Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many tests for hepatitis C virus (HCV) infection have been developed and have proved useful for prevention of post-blood transfusion hepatitis C. However, there are at least 4 genotypes of HCV and the predominant type is different among countries. None of the tests using antigens from one genotype are sensitive in detecting the antibodies against another genotype. More sensitive tests using a more stable part of the HCV RNA sequences such as 5'-noncoding region must be developed for clinical use. Automated PCR methods and DNA sandwich hybridization methods using branched DNA amplification multimers may be candidates. Recently a hepatocyte growth factor test has been developed in Japan. Multicenter trials of this test reveal that it is useful for assessment of acute severe hepatitis. Tests for collagen type IV, fibronectin receptor, and prolyl hydroxylase have been reported useful for assessment of liver fibrosis. However, serum prolyl hydroxylase is prone to increase in response to hepatocellular damage as well as fibrotic processes. Enzymatic methods for determination of branched amino acids and tyrosine have been developed. The molar ratio of branched amino acids to tyrosine seems to have same pathophysiological meaning as the ratio of branched amino acids to aromatic amino acids (Fischer ratio) in assessment of liver cirrhosis. Lidocaine test is reported to be useful for predicting survival of transplanted liver and also assessing the function of the cirrhotic liver. Profiles of alpha-fetoprotein subfractions based on lectin-reactivity and galactosyl transferase II isoenzyme have been reported to be useful for detecting hepatocellular carcinoma but this remains to be proved.
 ...
PMID:[Recent advances in laboratory tests for liver diseases]. 130 30

To examine the consequences of liver blood flow variations on drug disposition in cirrhosis, we studied the effects of portacaval shunt on drug clearance in 35 cirrhotic patients. Lidocaine clearance and bioavailability, indocyanine green (ICG) clearance, aminopyrine breath test, and hepatic blood flow were measured before and 18 months after surgery. The patients were divided into two groups according to severity of disease: 14 patients (group 1) had slight liver dysfunction (ICG extraction ratio greater than 0.25) and 21 patients (group 2) had severe liver disease (ICG extraction ratio less than 0.25). After portacaval shunt the decrease in hepatic blood flow was similar for both groups (-65%). In group 1, ICG systemic clearance decreased from 9.10 +/- 0.68 to 4.40 +/- 0.34 ml/min . kg (p less than 0.05), whereas ICG intrinsic clearance remained unchanged; lidocaine systemic clearance decreased from 7.93 +/- 0.93 to 5.09 +/- 0.33 ml/min . kg (p less than 0.05), whereas lidocaine intrinsic clearance remained unchanged; bioavailability increased from 0.601 +/- 0.076 to 1, resulting in an abrupt reduction of oral clearance from 18.01 +/- 4.90 to 5.09 +/- 0.33 ml/min . kg (p less than 0.05). In group 2, ICG systemic clearance decreased slightly from 3.90 +/- 0.39 to 2.28 +/- 0.16 ml/min . kg (p less than 0.01) and ICG intrinsic clearance was not modified; lidocaine systemic and intrinsic clearance remained unchanged; and bioavailability increased from 0.779 +/- 0.229 to 1, resulting in a decrease of oral clearance from 7.68 +/- 1.65 to 4.23 +/- 0.37 ml/min X kg (p less than 0.05). The aminopyrine breath test was not affected by surgery in either group. We conclude that reduction of hepatic blood flow after portacaval shunt has only minimal effects on drug disposition in patients with severe liver disease, but results in a notable reduction in the clearance of high-extraction drugs in cirrhotics with mild liver disease.
 ...
PMID:Effect of portacaval shunt on drug disposition in patients with cirrhosis. 371 65

