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)

In four control subjects and four patients with cirrhosis of the liver a multiple amino acid mixture was infused for 12 h at a constant rate of 68 and 56 mumol alpha-amino N/s, respectively. Before infusion the plasma amino N concentration was 2.4 +/- 0.2 (mean +/- SD) mmol/l in control subjects and 3.5 +/- 0.7 mmol/in patients (P less than 0.025). The concentration of alanine, proline, arginine, tyrosine, and citrulline was significantly increased in the cirrhosis group. 12 h after the infusion began approximately constant amino N concentrations of 11.4 +/- 1.8 mmol/l in controls and 13.7 +/- 3.9 mmol/l in patients were attained, and the urea N synthesis rate was 63 +/- 17 and 44 +/- 8 mumol/s, respectively (P less than 0.05). After correction for loss of amino acids in urine this means that on the average 94 per cent of the N load was recovered as urea. The plasma clearance of infused amino acids, calculated as the ratio between infusion rate and steady state concentration, was 6.0 +/- 1.2 and 4.1 +/- 0.9 ml/s for amino N in the control and cirrhosis group, respectively (P less than 0.025). The clearance of individual amino acids ranged between 2.5 and 28 ml/s. The clearance of most amino acids was decreased in the cirrhosis groups, and of glycine, proline, lysine, threonine, and arginine significantly so (P less than 0.05), reflecting accumulation of amino acids in patients. This indicates that a primary defect in the conversion of amino N in cirrhosis is the reduced urea synthesis.
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PMID:Elimination of infused amino acids from plasma of control subjects and of patients with cirrhosis of the liver. 680 68

Plasma amino-acid concentrations were measured in 167 patients with liver disease of varying aetiology and severity, all free of encephalopathy, and the results compared with those in 57 control subjects matched for age and sex. In the four groups of patients with chronic liver disease (26 patients with chronic active hepatitis, 23 with primary biliary cirrhosis, 11 with cryptogenic cirrhosis, and 48 with alcoholic hepatitis +/- cirrhosis) plasma concentrations of methionine were significantly increased, while concentrations of the three branched chain amino-acids were significantly reduced. In the first three groups of patients plasma concentrations of aspartate, serine, and one or both of the aromatic amino-acids tyrosine and phenylalanine were also significantly increased, while in the patients with alcoholic hepatitis +/- cirrhosis plasma concentrations of glycine, alanine, and phenylalanine were significantly reduced. In the three groups of patients with minimal, potentially reversible liver disease (31 patients with alcoholic fatty liver, 10 with viral hepatitis, and 18 with biliary disease) plasma concentrations of proline and the three branched chain amino-acids were significantly reduced. Patients with alcoholic fatty liver also showed significantly reduced plasma phenylalanine values. Most changes in plasma amino-acid concentrations in patients with chronic liver disease may be explained on the basis of impaired hepatic function, portal-systemic shunting of blood, and hyperinsulinaemia and hyperglucagonaemia. The changes in patients with minimal liver disease are less easily explained.
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PMID:Plasma amino-acid patterns in liver disease. 707 13

Femoral arterio-venous (A-V) differences of blood free amino acids and plasma ammonia (NH3) were simultaneously determined after an overnight fast in 16 patients with decompensated liver cirrhosis in the absence and presence of encephalopathy, as compared with those in 8 control subjects. In spite of increased releases of phenylalanine (Phe) and tyrosine (Tyr) from the peripheral tissue, releases of isoleucine (Ile) and leucine (Leu) as well as alanine (Ala) were found to be significantly reduced in decompensated liver cirrhosis, particularly in the presence of hepatic encephalopathy. Furthermore, NH3 was found to be significantly taken up by the skeletal muscle of these patients, and a positive correlation was observed between arterial NH3 level and the A-V differences of Leu, of Ile and of Ala. These findings strongly suggest that net degradation (or utilization) of branched-chain amino acids (in particular, Leu and Ile) is enhanced in the muscle for detoxication of ammonia (i.e., glutamine synthesis) by supplying the carbon skeleton and energy in cirrhosis of the liver.
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PMID:Augmented utilization of branched-chain amino acids by skeletal muscle in decompensated liver cirrhosis in special relation to ammonia detoxication. 722 60

