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)

To examine the clinical significance of serum collagenase activity in chronic liver disease, serum collagenase activity was determined in 50 patients with chronic liver disease and in 24 healthy controls. Collagenase activity was measured after reactivation by denaturing and dissociating the inhibitors with potassium thiocyanate and aminophenylmercuric acetate. In patients with chronic persistent hepatitis, serum collagenase activity was 37% lower than controls, 50% lower in those with chronic active hepatitis, 66% lower in those with cirrhosis and 68% lower in those with hepatocellular carcinoma. Serum collagenase activity was significantly and inversely correlated with serum levels of the aminoterminal propeptide of type III procollagen and type IV collagen 7S domain, indicating that serum collagenase activity decreased as liver active fibrogenesis and/or fibrosis occurred. In contrast, serum levels of the metalloproteinase inhibitor was 30% higher than controls in patients with chronic active hepatitis, 50% higher in those with cirrhosis and 80% higher in those with hepatocellular carcinoma and was inversely correlated with serum collagenase activity. These results suggest that in this assay condition serum collagenase activity is influenced by the metallo-proteinase tissue inhibitor and thus does not reflect the amount of collagenase in the fibrotic liver.
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PMID:Serum collagenase activity in patients with chronic liver disease. 822 26

A choline deficient L-amino acid defined (CDAA) diet led to the development of liver cirrhosis in male Wistar rats after 16 weeks. A new prolyl 4-hydroxylase inhibitor, 2,4-pyridine dicarboxylic acid bis [(2-methoxyethyl amide)] (HOE 077), prevented liver fibrosis in a dose-dependent manner without a reduction in increased serum alanine aminotransferase and aspartate aminotransferase in parallel with a reduction in preneoplastic enzyme-altered lesions stained with anti-glutathione S-transferase placental form antibody. HOE 077 reduced the increase in serum procollagen III peptide (PIIIP) in a dose-dependent manner and in proportion to the reduction in mRNA expression of type III procollagen in the liver of rats fed a CDAA diet.
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PMID:New prolyl 4-hydroxylase inhibitor reduces procollagen gene expression and enzyme-altered lesions in rat liver cirrhosis. 858 46

Diagnostic accuracy of two serum markers of liver fibrosis, hyaluronan (HA) and amino-terminal peptide of type III procollagen (P-III-P), was studied in a cohort of 326 untreated patients with chronic viral hepatitis C. Both P-III-P (RIA-gnost P-III-P, Behring Diagnostic) and HA (HA-test, Pharmacia) serum concentrations correlated with the histological grades of liver fibrosis (P < 0.001). Receiver-operating characteristic (ROC) curves showed that serum HA had greater diagnostic performance than P-III-P, both for discriminating patients with extensive liver fibrosis from those with no or mild fibrosis (area under the ROC curves: 0.864 vs 0.691, P <0.001) or for discriminating patients with cirrhosis from those without cirrhosis (area under the ROC curves: 0.924 vs 0.734, P <0.001). At cutoff values of 0.8 kU/L for serum P-III-P and 85 micrograms/L for serum HA, sensitivities were 70.0% and 64.5%, and specificities were 63.4% and 91.2%, respectively, for discriminating patients with extensive liver fibrosis from those with no or mild fibrosis. At the cutoff values of 1.0 kU/L for serum P-III-P and 110 micrograms/L for serum HA, sensitivities were 60.0% and 79.2%, and specificities were 74.0% and 89.4%, respectively, for discriminating patients with liver cirrhosis from those without cirrhosis. We conclude that, because the diagnostic accuracy of serum HA is greater than that of serum P-III-P as a marker of liver fibrosis, serum HA should be preferred when monitoring liver fibrosis in patients with chronic viral hepatitis C.
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PMID:Diagnostic accuracy of hyaluronan and type III procollagen amino-terminal peptide serum assays as markers of liver fibrosis in chronic viral hepatitis C evaluated by ROC curve analysis. 860 73

