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Quantitative analysis of scatter- and attenuation-compensated dynamic single-photon emission tomography for functional hepatic imaging with a receptor-binding radiopharmaceutical.

A new method for quantitative liver study was developed using the tracer technetium-99m diethylene triamine penta-acetic acid-galactosyl human serum albumin (99mTc-GSA), an analog ligand of the asialoglycoprotein receptor, which is a hepatocyte surface receptor specific for galactose-terminated glycoproteins. For quantitative dynamic single-photon emission tomographic (SPET) studies, attenuation compensation using transmission computed tomography (TCT) and the triple energy window (TEW) scatter compensation method were evaluated. As the TCT source, we used an uncollimated multi-tube source with the TEW scatter compensation method. To verify the accuracy of cross-calibrated SPET values as compared with measured radioactivities, we performed SPET of a cylindrical water pool phantom which contains seven hot rods filled with different concentrations of 99mTc activities, simulating the scan conditions in human studies. The results of the phantom studies showed good linearity and accuracy of the SPET values, with R2=0.993 and a regression line of y=0.941x+5.48. From the analysis of a kinetic model based on a one-compartment model, focussing on the initial stage of several minutes after 99mTc-GSA injection and taking the physiological expression presented in a three-compartment analysis into account, we introduced the Rutland equation (Patlak plot) in the 99mTc-GSA study by which the overall and regional effective hepatic blood flow (EHBF) and hepatic blood pool volume were determined. Preliminary clinical evaluations were performed for four normal male subjects (23-35 years of age) and one patient. Forty sequential 30-s dynamic SPET acquisitions were obtained for a period of 20 min following the intravenous injection of 99mTc-GSA with venous blood sampling at 10 min. After scatter compensation, the SPET images were reconstructed with attenuation compensation using an attenuation map obtained from TCT. The average normal value for the total EHBF was 468+/-83 ml/min and that for the hepatic blood pool volume, 777+/-123 ml. Functional images of the distribution of regional values of EHBF (ml/min/voxel) and hepatic blood pool volume (ml/voxel) were also generated corresponding to the original SPET images. The EHBF images showed regional liver function, higher in the right lobe than the left lobe in the normal cases, and the heptic blood pool volume images showed the distribution of intensified high values along major vascular structures. Receptor imaging with 99mTc-GSA using the Rutland method and dynamic SPET with scatter and attenuation compensation is an effective technique that allows the evaluation of total and regional hepatic functional parameters (EHBF, hepatic blood pool) in vivo.

Adult↗

Primary functioning hepatic paraganglioma: a case report.

An extra-adrenal pheochromocytoma is known as a paraganglioma. This report describes a patient with a rare primary functioning hepatic paraganglioma that resulted in hypertension. Computed tomography showed a highly vascular lesion located in segment 6 of the liver; it measured 6 x 5.5 cm. A right hemihepatectomy was subsequently performed; this was followed by an uneventful recovery and the disappearance of hypertension. The imaging characteristics and therapeutic principles of this rare tumor were gleaned from a review of the literature. Identification of this malignant tumor or possible recurrence is difficult, so longterm follow-up is recommended.

Adult↗

Hepatic function during prolonged isolated rat liver perfusion using a new miniaturized perfusion circuit.

Previous designs of isolated rat liver perfusion circuits used for toxicological investigations are often expensive, cumbersome, or traumatic in relation to hepatic biocompatibility following extended perfusion times. A new, miniaturized circuit that incorporates a novel design of organ bath, to maintain a buoyant preparation, and a high-efficiency miniaturized membrane tubing oxygenator is described. Livers from male Sprague-Dawley rats were perfused continuously for 6 hr in vitro using rat blood diluted to a perfusate hematocrit of 9.75 +/- 0.35% with Krebs-Henseleit buffer (KHB). Hepatic function was evaluated by measurement of perfusion pressure, flow rate, bile volume production, bile bilirubin content, hepatic oxygen uptake (HOU), bromosulphthalein (BSP) removal, hepatic enzyme activities, and electrolyte concentrations, and finally by histological examination. Perfusion pressure and flow rate remained stable at 8.7 +/- 1.7 mmHg and 1.92 +/- 0.06 mL min-1 g-1 liver, respectively. Bile volume production and HOU were maximal at 784 +/- 84 microL h-1 and 0.99 micromol/L min-1 g-1 respectively. Erythrocyte damage in the perfusate was evaluated by measurement of reduction in perfusate hematocrit from 9.75 +/- 0.35% to 9.27 +/- 0.24%, and increases in plasma free hemoglobin, which rose from 85.8 +/- 12.3 mg% to 650.1 +/- 53.3 mg% over the 6-hr perfusion period studied. Using bile volume production, hepatic oxygen uptake, and the liberation of plasma free hemoglobin as the most sensitive indices of adverse conditions, the new circuit was capable of supporting an isolated perfused rat liver for periods of up to 6 hr under close-to-physiological conditions.

