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At least 163 records · Page 9Linked to original sources
PubMed2001

The clinical importance of the trimethadione tolerance test as a method for quantitative assessment of hepatic functional reserve in patients with biliary atresia.

BACKGROUND: The trimethadione (TMO) tolerance test was performed to evaluate its usefulness in the assessment of hepatic functional reserve in patients with biliary atresia. METHOD: Nineteen patients with biliary atresia after hepatic portoenterostomy (age range: 2 months to 25 years; sex: 6 males and 13 females) were studied. The study was performed in the morning after a 12-h fast. TMO was given orally, at a dose of 4 mg/kg, with 5 mL of 5% glucose 2 h before breakfast. Blood samples (0.5 mL) were collected to determine serum TMO and dimethadione (DMO), a metabolite of TMO, levels 4 h after the administration of TMO. TMO and DMO were measured by a gas-liquid chromatographic method. RESULTS: A higher total bilirubin level (over 1 mg/dL) in patients with jaundice was reflected in the smaller serum DMO/TMO ratio 4 h after the oral administration of TMO. In addition, these patients with total bilirubin levels of 1 mg/dL or less had a significantly lower DMO/TMO ratio than the control group (healthy subjects). The serum DMO/TMO ratio showed a close correlation with the Child-Pugh score, which is used for overall evaluation of severity of cirrhosis and Mayo risk scores for primary biliary cirrhosis in adults (0.856, P < 0.01 and 0.788, P < 0.01, respectively). The TMO tolerance test shows the benefit of performing a relatively early test of dynamic liver function to evaluate hepatic functional reserve in pre- and post-operative biliary atresia patients.

Administration, Oral↗
PubMed2003

13C-methacetin breath test for monitoring hepatic function in cirrhotic patients before and after liver transplantation.

BACKGROUND: In patients with chronic liver disease, the measurement of liver function is critical for monitoring disease progression, predicting the prognosis and choosing therapeutic strategies. The 13C-methacetin breath test is a simple, non-invasive diagnostic tool based on an inexpensive, non-toxic substance, which allows the accurate measurement of liver functional reserve. AIM: To investigate the 13C-methacetin breath test as a tool to monitor hepatic function in liver transplant candidates and recipients. METHODS: Twenty-eight cirrhotic patients listed for orthotopic liver transplantation and 10 healthy controls were studied. The 13C-methacetin breath test (75 mg per os) was performed at baseline and at 12-week intervals. Intra-operative measurements were obtained during the liver transplantation procedure in nine patients. Results were expressed as the 13C-methacetin cumulative oxidation percentage 45 min after substrate ingestion. RESULTS: The mean 13C-methacetin cumulative oxidation at 45 min was 16.4 +/- 3.5% in healthy controls and 5.4 +/- 4.2% in cirrhotic patients at the time of listing. In 11 patients who underwent successful liver transplantation, mean oxidation increased from 3.3 +/- 1.6% before transplantation to 17.0 +/- 5.2% at 6 months of follow-up. Variations in methacetine oxidation were closely related to the recovery of liver function. The mean intra-operative 13C-methacetin cumulative oxidation increased from 0.1% during the anhepatic phase to 3.7 +/- 2.0% 2 h after reperfusion. CONCLUSIONS: The 13C-methacetin breath test is a simple and potentially useful tool for monitoring hepatic function in cirrhotic patients listed for liver transplantation, and during the intra-operative and post-operative phases.

Acetamides↗
PubMed1999

Total and functional hepatic blood flow decrease in parallel with ageing.

OBJECTIVES: To study changes in hepatic blood flow with age. DESIGN: Functional hepatic flow (FHF) and total hepatic flow (THF) were determined by non-invasive methods in 40 normal subjects in four age groups (<45, 45-60, 61-75 and >75 years). All subjects had normal routine liver function tests and no history of liver disease. RESULTS: THF was measured by pulsed echo-Doppler, as the sum of portal and hepatic artery blood flow; FHF was measured by the hepatic clearance of D-sorbitol. THF significantly decreased with age, particularly in subjects over 75 (from 1445+/-220 ml/min to 1020+/-148; P<0.001), and a similar reduction was observed in FHF (from 1514+/-250 ml/min to 1015+/-163; P<0.001). THF and FHF were strictly correlated in the whole population (r = 0.871; P<0.001) and both correlated with age (r = -0.510 and r = -0.596; P<0.005). CONCLUSION: With ageing there is a reduction of hepatic blood flow without any additional intrahepatic shunting.