Three main patterns of response are seen when interferon-alpha (IFN-alpha) is used for the treatment of chronic hepatitis C: 1 sustained response with alanine-aminotransferase (ALT) normalization that is maintained after cessation of therapy, with or without clearance of serum hepatitis C virus (HCV) RNA; 2 transient response with ALT normalization during therapy followed by relapse after its withdrawal, and 3 no response with no or only partial reduction in ALT levels. In order to define variables that could predict each of these three types of response we studied 321 cases of chronic hepatitis C treated with IFN-alpha in two consecutive trials conducted in our Unit. By univariate analysis, age < 45 years (P < 0.01), known disease duration < 60 months (P < 0.01), normal gamma-glutamyl-transpeptidase (gamma GT) levels (P < 0.01) and infection by HCV genotype 2 or HCV genotype 3 (P < 0.01) were found to be statistically associated with sustained response while age > 45 years (P < 0.01), body weight (P = 0.05), cirrhosis (P < 0.01) and elevated gamma GT levels (P < 0.01) were associated with no response. By multivariate analysis sustained response was predicted by HCV genotype 2 (P < 0.01) and HCV genotype 3 (P < 0.01), known disease duration (P < 0.01), patient's age (P < 0.05) and associated with the use of a more aggressive treatment schedule (P < 0.05). Transient response with relapse was predicted by known duration of disease (P < 0.05), HCV genotype 1 (P < 0.05) and female sex (P < 0.05). No response was statistically associated with elevated gamma GT levels (P < 0.01), higher body weight (P < 0.05) and with the less aggressive regimen of 3 MU of natural IFN-alpha given three times weekly for 6 months (P < 0.05). These results indicate that the HCV genotype as well as the schedule of treatment greatly affect the pattern of response to IFN in chronic hepatitis C and allow us to define criteria to predict which type of response is more likely in individual patients.
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PMID:Predictors of sustained response, relapse and no response in patients with chronic hepatitis C treated with interferon-alpha. 749 3

In testing for antibodies to the hepatitis C virus (anti-HCV) in 112 patients with primary hepatocellular carcinoma, 10 of 33 white patients (30%) and 15 of 79 Asian patients (19%) had a positive response to the antibody. The antibody profile to individual hepatitis C viral antigens and the presence of circulating hepatitis C viral RNA were determined in the 25 patients. The anti-HCV antibodies most frequently detected were toward the antigens from the core (C22) and NS3 regions. Serum hepatitis C viral RNA was present in 17 of the 25 patients (68%), and these patients tended to have serum levels of alanine and aspartate aminotransferases higher than those patients without viremia (136 +/- 22 U per liter versus 64 +/- 11 U per liter and 161 +/- 26 U per liter versus 79 +/- 14 U per liter, respectively, both P < .05). Of the 15 Asian patients with hepatocellular carcinoma and anti-HCV, 4 (27%) had coexisting hepatitis B surface antigen (HBsAg) and 13 (87%) had antibodies to either hepatitis B core or surface antigen. Of the 10 white patients with anti-HCV, however, only 1 (10%) had hepatitis B virus antibodies (P < .01). Among 4 Asian patients with coexisting anti-HCV and HBsAg, 1 was found to have serum hepatitis B viral DNA and the other 3 had hepatitis C viral RNA. A history of blood transfusion was obtained from 12 of the 25 patients with anti-HCV (48%); 20 (80%) had coexisting cirrhosis. Our findings support the hypothesis that hepatitis C virus is an important etiologic agent in the development of primary hepatocellular carcinoma in both white and Asian patients in the United States.
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PMID:Evidence for hepatitis C viral infection in patients with primary hepatocellular carcinoma. 751 78