Oral methotrexate (MTX) is a highly effective drug for the treatment of severe psoriasis. A limitation of this treatment is its potential hepatotoxicity. In the present prospective study the value of dynamic hepatic scintigraphy (DHS) and serum aminoterminal propeptide of type III procollagen (PIIINP) were investigated as screening methods for early detection of MTX-induced hepatic damage. These relatively non-invasive procedures were compared with the liver biopsy classification, until now the gold standard to assess MTX-induced liver damage. Twenty-five MTX patients were studied. The mean cumulative MTX dose was 3.9 g (range 0.2-11.1 g). Twenty-one patients had a normal liver histology (grade I), three patients had steatosis (grade II), and one patient mild fibrosis (grade IIIA). Seven additional patients with non-MTX related hepatic cirrhosis were included as disease controls. DHS showed a clear-cut separation between the portal contribution of the MTX patients with grade I liver histology, and that of all other patients. A portal contribution larger than 52% was associated with a > 95% chance of normal liver histology. If this cut-off value had been used to postpone the liver biopsy, this would have resulted in at least a 55% reduction in the number of biopsies in patients with a normal liver histology. DHS appeared to be very promising as a screening test to differentiate between the presence or absence of MTX-induced hepatic damage, but appeared not suitable to grade the severity of hepatic damage. Although a global relationship was demonstrated between serum PIIINP concentration and hepatic damage, single measurements in individual patients were not reliable. The combination of PIIINP measurements with DHS had only a limited additional value above DHS alone. The present study indicates that DHS has great promise for the detection of early MTX-induced hepatic damage. Pending further studies, regular liver biopsies remain mandatory for the safe prolonged use of MTX in psoriasis patients.
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PMID:The value of dynamic hepatic scintigraphy and serum aminoterminal propeptide of type III procollagen for early detection of methotrexate-induced hepatic damage in psoriasis patients. 873 73

This study was designed to establish whether measurement of a serological marker of fibrosis might reduce the need for liver biopsy in psoriatic patients receiving methotrexate (MTX). Levels of type III procollagen aminopeptide (PIIINP-O and PIIINP-B) and laminin P1 (LamP1-B) were measured in 147 serum samples taken at the time of liver biopsy in 87 patients receiving long-term MTX treatment for severe psoriasis. Biopsies were classified as: (1) normal, (2) steatosis, (3) inflammation, (4) fibrosis, or (5) cirrhosis. Groups 3-5 were considered to show clinically relevant abnormality. Compared with controls, PIIINP-O was significantly raised in the group of MTX-treated psoriatics (P < 0.001). Within this group, levels were significantly higher in patients with inflammation, fibrosis or cirrhosis compared with those with normal histology or steatosis alone (P < 0.0001). In contrast, PIIINP-B and LamP1-B did not distinguish between controls and MTX-treated patients or between histological groups. Forty-two patients had two or more biopsies with simultaneous PIIINP-O measurement. PIIINP-O levels at the time of the first biopsy were normal in six of the seven patients whose histology was initially normal and subsequently became abnormal. A single measurement of PIIINP-O thus did not predict which patients might develop abnormal histology following further MTX. In a group of 17 patients, PIIINP-O was measured 3-monthly for up to 6 years during MTX treatment. PIIINP-O was elevated at some time during follow-up in all three patients who developed abnormal histology but was consistently normal in eight of the 11 patients whose histology remained or became normal. Our findings indicate that PIIINP-O is of value in detecting liver damage and, particularly if measured serially, may reduce the need for liver biopsy in MTX-treated patients. Although the test does not detect all patients with fibrosis, it would appear that the risk of missing significant liver damage in patients with persistently normal PIIINP-O is low.
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PMID:Serum type III procollagen aminopeptide for assessing liver damage in methotrexate-treated psoriatic patients. 891 42