Adult↗
PubMed1987

Quantitative scintigraphy with deconvolutional analysis for the dynamic measurement of hepatic function.

A mathematical technique known as deconvolutional analysis was used to provide a critical and previously missing element in the computations required to quantitate hepatic function scintigraphically. This computer-assisted technique allowed for the determination of the time required, in minutes, of a labeled bilirubin analog (99mTc-disofenin) to enter the liver via blood and exit via bile. This interval was referred to as the mean transit time (MTT). The critical process provided for by deconvolution is the mathematical simulation of a bolus injection of tracer directly into the afferent blood supply of the liver. The raw data required for this simulation are obtained from the intravenous injection of labeled disofenin, a member of the HIDA family of radiopharmaceuticals. In this study, we perform experiments which document that the simulation process itself is accurate. We then calculate the MTT under a variety of experimental conditions involving progressive hepatic ischemia/reperfusion injury and correlate these results with the results of simultaneously performed BSP determinations and hepatic histology. The experimental group with the most pronounced histologic findings (necrosis, vacuolization, disorganization of hepatic cords) also have the most prolonged MTT and BSP half-life. However, both quantitative imaging and BSP testing are able to identify milder degrees of hepatic ischemic injury not reflected in the histologic evaluation. Quantitative imaging with deconvolutional analysis is a technique easily adaptable to the standard nuclear medicine minicomputer. It provides rapid results and appears to be a sensitive monitor of hepatic functional disturbances resulting from ischemia and reperfusion.

Animals↗
PubMedDate not supplied

Significance of portal hemodynamic investigation in prediction of hepatic functional reserve in patients with hepatocellular carcinoma undergoing operative treatment.

BACKGROUND/AIMS: To evaluate clinical significance of portal hemodynamic investigation in prediction of hepatic functional reserve in patients with hepatocellular carcinoma undergoing operative treatment. METHODOLOGY: By using the color Doppler velocity profile technique, preoperative portal hemodynamic status was assessed in 29 patients with hepatocellular carcinoma treated surgically, including 15 segmentectomies, 6 hemihepatectomies and 8 transarterial chemoembolizations. Forty-six normal volunteers were taken as control. Comparison of preoperative portal hemodynamics between patients recovering from operation smoothly (tolerant subgroup) and those with major complications or death (intolerant subgroup) was done, and discriminant analysis was employed to identify the cut-off value for significant parameters that maximally separate the tolerant subgroup from the intolerant subgroup. RESULTS: In the portal trunk, CSVmax (maximum cross-sectional mean velocity) was significantly lower in the hepatocellular carcinoma group compared with the normal group (P < 0.01); flow volume was not obviously different between the two groups; congestion index was markedly higher in the hepatocellular carcinoma group than that of the normal group (P < 0.05). In the splenic vein, CSVmax and congestion index was not obviously different between the hepatocellular carcinoma and the normal groups; flow volume was significantly higher in the hepatocellular carcinoma group than that of the normal group (P < 0.05). In the hepatocellular carcinomas, twenty-three patients recovered smoothly from the operation and the remaining 6 had severe complications or death. Tolerant subgroup had a significantly higher preoperative CSVmax and flow volume and lower congestion index of the portal trunk compared with the intolerant subgroup (all P < 0.01). Discriminant analysis revealed that portal trunk CSVmax > 13.50 cm/s and flow volume > 12.13 mL/min/kg could predict tolerance for surgery, with an accuracy of 82.7% and 89.7%, respectively. CONCLUSIONS: The results suggest that preoperative portal hemodynamic status in hepatocellular carcinomas had a close correlation with hepatic functional reserve, and CSVmax and flow volume of portal trunk might become valuable predictive parameters.

Adult↗
PubMed1991

[Hepatic functional evaluation using the galactose tolerance test in patients with obstructive jaundice].

