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PubMed1989

Risk factors before hepatectomy, hepatic function after hepatectomy and computed tomographic changes as indicators of mortality from hepatic failure.

The mortality rate from hepatic failure after extensive resection should be negligible in the presence of normal results from preoperative liver function tests in patients without pre-existing hepatitis and cirrhosis. Despite conventionally acceptable results from preoperative hepatic function tests in 56 patients undergoing extensive hepatic resection for tumours (47 metastatic, six hepatomas and three adenomas), however, five patients died of hepatic failure. Among the many preoperative and intraoperative risk factors studied, the important factors in the group with hepatic failure were very high levels of serum alkaline phosphatase (p less than 0.05) in the presence of normal levels of bilirubin and large tumor, preoperative administration of chemotherapy, the presence of hepatomas rather than metastatic carcinoma (p = 0.083) and intraoperative blood loss of greater than 5,000 milliliters (p = 0.03). The patients receiving preoperative chemotherapy or those with hepatoma showed a minimal rise of alkaline phosphatase (p less than 0.03) and a minimal regeneration of liver on computed tomographic (CT) scan after hepatic resection. In the group with hepatic failure, a consistent postoperative pattern of increasing bilirubin with normal or subnormal alkaline phosphatase levels corresponded with lack of regeneration of liver on repeated CT scans. Conversely, the pattern of decreasing bilirubin with reciprocal increase in alkaline phosphatase corresponded with hepatic regeneration on CT scan in the group of survivors. Thus, we observe that alkaline phosphatase is a good indicator of hepatic regeneration in the absence of jaundice in patients after hepatectomy. To avoid postoperative hepatic failure, we recommend more discriminant tests than conventional hepatic function tests in patients with large tumors associated with high alkaline phosphatase levels, preoperative chemotherapy and hepatoma even without pre-existing cirrhosis or hepatitis.

Adult↗

PubMed1986

Pharmacokinetics of etoposide in patients with abnormal renal and hepatic function.

Etoposide (VP16) pharmacokinetics was investigated in three groups of cancer patients: a control group of 18 patients with renal and hepatic function tests in the normal range; a group of 8 patients with renal insufficiency; and a group of 15 patients with abnormal hepatic function. In the control group plasma clearance (Clp), volume of distribution (Vd), and elimination half-life (t1/2 beta) of VP16 were, respectively, 22.8 +/- 1.0 (SE) ml/min/m2, 11.4 +/- 0.8 liters/m2, and 5.6 +/- 0.4 h. In patients with renal insufficiency Clp was 12.8 +/- 1.1 ml/min/m2, Vd was 20.8 +/- 4.9 liters/m2, and t1/2 beta was 19.2 +/- 4.7 h. A statistically significant correlation (P = 0.0000001) was found between VP16 Clp and creatinine clearance. In 12 of 15 patients with abnormal liver tests Clp, Vd, and t1/2 beta were, respectively, 27.9 +/- 2.7 ml/min/m2, 12.4 +/- 1.5 liters/m2, and 5.4 +/- 0.6 h and are thus similar to those of the control group. In the other three cases with abnormal liver function VP16 plasma levels were very low. In these cases VP16 t1/2 beta values were similar (5.1, 4.4, and 5.1 h) whereas Clp values (320, 87, and 96 ml/min/m2) and Vd values (142, 33, and 42 liters/m2) were much larger than in controls. These results suggest that VP16 doses should be reduced in patients with renal function impairment but not necessarily in patients with liver impairment. The high VP16 Vd and Clp values found in a subset of patients with liver impairment require further elucidation.

Adult↗

PubMed1983

Hepatic function in previously exposed thorium refinery workers as compared to normal controls from the health and nutrition survey.