Animals↗

[Further comments on changes in hepatic function after interposition meso-caval shunt (author's transl)].

Further to a previous paper, the Authors followed up ten cirrhotic patients who had all undergone meso-caval shunt with Dacron prosthesis, for ascites or haemorrhage, Functional and anzymatic investigations were carried on over periods up to 10 months. No constant changes in hepatic function parameters were found during the post-operative period, compared to those before surgery. This observation suggests that these investigations might be more useful in defining liver disease than in practical assessment of transient, post-operative liver failure.

Adult↗

Assessment of hepatic functional reserve in cirrhotic patients by computed tomography of the caudate lobe.

In order to investigate whether the size of the caudate lobe of the cirrhotic liver is related to the hepatic functional reserve, the morphometric analysis of the caudate lobe was preformed retrospectively using computed tomography in 106 consecutive patients of whom 67 had compensated (group 1), and 39 uncompensated (group 2) liver cirrhosis. In 51 patients, hepatic measurements were repeated in follow-up. Age- and gender-matched controls were studied. The size of the caudate lobe and the ratio of the caudate to right lobe were correlated with liver function. The caudate lobe was larger in the study patients than in the controls, and larger in group 1 than in group 2 (P<0.01). The caudate to right lobe ratios were also greater in the study patients especially in group 1 (P<0.01). In follow-up, the regression coefficient for the caudate to right lobe ratio was positive in group 1 and negative in group 2 (P<0.05). Even though the caudate lobe of patients with uncompensated liver cirrhosis was larger than that of the controls, patients with compensated liver cirrhosis had a larger caudate lobe and higher caudate to right lobe ratio compared to the patients with uncompensated liver cirrhosis. The caudate lobe may have played an important role in maintaining proper liver function in these patients.

Chronic Disease↗

Morphological regeneration and hepatic functional mass after right hemihepatectomy.

BACKGROUND/AIMS: Liver has a remarkable ability to regenerate after major resection. However, little is known about the process of morphological regeneration and hepatic functional recovery in human. METHODS: Sixteen donors who underwent right hemihepatectomy were enrolled in this prospective clinical study. The preoperative liver volume and remnant liver volume on postoperative days 5, 12 and 28 were calculated from serial transverse computed tomography images. Liver function was evaluated by measuring the intrinsic clearance of antipyrine before and on postoperative days 5 and 12 days, as well as the biochemical and coagulation assay. RESULTS: A smaller residual liver tended to regenerate faster in 28 days. Operative factors, including intraoperative blood loss, inflow occlusion time, liver transection time and duration of operation were not significantly correlated with postoperative liver regeneration. The intrinsic clearances of antipyrine on postoperative days 5 and 12 days were significantly reduced compared to the respective values before the operation (p < 0.001 and p < 0.05, respectively). On the contrary, the intrinsic clearance values per unit liver volume significantly increased on postoperative 12 days (p < 0.05). CONCLUSION: The microsomal function of individual hepatocytes may be upregulated after right liver resection perhaps in order to compensate for the reduced functional mass of the liver.

Adolescent↗

Absence of correlation between hepatic function and characteristics of migrating motor complexes in the gastrointestinal tract.

BACKGROUND: Cyclic changes in gallbladder filling and emptying during the migrating motor complex (MMC) cycle have been demonstrated by scintigraphy. However, a possible cyclic change in the hepatic function and handling of the pharmacologic agents used for scintigraphy during the MMC cycle could have an influence on these results. The aim of the present study was to investigate the hepatic handling of cholic acid and mebrofenin in relation to the MMCs of the gastrointestinal tract. METHODS: The plasma disappearance rate of 14C-cholic acid and the hepatic uptake and excretion of 99mTc-mebrofenin were examined during phase I and phase II of the MMC in six healthy male volunteers. RESULTS: The plasma disappearance rate of 14C-cholic acid showed a biexponential course with an initial rapid and late slow phase after a bolus injection. There were no significant differences between the initial or late plasma disappearance rate of 14C-cholic acid during phase I as compared with phase II. The results of the time-activity curves from the 99mTc-mebrofenin scintigraphy showed an exponential rapid increase in radioactivity followed by an almost linear slow decrease after a bolus injection. There was no significant difference between phase I and phase II in any of the variables studied. CONCLUSION: The lack of a relationship between hepatic handling of cholic acid and mebrofenin and MMC excludes this as a possible source of error in the investigations of the dynamic function of the enterohepatic circulation and especially gallbladder motility by the use of either cholic acids or iminodiacetic acid derivatives as investigative agents.

