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PubMed1978

Hepatic function testing.

The clinical situation determines the choice of hepatic function tests. Alkaline phosphatase (ALP) and aspartate aminotransferase (GOT) tests serve to detect disease, and when used in combination with a gammaglutamyl transferase (GGTP) test, to exclude it. The combination of ALP, GOT, bilirubin, lactate dehydrogenase (LDH), albumin, globulin, and GGTP tests is useful for routine differential diagnosis. Prothrombin time indicates severity of disease. Interpretation is facilitated by attention to ALP or GOT predominance; the relationship of LDH, ALP, and bilirubin; and the ratio of GGTP to ALP. Abnormalities on routine tests frequently do no more than point out the need for more definitive procedures.

Alkaline Phosphatase↗
PubMed1985

Fasting serum bile acid level in cirrhosis. A semi-quantitative index of hepatic function.

We examined the roles of the factors which influence bile acid levels in order to define to what extent fasting serum total bile acid (FSTBA) level might reflect hepatic function and/or anatomy of the portal circulation in patients with cirrhosis. In a first group of 13 patients having mild to moderately advanced cirrhosis we determined the apparent oral clearance (CLo) of chenodeoxycholic acid (764 mumol) and their FSTBA levels. In a second group of 15 similar patients we measured FSTBA levels and by hepatic vein catheterization the intrinsic clearance (CLi) of ICG as well as total hepatic blood flow (Q). We found a significant inverse log-log relationship (r = 0.752, P less than 0.01) between the FSTBA and the CLo on the one hand and significant inverse log-log relationship (r = 0.707, P less than 0.01) between the FSTBA and CLi on the other hand. Q was not found to bear any significant relation to FSTBA (r = 0.120, P greater than 0.1). To conclude, in view of the observed relationship between CLi and CLo vs FSTBA, the latter might serve as a simple non-invasive semiquantitative index of hepatic function and/or anatomy of portal circulation in cirrhosis.

Adult↗
PubMed1983

Electroacupuncture and its effect on rat hepatic functions.

The effect of single, acute (7 pulses/sec., 0.75 volt) and chronic (4 pulses/sec., 0.75 volt) electroacupuncture (EA) treatment on alternate days for a period of 21 days on hepatic functions of rats were studied at cellular and subcellular levels. The points used for EA were Shenshu, Dachangshu and Zusanli. After chronic treatment, (a) protein, RNA, phospholipid, and cholesterol contents of whole liver and liver microsomal fraction increased significantly, (b) liver microsomal G-6-Pase activity increased significantly, (c) microsomal lipid peroxidation value decreased, (d) lipase activity increased. After acute treatment, (e) phospholipid, and cholesterol contents of the whole liver and liver microsomal fraction increased significantly, (f) liver microsomal G-6-Pase activity increased significantly, (g) liver microsomal lipid peroxidation value decreased, (h) GPT and lipase activity of liver increased. The parameters unchanged in acute treatment were as follows: (i) protein, RNA content, (j) GOT activity of the liver, (k) SGOT and SGPT activity, (1) hepatic triglyceride. The parameters unchanged in chronic treatment were as follows: (m) GOT and GPT activity of the liver, (n) SGOT and SGPT activity, (o) hepatic triglyceride. No apparent harmful effect of EA on rat hepatic functions is obvious from present study.

Acupuncture Therapy↗
PubMed1989

Pharmacologic modulation of experimental postischemic hepatic function.