Basic fibroblast growth factor (FGF) is thought to be involved in carcinogenesis and, to clarify its clinical significance, the study of its blood level in cancer patients is important. Plasma levels of basic FGF are reported to be elevated in some cancers. However, little is known of basic FGF levels in plasma in hepatocellular carcinoma (HCC). In this study, we measured basic FGF plasma levels in patients with chronic liver disease and compared the levels in chronic hepatitis (CH), liver cirrhosis (LC), and HCC. We also examined whether these levels were related to serum levels of asparate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, alkaline phosphatase, leucine aminopeptidase, total bilirubin, total protein, and albumin, and to the indocyanine green test (i.e., liver function tests) and to type III procollagen. 7S domain of IV type collagen, and hyaluronic acid (i.e., markers of liver fibrosis). Levels of basic FGF, determined by a quantitative "sandwich" enzyme immunoassay, were significantly elevated with the progression of liver disease; being 3.67 +/- 2.37 (mean +/- SD). 7.78 +/- 6.61, and 12.37 +/- 7.67 pg/ml in the CH, LC, and HCC groups, respectively. FGF levels were elevated to a greater extent in the HCC patients than in the CH (P < 0.0001) and LC patients (P = 0.0117). Levels were higher in LC than in CH (P = 0.0204). None of the liver function test findings or levels of markers of liver fibrosis were correlated with levels of basic FGF. These results suggest that circulating basic FGF could serve as a new indicator of the progression of chronic liver disease. The extremely elevated plasma of level basic FGF in the HCC group suggests that basic FGF may be related to the development of HCC.
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PMID:Plasma level of basic fibroblast growth factor increases with progression of chronic liver disease. 905 7

To assess the clinical relevance of transforming growth factor beta1 (TGF-beta1) in chronic liver disease, urinary TGF-beta1 and circulating aminoterminal propeptides of type III procollagen (PIIINP) levels were determined by radioimmunoassay in 100 cirrhotic patients, 44 patients with chronic hepatitis, and 50 healthy controls. TGF-beta1 and PIIINP levels in cirrhotic patients were higher than those in patients with chronic hepatitis (each P < .0001) or healthy controls (each P < .0001), respectively. There was a correlation between TGF-beta1 and PIIINP levels in patients (r = .858, P < .0001). The higher the urinary TGF-beta1 level, the worse the severity of chronic liver disease (P < .001). TGF-beta1 levels in cirrhotic patients with antibodies to hepatitis C virus (anti-HCV) were higher than in those without (P < .0001). Compared with cirrhotic patients with hepatitis B surface antigen (HBsAg) alone, those with HBsAg and anti-HCV had higher TGF-beta1 levels (P < .001), a higher frequency of raised TGF-beta1 (P < .005), and a higher frequency of patients with Child-Pugh C (P < .005). Multivariate analysis indicated that the TGF-beta1 level was significantly correlated with the presence of cirrhosis. In conclusion, urinary TGF-beta1 levels may be used as a marker for hepatic fibrogenesis. Higher urinary TGF-beta1 levels correlate with more severe liver disease.
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PMID:Urinary transforming growth factor beta1 levels in hepatitis C virus-related chronic liver disease: correlation between high levels and severity of disease. 914 31

