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

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Query: EC:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The prognostic value of the aminoterminal propeptide of type III procollagen (P3NP) was investigated in 63 patients with primary biliary cirrhosis (PBC) followed for up to 87 months. No patient with an initially normal serum P3NP level died during the study; survival was significantly worse with increasing serum P3NP levels. Cox multivariate analysis confirmed that serum P3NP was an independent prognostic variable. Positive correlations were found between serum P3NP and histological stage, pericellular fibrosis, piecemeal necrosis, and serum concentrations of alanine aminotransferase and aspartate aminotransferase. Raised P3NP levels also correlated with the degree of cholestasis as evaluated by serum bilirubin, serum alkaline phosphatase, and copper binding protein deposition in the liver. Serum P3NP is of prognostic value because it reflects the major pathophysiological features of PBC.
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PMID:Type III procollagen peptide: a marker of disease activity and prognosis in primary biliary cirrhosis. 289 70

We assayed type III procollagen peptide in the sera of 213 patients with various liver diseases and 23 normal controls by radioimmunoassay. The non-cancerous limit of the serum level of type III procollagen peptide was defined as the mean +/- 2 SD of the patients with chronic hepatitis, liver cirrhosis and alcoholic liver disease; it was 50 ng/ml. The percentage of type III procollagen peptide in sera exceeding this limit was 22.2% in patients with hepatocellular carcinoma and 17.4% in metastatic liver cancer. Only patients with liver cirrhosis accompanied by alcoholic hepatitis exceeded this limit. In patients with hepatocellular carcinoma with peptide concentrations above 50 ng/ml, the serum level of GOT, GPT, LDH, T. Bil., LAP, gamma-GTP and T. Chol. was significantly higher than in patients with hepatocellular carcinoma whose serum peptide level was below 20 ng/ml.
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PMID:[Clinical significance of type III procollagen peptide in sera of patients with liver cancer]. 608 78

This study was carried out to evaluated the role of the fibronectin (FN) in chronic liver diseases. For these reasons FN plasmatic concentration was assayed in patient with different degrees of chronic liver disease. For these reasons FN plasmatic concentration was assayed in patient with different degrees of chronic liver disease; the correlation between FN and the most common parameters of liver function was also evaluated. Moreover we also correlated FN plasma levels with laminin and the N-terminale peptide of type III procollagen, serum levels, that are through to be markers of fibrogenesis. 172 patients were studied: twenty-one patients suffering from chronic persistent hepatitis (CPH), 45 from chronic active hepatitis (CAH) and 106 from liver cirrhosis (LC). Last patients were also divided according the Child-Pugh's classification. Control group was composed of 74 healthy blood donors. Significant reduction of plasmatic levels of FN was found in the LC groups in comparison with control group (p < 0.0001) and also with CPH group (p < 0.01) and with CAH group (p < 0.0001). Lower values of FN were found in the LC group at advanced stage (Child-Pugh's B and C classes). In the group of CAH significant correlations with the parameters of cholestasis (GGT, APh, Tot. Bil. p < 0.005) were found, while in the group of LC significant correlations both with the parameters of synthesis (Alb. and Protr. time p < 0.01) and necrosis (AST/ALT p < 0.001). A negative correlation was also found between FN and spleen volume (p < 0.05). No correlation between FN and the parameters of fibrosis was found.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Plasma fibronectin in chronic liver diseases]. 821 Jun 24

Serum levels of the tissue inhibitor of metalloproteinases-1 (TIMP-1) were measured in 268 patients with liver diseases by means of a one-step sandwich enzyme immunoassay. In the cases of acute hepatitis, chronic active hepatitis (CAH), liver cirrhosis (LC) and hepatocellular carcinoma (HCC), the levels of TIMP-1 were higher than those of the control group. Tissue inhibitor of metalloproteinases-1 levels correlated with type III procollagen peptide and with type IV collagen, indicating TIMP-1 as a useful marker for hepatic fibrosis. Levels of TIMP-1 also correlated with aspartate aminotransferase and alanine aminotransferase levels and showed the highest levels in acute hepatitis. Thus, TIMP-1 might also reflect hepatic inflammation. Serum levels of alpha-fetoprotein and TIMP-1 had a significant positive correlation in patients with HCC. A cut-off level of TIMP-1 between LC and HCC was set at 440 ng/mL, having a low sensitivity and a high specificity. These results suggest the usefulness of TIMP-1 as a tumour marker in cases of HCC where alpha-fetoprotein levels are not elevated.
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PMID:Clinical evaluation of serum tissue inhibitor of metalloproteinases-1 levels in patients with liver diseases. 821 91

To evaluate the effect of ursodeoxycholic acid (UDCA) treatment according to the severity of primary biliary cirrhosis, a long-term prospective open trial in 54 consecutive PBC patients, 19 with histological stage I-II, 24 stage III, and 11 stage IV was carried out. UDCA was administered at a dosage of 250 mg twice a day. Clinical and biochemical assessment (AST, ALT, alkaline phosphatase, GGT, bilirubin) were done initially and every six months. Serum hyaluronate (HY) and type III procollagen amino propeptide (PIIIP) were also evaluated, as they are considered markers of fibrosis and prognosis. All patients were followed-up for at least two years (24-36 months); results were analyzed at 24 months after treatment. The composite pruritus score failed to show significant changes during UDCA treatment, while intensity score demonstrated a significant reduction from the 6th month. Patients with histological stage I-II disease had a significant decrease of liver enzymes (AST, ALT, alkaline phosphatase, GGT) after six months and maintained the levels up to 24 months. The patients with histological stage III disease showed a significant decrease of AST, ALT, alkaline phosphatase (but not GGT) up to month 18; subsequently AST and ALT serum levels increased, reaching values comparable to baseline by 24 months. In patients with histological stage IV disease no significant change in liver enzymes was observed during the follow-up. HY and PIIIP serum levels failed to show significant changes during UDCA treatment in the three groups of patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Different response to ursodeoxycholic acid (UDCA) in primary biliary cirrhosis according to severity of disease. 828 73