The present study evaluated and compared the effects of SRI 63-441, a potent platelet activating factor antagonist, superoxide dismutase (SOD), an oxygen free radical scavenger, and ibuprofen, a cyclooxygenase inhibitor on hepatic function after 90 minutes of warm ischemia. After warm ischemia, livers were harvested and underwent 90 minutes of warm, oxygenated, sanguinous perfusion on an isolated liver perfusion apparatus. Pretreatment of donor animals with 20 mg/kg intravenous (I.V.) SRI 63-441 5 minutes before induction of total hepatic ischemia resulted in significantly increased bile production, a significant decrease in transaminase release, and a higher tissue adenosine triphosphate (ATP) content when compared with ischemic nontreated controls. SOD resulted in improved bile production and decreased transaminase liberation only when present in the perfusate at the time of in vitro reperfusion. Ibuprofen did not improve postischemic hepatic function in this model. Electron microscopy revealed patchy hepatocellular vacuolization with an intact sinusoidal endothelium in all ischemic livers. However, the degree of damage was less severe in the livers from those rats pretreated with 20 mg/kg SRI 63-441. This study demonstrates that SRI 63-441 pretreatment significantly reduces hepatic warm ischemic injury, and in the present model, appears superior to two other agents that have been advanced in the treatment of ischemic injury. The use of such agents singly or in combinations have important implications as regards gaining a better understanding of the basic mechanisms in organ ischemia, and moreover, for therapeutic applications in organ ischemia and preservation.

Animals↗
PubMed1988

Effect of allopurinol on oxidant stress and hepatic function following ischemia and reperfusion in the rat.

Reactive oxygen species generated by xanthine oxidase during reperfusion of ischemic liver might in part be responsible for ischemic organ injury. Therefore, the effect of allopurinol, an inhibitor of xanthine oxidase, on the oxidant stress associated with reperfusion and on hepatic function 24 h after ischemia was assessed in a model of partial hepatic ischemia in rats. The increase in circulating glutathione disulfide (GSSG) was used as an index of oxidant stress. Hepatic function was assessed using a breath test to quantitative the demethylation of aminopyrine in vivo. In control animals the plasma concentration of GSSG 1 h after onset of reperfusion increased from 0.9 mumol/l in sham-operated controls to 4.2, 5.5, and 8.0 mumol/l following 45, 90 and 120 min of ischemia, respectively. The percent of the administered dose of (dimethylamine-14C)-aminopyrine appearing in breath as 14CO2 was not significantly different from sham-operated controls (40.2%) 24 h after 45 min of ischemia (34.1%), but decreased progressively to 26.0% (p less than 0.05) and 20.6% (p less than 0.05) after 90 and 120 min of ischemia, respectively. Allopurinol, administered at a dose of 50 mg/kg 18 h and 1 h prior to ischemia, did not prevent the rise in plasma GSSG, did not alleviate the release of transaminases, and did not improve the demethylation of aminopyrine 24 h after ischemia, suggesting that reactive oxygen species generated by xanthine oxidase during reperfusion of ischemic liver do not contribute significantly to ischemic injury.

Allopurinol↗
PubMed1998

Exercise-training-induced alterations in hepatic function in mares.

The effects of exercise training on hepatic function in horses were determined by studying the plasma clearance of antipyrine (20 mg/kg iv) in adult mares that either underwent treadmill training for 5 wk (n = 7) or remained in box stalls for the same time period (n = 6). Training consisted of treadmill exercise at 60% (12 min/day) and 90% (3 min/day) of pretraining maximal oxygen consumption (V(O2)max) for 6 days/wk for 5 wk. V(O2)max and velocity to obtain a blood lactate concentration of 4 mmol/l were significantly increased (from 129 to 149 ml x min-1 x kg-1 and from 5.6 to 6.1 m/s, respectively) as a result of training. The plasma clearance and volume of distribution of antipyrine increased significantly in the trained group (from 5.5 to 6.4 ml x min-1 x kg-1 and from 813 to 881 ml/kg, respectively) and decreased significantly in the untrained group. Elimination half-lives did not change as a result of training or box rest. Increases in plasma antipyrine clearance were indicative of an increase in hepatic metabolism of antipyrine. Increases in the volume of distribution of antipyrine suggest that total body water increases as a result of exercise training.