Hepatic functional mass was evaluated in patients with obstructive jaundice using the galactose tolerance test (GaTT), which reflected cytosolic function of hepatocyte. The T-1/2 values as an index on the GaTT were significantly prolonged in patients with obstructive jaundice in comparison with control subjects whether before or after percutaneous transhepatic biliary drainage (PTBD). But in each cases, some showed nearly normal GaTT-T/2 value and others showed severely prolonged value. Patients with obstructive jaundice could be divided into two groups according to the GaTT-T/2 value before PTBD. The decreasing rate of serum bilirubin level "b" after PTBD was significantly fair in the group A patients (good GaTT-T/2 value before PTBD) than the group B (poor GaTT-T/2 value before PTBD) (P less than 0.05). It was that GaTT-T/2 before PTBD which represented hepatic cytosolic functional mass could predict the effect of PTBD in patients with obstructive jaundice.

Aged↗
PubMed2003

[The effect of repeated sevoflurane anesthesia on hepatic function and immunological system].

BACKGROUND: Sevoflurane is known as a useful and safe anesthetic because of its properties of fast uptake and elimination at the lungs and of no effects on hepatic function. In this study we examined the effect of repeated sevoflurane anesthesia on hepatic function and immunological system. METHODS: Eight patients (ASA, PS 2 or 3) received sevoflurane anesthesia three times in 6 months. Six patients had emergency operation for injuries. Aspirate transaminase (AST), alanine transaminase (ALT) and complements (CH50, C3, C4) were measured prior to anesthesia, and 1, 7 and 14 days after anesthesia. RESULTS: The values of AST and ALT were high prior to anesthesia at the first anesthesia. However, these were of no significant changes. CH50, C3, C4 increased significantly after the first anesthesia. However, there were no significant changes of these complements after the second and the third anesthesia. CONCLUSIONS: Our results suggest that sevoflurane is not likely to provide adverse effects on the liver and to suppress the production of complements accompanied by the surgical stress.

Adolescent↗
PubMed1997

Application of maximal removal rate of indocyanine green to the determination of hepatic functional mass in conscious rats.

We established a versatile method for the measurement of indocyanine green maximal removal rate (ICG Rmax) to detect hepatic functional mass in conscious rats using a repeated blood sampling procedure. On investigation of the optimal technical conditions, the appropriate intravenous administered doses of ICG were 2.5, 5, 10 or 20 mg/kg, and the best blood collection times for calculating plasma half-life at these doses were immediately before, and 4, 7 and 10 min after ICG injection. The interval among the respective ICG injections was more than 4 hr. In hepatectomized rats, the ICG Rmax value was reduced to about 50% and 20% of sham-operated rats in mean 2/3 and 4/5 liver resections, respectively, suggesting that it would almost extrapolate to hepatic surviving reserves under these experimental conditions. In rats treated subcutaneously with carbon tetrachloride (CCl4, 0.1 and 0.25 ml/kg) thrice weekly during a 17-week period (120 days), a decrease in ICG Rmax value did not correlate with increases in serum alanine transaminase (ALT), alkaline phosphatase (ALP) and total bilirubin values throughout the experimental periods. However, the reduced ICG Rmax well correlated with decreases in serum albumin and cholinesterase (CHE) values from day 50. Histological examinations in the liver revealed that nodules of hepatocytes were separated by thick fibrous bands, defining the typical aspect of cirrhosis on day 30 to 90. These results suggest that the measurement of ICG Rmax is a valuable tool for the estimation of hepatic functional integrity in rats.

Alanine Transaminase↗
PubMed2003

Quantitative liver-spleen scan using single photon emission computerized tomography (SPECT) for assessment of hepatic function in cirrhotic patients.

BACKGROUND/AIMS: Accurate quantitative determination of liver function is critical in cirrhotic patients in order to predict outcome, particularly in patients who undergo hepatic resection or non-hepatic surgery. As colloid uptake by perfused Kupffer cells is proportional to perfused hepatocyte mass, quantitative liver spleen scan may be used as an index of perfused hepatocyte mass. Thus, this study was conducted to evaluate quantitative single photon emission computerized tomography (SPECT) of Tc-99mm-phytate colloid uptake by the liver as a test for hepatic function in cirrhotic patients. METHODS: Quantitative SPECT was used to measure liver volume, quantitative colloid uptake by the liver and percentage of injected dose/ml of liver tissue in cirrhotic patients (n=75), non-cirrhotic patients with chronic liver disease (n=52) and patients without liver disease (n=36). RESULTS: Although liver volume was similar among the three groups, the cirrhotic patients had significantly lower total quantitative uptake and quantitative uptake/ml compared to groups 2 and 3 (P<0.001). Quantitative liver uptake in the cirrhotic patients was highly correlated with Child-Pugh score (r=-0.64, P<0.0001) and with indocyanine green retention at 15 min (r=-0.84, P<0.0001). CONCLUSIONS: Quantitative SPECT of the liver may be an additional, useful, non-invasive quantitative test for assessment of hepatic function and severity of liver disease in cirrhotic patients.

