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)

1. The clearance and biotransformation of caffeine (1,3,7-trimethylxanthine) were investigated in eight healthy control subjects and 16 patients with cirrhosis, by measuring serial serum caffeine concentrations and recoveries of methylxanthine metabolites in urine for 48 h after a 400 mg oral caffeine load. 2. In the control group, the mean (+/- SD) serum caffeine clearance was 1.3 +/- 0.4 ml min-1 kg-1 and a mean of 56.4 +/- 16.5% of the administered caffeine was recovered from the urine over 48 h as methyluric acids and methylxanthines. The majority of the metabolites were excreted in the first 24 h period and only 2.0 +/- 1.4% of the administered caffeine was excreted unchanged. 3. Patients with compensated cirrhosis (n = 10) metabolized caffeine similarly to the control subjects. Thus the mean serum caffeine clearance was 1.4 +/- 1.2 ml min-1 kg-1 and a mean of 57.2 +/- 11.7% of the administered caffeine was recovered from the urine over 48 h. The majority of the metabolites were excreted in the first 24 h; the pattern of metabolic excretion was unaltered and only 2.2 +/- 0.9% of the administered caffeine was excreted unchanged. 4. In the patients with decompensated cirrhosis (n = 6), significant changes were observed in caffeine metabolism. The mean serum caffeine clearance (0.4 +/- 0.2 ml min-1 kg-1) was significantly impaired compared with controls (P less than 0.01) and a significant delay was observed in metabolite excretion in the urine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Caffeine clearance and biotransformation in patients with chronic liver disease. 335 10

The elimination of caffeine from the plasma and the elimination of metamizol-metabolites in urine were determined in 37 patients with different liver diseases. In severe liver diseases the demethylation of caffeine as well as the metabolism of metamizol is significantly reduced. The extent of reduced elimination capacity depends on the severity of the disease rather than on the type of disease. In patients with liver cirrhosis the determination of synthesis capacity and of humoral activity (s. tab. I) is suitable to evaluate the capacity of the cytochrome P-450 system. In noncirrhotic diseases only the activity of liver disease (tab. I.) determines the extent of reduced biotransformation capacity. Beside biotransformation-phase I, the acetylation--phase II biotransformation--also appears to be reduced.
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PMID:[Effect of various liver diseases on the activity of 2 subtypes of cytochrome P-450]. 358 33

The effects of verapamil on portal pressure, microsomal liver function and extravascular albumin space were investigated in rats rendered cirrhotic by chronic exposure to phenobarbital and carbon tetrachloride. Verapamil significantly decreased splenic pulp pressure by 28% (P less than 0.05). In cirrhotic animals it improved liver function, measured by the aminopyrine and caffeine breath tests, by 36% (P less than 0.025) and 53% (P less than 0.05), respectively. The extravascular albumin space, an important determinant of drug clearance, was measured by a multiple indicator dilution technique. It was significantly larger in verapamil treated than in untreated cirrhotics (4.41 +/- 1.06 vs 2.73 +/- 0.79 ml/g; P less than 0.01). We conclude that verapamil has significant potential as a portal antihypertensive agent and its value in treating cirrhosis in man should be explored by controlled studies.
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PMID:Chronic verapamil administration lowers portal pressure and improves hepatic function in rats with liver cirrhosis. 374 84

Fasting plasma caffeine concentration and various parameters of caffeine elimination from plasma obtained after a standardized oral dose of 140 mg caffeine have been compared in nine patients with liver cirrhosis, eight patients with non-cirrhotic liver disease and ten healthy volunteers with regard to their ability to discriminate between the different groups. Fasting plasma caffeine concentrations were significantly higher in cirrhotics (11.1 +/- 10.5 mumol/l) than in healthy volunteers (1.5 +/- 0.8 mumol/l). The respective values measured in patients with non-cirrhotic liver disease (3.1 +/- 3.1 mumol/l) did not differ significantly from the controls. Plasma disappearance rate and clearance of caffeine were significantly decreased in cirrhotics (0.11 +/- 0.02 h-1; 1.0 +/- 0.3 ml/min per kg) and in patients with non-cirrhotic liver disease (0.18 +/- 0.04 h-1; 2.2 +/- 0.7 ml/min per kg) as compared to healthy volunteers (0.23 +/- 0.04 h-1; 3.1 +/- 0.9 ml/min per kg). Plasma caffeine concentration determined 12 h after administration of the test dosage discriminated best between patients with cirrhosis (5.4 +/- 1.6 mumol/l), patients with non-cirrhotic liver disease (2.0 +/- 1.4 mumol/l) and healthy volunteers (0.8 +/- 0.2 mumol/l). These results, the safety of the test compound and the simplicity of a single caffeine determination in plasma 12 h after a standardized dose of caffeine make this test attractive for evaluation of liver function.
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PMID:Caffeine elimination: a test of liver function. 407 79