The amino acid composition of proteins from liver microsomes has been studied in rats and in human subjects with normal liver, with obstructive jaundice or liver cirrhosis. The pattern of the amino acid composition of microsomes appeared to be species-specific. Phenylalanine, threonine, serine, proline, histidine and [aspartic acid plus asparagine] were increased, while alanine, tyrosine, glycine and arginine were decreased in the human compared to the rat microsomes. In patients with obstructive jaundice of short duration (less than two months) only a slight decrease in leucine and phenylalanine could be noticed, while in the case of liver cirrhosis amino acid composition was markedly changed.
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PMID:Amino acid composition of rat and human liver microsomes in normal and pathological conditions. 757 35

beta-Blockers are widely used to prevent gastrointestinal hemorrhage in cirrhosis. The metabolic effects of treatment are scarcely studied: hepatic function reportedly does not change significantly, but beta-adrenoceptors have been reported to regulate protein and amino acid metabolism. We studied hepatic nitrogen metabolism in response to constant alanine infusion in seven patients with cirrhosis before and 7 to 10 days after treatment with oral propranolol (60 to 100 mg/d). Beta-blockade was effective: it decreased heart rate by 25%, abolished orthostatic tachycardia, and reduced portal blood flow by 20%. Alanine-stimulated urea nitrogen synthesis rate (UNSR) was higher in patients with propranolol treatment, without any difference in aminonitrogen concentration. The kinetics of hepatic conversion of amino acid nitrogen into urea--ie, functional hepatic nitrogen clearance (FHNC)--increased by 30%, from (mean +/- SD) 17.0 +/- 4.1 to 22.0 +/- 6.6 L/h (P < .01). Increased urea production during alanine infusion resulted in negative nitrogen exchange even at the peak of alpha-aminonitrogen concentration. Basal insulin level was only slightly reduced during propranolol treatment, whereas the insulin response to alanine was significantly blunted. No differences in glucagon and cortisol were demonstrated. Epinephrine and norepinephrine levels were high-normal and did not vary after treatment. Increased urea production and stimulation of hepatic nitrogen clearance during beta-blockade may be mediated by relative hypoinsulinemia or by direct involvement of beta-adrenoceptors in the control of nitrogen metabolism, possibly by regulation of amino acid uptake and release in peripheral tissues.
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PMID:Effects of beta-blockade on hepatic conversion of amino acid nitrogen and on urea synthesis in cirrhosis. 761 49

The preliminary results of a prospective double-blind controlled trial of colchicine in 100 patients with hepatitis B virus-related cirrhosis are reported. The patients, 94 males and 6 females, aged 32-80, were assigned to receive either 1 mg of colchicine or an identical placebo orally on a daily basis. The duration of the follow up ranged from 15 to 51 months (median 26 months). Seventy percent had histological proof of cirrhosis. On entry, 80 patients were in Child-Pugh class A, 19 were in class B, and one was in class C. Compared to the placebo group, there was no improvement in the colchicine group after a 24-month follow up in any of the biochemistry data, for example, serum albumin, alkaline phosphatase, alanine and aspartate aminotransferase, bilirubin, and prothrombin time. The difference in the cumulative survival rates at 51 months did not reach statistical significance (p = 0.8) in either group. There was no histological improvement in 30 patients who were willing to undergo repeated liver biopsies. No trend toward improvement of the hepatic pressure gradient was observed in these patients. The serum levels of aminopropeptide of type III procollagen increased significantly in patients in both groups after 24 months of therapy (1.07 +/- 0.06 vs. 1.36 +/- 0.06 U/ml in the colchicine group, 0.93 +/- 0.09 vs. 1.25 +/- 0.07 U/ml in the placebo group; p < 0.05). In addition, neither the clinical deterioration of cirrhosis nor death was prevented in patients receiving colchicine therapy. This report indicates that colchicine has no effect in the treatment of HBV-related postnecrotic cirrhosis.
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PMID:A double-blind randomized controlled trial of colchicine in patients with hepatitis B virus-related postnecrotic cirrhosis. 789 Sep 5