Liver microcirculation in the perfused rat liver was assessed by the multiple indicator dilution technique. Comparative studies were carried out in noncirrhotic rats and in rats with cirrhosis secondary to chronic exposure to phenobarbital and carbon tetrachloride. The alterations of the sinusoidal bed were characterized by changes in the displacement of hepatic venous outflow curves of various diffusible substances (labeled albumin, sucrose, and water) relative to that of labeled erythrocytes (vascular reference). Outflow recoveries of lidocaine (a substance that penetrates the liver cell membrane freely and completely) and of labeled microspheres (15 microns diam) were also appraised. In all cirrhotic rats, unimodal erythrocytes and albumin curves were obtained. The sinusoidal space was significantly decreased when compared with normal rats (P less than 0.001) and the total space accessible to albumin became progressively restricted. In seven cirrhotic rats, the profiles of labeled sucrose and water curves were compatible with a flow-limited diffusion and the total distribution volumes were not significantly different from values found in noncirrhotic rats (P = NS), which indicates that sucrose and water were still able to diffuse into an extravascular space not accessible to albumin. In the other cirrhotic rats, labeled sucrose and water curves showed progressive bimodal changes not compatible with a flow-limited diffusion. Such alterations were not due to large intrahepatic shunts, since only 0.25% of the 15-microns microspheres were recovered in the outflow of cirrhotic rats. However, an early lidocaine outflow peak related in time to the peak erythrocyte curve was observed in cirrhotic, but not in noncirrhotic, rats. Lidocaine recovery varied greatly in cirrhotic rats and appeared to increase as the liver disease progressed. These data can be explained by capillarization of sinusoids and/or by the development of channels with poor permeability. Electron microscopic observations of these rat livers favored the latter. Thus, in cirrhotic rat liver, two kinds of alteration are likely: (a) the vascular space is decreased with collagenization of the extravascular space, limiting the diffusion of large molecules such as albumin; and (b) small channels with poorly permeable walls develop, limiting the diffusion of small molecules such as lidocaine, sucrose, and water. Large intrahepatic shunts are not a common feature.
 ...
PMID:Hepatic microcirculation in the perfused cirrhotic rat liver. 405 57

In clinical practice, the seriousness of liver disease is assessed based on the combined information from clinical examination, routine biochemical tests, and liver histology. Recently, the assessment of hepatic lidocaine metabolism has been proposed as a quantitative liver function test offering valuable additional information. To evaluate whether this new liver function test reflects the combined clinical assessment, we prospectively measured lidocaine metabolism in 111 patients with well characterized liver disease. In addition, lidocaine test results were compared with the aminopyrine breath test and the galactose elimination capacity. Lidocaine (1 mg/kg) was injected i.v. and serum concentrations of its main metabolite monoethylglycinexylidide were determined after 15 min. The results varied widely and the means (+/- S.D.) were similar among patients with mild liver disease (46 +/- 23 ng/ml), but significantly (P < 0.05) lower among patients with Child class A cirrhosis (19 +/- 11 ng/ml) or Child class B or C cirrhosis (21 +/- 19 ng/ml). The [13C]aminopyrine breath test, however, gave a better discrimination among patients with increasing severity of liver disease than lidocaine metabolite formation. The galactose elimination capacity finally best separated patients with mild liver disease from those with cirrhosis. The correlations between any two of the different quantitative liver function tests were weak (R2 consistently < 0.2). We conclude that lidocaine metabolite formation, like other quantitative liver function tests that are based on the microsomal metabolism of model compounds, quantitates a very particular enzymatic reaction which may not be representative for the functional reserve of the entire organ.
 ...
PMID:Assessment of lidocaine metabolite formation in comparison with other quantitative liver function tests. 830 Oct 33

Lidocaine is metabolized to form monoethylglycinexylidide (MEGX) via oxidative N-deethylation in the liver. To assess the clinical value of this lidocaine metabolite as a quantitative liver function test, we measured the serum MEGX concentration 15 min after intravenous administration of a single dose of lidocaine (1 mg/kg) in 24 adults with chronic hepatitis, 47 patients with cirrhosis and 26 normal controls. A fluorescence polarization immunoassay was used to obtain the MEGX value. The MEGX concentration in controls was 67 (54-95) ng/ml (median with 16th-84th percentile in parentheses), which was higher than 43 (23-61) ng/ml in patients with chronic hepatitis and 24 (7-52) ng/ml in those with cirrhosis (P < 0.05). In addition, the serum MEGX levels are proportional to the galactose elimination capacity, and inversely proportional to Pugh's score, the prothrombin time and indocyanine green retention ratio. If a MEGX concentration of below 54 ng/ml is taken as an indicator of hepatic dysfunction, its diagnostic sensitivity for hepatic disorder is 84.5%, specificity 88.5% and accuracy 85.6%. Furthermore, after a 10-month follow-up, patients with MEGX formation above 30 ng/ml had a higher survival rate than those with a MEGX concentration below this level (P = 0.004). In conclusion, the MEGX formation test reflects the severity of hepatic dysfunction quite well, making it valuable both in the quantitative evaluation of liver function and in the prognostic prediction of adults with liver diseases.
 ...
PMID:Measuring lidocaine metabolite--monoethylglycinexylidide as a quantitative index of hepatic function in adults with chronic hepatitis and cirrhosis. 830 Oct 34

