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)

Compared to healthy subjects, patients with severe liver cirrhosis (LC) are reported to show lower values in the L-[1-(13)C] phenylalanine breath test (PBT). We performed this test several times during the clinical course in two patients with severe liver cirrhosis (LC). Patient 1 was a 67-year-old woman with non-B, non-C LC and hepatocellular carcinoma (HCC) in the lateral hepatic segment. Because the patient wanted to receive nonsurgical treatment for HCC, intraarterial administration of zinostatin stimalamer was performed. The patient was hospitalized four times before her death from liver failure on December 20, 2000. During her clinical course, PBT was performed four times. Values for both the rate of hepatic phenylalanine oxidation (%(13)C dose h(-1)) and %(13)C cumulative excretion gradually decreased during her clinical course. Patient 2 was a 57-year-old man with hepatitis C virus (HCV)-positive LC. He was hospitalized seven times between December 1998 and his death on May 24, 2001. During his clinical course, PBT was performed four times. Values for both %(13)C dose h(-1) and %(13)C cumulative excretion decreased during his clinical course. We confirmed that PBT was useful for following the course of LC.
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PMID:Patients with severe liver cirrhosis followed up by L-[1-(13)C] phenylalanine breath test. 1467 28

The Z variant of alpha1-antitrypsin (Z-AT) is present in 4% of Northern Europeans and is associated with liver cirrhosis and emphysema. Polymers accumulate within the hepatocyte and the subsequent plasma deficiency of AT renders the lungs susceptible to proteolysis and early onset emphysema. We have previously demonstrated that the Phe-Leu-Glu-Ala-Ile-Gly (6 mer) peptide specifically binds to Z-AT and inhibits polymerization. Here we present the first detailed biochemical study of the purified Z-AT-6 mer binary complex. Biochemical studies indicated that this complex was inactive as a proteinase inhibitor and the peptide annealed to beta-sheet A of Z-AT. Removal of the N-acetyl terminus of the 6 mer peptide did not affect the peptide's ability to prevent polymer formation. However, the nonacetylated 6 mer-Z-AT complex dissociated at a rate 2.75 x faster than the acetylated 6 mer-Z-AT complex to yield an active inhibitor; Koff 5.5 +/- 1.07 versus 2.0 +/- 0.25 10(6) s(-1), respectively. These biochemical data indicate a potential therapeutic approach whereby polymerization is prevented in the liver, with the gradual release of the peptide from the binary complex restoring proteinase inhibitory function within the tissues. Thus, it raises the novel prospect of ameliorating both the cirrhosis and the emphysema associated with Z-AT.
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PMID:Inhibiting polymerization: new therapeutic strategies for Z alpha1-antitrypsin-related emphysema. 1501 19

13C-phenylalanine (PheBT) and 13C-galactose breath tests (GBT) explore non invasively the hepatic functional mass by measuring two enzymatic activities localized into the cytosol of liver cells: the phenylalanine hydroxylase (which converts phenylalanine into tyrosine) and the galactose kinase (which catalyzes the ATP-dependent phosphorylation of galactose to galactose 1-phosphate). Both BTs are safe and accurate in predicting the severity of liver cirrhosis showing a good correlation with the Child-Pugh score. PheBT is also used in predicting postoperative complications and monitoring liver regeneration in patients undergoing partial hepatectomy. GBT has been also used to assess liver fibrosis in patients with chronic hepatitis C. PheBT and GBT could be used in the diagnosis of two inborn errors of metabolism, phenylketonuria and galactosemia, respectively. Both BTs are not affected by enzymatic induction due to drugs which may interfere with the results of the classic "microsomial" BTs (such as the aminopyrine or caffeine BTs).
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PMID:13C-breath tests in hepatology (cytosolic liver function). 1520 54

The evaluation of the presence and degree of liver fibrosis in patients with chronic liver disease is a fundamental diagnostic and prognostic issue. This is mainly due to the repercussions of liver fibrosis on liver function, whose derangement, in turn, is mainly responsible for the negative events of advanced liver disease. 13C-Breath Tests ((13/14)C-BTs) for the study of liver function were developed more than twenty years ago in order to non-invasively assess residual liver function in patients with various degrees of liver fibrosis, from minimal stages up to liver cirrhosis. Sequential studies that were performed over the years using various 13C-BT substrates showed that increasing degrees of liver fibrosis are paralleled by concomitant modifications in 13C-BT results. The 13C-BT probes that reportedly obtained interesting results were aminopyrine, galactose, and more recently phenylalanine. As the knowledge in this field evolved, probes for the study of specific functions, such as the 13C-Octanoate Breath Test were sought. Analysis of the published studies would seem to show that 13C-BTs alone, or in combination may provide a non-invasive picture of the functional alterations secondary to liver fibrosis. Further studies are needed to evaluate the diagnostic yield of the 13C-BT in particular clinical situations, such as in patients with normal static parameters of liver function, or after therapy.
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PMID:13C-breath tests and liver fibrosis. 1520 55