The effect of thorium exposure on hepatic function was investigated in 275 former workers of a thorium refinery. Body burden of radioactivity from the decay chain of thorium was measured as 212Bi and 220Rn in the exhaled breath. Asparate aminotransferase, globulin and total bilirubin in sera were found to be associated with body burden of radioactivity at high levels of significance. Thorium-exposed workers were also compared with a population of white males from the Health and Nutrition Survey conducted by the National Center for Health Statistics from 1971 to 1975. The results showed the means of aspartate aminotransferase alkaline phosphatase to be significantly higher (P = 0.0001) in the thorium-exposed workers when corrected for age, alcohol use and weight. The changes observed in liver function may be compatible with a toxic effect of thorium or daughter products on hepatocytes. The correlation of some hepatic function tests with body burden of radioactivity suggests a radiation effect of thorium although a chemical toxic effect cannot be ruled out and further investigation of chemical toxicity of rare earths are indicated.

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↗

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↗

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↗

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↗

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

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↗

PubMedDate not supplied

Predetermining postoperative hepatic function for hepatectomies.

To perform major resections safely in liver cancer operations, we have developed a reliable preoperative method to estimate postoperative liver function. We first conducted a series of studies using dogs to determine the various correlations between the volume of the remaining liver and postresectional hepatic function. We calculated Indocyaningreen (ICG) plasma disappearance and retention rates 15 minutes after intravenous injection of ICG at 0.5 mg/kg and found a 1:1 ratio, thus: ICG(K) postop. = ICG(K) preop. x functional remaining rate. This was applicable in our study of dogs with normal livers; in clinical cases complicated by liver cirrhosis and cancer, however, the functional rate of the remaining liver cannot be calculated only by the volumetric ratio of the whole liver and the remaining part. In clinical cases it must also be calculated by using hepatic vein catheterization and by measuring the ICG extraction rate of each segment of the part to be resected and the part to remain. By using this segmental liver function test, the postoperative hepatic function can be estimated accurately before the operation, thus enabling the surgeon to perform major hepatectomies safely and efficiently.

Animals↗

PubMed1987

Short-term and long-term changes in hepatic function in 60 patients with blunt liver injury.

We treated 60 patients with blunt liver injury over 14 years. According to Makiya's scale of severity, 22 of these lesions (37%) were of Type I, 23 (38%) of Type II, and 15 (25%) of Type III. The overall mortality rate was 23% (14 patients). Changes in hepatic function were studied in these patients. Transaminase levels showed abnormal elevations immediately after the injury but rapidly decreased to normal levels within about 40 days in both the patients who survived the injury and those who died. The alkaline phosphatase activity showed moderate gradual elevations with time, exceeding 20 K.A. units 10 days after the injury in those who died. The total bilirubin level increased to only about 4 mg/dl in those who survived but exceeded 8 mg/dl 10 days after the injury in about 80% of those who died. The total cholesterol level decreased below 100 mg/dl in those who died. In chloric cobalt reaction, the R-value shifted to the left in those who survived but to the right in those who died. Total plasma protein, which decreased to about 6.0 gm/dl immediately after the injury, gradually recovered in those who survived but further declined in those who died. Percentage of gamma-globulin increased but remained below 20% in those who survived but exceeded 20% within 10 days of injury in many of those who died. Hepatic functions 5 years after the injury were generally within the normal range.

Adolescent↗

PubMed1984

Effect of taurine supplementation on hepatic function during short-term parenteral nutrition in the premature infant.

To evaluate the potential role of taurine deficiency in the pathogenesis of parenteral nutrition-induced cholestasis, 20 premature (less than 34 weeks AGA) infants were randomized to receive parenteral nutrition with and without taurine (10.8 mg/kg/day) during the first 10 days of life. Birth weight, gestational age, and protein and caloric intake were similar in both groups. Plasma taurine levels and hepatic function were assessed before the study began (3 +/- 1 days of age), at 5 +/- 1 days of age, and at 9 +/- 1 days of age. Although plasma taurine levels were significantly greater at 5 +/- 1 and 9 +/- 1 days of age (p = 0.009) in the group receiving supplementation, no differential effect on hepatocellular function could be detected during this short period of time. A decrease in plasma ammonia (p = 0.001), alanine aminotransferase (ALT) (p = 0.036), gamma-glutamyltranspeptidase (GGTP) (p = 0.05), 5'-nucleotidase (5'N) (p = 0.001), and bile salt concentrations was noted in both groups, indicating the rapid maturation of hepatic function even in the presence of parenteral nutrition during the first 10 days of life.

Animals↗