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PubMed2003

Relationship between thrombopoietin serum levels and liver function in patients with chronic liver disease related to hepatitis C virus infection.

OBJECTIVES: Thrombopoietin (Tpo) is an important regulator of megakaryocyte maturation and platelet production, and is mainly produced by the liver. A decrease in Tpo production is partly responsible for the thrombocytopenia observed in patients with chronic liver disease (CLD). The aim of this study was to evaluate the relationship between Tpo serum levels and liver function in patients with CLD related to hepatitis C virus (HCV) infection. METHODS: We studied 37 patients with various degrees of HCV-related CLD. Of the patients, 17 had chronic hepatitis and 20 liver cirrhosis. Liver function was evaluated in all patients by the following hepatic blood flow dependent and independent tests that explore various hepatic metabolic functions: carbon-13 (13C)-aminopyrine breath test (13C-ABT), 13C-galactose breath test (13C-GBT), and monoethylglycinexylidide (MEGX) test. Liver function tests results were correlated with Tpo serum levels. RESULTS: Tpo serum levels were significantly lower in patients with liver cirrhosis (88 +/- 23 pg/ml) as compared to those in patients with chronic hepatitis (128 +/- 55 pg/ml, p=0.0031). However, they did not correlate with serum albumin, bilirubin, or prothrombin activity. Tpo serum levels showed a significant positive correlation with 13C-ABT results (hourly dose at 30 min, rs=0.489, p=0.002; cumulative dose at 120 min, rs=0.425, p=0.008). Moreover, they showed a fair, positive correlation with 13C-GBT hourly dose at 30 min (rs=0.366, p=0.028), and a trend toward a positive correlation with the various MEGX test sampling times (MEGX15, rs=0.314, p=0.059; MEGX30, rs=0.284, p=0.088; and MEGX60, rs=0.320, p=0.059). CONCLUSIONS: In this study we have shown that a progressive decline in liver function in patients with HCV-related CLD is paralleled by a decrease in Tpo production. The different correlations observed between Tpo and the various liver function tests suggests that this finding is mainly the result of a decrease in hepatic functional mass rather than dependent on alteration in splanchnic hemodynamic.

Adult↗
PubMed2000

Evaluation of balloon-occluded hepatic venography with carbon dioxide for portography and correlation between retrograde portogram and liver function in patients with liver cirrhosis.

Background/Aim: Hepatic venography with a positive-contrast medium has been reported as a method for evaluating liver disease. However, the contrast medium used in this method provides insufficient portal vein observation and may cause severe liver injuries. Carbon dioxide (CO(2)), a negative-contrast medium, may be able to depict the portal vein system with minimal hepatic toxicity. The aim of this study was to evaluate the usefulness and side-effects of balloon-occluded hepatic venography with CO(2) (CO(2) venography) and to evaluate the correlation between retrograde portogram and liver function in patients with cirrhosis. Subjects and methods: The subjects consisted of 23 biopsy-proven cirrhotic patients (male:female, 16:7; age, 58+/-12 years, range 34-80). The causes of cirrhosis were alcohol intake in ten, HCV infection in ten, HBV infection in one, primary biliary cirrhosis in one and Budd-Chiari syndrome in one. Of these patients, six were complicated with hepatocellular carcinoma (HCC). CO(2) venography was performed with an occlusion balloon catheter, and 25 ml of CO(2) was infused. CO(2) portograms were scored as follows: 0, no visualization of portal veins; 1, visualization of peripheral portal branches; 2, unilateral first portal branch; 3, bilateral first portal branches; 4, main portal vein; 5, left gastric vein, superior mesenteric vein and splenic vein. Hepatic venous pressure gradient (HVPG), cardiac functions, biochemical analysis, blood gas analysis and oxygen (O(2)) saturation monitoring were measured simultaneously. Arterio-portography was also performed. To evaluate the usefulness of CO(2) venography in patients with HCC accompanied by portal vein tumor thrombus (PVTT), three patients were also examined. Results: No significant changes in ALT, AST, O(2) saturation or blood gas data were observed after CO(2) venography. A statistically significant positive correlation was observed between CO(2) portogram scores and Child-Pugh scores (r=0.68, P=0.003). The correlations between CO(2) portogram scores and HVPG, and the forms of gastroesophageal varices in patients without PVTT and major shunts were not significant. The CO(2) portogram score was significantly higher in patients with alcoholic liver cirrhosis than in those with HCV-positive cirrhosis (P=0.04). Cavernous transformation and peripheral portal branches were demonstrated in patients with HCC accompanied by PVTT. These findings could not be observed by arterio-portography. Conclusion: CO(2) venography to obtain retrograde portogram is a safe and useful method for evaluating the portal vein system and liver function in patients with liver cirrhosis.

