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)

Hepatic metabolism is the primary process of elimination of propafenone. It therefore is important to understand the effect of altered liver function on the disposition and elimination kinetics of this drug. Patients with abnormal liver function probably will require treatment with propafenone for cardiac arrhythmias; an understanding of the relationship between liver function and the pharmacokinetics of propafenone will provide a rational basis for optimal dosage adjustments in these individuals. Our results demonstrate that both systemic clearance and bioavailability of propafenone are sensitive to variability in liver function. The bioavailability of propafenone is inversely related to the clearance of indocyanine green (ICG), whereas a direct relationship exists between systemic clearance of propafenone and ICG clearance. Comparisons of clinical parameters with the propafenone data yielded interesting results. An overall clinical grading of severity of liver disease based on the presence or absence of portal hypertension (i.e., varices and/or splenomegaly), prior encephalopathy, and ascites did not correlate well with propafenone results. However, albumin, total bilirubin, serum glutamic oxaloacetic transaminase (SGOT) concentrations and prothrombin time values correlated strongly with the overall results. No definite relationships with subjects' age; weight; and hemoglobin, alkaline phosphatase, lactic acid dehydrogenose, cholesterol, blood urea nitrogen, or creatinine levels were detected. These results demonstrate that moderate to severe liver disease significantly affects the absorption and disposition of propafenone. In patients with cirrhosis, and presumably other forms of hepatic dysfunction, careful adjustments of propafenone doses are needed to optimize therapy.
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PMID:Influence of hepatic dysfunction on the pharmacokinetics of propafenone. 369 82

Hepatic hemodynamics in patients with chronic liver disease has been studied by reflectance spectrophotometry of the liver in situ during peritoneoscopy. An organ-reflectance spectrophotometer used in this study was equipped with a branched optic fiber bundle, which coupled the liver surface with the spectrophotometer. The spectrophotometry could measure qualitatively and quantitatively the absorption of hemoglobin in the liver in situ, thus estimating the regional hepatic tissue blood hemoglobin concentration and the saturation level of hemoglobin in the regional tissue blood. The analysis of 42 cases has shown that the estimated regional hepatic tissue blood hemoglobin concentration and saturation level of hemoglobin decreased in most cirrhotic livers, suggesting that even in cirrhotic livers the hepatic oxygen extraction increased, concomitant with a decrease in the regional hepatic tissue blood hemoglobin concentration. The hepatic blood hemoglobin concentration estimated on the surface layer of the liver was positively correlated with the regional hepatic blood flow measured by radioisotope clearance technique. The estimated hepatic blood hemoglobin concentration was also correlated positively with serum albumin level and prothrombin time, and negatively correlated with plasma retention of indocyanine green at 15 min. It is concluded that the hepatic tissue blood hemoglobin concentration decreases significantly with progress of chronic hepatitis to cirrhosis. This decrease in hepatic blood hemoglobin concentration and flow is concomitant with a decrease in metabolic functions, which is not compensated by an increased hepatic oxygen extraction.
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PMID:Hepatic hemodynamics in patients with chronic hepatitis or cirrhosis as assessed by organ-reflectance spectrophotometry. 621 8

In 15 patients with hepatocellular carcinoma (HCC) and 14 patients with liver cirrhosis (LC), urinary excretions of delta-aminolevulinic acid (ALA), porphobilinogen (PBG), uroporphyrin (UP), coproporphyrin (CP), and erythrocyte contents of CP and protoporphyrin (PP) were examined. In patients with HCC, urinary excretions of ALA and PBG and erythrocyte contents of CP and PP were not increased, but urinary excretions of UP and CP were significantly increased more than those of LC patients. Urinary excretions of UP and CP had no correlations with liver function tests and excretion of UP correlated slightly with blood hemoglobin level. After administration of ALA intravenously, urinary excretions of UP and CP were clearly increased in patients with HCC compared to normal controls. A Red fluorescent area was present at the cancerous area but not in the noncancerous cirrhotic area in a patient with HCC. These results suggest that aberrant porphyrin metabolism occurred in patients with HCC compared to other liver diseases.
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PMID:Aberrant porphyrin metabolism in hepatocellular carcinoma. 632 59