Adult↗

Portohepatic pressures, hepatic function, and blood gases in the combination of nitroglycerin and vasopressin: search for additive effects in cirrhotic portal hypertension.

We studied the effects of the combination of nitroglycerin and vasopressin on portohepatic hemodynamics, hepatic function, and blood gases in nine patients with cirrhosis and portal hypertension. Vasopressin infusion at a dose of 0.4 U/min caused a significant fall in portal pressure, which is evaluated by portal venous pressure gradient (-34%, p less than 0.01), associated with a decrease in hepatic perfusion (-33%, p less than 0.01) and intrinsic clearance (-20%, p less than 0.01) after 30 min. The arterial oxygenation, however, was not modified (paO2; from 73 +/- 8 to 72 +/- 7 mm Hg, NS). Nitroglycerin infusion at a dose of 100 micrograms/min was then administered for 20 min. The addition of nitroglycerin produced a further reduction in free portal venous pressure (-12%, p less than 0.01), but this was not associated with a significant improvement in both hepatic perfusion (+16%, NS) and intrinsic clearance (-7%, NS). In addition, there was a significant fall in arterial oxygenation (paO2; from 72 +/- 7 to 59 +/- 5 mm Hg, p less than 0.01). We conclude that the addition of nitroglycerin to vasopressin has a beneficial effect on free portal venous pressure, but does not have hepatic benefit. Moreover, sufficient care must be taken, when treating portal hypertension with this combination, to avoid arterial hypoxemia.

Aged↗

Hepatocyte volume as an indicator of hepatic functional reserve in cirrhotic patients with liver tumours.

Using computed tomography (CT), measurements of whole liver volume have been used for the assessment of pre-operative functional reserve in cirrhotics. However, measurements of hepatocyte volume, which exclude stromal fibrous tissue, are considered to more directly reflect hepatic functional reserve. We investigated the relationship between total hepatocyte volume and each of the parameters of conventional liver function. Indocyanine green (ICG) tests and blood analyses for the assessment of liver function were performed prior to surgery in cirrhotic patients with liver tumours. Pre-operative liver volume was determined by integrating images of each liver area obtained by CT. Liver area was measured by an image processing program that traced the profile of the liver image while excluding the tumorous area. Sections of normal tissue stained by the haematoxylin-eosin method, were obtained from the resected liver. Using these sections, a hepatocyte area: whole tissue area ratio was calculated using the image processing program, by tracing the profiles of the hepatocyte nodules. The total volume of hepatocytes was then calculated by multiplying the liver volume by this ratio. The hepatocyte volume per unit bodyweight was significantly correlated with ICG tests and with many other parameters of normal liver function. However, the liver volume per unit bodyweight was correlated only with the plasma ICG disappearance rate and with the blood platelet count. These observations suggest that the functional reserve of the cirrhotic liver is assessed more precisely by hepatocyte volume than by liver volume.

Adult↗

Functioning hepatic cell mass and the hyperdynamic state in cirrhosis.

Seventeen patients with advanced hepatic cirrhosis underwent cardiopulmonary assessment by means of Swan-Ganz catheters combined with indocyanine green clearance studies to measure functioning hepatic cell mass. The indocyanine green clearance test was found to have a statistically significant linear correlation with such indicators of the hyperdynamic circulatory state as cardiac index and total peripheral resistance. Results from these studies also showed that the hyperdynamic state in cirrhosis is associated with limited oxygen consumption as compared with a control series of patients. Of the 14 patients who required operations, eight survived and six died. The mean indocyanine green clearance was a statistically significant predictor of death.

Adult↗

Hormone replacement therapy may improve hepatic function in women with Turner's syndrome.