Fasting plasma caffeine concentrations (FPCC) were measured in 86 outpatients being examined for suspected or known liver disease. Seven patients (8%) who avoided caffeine consumption had nonmeasurable FPCC; they were dropped from further consideration. The remaining 79 subjects were divided into 4 diagnostic groups: surgical shunt (n = 11); alcoholic, posthepatitic, or primary biliary cirrhosis (n = 29); miscellaneous liver disease (n = 23); and normal liver (n = 16). FPCC was highest (mean, 17.8 mumol/l) in the shunt group, followed by the cirrhosis (12.3), miscellaneous liver diseases (4.6), and normal liver (2.1) groups. FPCC seemed to reflect severity of functional impairment, further supported by highly significant correlations with quantitative liver function tests, such as aminopyrine breath test (Rs = -0.89; n = 66), indocyanine green disappearance (Rs = -0.85; n = 65), and galactose elimination capacity (Rs = -0.70; n = 75). A careful dietary history showed no significant difference in caffeine consumption among the groups. It is suggested that in regular coffee drinkers FPCC might serve as a simple and convenient guide to the severity of functional impairment in chronic liver disease.
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PMID:Fasting plasma caffeine concentration. A guide to the severity of chronic liver disease. 408 23

The effects of liver disease on caffeine plasma clearance (Cl) and on exhalation of 14CO2 following i.v. injection of 2 mu Ci of [3-methyl-14C]caffeine together with 125 mg of the unlabeled compound were measured in 15 patients with cirrhosis, 11 subjects with miscellaneous liver disease, and 10 normal volunteers. Compared to mean values for Cl (2.02 +/- S.D. 0.68 ml per min per kg) and t1/2 (3.8 +/- 0.9 hr) in normal volunteers, cirrhotics were characterized by highly significant reductions in Cl (to 0.76 +/- 0.40) and prolongation in t1/2 (to 13.7 +/- 13.0), whereas the volume of distribution (VD) remained relatively unchanged (0.57 +/- 0.16 vs. 0.64 +/- 0.13 liter per kg in normals). Cumulative 14CO2 production and specific activity of 14CO2 in breath decreased in parallel (r = 0.83) with Cl. Patients with miscellaneous liver disease exhibited only small changes in Cl and t1/2; however, 14CO2 parameters in breath appeared more sensitive in indicating the slight functional derangement. In view of the correlation (Rs = 0.83) of cumulative 14CO2 excretion with the initial disappearance constant for bromosulfophthalein, the caffeine breath test may be considered as a quantitative measure of hepatic microsomal activity; based on a surprisingly close, hyperbolic relationship between Cl and fasting caffeine plasma concentrations, the latter might serve as a simple guide to severity of liver disease.
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PMID:Caffeine: a model compound for measuring liver function. 642 Mar 3

[1-Methyl-14C], [3-Methyl-14C] and [7-Methyl-14C] caffeine were used to investigate demethylation in control rats, and in rats pretreated with phenobarbital or 3-methylcholanthrene, by a 14CO2-exhalation test. Compared to controls, pretreatment with phenobarbital did not enhance demethylation of any of the labelled caffeines. In contrast, induction by 3-methylcholanthrene, presumably of cytochrome P-448, resulted in highly significant increases in peak 14CO2 exhalation rates, 14CO2 disappearance constants and areas under the exhalation rate - time curves. Based on these results, [7-methyl-14C] and [3-methyl-14C] caffeine were chosen for assessing the feasibility of a caffeine breath test in man, using 5 normal volunteers and 2 patients with compensated liver cirrhosis. 14CO2 exhalation curves in cirrhotics were clearly different from those in normal volunteers, being characterised by a slower rise and a lower specific activity of exhaled 14CO2. Since the variability of the levels of the specific activity in subjects with normal livers suggested the influence of extraneous factors, a second group of normal volunteers, smokers and nonsmokers, was investigated. With either labels, the average 14CO2 exhalation rate was doubled in smokers. From these studies in rats and preliminary results in man it is concluded that specifically labelled caffeine is a suitable and promising substrate for studying demethylation by breath analysis. Presumably, caffeine represents a safe and sensitive indicator of the activity of the cytochrome P-448 system.
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PMID:Assessment of the cytochrome P-448 dependent liver enzyme system by a caffeine breath test. 680 Aug 27