Journal Article↗
PubMed2000

Comparative study on the correlation of plasma gamma-aminobutyric acid and pipecolic acid with liver function in patients with liver cirrhosis.

gamma-Aminobutyric acid (GABA) is an inhibitory neurotransmitter, elevated in plasma of patients with liver cirrhosis. Pipecolic acid (PA), a metabolite of lysine, and known to be a GABA receptor agonist, is also seen high levels in the plasma. To clarify the relationship of GABA, PA and liver function, plasma GABA and PA in three groups of chronic liver diseases (compensated cirrhosis, decompensated cirrhosis and decompensated cirrhosis with hepatic encephalopathy, HE) were analyzed and their liver functions were compared. This analysis demonstrated that both plasma GABA and PA were higher in these patients than in normal subjects. Plasma PA, but not plasma GABA, was closely correlated with plasma ammonia concentration in each group. No correlation was noted between plasma GABA and PA in each group. Plasma pipecolic acid was significantly higher in patients with esophageal varices than in patients with no varices. These findings suggest that increased PA may reflect the degree of portal hypertension. Although both GABA and PA are increased in chronic liver disease, they may have a different origin and disappearance rate including metabolic mechanism.

Journal Article↗
PubMed2001

Effect of methylprednisolone on the kinetics of cytokines and liver function of regenerating liver in rats.

The participation of cytokines in the early stage mechanism of hepatocyte proliferation has already attracted attention. We investigated the effect of methylprednisolone (MDS), which inhibits the inflammatory response, given before and after a 70% partial hepatectomy in rats on the kinetics of tumor necrosis factor-alpha and Interleukin-6, liver cell function and the rate of liver regeneration. Serum Interleukin-6 levels of the MDS groups were significantly lower than those of the control group. Serum alanine aminotransferase, aspartate aminotransferase and hyaluronic acid levels were also significantly decreased, however, the serum albumin level showed high values in the MDS groups. In the MDS groups, MIB-5 labeling indices, a novel antibody reactive with the equivalent Ki-67 protein, which detects immunohistochemically all active parts of the cell cycle in the rat liver, were more pronounced than in the control group at an earlier time. However, in regard to 5-bromo-2-deoxyuridine (BrdU), there were no significant differences among the three groups. There were no differences in residual liver weight/body weight between the three groups after 336 h. In our study, MDS administration before or after a 70% partial hepatectomy decreased serum Interleukin-6 levels, and inhibited hepatic dysfunction. Therefore, we considered that beneficial effects of physiological doses of MDS in the peri-operative period should be confirmed in humans.

Journal Article↗
PubMedDate not supplied

[Liver function tests].

The liver function tests are basic tools in the assessment of liver disease, they supply information about severity, progression of the illness and help to discriminate among treatment options. They are divided into two sections: biochemical test of liver function per se and serum markers of hepatobiliary disease. Although there are no new tests, liver transplant programs have stimulated development of metabolic capacity measurements to estimate liver function. At present the liver function tests, still are the best method to assess patients with liver diseases.

Biomarkers↗
PubMed1996

Metabolic, endocrine, haemodynamic and pulmonary responses to different types of exercise in individuals with normal or reduced liver function.