Animals↗
PubMed2003

Pharmacokinetics of E5564, a lipopolysaccharide antagonist, in patients with impaired hepatic function.

E5564 is a structural analog of the Lipid A portion of lipopolysaccharide (LPS). E5564 has been tested in several in vitro and in vivo models and has demonstrated its effectiveness against LPS. It is intended to be an antagonist of LPS to reduce the morbidity and mortality associated with sepsis syndrome. This study assessed the pharmacokinetics (PK) of E5564 in patients with impaired hepatic function. E5564 was administered via intermittent intravenous infusion every 12 hours for six times to 24 hepatic-impaired patients (12 each to Child-Pugh Classifications A and B) and 24 matching healthy volunteers. Plasma samples were analyzed by LC/MS/MS. A one-compartment model resulted in good and comparable fits for all volunteers. Regardless of liver disease state, none of the PK parameters compared (i.e., Cmax (0-12),tmax (0-12),CL,t1/2, Vss, AUC(0-12), AUC(0-last), AUC(0-infinity), C(ss,min), C(ss,max), and C(ss,av)) exhibited any difference between these two groups. This suggested that the exposure of E5564 in volunteers was independent of hepatic function. Thus, no dose adjustment is needed in patients with hepatic impairment classified as Child-Pugh A and B.

Adult↗
PubMedDate not supplied

[Analysis of a complex of biochemical parameters of hepatic functions in opisthorchiasis].

A complex of biochemical parameters of hepatic functions was analyzed in 170 patients with chronic opisthorchiasis and in 90 apparently healthy dwellers from a region wherein opisthorchiasis is endemic. The activity of aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, alpha-amylase, and choline esterase and the serum concentrations of bilirubin, cholesterol, and glucose were studied. A correlation analysis indicated that prolonged Opisthorchis invasion rearranged the system of interactions of the biochemical parameters of the functions of the liver and pancreas. The auxiliary ("local") standards obtained from a study of a group of apparently healthy dwellers from an opisthorchiasis-endemic region may be use to consider the results of individual examinations of patients with chronic opisthorchiasis in order to correct the processes of treatment and rehabilitation.

Adult↗
PubMed1982

The effect of D,L-carnitine supplementation on muscle metabolism, neuropathy, cardiac and hepatic function in hemodialysis patients. A pilot study.

Three patients on regular hemodialysis treatment were perorally supplemented with D.L-carnitine, 900 mg/d, during four weeks. Before treatment, muscle carnitine concentrations were low and the patients showed signs of hypometabolism in skeletal muscle, cardiomyopathy, impaired hepatic function and a moderate hyperlipoproteinemia. After treatment, the skeletal muscle metabolism normalized. The results further indicate improvement of the cardiac and hepatic function and of the neuropathy on the sensory side. No improvement was found, however, in plasma lipoprotein pattern or in variables reflecting plasma lipid transport (lipoprotein lipase activity and intravenous fat tolerance).

Adult↗
PubMedDate not supplied

Hepatic functional reserve in patients with biliary malignancies: an assessment by technetium 99m galactosyl human serum albumin hepatic scintigraphy.

PROBLEM: Technetium 99m galactosyl human serum albumin (99mTc-GSA) is a hepatic scintigraphy agent that binds to the asialoglycoprotein receptors. We evaluated the clinical use of the scintigraphy for the pre-operative assessment of biliary malignancies. PATIENTS AND METHODS: Scintigraphy was performed before operation in 56 patients with biliary malignancies. A hepatic uptake ratio of 99mTc-GSA (LHL15; the count ratio of the liver to the sum of the heart and liver 15 min after injection of 99mTc-GSA) was calculated. RESULTS: LHL15 was significantly associated with bilirubin half-life in patients treated before operation with percutaneous transhepatic biliary drainage (P = 0.007). After operation, 4 of 18 patients with LHL15 < 0.925 died within 30 days. The postoperative mortality was significantly greater in patients with LHL15 < 0.925 than in patients with LHL15 > or = 0.925 (P = 0.033). CONCLUSION: 99mTc-GSA scintigraphy is useful in evaluating the hepatic functional reserve in patients with biliary malignancies.