The effect of cirrhosis on the disposition and elimination of caffeine was examined. Caffeine (250 mg) was administered orally to 15 healthy controls and eight patients with cirrhosis. The elimination half-life was prolonged from 5.2 +/- 2.4 hr (mean +/- SD) in controls to 6.1 +/- 1.9 hr in cirrhotics, although this did not reach statistical significance. The plasma clearance, however, was significantly higher (1.4 +/- 0.5 ml/min/kg) in controls as compared to cirrhotics (0.9 +/- 0.3 ml/min/kg) (P less than 0.05). The plasma binding of caffeine was also lower in cirrhotics (31.3 +/- 1.8% vs 25.5 +/- 4.0%, P less than 0.01). The plasma clearance of unbound caffeine therefore was reduced from 2.0 +/- 0.7 ml/min/kg in controls to 1.2 +/- 0.4 ml/min/kg (P less than 0.01) in cirrhotics, demonstrating impaired elimination of caffeine in cirrhosis.
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PMID:Impaired elimination of caffeine in cirrhosis. 737 63

Caffeine elimination was studied in 419 patients with cirrhotic and noncirrhotic liver disease of different etiology (hepatitis B virus infection n = 79; hepatitis NANB virus infection n = 74; ethanol-induced liver damage n = 143; primary biliary cirrhosis I-IV n = 63; cryptogenic liver cirrhosis n = 60) following oral administration of 366 mg caffeine. Caffeine clearance in the control group was 69 +/- 33 ml/min (age-matched healthy volunteers and patients without liver disease). Caffeine clearance in acute hepatitis B (70 +/- 60 ml/min) chronic persistent hepatitis B (81 +/- 56 ml/min), chronic aggressive hepatitis B (107 +/- 66 ml/min), posthepatitic liver cirrhosis B (84 +/- 62 ml/min), acute hepatitis NANB (94 +/- 69 ml/min), chronic persistent hepatitis NANB (122 +/- 60 ml/min), chronic aggressive hepatitis NANB (87 +/- 52 ml/min) and posthepatitic cirrhosis NANB (59 +/- 26 ml/min) is not reduced in comparison with controls. In patients with alcoholic fatty liver (127 +/- 71 ml/min, p < 0.05) caffeine clearance is enhanced, in alcoholic hepatitis (57 +/- 72 ml/min) comparable to controls and in alcoholic cirrhosis reduced (36 +/- 44 ml/min, p < 0.05). In primary biliary cirrhosis I-IV caffeine clearance is higher than in controls (117 +/- 59 ml/min, p < 0.05). In cirrhotic liver disease of different origin caffeine clearance is inversely related to the serum bilirubin level. However, the absolute value is determined in addition by the underlying disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Caffeine elimination in cirrhotic and non-cirrhotic liver disease of different etiology. 748 16

Data from the past few years have shown that as caffeine metabolizes solely in the liver, caffeine elimination can serve as a liver function test. We have collected data by monitoring 40 persons with liver diseases (11 chronic alcoholic hepatitis, 24 liver cirrhosis, 5 non-cirrhotic liver disease). Eight subjects served as controls. The patients with liver cirrhosis were classified according to the Child--Pugh scoring system. To determine caffeine elimination blood samples were collected before and at 3, 6, 9 and 12 hours after oral administration of 0.2 g caffeine. Fasting serum caffeine concentration and concentration 12 hours after administration, serum clearance, half life, peak concentration and volume of distribution have been compared. The respective values measured in patients with non-cirrhotic liver diseases did not differ significantly from the controls. The disappearance of caffeine was significantly decreased in cirrhotics. Our results demonstrated a good correlation between impairment of caffeine elimination and assessment of severity of liver disease by the Child--Pugh classification. Measuring serum levels in samples taken 12 hours after caffeine administration is a simple and useful method in the diagnosis of liver diseases at cirrhotic stage.
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PMID:[Diagnostic value of the study of caffeine elimination in chronic liver diseases]. 773 51


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