UNLABELLED: The liver is central to the metabolic response to exercise but measurements of effects of reduced liver function on the physiological adaptation to exercise are scarce. We investigated metabolic, endocrine, pulmonary and haemodynamic responses to exercise in 15 healthy untrained controls (Co) and in 30 subjects with reduced liver function (i.e. liver cirrhosis, Ci). The following protocols were used: protocol 1 maximal oxygen uptake (VO2max) and anaerobic threshold (AT), protocol 2 stepwise increases in exercise intensity from 0 to 40% VO2max giving steady-stage conditions, protocol 3 1 h exercise at 20% VO2max. Muscle glycogen content was determined in 15 Ci. Spirometry was essentially normal in Ci. RESULT: protocol 1 Ci had impaired VO2max and reduced AT (P < 0.05). Basal plasma concentrations of insulin, glucagon, growth hormone and adrenaline were increased in Ci (P < 0.05); cortisol was normal. During exercise, only glucagon remained different between groups. In protocol 2 Ci had decreased resting respiratory exchange ratio (RQ: p < 0.05) associated with increased plasma concentrations of free fatty acids and glycerol. They had disproportionately enhanced lipolysis and RQ. heart rate (+24%), ventilation (+28%), thermal effects of exercise (+31%) and intrapulmonary shunt volume (+76%), which accounted for 11.7 (SD 3.0) or 7.4 (SD 0.9%) of cardiac output during exercise in Ci and Co, respectively (P < 0.05 for all the differences reported). The metabolic effects of Ci were independent of the clinical and nutritional state of the patients. In protocol 3 muscle glycogen content was highly variable in Ci, but mean values were normal [16.9 (SD 8.9) mumol.g-1 wet mass]. Glycogen content positively correlated with resting and exercise-induced RQ, but negatively correlated with the exercise-induced alterations in plasma glucose concentration. From these results we concluded that with reduced liver function VO2max and AT are reduced, but metabolic, pulmonary and haemodynamic responses per unit power output are enhanced. Muscle glycogen content would seem to contribute to the metabolic response, but its mobilization to be limited in individuals with reduced liver function.

Adult↗
PubMed1997

Quantitative liver function tests define the functional severity of liver disease in early-stage cirrhosis.

Some patients with early-stage cirrhosis preserve hepatic function, whereas others have little hepatic reserve and rapidly deteriorate. The aim of this study was to use quantitative tests of liver function (QLFTs) to define the degree of functional hepatic impairment in patients with early-stage cirrhosis (Child-Pugh score 5-7) and to determine whether the tests predicted subsequent hepatic decompensation. We recruited 10 cirrhotic (Cr) patients and 10 healthy controls (NI), who were well matched for race, age, weight, and gender. Clearances of caffeine (CF) and antipyrine (AP) after oral administration were measured from timed samples of saliva. The clearance of cholate (CA) was measured from serum samples obtained after simultaneous oral ([2,2,4,4-2H]CA) and intravenous ([24-13C]CA) administration. CA shunt was calculated as (Cl i.v./Clo x 100%). CF elimination rate (Cr v NI, mean +/- SD: 0.03 +/- 0.02 v 0.075 +/- 0.018 h-1, P < .0005) and AP clearance (24 +/- 16 v 40 +/- 7 mL/minute, P < .02) were reduced in Cr patients. CA shunt was increased in Cr patients (43 +/- 18 v 18 +/- 7%, P < .002). Five Cr patients decompensated during follow-up and had the worst CA shunts (76%, 66%, 51%, 48%, and 45%). Three subsequently received successful orthotopic liver transplantation, 1 died of hepatoma, and 1 is on the waiting list for transplantation. In conclusion, QLFTs define the degree of functional impairment in early cirrhosis and may identify Cr patients at greatest risk of decompensation who may require transplantation for survival.

Administration, Oral↗
PubMed2001

Measurement of serum hyaluronic acid level during the perioperative period of liver resection for evaluation of functional liver reserve.

BACKGROUND AND AIM: The serum hyaluronic acid (HA) concentrations reflect the degree of hepatic fibrosis and sinusoidal endothelial cell damage. The HA concentrations were examined to evaluate liver damage during the perioperative period of hepatectomy. METHODS: The HA level of serum samples from 79 patients who underwent a hepatectomy was measured, and the results were compared to conventional liver function tests, the degree of fibrosis, liver regeneration and complications. RESULTS: Hyaluronic acid concentrations correlated with the severe fibrosis or histological activity index, and also correlated with liver function tests including transaminase level, platelet counts, prothrombin time activity, indocyanine green retention rate at 15 min (ICG R15), liver activity at 15 min by technetium-99m galactosyl human serum albumin scintigraphy (LHL 15), and portal pressure. The HA level postoperatively correlated with liver function, especially with total bilirubin. Hyaluronic acid levels at day 28 postoperatively correlated with ICG R15 and LHL 15. The hyaluronic acid level before surgery and at day 28 postoperatively correlated with the regeneration of remnant liver in major hepatectomy. The HA levels were significantly higher in patients with hepatic failure or prolonged ascites. CONCLUSION: Our results indicate that the measurement of the HA level is useful for monitoring liver damage or predicting complications associated with liver surgery.

Adult↗
PubMed1991

[Functional liver status in occupational contact with acrylonitrile].

