum samples from 150 hospitalised patients were analysed on the different analysers. Specific protein assays were calibrated using solutions standardised against reference material on Dimension and BN2 analysers. Total bilirubin assays were performed by a diazoreaction on Dimension and Modular DP analysers. The GGT and ALAT activity measurements on the Dimension analysers were performed in accordance with the reference methods defined by the International Federation of Clinical Chemisty and Laboratory Medicine (IFCC). On the Modular, enzyme activity measurements were performed according to the Szasz method (L-gamma- glutamyl-4-nitroanilide as substrate) modified by Persijn and van der Slik (L-gamma- glutamyl-3-carboxy- 4-nitroanilide as substrat) for GGT and according to the IFCC specifications for ALAT. The methods of enzymatic activity measurement were calibrated on the Modular only. Liver fibrosis and necroinflammatory activity indices were determined using calculation algorithms, after having adjusted each component's result of Fibrotest and Actitest for gender and age. Our study has shown, for each parameter, harmonious results between the Dimension analysers and between RXL and BN2- Modular DP. Disregarding alpha-2 macroglobulin which cannot be assayed on RXL, the results of Fibrotest and Actitest were similar as performed on BN2- Modular DP and RXL.
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PMID:[Results transferability on RXL, ARX, X-Pand, BN2 (Dade Behring) and modular DP (Roche Diagnostics) analysers: application to component assays of fibrotest and Actitest]. 1595 Dec 62

The present investigation was designed to identify potential biomarker(s) and assess the involvement of inflammatory pathway in dimethylnitrosamine (DMN)-induced liver fibrosis in rats. Following DMN-treatment (10 mg/ml/kg, i.p., given three consecutive days each week for 4 weeks) body and liver weights were significantly decreased concurrent with increasing severity of liver damage assessed by bridging fibrosis, a histopathologic assessment and characteristic of human liver disease. Protein C along with albumin, C-reactive-protein (CRP), haptoglobin and total protein were significantly reduced and correlated with changes in liver histopathology. Biochemical markers of liver functions were significantly increased and correlated with changes in liver histopathology and plasma levels of protein C. Soluble intracellular-adhesion-molecule-1 (sICAM-1) levels were increased significantly but were poorly correlated with histopathology and protein C levels. Inflammatory chemokines and other analytes, monocyte-chemoattractant-protein-1 and 3 (MCP-1 and MCP-3), macrophage-colony-stimulating-factor (M-CSF) were significantly increased during the disease progression, whereas macrophage-derived-chemokine (MDC) and CRP were significantly suppressed. Circulating neutrophils and monocytes were also increased along with disease progression. The differential changes in sICAM-1, hyaluronic acid, gamma-glutamyltranspeptidase (GGT), neutrophil and other inflammatory chemokines suggest the involvement of inflammatory pathways in DMN-induced liver fibrosis. In conclusion, the progressive changes in protein C along with other noninvasive biochemical parameters whose levels were significantly correlated with disease progression may serve as biomarkers for pharmacological assessment of targeted therapy for liver fibrosis.
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PMID:Study of plasma protein C and inflammatory pathways: biomarkers for dimethylnitrosamine-induced liver fibrosis in rats. 1771 30

Utility of plasma circulating mRNA as a molecular marker to detect hepatic injury was evaluated. Total RNA was isolated from plasma of the rat liver fibrosis models at various time points, and plasma circulating mRNAs of major liver-derived genes, albumin and haptoglobin, were measured by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Sensitivity and kinetics of plasma circulating mRNA were compared with those of plasma alanine aminotransferase (ALT) activity. We have found that the measurement of plasma circulating mRNA is more sensitive than plasma ALT activity, and enables early detection of hepatic injury. The plasma circulating mRNA will serve as a novel and highly sensitive molecular marker for hepatic injury.
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PMID:Utility of plasma circulating mRNA as a marker to detect hepatic injury. 1884 Sep 78