The prognostic significance of a battery of clinical, laboratory, and histological indicators was assessed in relation to mortality risk in a 1-year study of 253 patients with alcoholic liver disease, of whom 51 died within such time. The relative risk associated with each abnormality was calculated. A number of abnormalities was found to be statistically associated with a higher risk of death. Among the clinical abnormalities, these were: collateral circulation, edema, ascites, encephalopathy, spider nevi, anorexia, and weakness. Among the laboratory tests, these were: albumin, bilirubin, hemoglobin, abnormal prothrombin time, and alkaline phosphatase. Two hundred and sixteen of these patients had liver biopsies in which the quantifiable abnormalities were scored. Among the histological findings, the alterations significantly related to mortality were necrosis, Mallory, and inflammation, while the presence of cirrhosis per se did not influence the mortality risk. The relative risk factors for mortality associated with the histological alterations were lower than those derived from clinical or laboratory measurements. The advantage of using only clinical and laboratory items to derive a global, quantitative expression of severity is discussed. The relative mortality risks provided a means of calculating a "unit of severity" for each clinical and laboratory abnormality. A combined clinical and laboratory index (CCLI) results when these mortality-risk units are added. Such a combined index had a quasi-linear relationship with the risk of mortality for the complete population. This method compared well with severity scores derived from computerized, linear step-wise discriminant function (SDF) analysis and from a logistic regression (LR) analysis. The factors chosen to have independent prognostic significance by the SDF analysis were: encephalopathy, albumin, prothrombin time, and hemoglobin, while only encephalopathy, albumin, and hemoglobin were chosen by the LR analysis. Within a range of values, LR can provide a good discrimination in relation to mortality, similar to that observed for the CCLI in its complete range. However, there are some advantages to the CCLI method vs. the LR or SDF analyses. The CCLI is less susceptible to being unduly influenced by a nonspecific effect of treatment on the items chosen than the SDF and LR analyses, as the CCLI contains a large number of factors. Obtaining a single-severity score such as the CCLI is of value in: (a) assessing the effectiveness of treatment modalities; (b) analyzing the success of randomization; (c) separating cohorts of different severity, and (d) comparing new liver tests, histological abnormalities, or specific biological events with the severity of alcoholic liver disease.
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PMID:Assessment of prognostic factors in alcoholic liver disease: toward a global quantitative expression of severity. 662 18

Hepatic ethanol metabolism in the liver from carbon tetrachloride (CCl4)- treated animals was studied using non-recirculating hemoglobin-free liver perfusion system. CCl4-administration decreased ethanol uptake by the liver to 56% and 30% of the control values following the acute (24 hrs. after treatment) and chronic (8-12 weeks) treatments, respectively. In addition, 4 mM fructose, a well-known agent to increase ethanol metabolism in the liver, did not increase the hepatic uptake of ethanol in CCl4-treated livers. Hepatic alcohol dehydrogenase activity was not changed following acute and chronic CCl4 treatments. The lactate/pyruvate (cytosolic NADH/NAD) ratio as well as beta-hydroxybutyrate/acetoacetate (mitochondrial NADH/NAD) ratio significantly increased, whereas both hepatic oxygen uptake and oxidation of NADH in mitochondria remarkably decreased in parallel with the magnitude of liver injury induced by CCl4. Histological studies revealed that the liver had centrilobular coagulative necrosis with fatty droplet formations at acute phase, while bridging fibrosis between central and portal areas and the pattern of cirrhosis with conspicuous changes in the mitochondria were seen at chronic phase. These data indicate that CCl4-treatment significantly reduces hepatic ethanol metabolism via the inhibition of reoxidation of NADH, a rate limiting step of ethanol metabolism in the liver.
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PMID:Alteration of hepatic ethanol metabolism in CCL4-intoxicated rats: analysis using isolated liver perfusion system. 676 60