Experiment was performed on 133 workers engaged in the production "Acrylonitrile" by number of tests, giving information on the status of the enzyme, detoxifying and lipidic liver functions. Significant deviations are established in 22 workers, whose length of service in industry is 10 to 21 years. Most significant is the number of workers with changes from group I, where the total index of exposure surpasses 10 times the maximum admissible. The comparison of the present results with those from the performed experiments in 1971 and 1981 shows an increase in the frequency of changes, which proves the existence of real risk for the health of the workers from this production. The workers showing deviations are subject to active follow-up care and diagnostic specification.

Acrylonitrile↗
PubMed1997

Index for predicting post-operative residual liver function by pre-operative dynamic liver SPET.

To predict residual liver function before hepatic resection, we devised a predictive index by combining clearance values with functional liver volume measured by liver dynamic single photon emission tomography (SPET). Forty-seven patients with liver disease underwent liver dynamic SPET with 99Tcm-Sn colloid before hepatic resection. There were no operation-related deaths. Three patients died from hepatic failure more than 1 month following the operation. Their predictive indices were 0.24, 0.33 and 0.34. When the predictive index was above 0.35, no patient had symptoms of hepatic failure or died. Our data suggest that when the predictive index is above 0.35, there is a low probability of hepatic failure after hepatectomy.

Adult↗
PubMed1998

The impact of donor organ quality on postoperative liver function after orthotopic rat liver transplantation.

The impact of donor factors for posttransplant liver function was evaluated in the model of orthotopic rearterialized liver transplantation in the rat. The effect of donor fasting, parenteral hyperalimentation, hypotension, warm ischemia and endotoxins on histology, clinical chemistry and MEGX test was analyzed in syngeneic and allogeneic recipients of livers stored for 4 hrs on ice. In syngeneic animals, 20 min of warm ischemia led to significantly elevated serum transaminase levels and degree 2 histological damage on POD 2. Endotoxins produced a grade 1 histological damage. All groups had a lower MEGX formation rate compared to controls. In allogeneic animals, warm ischemia was the single most detrimental parameter. The strength of the rejection response on POD 8 did not depend on the type of donor pretreatment. The major finding of this non-survival study is the deleterious effect of warm ischemia and endotoxin on the functional and structural integrity of liver grafts after 4 hrs of cold ischemia.

Animals↗
PubMed1986

Orthotopic liver transplantation in pigs without cold perfusion of the donor liver. Evaluation by quantitative liver function tests.

Orthotopic liver transplantation (OLT) was performed in 12 pigs and liver function assessed before and after transplantation. In 6 pigs OLT was carried out without cold perfusion of the donor liver, whereas in the other 6 animals the donor organ was perfused in situ. 5/6 animals without perfusion and 4/6 with cold perfusion survived for more than 10 days. Significantly better liver function was revealed by the aminopyrine breath test (ABT) and the indocyanine green (ICG) disappearance in the group with the cold perfusion of the liver, whereas no differences in routine liver function tests were seen between the two groups. Although OLT without cold perfusion of the donor liver is feasible and prolonged survival of animals is possible, the function of these organs is markedly reduced compared to the cold perfused organs. This method can, therefore, not be recommended. ABT and ICG disappearance are sensitive tests for the evaluation of the liver function in the post-transplant period.

Aminopyrine↗
PubMed1982

[Evaluation of liver function in chronic liver diseases using the bile acid spectrum].

In 24 persons with healthy liver and 44 patients with without exception morphologically ascertained chronic hepatopathies of different degree of severity the diagnostic valency of the bile acids was tested. In these cases the bile acids estimated in the C-bile proved as sensitive indicators of a chronic lesion of the liver parenchyma. Quantitative deviations of the bile acids, the relation from tri- to dihydroxycholan acids, qualitative alterations in the spectre of the free bile acids as well as changes of the form of conjugation were of importance concerning the functional diagnosis. The concentration of bile acids decreased the more expressed was the chronic lesion of the liver parenchyma. Trihydroxycholan acids and dihydroxycholan acids variably participated in the reduction of the bile acids in different forms of chronic hepatopathies. From the change of the quotient tri- to dihydroxycholan acids causal connections between the degree of severity of the chronic hepatopathy and the dominance of the chenodesoxycholic acid could be derived. Moreover, the conjugation of the bile acids with glycine prevailing in chronic hepatopathies underwent a degradated change. From the examinations results that quantitative and qualitative deviations of the bile acid spectre under defined morphological prerequisites render possible a differentiated judgment of the liver function in chronic hepatopathies.

Adult↗