OBJECTIVE: Women with Turner's syndrome (TS) have recently been shown to be at an increased risk of developing chronic liver disease. There has been some concern that oestrogen replacement therapy may exacerbate hepatic dysfunction. The aim of this study was to assess hepatic function in women with TS and to determine the effect of oral oestradiol valerate on liver enzymes. DESIGN AND PATIENTS: A retrospective review of liver enzymes of 80 women with TS, followed by a prospective study looking at serum liver enzyme concentrations in 20 women with TS following 3 months on and off hormone replacement therapy (HRT) (oestradiol valerate, 2 mg/levonorgestril 75 microg). MEASUREMENTS: Liver enzymes (gamma glutamyl transferase, aspartate transaminase and alkaline phosphatase), albumin and bilirubin were measured on and off HRT. Viral hepatitis serology and liver autoantibodies were tested in patients with abnormal liver function. RESULTS: Thirty-five out of 80 women (44%) had elevated serum liver enzyme concentrations. Two women (2.5%) had a mildly raised serum bilirubin, but protein synthesis was normal in all subjects. HRT resulted in a significant fall in all liver enzymes (P < 0.05) but did not affect serum protein concentrations CONCLUSIONS: Women with Turner's syndrome often have elevated liver enzymes. Oestrogen/progestagen therapy using oestradiol valerate improves liver function in this group of patients. The mechanisms behind this are unclear.

Adolescent↗

Effects of alcohol and fluvastatin on lipid metabolism and hepatic function.

OBJECTIVE: To determine the effects of fluvastatin, a synthetic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, combined with moderate alcohol consumption on lipid profiles and hepatic function in patients with primary hypercholesterolemia. DESIGN: Randomized, placebo-controlled, crossover study. SETTING: Lipid clinic of a university hospital. PATIENTS: 31 patients with primary hypercholesterolemia (low-density lipoprotein cholesterol levels > or = 4.2 mmol/L) who had previously received a lipid-lowering diet. INTERVENTIONS: After a dietary baseline period, 26 patients were randomly assigned to receive 6 weeks of treatment with either 1) fluvastatin, 40 mg/d, added to 20 g of ethanol and diluted to 20% with orange juice or 2) fluvastatin added to orange juice alone. After a 6-week washout period, the two groups crossed over. MAIN OUTCOME MEASURES: Plasma fluvastatin levels, lipid levels, and clinical variables were determined at the end of each treatment period. RESULTS: Six patients left the study prematurely. The remaining patients (15 men, 5 women; mean age +/- SD 49.1 +/- 14.5 years; mean body mass index +/- SD 24.5 +/- 2.2 kg/m2) completed the study. Fluvastatin, alone and combined with alcohol, resulted in similar decreases in levels of total cholesterol (22% and 23%, respectively; P < 0.001 when compared with baseline), low-density lipoprotein cholesterol (28% and 29%, respectively; P < 0.001 compared with baseline), and apolipoprotein B (17% and 20%, respectively; P < 0.001 compared with baseline). High-density lipoprotein cholesterol and triglyceride levels were not changed. Fluvastatin with alcohol resulted in a significantly greater area under the plasma concentration curve (23.4 +/- 4.7 compared with 18.2 +/- 3.2 x 10(3) ng.min/mL) and in a greater time to maximum concentration (187.5 +/- 16.6 min compared with 130.9 +/- 7.0 min) than fluvastatin alone. Terminal half-life tended to increase. No important adverse clinical effects were observed. CONCLUSION: Six weeks of daily, moderate alcohol consumption influenced the metabolism of fluvastatin but did not interfere with its lipid-lowering efficacy and had no adverse effects.

Adult↗

Fatty liver and hepatic function for residents with markedly high serum PCDD/Fs levels in Taiwan.

This study was designed to examine the associations between serum polychtorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) levels and adverse hepatic-related health outcomes. Residents living in the vicinity of a closed pentachlorophenol (PCP) manufacturing factory (exposure area) and other areas nearby (control area) were identified from prior investigation of serum PCDD/Fs measurements. A total of 85 subjects were recruited for the study, 52 from exposure area and 33 from control, respectively. Average level of serum PCDD/Fs was 80.1 6 50.9 pg WHO-TEQ/g lipid for those residing in exposure area, and 25.5 6 18.2 in control area. Statistically higher odds ratio (ORs) for fatty liver and gamma-glutamyltransferase (GGT) activity was found in subjects with higher serum PCDD/Fs levels and high body mass index (BMI) as compared to those with lower PCDD/Fs levels and less BMI. Data suggest that dioxin exposure and high lipid content affect the prevalence of fatty liver in exposed subjects. Future study should be directed to prevent continuous exposure to environmental PCDD/Fs from the defunct PCP factory, and to characterize prospectively, with a larger study sample size, the potential long-term consequences on hepatic function associated with contaminant exposure.