In several pathophysiologic states, i.e., cirrhosis of liver, protein calorie malnutrition, starvation, carbohydrate deprivation, etc., thyroid hormone metabolism is reported to be altered with a decrease in serum T3 and a reciprocal increase in TR3. Uncontrolled diabetes mellitus is a similar state in which glucose does not enter the cells causing cellular starvation and hyperglycemia ensues. Therefore, serum T4, T3, RT3, T3-resin uptake, TSH, and glucose were determined after an overnight fast in 94 male diabetics (aged 28 to 85 years) during a routine follow-up visit to the outpatient clinic and 24 healthy male adults (aged 24 to 81 years). Glycosylated hemoglobin concentrations were measured as well in normal subjects and 16 newly discovered diabetics. In normal subjects, no significant relationships between fasting plasma glucose and T3 and RRT3 levels were observed. In diabetics there was a significant positive (r = 0.611; p less than 0.001) correlation between glucose and RT3. Similarly, a significant negative relationship was observed between glucose and T3 (r = 0.491; p less than 0.001). T4, free T4, T3-resin uptake, and TSH were normal in diabetics. In 16 newly discovered diabetics, with fasting plasma glucose greater than 200 mg/dl, serum T3 rose (96 +/- 5 to 128 +/- 5 ng/dl) and RT3 declined (26.3 +/- 10.4 +/- 1.4 ng/dl) on improvement of hyperglycemia (fasting plasma glucose less than 140 mg/dl) after intensive therapy for 6 to 8 weeks. Glycosylated hemoglobin levels declined as well (14.6 +/- 0.9% to 9.3 +/- 0.7%). These data indicate: (1) thyroid hormone metabolism may be altered in diabetes mellitus with a fall in serum T3 and a reciprocal rise in RT3; and (2) T3 and RT3 concentrations may serve as indicators of metabolic control in diabetes mellitus.
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PMID:Low serum 3, 5, 3'-triiodothyronine (T3) and raised 3, 3', 5'-triidothyronine (reverse T3 or RT3) in diabetes mellitus: normalization on improvement in hyperglycemia. 714 29

Clinical and laboratory observations were made on 220 chronic alcoholics, regularly taking at least 150 g of alcohol daily. Haematological data concerning white blood cells, platelets and red cells counts, mean corpuscolar volume, hemoglobin and serum iron in these patients were compared with control values obtained from 150 healthy teetotal subjects. Hematological changes in chronic alcoholics were correlated with histological liver damages in transcutaneous needle-biopsies. No statistical differences were evident for white cells and platelets counts and for serum iron content; however, in chronic alcoholics, serum iron content showed a great dispersion around the mean. Mean corpuscolar volume (MCV) was significantly increased (P less than 0,001) in chronic alcoholics (even in those with a normal liver biopsy) but there was no significant difference in the degree and the incidence of macrocytosis between patients showing normal liver appearances or fatty changes only, and those showing more severe damage, i.e, acute alcoholic hepatitis (with or without steatosis), central hyaline-sclerosing necrosis and or hepatofibrosis, cirrhosis and hepatocarcinoma. No significant difference was seen between male and female alcoholics. Macrocytosis may be considered as an early marker for alcoholism but it does not correlate with the type of histological liver damage. Hemoglobin levels were significantly reduced in chronic alcoholics (P less than 0,01): the degree and incidence of anemia were more severe in those patients with advanced liver diseases and in female alcoholics. There is no statistically significant correlation between macrocytosis and anemia.
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PMID:[Macrocytosis and anemia in chronic alcoholism. Correlation with the results of hepatic needle biopsy]. 724 21