Adult↗
PubMed1996

Calculation of maximal removal rate of indocyanine green to measure hepatic functional mass in dogs by use of the nine-hour method.

OBJECTIVE: To establish a versatile and reliable procedure for the determination of indocyanine green maximal removal rate (ICG Rmax) to measure hepatic functional mass in dogs within 9 hours (9-hour method). DESIGN: Relation between 9-hour and standard 3-day methods was examined. ANIMALS: 101 healthy dogs. PROCEDURE: On investigation of the optimal technical conditions allowing completion of all procedures in a day, the appropriate IV administered doses of ICG were 0.125, 0.5, and 2.0 mg/kg of body weight, and the best blood sample collection times for obtaining plasma half-life at these 3 doses were before and 3, 6, and 9 minutes after ICG administration. RESULTS: Comparison of the 9-hour with 3-day method yielded a correlation coefficient (r) of 0.84, indicating close (P < 0.01) correlation. In the 9-hour method, mean +/- SD of ICG Rmax in healthy dogs was 0.24 +/- 0.09 mg/kg/min in male (n = 62) and was 0.23 +/- 0.06 mg/kg/min in female (n = 21) Beagles, and was 0.21 +/- 0.10 mg/kg/min in male (n = 11) and 0.20 +/- 0.07 mg/kg/min in female (n = 7) mixed-breed dogs. In Beagles treated orally with carbon tetrachloride (0.1 ml/kg in gelatine capsules) thrice weekly during a 10-week period, plasma alanine transaminase activity plateaued at a high value (> 2,000 IU/L) on day 5, and remained at this value until the end of the study. The ICG Rmax changed accordingly: day 5, 0.17; day 10, 0.11; day 40, 0.05; and day 60, 0.06 mg/kg/min. CONCLUSION: The 9-hour method for determination of ICG Rmax correlates favorably with the 3-day method. CLINICAL RELEVANCE: This procedure may be practically applied in veterinary clinics in terms of prediction of hepatic functional mass, and for diagnosis of hepatotoxicosis induced by certain compounds.

Alanine Transaminase↗
PubMed2006

Sequential evaluation of hepatic functional reserve by 99mTechnetium-galactosyl human serum albumin scintigraphy after proton beam therapy: a report of three cases and a review of the literatures.

The treatment strategy for malignant liver tumors should be appropriately determined because post-treatment quality of life greatly depends on the patients' residual hepatic function. In this report, we present three patients with malignant liver tumors treated by proton beam therapy in whom pre- and post-therapeutic hepatic functional reserves were evaluated sequentially for more than a year by 99mTechnetium-galactosyl human serum albumin (99mTc-GSA) scintigraphy. All three patients exhibited the distinctive time course of 99mTc-GSA uptake efficiency, which suggested a transient decline in the ratio of liver activity to heart and liver activity at 15 minutes (LHL15) 3-6 months after proton beam therapy. This change was not in parallel with that expected from a functioning normal liver tissue volume. In a year after proton beam therapy, LHL15 recovered nearly to the pre-treatment level in all three patients. Our observations may be related to the up-regulation of receptor-mediated 99mTc-GSA uptake during hepatic regeneration after proton beam therapy.

Aged↗
PubMedDate not supplied

Correction of vitamin E deficiency in children with chronic cholestasis. II. Effect on gastrointestinal and hepatic function.