Endothelin, one of the most potent vasoconstrictors known today, is released by the vascular endothelium. Patients after liver transplantation and patients with liver cirrhosis show significantly higher plasma endothelin concentrations and significantly reduced results in the quantitative liver function tests (ICG-HL, GEC, Lidocaine-HL, MEGX) compared with healthy control persons. The plasma endothelin concentrations were better correlated with the more liver bloodflow dependent function tests (ICG-HL, Lidocaine-HL) than with the more metabolic-capacity dependent function tests (GEC, MEGX). As cyclosporine A in vitro can increase the liberation of endothelin, we conclude that in patients after liver transplantation an endothelin mediated cyclosporine induced hepatotoxicity might be the reason for the demonstrated association.
 ...
PMID:[Increased plasma endothelin concentrations in patients after liver transplantation and in liver cirrhosis]. 847 3

Lidocaine is converted to its primary metabolic product monoethylglycinexylodide (MEGX) via cytochrome P-4503A4 within the liver. A steady-state concentration of MEGX appears in serum within 15 min following the intravenous administration of lidocaine. The present article reviews some of the data suggesting that this MEGX value can be utilized to assess hepatic function. MEGX production declines stepwise with the severity of chronic hepatitis. In patients with cirrhosis, MEGX declines further with worsening Child class. Nearly all persons with MEGX of < 20 ng/ml had cirrhosis confirmed upon histologic evaluation. Severe life-threatening complications of cirrhosis were observed only in patients with MEGX production below 20 ng/ml. One-year survival for patients with an MEGX value of < 10 ng/ml was only 50%. In contrast, 1-year survival for patients with MEGX of > 10 ng/ml was approximately 80%. These data suggest that MEGX could be utilized as an accurate test of hepatic function and to predict morbidity and mortality related to complications of chronic liver disease. However, this test does have several limitations. There is wide interpatient variability between MEGX and hepatic histology, which severely impairs the ability of this test to accurately predict hepatic histology. In addition, MEGX is affected by gender and several medications. However, since MEGX does decline stepwise with advancing histology in any given patient, the available data suggest that serial monitoring of MEGX could be utilized to track hepatic metabolic capacity in patients with chronic hepatitis and cirrhosis.
 ...
PMID:Use of hepatic lidocaine metabolism to monitor patients with chronic liver disease. 885 53

Pharmacokinetic studies demonstrated that the decrease in drug biotransformation in hepatic failure depends on the metabolic pathways involved. To test whether glucuronidation reactions supported by UDP-glucuronosyltransferases are differentially affected in such conditions, we investigated the in vitro glucuronidation of four selected drugs and xenobiotics (zidovudine, oxazepam, lamotrigine, and umbelliferone) by using microsomes from human healthy and unhealthy (cirrhosis, hepatitis) livers as enzyme sources. Theses substances are glucuronidated by several UDP-glucuronosyltransferase isoforms. Lidocaine N-deethylation activity measured concomitantly was used as a positive control, because the inhibition of this reaction in patients with hepatic diseases is well documented. The metabolic clearances of zidovudine and lidocaine were decreased significantly in liver cirrhosis (0.17 versus 0.37 microliter/min/mg protein and 0.40 versus 2.73 microliter/min/mg protein, respectively) as a consequence of a decrease of their corresponding Vmax of metabolism. By contrast, the metabolic clearances of oxazepam, umbelliferone, and lamotrigine glucuronidation remained unchanged. Previous studies reported that the in vivo oral clearances of zidovudine and lidocaine were decreased by 70% and 60%, respectively, in cirrhotic livers, whereas those of lamotrigine and oxazepam were not affected. Consequently, it is likely that the in vitro metabolic data, which support the in vivo results, therefore could contribute to reasonably predict the level of impairment of hepatic clearance in patients with liver cirrhosis.
 ...
PMID:Glucuronidation of drugs by hepatic microsomes derived from healthy and cirrhotic human livers. 1021 1