Carboxy-terminal telopeptide of type I collagen (ICTP) is a degradation product of type I collagen. In this study, we investigated the usefulness of measuring the serum ICTP concentration for diagnosing and monitoring bone metastasis from hepatocellular carcinoma (HCC). The serum concentrations of ICTP, type I procollagen carboxy-terminal propeptide (PICP), type III procollagen aminoterminal propeptide (PIIIP), type IV collagen (Ty IV), type IV collagen 7S-domain (7S), and hyaluronic acid (HA) were measured in patients with liver cirrhosis, HCC with or HCC without bone metastasis, and in healthy controls. The diagnostic efficiency of the serum ICTP and fibrosis marker levels in the HCC patients with and without bone metastasis was evaluated using receiver operating characteristic curves. We also retrospectively examined the changes in the serum ICTP levels before and after bone metastasis in the HCC patients. The serum ICTP level was significantly higher in the HCC patients with bone metastasis than in the patients with other diseases and the healthy controls. The serum PICP, PIIIP, Ty IV, 7S and HA levels of the HCC patients with bone metastasis did not differ significantly from those of the patients without bone metastasis. The diagnostic efficiency for HCC with bone metastasis was 87% for ICTP, 51% for PICP, 65% for Ty IV, 55% for PIIIP and 51% for HA. During the follow-up, the changes in the serum ICTP values paralleled the behavior of bone metastasis. These results indicate that the measurement of serum ICTP concentration is useful for detecting and monitoring HCC patients with bone metastasis.
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PMID:Serum carboxy-terminal cross-linked telopeptide of type I collagen reflects bone metastasis in hepatocellular carcinoma. 966 25

Antioxidant and antifibrotic properties of colchicine were investigated in the carbon tetrachloride (CCl(4)) rat model. (1) The protective effect of colchicine pretreatment on CCl(4) induced oxidant stress was examined in rats subsequently receiving a single lethal dose of CCl(4). Urinary 8-isoprostane, kidney and liver malondialdehyde and kidney glutathione levels increased following CCl(4) treatment, but only the rise in kidney malondialdehyde was significantly inhibited by colchicine pretreatment. Serum total antioxidant levels were significantly higher in the colchicine pretreatment group. (2) The long term effects of colchicine treatment on CCl(4) induced liver damage were investigated using liver histology and biochemical markers (hydroxyproline and type III procollagen peptide). Co-administration of colchicine with sub-lethal doses of CCl(4) over 10 weeks did not prevent progression to cirrhosis. However, rats made cirrhotic with repeated CCl(4) challenge and subsequently treated with colchicine for 12 months, all showed histological regression of cirrhosis. (3) The antioxidant effect of colchicine in vitro was evident only at very high concentrations compared to other plasma antioxidants. In summary, colchicine has only weak antioxidant properties, but does afford some protection against oxidative stress; more importantly, long term treatment with this drug may be of value in producing regression of established cirrhosis.
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PMID:Antioxidant properties of colchicine in acute carbon tetrachloride induced rat liver injury and its role in the resolution of established cirrhosis. 1106 78

Chronic hepatitis C virus (HCV) infection results in the development of liver fibrosis and cirrhosis in 20 to 25% of patients. The main task of the physician when examining a patient with a verified HCV infection is to identify the activity of inflammatory and necrotic processes in the liver, as well as the stage of fibrosis, and the reversibility of detected changes. Along with other clinical and laboratory parameters, this plays a major role in forecasting the course of hepatitis, as well as determines the therapeutic approach in each specific case. Liver biopsy remains the best way to assess the severity of chronic hepatitis C. The risk of developing cirrhosis depends on the stage (degree of fibrosis) and the grade (degree of inflammation and necrosis) observed in the initial liver biopsy. Non-invasive diagnostic approaches attempt to evaluate the serum markers of fibrogenesis. Biochemical markers of fibrosis scoring include thrombocyte counts, the prothrombin time, ratio of alaninaminotransferase (ALT) and aspartataminotransferase (AST) levels, the level of g-glutamyl transferase and the quantity of blood serum albumin. Another set of markers is based on the detection of molecular junctions that activate fibrosis, or participate in the generation of the liver extracellular matrix. The most applicable include hyaluronic acid (HA), type IV collagen (IV-C), N-terminal propeptide of type III procollagen (PIIIP), metalloproteinases (MMP), inhibitors of metalloproteinases (TIMP), and growth-transforming factor betta (GTFbeta). The review discusses the clinical significance of each of the criteria and possibility of their combination in the non-invasive monitoring of liver fibrosis.
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PMID:Invasive and non-invasive monitoring of hepatitis C virus-induced liver fibrosis: alternatives or complements? 1276 63


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