Although secondary vitamin E deficiency causes a reversible neurologic disorder in children with chronic cholestasis, the effect of this deficiency state on other organ systems is unknown. We studied the effects of vitamin E therapy on selected gastrointestinal and hepatic functions in five children with chronic cholestasis and well-documented biochemical and neurologic evidence of vitamin E deficiency. After 2 to 3 years of oral or parenteral vitamin E therapy, there was no improvement in fecal fat losses, severity of vitamin E malabsorption (as measured by an oral vitamin E tolerance test) or total serum fatty acid concentrations. Serial analyses of liver function blood tests demonstrated a marked decline in fasting serum cholylglycine concentrations during 18 to 31 months of vitamin E therapy, while other liver function tests showed no consistent changes. We conclude that vitamin E deficiency does not appear to alter intestinal absorption of fat or vitamin E; however, vitamin E deficiency may further impair already compromised hepatic function during pathologic conditions such as cholestasis.

Child↗
PubMed1990

Ionization and hemodynamic effects of calcium chloride and calcium gluconate in the absence of hepatic function.

Serial serum ionized calcium concentrations were measured before and after administration of either calcium chloride or calcium gluconate during the anhepatic stage of liver transplantation in 15 patients to determine the release of ionized calcium in the absence of hepatic function. When hypocalcemia (Ca++ less than 0.8 mM) occurred during the anhepatic stage, patients were randomly assigned to treatment with chemically equivalent doses of either calcium chloride (10 mg/kg, n = 8) or calcium gluconate (30 mg/kg, n = 7). Serum concentrations of ionized calcium and citrate, hematocrit, arterial blood gas tensions, acid-base state, and hemodynamic profiles were determined before and up to 10 min after calcium therapy. In both groups of patients initial similar and rapid increases in Ca++ (0.98 +/- 0.14 mM in the calcium chloride group and 1.05 +/- 0.10 mM in the calcium gluconate group) were followed by gradual decreases over the next 10 min. Measured hemodynamic values were similar in the two groups, and neither group showed improvement in cardiovascular function after calcium therapy, possibly because of the decrease in preload that occurred during the anhepatic stage. Equally rapid increases in Ca++ after administration of calcium chloride and gluconate in the anhepatic state suggest that calcium gluconate does not require hepatic metabolism for the release of Ca++ and is as effective as calcium chloride in treating ionic hypocalcemia in the absence of hepatic function.

Adult↗
PubMed2006

99mTc-DTPA-galactosyl-human-serum-albumin liver scintigraphy for evaluating hepatic functional reserve before hepatectomy in a patient with indocyanine green excretory defect: report of a case.

A 78-year-old woman with indocyanine green (ICG) excretory defect underwent left hepatectomy for cystadenocarcinoma. The retention rate of ICG at 15 min (ICGR(15)) was high, at 79.3%, despite all other liver function tests showing normal values. Conversely, 99mTc-DTPA-galactosyl-human-serum-albumin (GSA) liver scintigraphy showed a reduced accumulation of GSA in the left lateral lobe, the hepatic uptake ratio of the GSA scintigraphy was 0.96, and the arterial ketone body ratio was 1.67. Based on these results, we judged that the hepatic functional reserve of this patient was adequate for left hepatectomy, which was subsequently performed uneventfully. Histopathological examination of the resected liver showed neither fibrosis nor inflammatory cell infiltration. Thus, we consider that GSA liver scintigraphy is the best diagnostic modality for evaluating hepatic functional reserve in a patient with ICG excretory defect.

Aged↗
PubMed1993

HNF4 and HNF1 as well as a panel of hepatic functions are extinguished and reexpressed in parallel in chromosomally reduced rat hepatoma-human fibroblast hybrids.

Rat hepatoma-human fibroblast hybrids of two independent lineages containing only 8-11 human chromosomes show pleiotropic extinction of thirteen out of fifteen hepatic functions examined. Reexpression of the entire group of functions most often occurs in a block, and except for one discordant subclone, correlates with loss of human chromosome 2. The extinguished cells and their reexpressing derivatives have been examined for the expression of seven liver-enriched transcription factors. C/EBP, LAP, DBP, HNF3, and vHNF1 expression are not systematically extinguished in parallel with the hepatic functions. However, HNF1 and HNF4 show a perfect correlation with phenotype: these factors are expressed only in the cells showing pleiotropic reexpression. Since recent evidence indicates that HNF4 controls HNF1 expression, it can be proposed that the HNF4 gene is the primary target of the pleiotropic extinguisher.