Adult↗
PubMed1993

Sodium retention and hepatic function following partial portal vein ligation in the rat.

Recent studies have suggested that the development of sodium retention in experimental cirrhosis in the rat occurs when hepatic function, measured by the aminopyrine breath test, decreases below a critical threshold. The present study evaluated the relationship between renal sodium handling and hepatic function and determined whether sodium retention occurs following partial portal vein ligation. Sodium balance, urine volume, creatinine clearance and the aminopyrine rate constant of elimination, on a constant sodium intake, were evaluated daily, from 1 day before surgery to 5 days after surgery, in both sham-operated (n = 6) and partially portal vein-ligated rats (n = 14). In the partially portal vein-ligated group, sodium retention occurred in 9 rats between 1 and 4 days after surgery, accompanied by a 45% reduction in the aminopyrine rate constant of elimination. Spontaneous natriuresis occurred within 5 days after surgery, and was associated with an increase in the aminopyrine rate constant of elimination from 0.94 +/- 0.07 x 10(-2) min-1 on the last day of sodium retention to 1.36 +/- 0.06 x 10(-2) min-1 on the day of diuresis (P < 0.05). In contrast, creatinine clearance did not change throughout the study. There was a negative curvilinear association between sodium balance and the aminopyrine rate constant of elimination (r = 0.70, P < 0.001). In the five rats without sodium retention, there was no change in the aminopyrine rate constant of elimination and creatinine clearance over the 5 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminopyrine↗
PubMed1984

Effect of trimethoprim administration on hepatic functions of albino rats.

The effects of chronic and high-dose administration of trimethoprim (TMP) i.p. for different periods on serum and hepatic functions of rats were studied at cellular and subcellular levels. Most of the parameters studied were unaffected after chronic administration of TMP (10 mg/kg/day) for 90 days except an increase in total lipid content of liver and liver microsomes. Administration of TMP in doses of 40 mg and 80 mg/kg/day for 21 days caused a significant increase in total lipid, cholesterol and transaminases activities of serum and liver. Protein, RNA and phospholipid contents of liver and microsomes decreased significantly while DNA content remained unchanged. Glycogen content of liver decreased significantly but alkaline phosphatase activity did not show any noticeable alteration. Histopathological findings showed fatty infiltration and distorted liver architecture. Administration of TMP in doses of 40 mg and 80 mg/kg/day for 14 days changed all the parameters and enzymes in a similar pattern but with less intensity. From the present study it is obvious that high doses of this drug cause harmful toxic effects on serum and hepatic function with liver injury whereas chronic administration has no effect so far.

Animals↗
PubMed1991

Sodium retention and hepatic function after two-thirds hepatectomy in the rat.

Recently it was suggested that the onset of sodium retention in experimental cirrhosis in rats is related to a critical threshold of hepatic function, as assessed by the aminopyrine breath test. The aim of this study was to evaluate whether sodium retention occurred after two-thirds hepatectomy in rats and to investigate the relationship between sodium retention and changes in hepatic function associated with liver regeneration in this model. Sodium balance, creatinine clearance, serum sodium and the aminopyrine rate constant of elimination were evaluated daily for 4 days after surgery in partially hepatectomized (n = 6) and sham-operated rats (n = 6). All rats in the partial hepatectomy group exhibited sodium retention (sodium balance greater than 0.7 mmol/day) 24 hr after surgery. This was associated with a 62% reduction of the aminopyrine rate constant of elimination. Spontaneous natriuresis which occurred between 2 and 4 days after surgery, was associated with an increase in the aminopyrine rate constant of elimination (from 0.73 +/- 0.02 x 10(-2) min-1 on the last day of sodium retention to 0.95 +/- 0.04 x 10(-2) min-1 on the first day of natriuresis [p less than 0.05]). In contrast, no change in creatinine clearance occurred over the same period. A negative curvilinear association was found between sodium balance and the aminopyrine rate constant of elimination in all animals (r = -0.72, p less than 0.001). These observations indicate that natriuresis is related to the recovery of liver function, not to changes in creatinine clearance. In conclusion, the concept of a critical threshold of liver function below which sodium retention occurs has been substantiated in this model of hepatic dysfunction.