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

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

We evaluated variations in serum levels of N-terminal peptide of type III procollagen (PIIIP) and laminin (Lam-P1) in 36 anti-HCV positive patients, confirmed by RIBA II, with chronic hepatitis treated with alpha interferon (IFN) at a dose of 6 million units (MU) three times for week for 6 months, followed by 3 MU three times for week for a further 6 months. We consider responders (R) those patients who after one year of therapy had normalized ALT levels, and non-responders (NR) the remaining subjects. Serum PIIIP and Lam-P1 were determined by RIA on entry to the study and at 12 months. Ten patients underwent a percutaneous liver biopsy also at the end of the therapy for the histological evaluation of the necroinflammatory activity and fibrosis according to the Knodell score system. Overall, at the end of therapy, the mean levels of both markers were lower than at entry to the study, with a statistically significance only for the Lam-P1 values (p < 0.05). When, however, we divided the patients into R (n = 15) and NR (n = 21) subgroups, the mean baseline values of both markers were significantly higher in NR vs controls and after therapy there was a significantly reduction only for PIIIP values (p < 0.01). In the group of R there is a slight, but not significantly reduction of both markers. The comparison of the Knodell's score before and after IFN treatment showed an improvement of the necroinflammatory activity, but not of fibrosis. In conclusion patients R to IFN therapy have lower baseline values of PIIIP and Lam-P1 than NR and therapy with IFN improves the serum values of PIIIP as well as the score of the necroinflammatory activity.
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PMID:[Serum variations of 2 markers of fibrogenesis in chronic hepatitis C treated with alpha interferon]. 914 70

The aim of this study was to evaluate the antifibrotic effect of interferon (IFN)-alpha in chronic hepatitis C (CH-C) patients with no response to IFN-alpha therapy. We studied 76 patients (46 men, 30 women; mean age, 55.6 years) who received IFN-alpha intramuscularly, at a total close of 480 to 880MU for 6 months (group A). As a control group, we studied 50 patients (32 men and 18 women; mean age, 58.5 years) with CH-C who received medication other than IFN (ie, Strong-Neo-Minophagen C, ursodeoxycholic acid, and a herbal medicine, Sho-saiko-to [TJ-9]) and who had persistent alanine aminotransferase (ALT) elevation (group B). All patients were subdivided into three subgroups according to different patterns of ALT changes during the observation period, ie, (a) persistent ALT level < 60IU/ 1 (below about twice the upper limit of the normal range), (b) persistent ALT level > or = 60IU/1, (c) ALT levels other than (a) and (b). Liver biopsy was performed within 6 months prior to IFN therapy and more than 6 months after IFN therapy, while two liver biopsies were performed during therapy in group B. Liver fibrosis was compared between two specimens by staging. When the fibrosis stage was the same in the two specimens, we determined whether the fibrosis had improved or worsened by comparing the fibrotic ratio, ie, the ratio of the area of fibrosis to the area of the entire liver tissue specimen, calculated using computed graphic software. Serum aminoterminal peptide of type III procollagen (PIIIP) levels were measured on the day of the liver biopsy and their mean yearly changes were compared between the two groups. Improvement of liver fibrosis was found in 12% to 30% of patients in each ALT subgroup and in 24% of all patients in group A and there were no significant differences in liver fibrosis in comparison with findings in of group B when assessed by staging alone. However, these percentages rose to 59% to 75% and 66%, respectively, when liver fibrosis was assessed by the fibrotic ratio together with staging, resulting in a significant difference in fibrosis between groups A and B in total (P < 0.01). The mean yearly changes in serum PIIIP levels in each subgroup and in all patients in group A were below zero, indicating a tendency to improvement of fibrosis after IFN therapy, while these changes in group B were all above zero, except for subgroup (c). Improvement of fibrosis after IFN therapy was found in 15 of 24 patients (64%) whose ALT changes had the same pattern before and after IFN therapy, although no significant difference was noted between improved and worsened patients. These results suggest that IFN-alpha may have an antifibrotic effect even in CH-C patients with no overt response to IFN-alpha therapy, compared with the effect of medications other than IFN.
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PMID:Changes of liver fibrosis in chronic hepatitis C patients with no response to interferon-alpha therapy: including quantitative assessment by a morphometric method. 1068 Jun 65

Serum hepatic fibrosis markers (7s domain of type IV collagen, N-terminal peptide of type III procollagen, and hyaluronate) were determined during and after a 6-month interferon treatment of patients with chronic hepatitis C. Changes in these markers were compared among the patients who showed a sustained normalization of serum alanine transaminase (ALT) levels with and without eradication of serum hepatitis C virus RNA (complete responders and biochemical responders) and nonresponders. In the case of complete responders, the serum 7s domain of type IV collagen and the N-terminal peptide of type III procollagen levels decreased at the end and 24 weeks after the end of the treatment. Hyaluronate levels were significantly decreased 24 weeks after the end of the treatment, as compared with those prior to the treatment. During and after interferon treatment, changes in these markers in the case of biochemical responders were nearly the same as those in the complete responders. These results suggest that serum hepatic fibrosis markers decrease in patients with chronic hepatitis C who show a sustained normalization of ALT after interferon treatment, even if serum hepatitis C virus RNA fails to be eradicated.
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PMID:Changes in serum hepatic fibrosis markers in biochemical responders to interferon therapy for chronic hepatitis C. 1070 9


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