We present the clinical data of five infants with type I (hepato-renal) tyrosinaemia on NTBC therapy. All presented initially at the local hospital in the 1st year of life with progressive abdominal distension owing to hepato-splenomegaly and with radiological evidence of liver cirrhosis, except for one child who was diagnosed during screening because of an affected sibling. Age at commencement of NTBC therapy ranged from 6 to 30 months. All infants showed remarkable improvement within 2-6 months of starting NTBC treatment, except one who died 2 months after commencement of therapy from uncontrolled liver failure, severe coagulopathy and Streptococcus pneumoniae septicaemia. NTBC treatment along with a phenylalanine- and tyrosine-restricted diet has effectively reversed most clinical manifestations of this disease. To date, none of our patients has developed hepatic carcinoma and NTBC was well tolerated without side-effects. NTBC is costly but life-saving and is an obvious alternative to more hazardous liver transplantation.
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PMID:Experience with NTBC therapy in hereditary tyrosinaemia type I: an alternative to liver transplantation. 1547 77

The reason branched chain aminoacids are decreased and aromatic aminoacids increased in chronic liver failure is unclear. Branched chain aminoacids are mainly catabolised in muscles, and it is known that protein energy malnutrition may decrease the concentration of these aminoacids in plasma. In this study we have evaluated the nutritional status of a group of cirrhotics and compared it with their plasma aminoacid imbalance. Fourteen patients were considered as well-nourished and nine as malnourished. Plasma levels of branched chain aminoacids were significantly decreased and the phenylalanine increased in the malnourished group. Arm muscle circumference was significantly correlated with branched chain aminoacids. In conclusion our data suggest that malnutrition may contribute to the low levels of these aminoacids in patients with liver cirrhosis.
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PMID:Aminoacid imbalance and malnutrition in liver cirrhosis. 1683 40

The stable-isotopic composition of nitrogen (delta15N) or carbon (delta13C) of body tissues depends on the isotopic composition of food sources and on shifts due to isotopic fractionation during metabolism. As little is known about the effects of pathophysiological conditions we measured delta15N and delta13C values in hair and hair amino acids of patients with cirrhosis (n = 21) and compared the results with those of healthy subjects (n = 100) randomly selected from the 1987-1988 VERA German nutrition survey population. Cirrhosis was reflected in lower hair 15N abundances (6.7 vs. 9.9 per thousand delta15N; P < 0.001) whereas hair 13C abundances did not differ from healthy subjects (-19.4 vs. -19.6 per thousand 13C). Distinct patterns of delta15N and delta13C values were measured in hair amino acids. The delta15N values of phenylalanine were significantly higher in cirrhotics (P < 0.001). With the exception of isoleucine, threonine, and proline all other measured amino acids showed lower delta15N values than healthy subjects (P < 0.001). Lower hair delta15N values were associated with cirrhotic liver disease which suggests that under this condition the altered liver amino acid metabolism affects the nitrogen isotopic composition of the amino acids used for hair protein synthesis. It remains to be determined in controlled studies whether the altered nitrogen isotopic composition directly reflects the pathophysiological condition or is related to differences in dietary protein intake from plant or animal food sources.
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PMID:Nitrogen isotopic composition in hair protein is different in liver cirrhotic patients. 1695 36

Liver failure is associated with hepatic encephalopathy (HE). An imbalance in plasma levels of aromatic amino acids (AAA) phenylalanine, tyrosine, and tryptophan and branched chain amino acids (BCAA) and their BCAA/AAA ratio has been suggested to play a causal role in HE by enhanced brain AAA uptake and subsequently disturbed neurotransmission. Until recently, data on this subject and the role of the liver and splanchnic bed were scarce, particularly in humans, due to inaccessibility of portal and hepatic veins. Here, we discuss, against a background of relevant literature, data obtained in patients undergoing liver resection or with a transjugular intrahepatic portasystemic stent shunt (TIPSS), where these veins are accessible. The BCAA/AAA ratio remained unchanged after major liver resection, but plasma AAA levels were inversely correlated (P < 0.001) with residual liver volume, in keeping with the observed hepatic AAA uptake. In patients with stable cirrhosis and a TIPSS, the plasma BCAA/AAA ratio was lower than in controls (1.19 +/- 0.09 vs. controls: 3.63 +/- 0.34). Gastrointestinal bleeding in cirrhotics with a TIPSS induced disturbances in BCAA levels and the BCAA/AAA ratio and induced catabolism, which could partly be corrected by isoleucine administration. AAA may be important in the pathogenesis of HE, but it is unlikely that they are the sole factors. HE most likely is a syndrome with multifactorial pathogenesis, where hyperammonemia, AAA/BCAA imbalances, inflammation, brain edema, and neurotransmitter changes interact. Novel therapies to normalize AAA levels in patients with liver failure (such as the molecular adsorbent recirculating system dialysis device) should probably be combined with supplementation of e.g. isoleucine and enhancing ammonia excretion by the kidneys.
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PMID:Aromatic amino acid metabolism during liver failure. 1751 30