The changes of biotransformation enzyme system (b.e.s.) activity and capacity in liver diseases significantly influence the metabolism of various xenobiotics. Lidocaine is metabolised through oxidative N-deethylation by b.e.s. resulting in the production of monoethylglycinexylide (MEGX). The aim of this study was the determination of serum MEGX concentration as a model substance for indirect evaluation of liver b.e.s. function in patients with liver steatofibrosis and cirrhosis and the assessment of the possibilities to use it as a quantitave test of liver functional state. The study group consisted of 53 patients, 36 of them with liver disease of different etiology (postviral, ethyltoxic, cryptogenic, liver cirrhosis on the basis of autoimmune hepatitis, liver cirrhosis induced by primary sclerosing cholangitis, primary biliary cirrhosis in the stage of cirrhosis, Wilson's disease in the stage of cirrhosis), 7 patients with liver steatofibrosis and 10 control persons. After intravenous administration of lidocaine (1 mg/kg of body weight), concentration of MEGX was assessed by fluorescence polarization immunoassay (FPIA) using Tdx system in venous blood. The concentration was assesed prior to administration of lidocaine and 15 and 30 minutes after. In the group of liver steatofibrosis the concentrations in the 15th minute after administration were lower comparing to controls, in the 30th minute the difference was less significant. The values of MEGX in cirrhosis group were significantly decreased 15 and 30 minutes after lidocaine administration in comparison with control group. The cirrhosis group was divided into two subgroups: compensated (Ci c) and decompensated (Ci d) and independently of this division into three parts according to score system of Child-Pugh classification (Ci A, Ci B, Ci C). The concentrations 15 and 30 minutes after lidocaine administration in patients with Ci c and Ci d were significantly different, similarly there were statistically significant differences among Ci A, Ci B and Ci C. Statistically significant differences were also between the group of steatofibrosis and whole group of cirrhosis. The concentration of MEGX 15 and 30 minutes after lidocaine administration correlated significantly with the values of albumin, prothrombin time, cholinesterase, Child-Plugh score and bilirubin. MEGX test represents an appropriate and rapid method for the determination of functional liver capacity in patients with liver cirrhosis and liver steatofibrosis, not yet used in Slovak republic. It is a noninvasive test, low time consuming, and when repeated it may provide prognostic information about further development of the disease. MEGX test is an appropriate index of liver function and may contribute to early treatment of chronic liver diseases. (Tab. 9, Fig. 10, Ref. 47.)
 ...
PMID:[Monoethylglycinexylidide--a metabolite of lidocaine--as an index of liver function in chronic hepatic parenchymal diseases]. 1049 93

Lidocaine (LID) is an aminoethylamide used in hepatology to perform the monoethylglycinexylidide (MEGX) test for the evaluation of liver function in patients with cirrhosis (CIR) or chronic hepatitis (CH). The authors evaluated whether the MEGX test changes psychometric performance in patients with chronic liver disease and, in particular, whether it might trigger subclinical portosystemic encephalopathy in patients with CIR. Thirty patients with CIR and 20 patients with CH were studied. They underwent a standard-dose MEGX test, before and after which a psychometric test was administered and blood pressure, heart rate, and adverse effects were recorded. The MEGX test did not modify psychometric performance. Mean arterial blood pressure and heart rate did not change at the end of the MEGX test in either patients with CH or CIR. Adverse effects were present in 66% of all patients during lidocaine injection and lasted up to 3 minutes afterwards. They were more frequent in patients with CH than in patients with CIR (85% vs 53%). No relationship was found between adverse effects and lidocaine dosage, nor between adverse effects and MEGX or lidocaine concentration at 15 minutes. Standard-dose MEGX test does not worsen or trigger portosystemic encephalopathy in CIR. Adverse effects were frequent but mild.
 ...
PMID:The monoethylglycinexylidide test does not impair psychometric performance in patients with chronic hepatitis or cirrhosis. 1094 73


1 2 Next >>