Analysis of Variance↗
PubMed2004

Brain volumes, RBC status, and hepatic function in alcoholics after 1 and 4 weeks of sobriety: predictors of outcome.

OBJECTIVE: The authors asked if hematological indices of RBC status and hepatic function in newly sober alcoholic men are related to abnormalities in brain morphology, change with normalization of brain function during short-term sobriety, and predict prolonged sobriety. METHOD: Alcoholic men received brain magnetic resonance imaging and laboratory assessments on admission and before discharge from an inpatient treatment program. Healthy comparison men were similarly tested. RESULTS: On admission, RBC count, hemoglobin level, and hematocrit were significantly lower in alcoholic subjects than comparison subjects; mean corpuscular volume, SGOT, SGPT, and gamma-glutamyl transpeptidase were significantly higher. By discharge, all measures had improved, although RBC count, mean corpuscular volume, and gamma-glutamyl transpeptidase levels remained significantly different from those of comparison subjects. Upon admission, alcoholic men had smaller cortical white and gray matter and larger lateral and third ventricle volumes, with reduced lateral ventricle and increased anterior cortical gray matter volumes by discharge. Lower RBC count, hemoglobin level, and hematocrit were associated with lower white matter and higher ventricular volumes at admission. Change in these measures was related to reduction in ventricular volume with treatment. By discharge, associations among RBC count, hemoglobin level, and hematocrit and white matter and ventricular volumes were less marked than at admission. Discharge hemoglobin value and hematocrit discriminated patients who maintained sobriety from those who relapsed. Hepatic function showed limited association with brain measures at admission and discharge. CONCLUSIONS: Hemograms reflect alcohol-related abnormalities in brain morphology, improvement over short-term sobriety, and liability to relapse after treatment.

Adult↗
PubMed2000

The lidocaine (MEGX) test as an index of hepatic function: its clinical usefulness in liver surgery.

BACKGROUND: The purpose of this study was to evaluate the clinical usefulness of the lidocaine test, as an index of hepatic function, in the different fields of liver surgery. METHODS: The lidocaine (MEGX [monoethylglycinexylidide]) test, which was performed in 200 patients with different liver diseases and in 23 organ donors, was compared with common laboratory tests. The MEGX value was related to postoperative complications in patients who undergo liver resection and to the survival of patients with cirrhosis who are awaiting transplantation. In organ donors, the test was related to the outcome of patients who underwent transplantation. RESULTS: The MEGX value was significantly higher in patients without cirrhosis compared to patients with cirrhosis (77.8 +/- 25 ng/mL vs 35.6 +/- 30 ng/mL; P < .05); among patients with cirrhosis, there was a significant difference between those patients classified Child A and those classified Child B and C (43.3 +/- 25 ng/mL vs 11.5 +/- 7.1 ng/mL; P < .05). The patients classified Child A who underwent liver resection with MEGX value less than 25 ng/mL had a significantly higher rate of postoperative complications compared with other patients (P < .001). Patients with cirrhosis who were awaiting liver transplantation and who had a MEGX value of less than 10 ng/mL had a life expectancy of no longer than 1 year. CONCLUSIONS: The MEGX test is a reliable index of hepatic function. Patients carrying hepatocellular carcinoma with MEGX value of less than 25 ng/mL have a high risk of liver insufficiency after hepatic resection. Patients with decompensated cirrhosis who have an MEGX value of less than 10 ng/mL should undergo transplantation as soon as possible.

Adult↗
PubMed1996

Phase I and pharmacologic studies of topotecan in patients with impaired hepatic function.