Liver fibrosis/cirrhosis is a serious health issue in hepatitis C virus (HCV-) infected patients and is currently diagnosed by the invasive liver biopsy. The aim of this study was to find useful fibrosis markers in HCV-patients' sera of different fibrosis degrees (METAVIR F0-F4) based on proteomics. Serum proteome profiles were created by two-dimensional gel electrophoresis. Profiles were analysed between different degrees of fibrosis (F0-F4) and between early (F0F1) and late (F2F3F4) fibrosis by univariate analyses (P <or= 0.05). Differentially expressed proteins were subsequently identified by mass spectrometry. Mac-2-binding protein, alpha-2-macroglobulin and hemopexin were increased in F4 opposite F0/F1. A-1-antitrypsin, leucine-rich alpha-2-glycoprotein and fetuin-A were decreased in F4 opposite F0/F1. Late fibrosis was characterized by an increase in Mac-2-binding protein, alpha-2-macroglobulin and alpha-1B-glycoprotein expression and a decrease in haptoglobin expression. Mac-2-binding protein expression was confirmed by dot blot assay and enzyme-linked immunosorbent assay in a secondary population. In conclusion, serum proteome analysis enabled the detection/identification of existing and new candidate markers in line with fibrosis progression in HCV-patients.
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PMID:The HCV serum proteome: a search for fibrosis protein markers. 1922 29

The purpose of this prospective study was to verify and compare the strengths of various blood markers and fibrosis models in predicting significant liver fibrosis. One hundred fifty-eight patients with chronic liver disease who underwent liver biopsy were enrolled. The mean age was 41 yr and male patients accounted for 70.2%. The common causes of liver disease were hepatitis B (67.7%) and C (16.5%) and fatty liver (9.5%). Stages of liver fibrosis (F0-4) were assessed according to the Batts and Ludwig scoring system. Significant fibrosis was defined as > or =F2. Sixteen blood markers were measured along with liver biopsy, and estimates of hepatic fibrosis were calculated using various predictive models. Predictive accuracy was evaluated with a receiver-operating characteristics (ROC) curve. Liver biopsy revealed significant fibrosis in 106 cases (67.1%). On multivariate analysis, alpha2-macroglobulin, hyaluronic acid, and haptoglobin were found to be independently related to significant hepatic fibrosis. A new predictive model was constructed based on these variables, and its area under the ROC curve was 0.91 (95% confidence interval, 0.85-0.96). In conclusion, alpha2-macroglobulin, hyaluronic acid, and haptoglobin levels are independent predictors for significant hepatic fibrosis in chronic liver disease.
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PMID:Usefulness of non-invasive markers for predicting significant fibrosis in patients with chronic liver disease. 2005 50

Glycoprotein 130 (gp130)/signal transducer and activator of transcription 3 (STAT3) signaling in hepatocytes controls a variety of physiological and pathological processes including liver regeneration, apoptosis resistance and metabolism. Recent research has shed light on the importance of acute phase proteins (APPs) regulated by hepatic gp130/STAT3 in host defense through suppression of innate immune responses during systemic inflammation. To examine whether these STAT3-regulated soluble factors directly affect liver fibrogenic responses during liver injury, hepatocyte-specific STAT3 knockout (L-STAT3 KO) mice and control littermates were subjected to bile duct ligation (BDL) and examined 10 days later. In contrast to controls, L-STAT3 KO mice failed to produce APPs, such as serum amyloid A and haptoglobin, after BDL. Whereas L-STAT3 KO mice displayed similar levels of cholestasis, inflammatory cell infiltration and regeneration in the liver, they developed exacerbated liver injury and fibrosis with significant increases in expression of alpha-smooth muscle actin and type I collagen genes. In vitro experiments revealed that attenuated expression of APPs in primary hepatocytes isolated from L-STAT3 KO mice with IL-6 exposure, compared to wild-type hepatocytes. The cultured supernatant from IL-6-treated wild-type hepatocytes inhibited expression of alpha-smooth muscle actin and type I collagen genes in activated hepatic stellate cells (HSCs), whereas this did not occur with the supernatant from IL-6-treated knockout hepatocytes or with control medium. In conclusion, the absence of STAT3 in hepatocytes leads to exacerbation of liver fibrosis during cholestasis. Soluble factors released from hepatocytes, dependent on STAT3, collectively play a protective role in liver fibrogenesis through an inhibitory effect on activated HSCs.
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PMID:Involvement of STAT3-regulated hepatic soluble factors in attenuation of stellate cell activity and liver fibrogenesis in mice. 2135 97


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