In liver cirrhosis, elevated levels of NO and ROS (reactive oxygen species) might greatly favour the generation of peroxynitrite. Peroxynitrite is a highly reactive oxidant and it can potentially alter the vascular reactivity and the function of different organs. In the present study, we evaluated whether peroxynitrite levels are related to the progression of renal vascular and excretory dysfunction during experimental cirrhosis induced by chronic BDL (bile-duct ligation) in rats. Experiments were performed at 7, 15 and 21 days after BDL in rats and in rats 21 days post-BDL chronically treated with L-NAME (N(G)-nitro-L-arginine methyl ester). Sodium balance, BP (blood pressure), basal RPP (renal perfusion pressure) and the renal vascular response to PHE (phenylephrine) and ACh (acetylcholine) in isolated perfused kidneys were measured. NO levels were calculated as 24-h urinary excretion of nitrites, ROS as TBARS (thiobarbituric acid-reacting substances), and peroxynitrite formation as the renal expression of nitrotyrosine. BDL rats had progressive sodium retention, and decreased BP, RPP and renal vascular responses to PHE and ACh in the time following BDL. They also had increasing levels of NO and ROS, and renal nitrotyrosine accumulation,especially in the medulla. All of these changes were either prevented or significantly decreased by chronic L-NAME administration. In conclusion, these results suggest that the increasing levels of peroxynitrite might contribute to the altered renal vascular response and sodium retention in the development of the experimental biliary cirrhosis. Moreover, the beneficial effects of decreasing NO synthesis are, at least in part, mediated by anti-peroxinitrite-related effects.
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PMID:Effects of chronic L-NAME on nitrotyrosine expression and renal vascular reactivity in rats with chronic bile-duct ligation. 1818 8

It is often difficult to distinguish benign ascites from malignant ascites by conventional examination of ascitic fluid. Therefore, (1)H NMR spectroscopy of ascitic fluid specimens was explored as a one-shot experiment to identify potentially interesting metabolic indices that might help to differentiate between the two. Seventy ascitic fluid specimens (15 cytologically positive for malignant cells, eight cytologically negative for malignant cells but remaining suspicious for malignant ascites, and 47 due to liver cirrhosis) were subjected to (1)H NMR spectroscopy for quantitative estimation of 14 metabolites. Mean concentrations of the metabolites were compared with the Mann-Whitney U test. Multivariate discriminant function analysis was performed to determine important descriptors in the discrimination process. The sensitivity and specificity of the proposed model were compared with conventional methods using ascitic fluid protein and serum ascitic albumin gradient. Then, probable predictions for the doubtful cases were made using the proposed model. Patients with malignant ascites had significantly higher mean concentrations (microM) of beta-hydroxybutyrate (594 vs 61), lactate (5384 vs 2104), acetone (136 vs 69), and acetoacetate (122 vs 48) than patients with cirrhotic ascites, and significantly lower concentrations of glutamine (359 vs 615), citrate (62 vs 118), glucose (4933 vs 8411), tyrosine (44 vs 124), and phenylalanine (51 vs 93) (P < 0.05 for all). In the discriminant function analysis model, the best discrimination (P < 0.001) was achieved when beta-hydroxybutyrate, lactate, citrate and tyrosine were considered together as markers. Sensitivity and specificity of the proposed model, ascitic fluid protein and serum ascitic albumin gradient were found to be 100% and 97.9%, 53.3% and 76.6%, and 60% and 87.2%, respectively. The proposed model put five of the eight doubtful cases in the malignant group. This is encouraging and may provide useful information for clinical purposes.
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PMID:(1)H NMR spectroscopy of ascitic fluid: discrimination between malignant and benign ascites and comparison of the results with conventional methods. 1820 45


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