BACKGROUND: Topotecan, a topoisomerase I inhibitor that has demonstrated anticancer activity toward leukemias and solid tumors in clinical trials, is eliminated via hepatic and renal routes. However, dosing guidelines for the administration of topotecan to patients with impaired hepatic function have not yet been established. PURPOSE: We compared the maximum tolerated doses (MTDs), the toxic effects, and the pharmacokinetics and pharmacodynamics of topotecan in patients who had refractory, malignant, solid tumors and who either had or lacked hepatic injury. The potential role of three substrate markers of liver function (indocyanin green [ICG]-- a marker of hepatic blood flow; lorazepam--a substrate marker of hepatic glucuronidation; and antipyrine--a substrate marker for cytochrome P450 activity) in optimizing topotecan doses for patients with liver injury was also evaluated. METHODS: Twenty-one cancer patients, 14 of whom had hepatic injury due to metastatic disease, biliary obstruction, or cirrhosis, were treated with intravenously delivered courses of topotecan consisting of 0.5, 1.0, or 1.5 mg/m2 of drug per day for 5 days. Most patients received more than one course of treatment, with new courses initiated at 3-week intervals. Patient responses (evaluated by tumor measurements) and treatment-induced toxic effects were assessed. Prior to the initiation of topotecan treatment, patients were given intravenous injections of ICG, lorazepam, and antipyrine to determine the plasma pharmacokinetics of these compounds. The pharmacokinetics of topotecan (both the lactone and the carboxylate forms) were determined by analysis of plasma and urine samples collected on the first day of the first course of drug treatment. Scatter plots of area under the plasma concentration versus time curves in relation to percent decreases in either absolute neutrophil count or platelet count were used to explore the pharmacodynamics of topotecan. The Student's t test and the Mann-Whitney U test were used to compare pharmacokinetic parameters between patients with and without abnormal hepatic function. Correlations were assessed using the Spearman's rank correlation coefficient (rs). Reported P values are based on two-tailed tests of significance. RESULTS: Patients with hepatic injury tolerated topotecan doses up to 1.5 mg/m2, i.e., the MTD of this drug established in previous studies. The nature and severity of treatment-induced toxic effects and the pharmacokinetics of topotecan were similar in patients with and without liver injury. No differences were observed in the urinary excretion of topotecan between the two patient groups. Clearances of total topotecan and its lactone species correlated only with clearance of ICG (rs = .64, P = .004; and rs = .68, P = .0017, respectively). The pharmacodynamic effects of topotecan were not altered by liver dysfunction. CONCLUSIONS AND IMPLICATIONS: Cancer patients with hepatic injury can be treated with topotecan at a starting dose of 1.5 mg/m2, given daily for 5 days and administered every 3 weeks. Topotecan dose modifications do not appear to be required for patients with hepatic dysfunction and normal renal function.

Adult↗
PubMed2001

Central regulation of hepatic function by neuropeptides.

In addition to classical neurotransmitters, such as acetylcholine and noradrenaline, neuropeptides have been recognized as new neurotransmitters and neuromodulators. Neuropeptides are widely distributed in the central nervous system as well as in peripheral nerves, and act as neurotransmitters to regulate various physiological functions. The digestive organs are no exception, and several neuropeptides in the central nervous system are shown to act in specific brain sites and control gastrointestinal functions, such as gastric acid secretion, and gastrointestinal motility, through the autonomic nervous system. Recently, a relationship between central neuropeptides and hepatic function through the autonomic nervous system has been revealed in animal models. Thyrotropin-releasing hormone acts in the medulla, in particular in the left dorsal vagal complex, to induce stimulation of hepatic blood flow and hepatic proliferation, and protect against experimental liver injury through vagal and cholinergic pathways. Corticotropin-releasing factor injected intracisternally elicits inhibition of the hepatic blood flow and exacerbates experimental liver injury through sympathetic and noradrenergic pathways. Neuropeptide Y acts in the left dorsal vagal complex, in particular in regard to the Y1 receptor subtype, to stimulate bile secretion. Other neuropeptides such as beta-endorphin and bombesin in the brain modulate hepatic proliferation and bile secretion. Through the use of neuropeptides, new knowledge of the central and peripheral mechanisms underlying brain regulation of hepatic function will be revealed. Further studies in regard to the physiological relevance of the central action of neuropeptides on specific brain sites should be performed to unravel the underlying pathways that mediate brain-liver interaction.

Central Nervous System↗