Albumins↗
PubMed1998

Effect of ursodeoxycholic acid therapy on hepatic function in children with intrahepatic cholestatic liver disease.

BACKGROUND: Ursodeoxycholic acid (UDCA) has been shown to improve pruritus, alanine aminotransferase (ALT), and cholesterol levels in children with intrahepatic cholestatic liver disease. However, the effect of UDCA on quantitative tests of hepatic function in children is uncertain. METHODS: A 2.5-year, open label, crossover study, was designed to determine the effect of UDCA (15-20 mg/kg per day for 12 months, off for 6 months, and on again for 12 months) on clinical symptoms, biochemical test results, galactose and caffeine elimination half-lives (t1/2), and quantitative hepatic scintigraphy in 13 subjects aged 13.1 +/- 2.1 years (10 of whom completed the entire study), with intrahepatic cholestasis. RESULTS: Pruritus improved with UDCA in the 6 patients with pruritus on entry into the study. At 12 months, there was a significant decline in ALT, gamma-glutamyl transpeptidase, and plasma levels of copper and manganese, with no further decline in these levels at 24 months. There were no changes in bilirubin or cholylglycine levels. After therapy was discontinued at 12 months, UDCA was restarted within 1 month in 9 of 12 patients in response to a doubling of ALT (n = 6) or worsening pruritus (n = 3). Galactose t1/2 increased after 12 months, with no further increases after 24 months of UDCA therapy, whereas caffeine t1/2 did not change. There were no significant changes in hepatic scintigraphy throughout the study. CONCLUSIONS: These data suggest that although UDCA therapy improves pruritus and results in a reduction in ALT and gamma-glutamyl transpeptidase, UDCA therapy did not improve quantitative measures of hepatic function in children with intrahepatic cholestasis.

Adolescent↗
PubMedDate not supplied

The hippurate ratio as an indicator of functional hepatic reserve for resection of hepatocellular carcinoma in cirrhotic patients.

Predicting the ability of the cirrhotic liver to withstand resection remains a challenge for the surgeon. This study evaluates the use of the hippurate ratio, a novel assessment of glycine conjugation of para-aminobenzoic acid by the liver, as a preoperative indicator of functional hepatic reserve. Between 1998 and 2000, sixty-one cirrhotic patients were prospectively assessed for hepatic resection using the hippurate ratio, indocyanine green retention at 15 minutes (ICG R-15), and other standard measures of liver function. Twenty-six patients were excluded as candidates for resection on the basis of inadequate functional hepatic reserve. Patients excluded from resection had significantly higher ICG R-15 values (29% +/- 9% vs. 16% +/- 12%, P = 0.001), higher Child-Pugh scores (5.9 +/- 0.9 vs. 5.3 +/- 0.4, P = 0.01), and lower hippurate ratios (30% +/- 14% vs. 45% +/- 15%, P = 0.005). There was a significant correlation between the hippurate ratio and ICG R-15. Other indicators of liver function such as factor V, factor VII, albumin, bilirubin, prothrombin time, and transaminases were no different between patients who did and those who did not undergo resection. Of the 35 patients resected, there were seven (20%) who developed varying degrees of liver failure with three perioperative deaths (8.5%). Patients who had some degree of liver failure had significantly lower hippurate ratios than patients who had no liver failure (29% +/- 10% vs. 48% +/- 14%, P = 0.002). There was no difference in ICG R-15 values between patients who had liver failure and those who did not. The hippurate ratio offers information on hepatocellular reserve that is not provided by other measures of liver function and may allow better selection of cirrhotic patients for liver resection.

4-Aminobenzoic Acid↗