Glucose reduces the hepatic conversion of aminonitrogen to urea, quantified by the functional hepatic nitrogen clearance (i.e., the slope of the linear relation between urea synthesis rate and blood alpha-aminonitrogen concentration). This is due to a direct effect of glucose and to inhibition of glucagon. In this study, the effect of glucose on functional hepatic nitrogen clearance was examined during spontaneous hormone responses and during hormonal control by somatostatin. In 7 control subjects (study 1) and 9 patients with cirrhosis (study 2), functional hepatic nitrogen clearance was assessed twice in each subject: during infusion of alanine and during alanine administration superimposed on a continuous glucose infusion (blood glucose, on average = 8.4 mmol/L). In study 3, 6 patients with cirrhosis had functional hepatic nitrogen clearance determined on three occasions: during infusions of alanine and of alanine superimposed on infusion of somatostatin with either euglycemia or hyperglycemia (blood glucose = 8.4 mmol/L). In the control subjects (study 1), functional hepatic nitrogen clearance was 32.5 +/- 1.9 L/hr, and glucose reduced it to 18.4 +/- 0.9 L/hr (p < 0.01). In the cirrhotic patients, functional hepatic nitrogen clearance was only 9.8 +/- 1.3 L/hr (p < 0.01 vs. controls), and glucose did not change it. In the control subjects, glucose reduced the glucagon response to alanine from 204 +/- 36 ng/L to 106 +/- 8 ng/L (p < 0.05). In the cirrhotic patients the mean fasting glucagon level was increased twofold (180 +/- 21 ng/L). The response to alanine increased to 968 +/- 265 ng/L; it was not reduced by glucose. In study 3, somatostatin and hyperglycemia reduced functional hepatic nitrogen clearance from 13.2 +/- 1.5 L/hr to 6.4 +/- 0.7 L/hr (p < 0.01). Somatostatin and euglycemia reduced functional hepatic nitrogen clearance to 9.2 +/- 1.2 L/hr (p < 0.01 vs. alanine and hyperglycemia). The results show that the reduction by glucose of hepatic aminonitrogen conversion is lost in cirrhotic patients. The markedly increased glucagon response to alanine was not suppressed by glucose. Inhibition of the glucagon response by somatostatin reestablished the glucose effect, which was in part due to inhibition of glucagon in itself. Thus hepatic aminonitrogen conversion in cirrhosis depends on increased glucagon levels. The hormone-independent effect of glucose is preserved if the hyperglucagonemia is abolished, but the spontaneous high glucagon level overrules the glucose effect. The results indicate reduced hepatic contribution to the nitrogen-sparing effect of glucose in cirrhotic patients.
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PMID:Effects of glucose on hepatic conversion of aminonitrogen to urea in patients with cirrhosis: relationship to glucagon. 790 54

A prospective non-A, non-B follow-up program, implemented in a hepatitis B surface antigen-free dialysis unit, enabled us to report on the natural history of hepatitis C virus (HCV) infection in hemodialyzed patients between 1980 and 1992. For this program, every patient was prospectively monitored every two weeks for alanine amino transferase (ALT) activity, and every month for gammaglutamyl transpeptidase (GGT) activity and systematic collection of frozen sera. Sequences of stored sera from 217 patients were repeatedly tested for anti-HCV antibodies using second generation assays. Eighty-six of the 217 patients (39.6%), including 61 of the 67 patients with non-A, non-B hepatitis (91%), had HCV infection repeatedly evidenced by positive ELISA in all, and confirmed by RIBA in 84 of 86 (97.5%). In addition, 19 out of 23 patients (82.6%) were positive for HCV RNA by the polymerase chain reaction (PCR). Of the 86 anti-HCV positive patients, 41 had previously acquired HCV infection, and 45 seroconverted during chronic dialysis. Of these, all but one patient developed hepatitis with raised ALT activity which lasted for at least six months in all. Only 29 of 45 patients (64.5%) had a history of blood transfusion. Seventy-eight of the 86 patients (91%) who were followed up for one to 11.5 years (median 5) retained anti-HCV for several years. Nineteen liver biopsies performed in 16 patients showed chronic active hepatitis in 8 (50%) and hepatocellular carcinoma without cirrhosis in one patient.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A twelve year natural history of hepatitis C virus infection in hemodialyzed patients. 796 64


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