In a prospective trial with 120 chronic alcoholics (July, 1978 to January, 1980) on admission the following haematological values significantly different from those of the normal population were found: elevated erythrocyte mean corpuscular volume (64%), increased mean corpuscular hemoglobin (32%), thrombocytopenia (48%), increased percentage of bone marrow sideroblasts (35%), decreased percentage of sideroblasts (37%), megaloblastic bone marrow changes (55%) including nuclear abnormalities (32%), and vacuolization in red cell (20%) and white cell (16%) precursors. These changes were independent of liver cirrhosis with hypersplenism (increased mean corpuscular volume in 52% of the patients who did not have liver cirrhosis, increased mean corpuscular volume in 76% of the patients who were cirrhotic but not suffering from major bleeding). Platelets returned to normal values within 6 days of discontinuation of alcohol ingestion. In respect to iron metabolism we found the following changes: decreased serum iron concentration (32%), increased iron concentration (42%), increased total iron binding capacity (54%), increased ferritin (41%), decreased transferrin (20%). In contrast to data from the Anglo-American literature, serum folate concentrations were mostly normal in our patients (87%). This may be due to different eating and drinking habits. The percentage of bone marrow sideroblasts was also lower in our patients than those described in the literature mentioned above. The changes in maturation are likely to be caused partially by a toxic effect of alcohol on nuclear metabolism of bone marrow cells.
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PMID:[Alcohol induced changes in hemopoiesis (author's transl)]. 731 98

In clinical studies, frequent hepatic dysfunction associated with crises in sickle cell disease has been noted, but whether irreversible morphologic changes arise from these transient episodes is uncertain. We studied 70 patients with sickle cell disease (57 SS, 12 SC and one S-thalassemia (S-thal) hemoglobin) autopsied at The Johns Hopkins Hospital. They ranged in age from five months to 75 years (average 21 years) and 35 (50 percent) were female, In 64 patients (91 percent), livers were enlarged and had distention of Kupffer cells with phagocytized sickled red cells; this was massive in 10. In 19 patients (27 percent) the sinusoids were markedly distended with sickled red cells and appeared obstructed. Focal parenchymal necroses were present in 24 patients (34 percent) and were explained in 12, eight by cardiac dysfunction and four by sepsis. Reparative changes, portal fibrosis and regenerative nodules were each found in 14 patients (20 percent), only one of whom had a known history of viral hepatitis despite the frequency of transfusions. Cirrhosis of unknown cause was present in seven patients and cardiac cirrhosis in one. Cirrhosis with hemochromatosis was present in three patients and 30 others had parenchymal iron accumulation. Thus, unexplained hepatic necroses, portal fibrosis, regenerative nodules and cirrhosis were frequently encountered in these patients. This spectrum of liver disease appears to be best understood as a consequence of recurrent vascular obstruction, necrosis and repair arising as a component of sickle cell disease.
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PMID:The liver in sickle cell disease. A clinicopathologic study of 70 patients. 744 49

Chronic anemia is frequently observed in patients affected by cirrhosis. To investigate the possible role of erythropoietin (Epo) in the pathogenesis of anemia in cirrhosis, we measured the immunoreactive Epo levels and the respective hemoglobin (Hb) concentrations in 48 anemic and nonanemic cirrhotic patients and in a control group of healthy subjects and patients with iron-deficiency anemia. Epo concentrations were determined in serum using a sensitive enzyme immunoassay. The regression curve between Epo values and Hb concentrations showed a significant inverse exponential trend both in cirrhotic patients (r = -.55; P < .0001) and controls (r = -.92; P < .0001). In a semilogarithmic plot, the line slope obtained in cirrhotic patients was significantly lower (P < .005) than that of controls, suggesting a blunt Epo response to anemia in cirrhosis. Moreover, covariance analysis showed that the Epo levels for a given degree of anemia were further reduced in the patients with a more severe disease, suggesting a close relation between cirrhosis and the mechanisms involved in the derangement of the Epo feedback system. Finally, the Epo concentrations measured in the cirrhotic patients without anemia did not significantly differ from Epo values obtained in healthy subjects. An impaired Epo response may play a role in maintaining low Hb concentrations in cirrhotic patients with anemia. However, the evidence of a residual Epo response to anemia in cirrhosis and the presence of normal basal Epo levels in nonanemic cirrhotic patients do not support an inadequate Epo secretion as one of the primary causes of anemia in cirrhosis.
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PMID:Reduced serum levels of immunoreactive erythropoietin in patients with cirrhosis and chronic anemia. 755 62


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