Adult↗

Proton magnetic resonance spectroscopy (1H-MRS) findings for the brain in patients with liver cirrhosis reflect the hepatic functional reserve.

OBJECTIVE: Proton magnetic resonance spectroscopy (1H-MRS) has been used to assess the metabolic changes in the brain in patients with liver cirrhosis. Decreased myo-inositol and increased glutamine levels were noted to be the most sensitive spectroscopic markers for cirrhotic patients with hepatic encephalopathy (HE). The purpose of this study was to assess how the abnormalities seen on the 1H-MRS of the brain in patients with liver cirrhosis are related to clinical and laboratory parameters. METHODS: In a prospective study, localized 1H-MRS was performed in the basal ganglia and parietal white matter regions in liver cirrhosis patients with (n = 48) and without (n = 52) HE and chronic hepatitis (CH) (n = 15), and in normal controls (n = 20). RESULTS: Among cirrhotic patients, the myo-inositol levels were significantly lower (p < 0.01) and the glutamine levels were higher (p < 0.05) for patients with HE than for those without HE. The myo-inositol and glutamine levels, respectively, were inversely (r = -0.50; p < 0.001) and linearly (r = 0.50; p < 0.001) related to the Child-Pugh score. However, by subgroup analysis of Child-Pugh class C patients, there were no significant differences in the myo-inositol and glutamine levels between cirrhotic patients with (n = 40) and without HE (n = 24). A follow-up study of eight cirrhotic patients with HE showed no significant differences in the myo-inositol and glutamine levels after clinical improvement of HE. CONCLUSIONS: The abnormalities seen on the 1H-MRS of the brain of patients with liver cirrhosis are not likely to reflect the severity of HE or acute alteration in the level of consciousness. Rather, we believe they represent the chronic metabolic derangement of the brain associated with hepatic functional reserve.

Adult↗

Influence of hepatic function on serum levels of prostate specific antigen.

PURPOSE: Recent studies have suggested that the primary site of metabolism for prostate specific antigen (PSA) is the liver. We evaluated men undergoing liver transplantation to determine whether chronic hepatic insufficiency affected serum PSA levels and whether improved hepatic function altered serum PSA levels. MATERIALS AND METHODS: Ten men with a mean age of 46 years (range 23 to 67) undergoing liver transplantation were evaluated. Liver function tests, including serum bilirubin, serum glutamic-oxaloacetic transaminase and serum glutamic pyruvic transaminase, as well as serum PSA were determined 1 day before and a mean of 12.6 months (range 4 to 18) after transplantation. RESULTS: Serum bilirubin and serum glutamic-oxaloacetic transaminase declined significantly after liver transplantation. There was no difference in mean serum PSA levels before and after liver transplantation. CONCLUSIONS: Our results suggest that severe hepatic dysfunction does not significantly alter the serum concentration of PSA. These data, combined with recent investigations demonstrating an intrahepatic mechanism for PSA elimination, suggest that the liver has a significant reserve to metabolize the relatively small quantities of PSA in the circulation.

Adult↗

Prostaglandin E1 infusion and functional hepatic flow in control subjects and in patients with cirrhosis.

Metabolic effects of prostaglandin E1 have been previously demonstrated in cirrhosis, apparently independent of changes in large splanchnic vessel hemodynamics. The effects of prostaglandin E1 on functional liver blood flow were tested by measuring the extrarenal clearance of D-sorbitol in six controls and eight patients with cirrhosis during systemic superinfusion of saline or prostaglandin E1 (30 microg/hr), in random order. Doppler ultrasonography of systemic and splanchnic circulation was also performed before the test and at the end of the two study periods. Prostaglandin E1 infusion increased femoral blood flow by nearly 60% in controls and over 30% in cirrhosis, without any effect on mean arterial pressure and heart rate. Mesenteric artery and portal blood flow were unchanged, as were Doppler-measured resistance indices in the liver, spleen and kidney. Sorbitol-assessed functional hepatic flow was 30% lower in cirrhosis, and did not change systematically during prostaglandin E1 infusion. We conclude that prostaglandin E1, at doses able to elicit metabolic effects and changes in systemic hemodynamics, does not affect splanchnic blood flow and/or hepatic microcirculation in normal subjects and in portal-hypertensive patients with cirrhosis.

Aged↗

Donor hepatic function: a factor in postreperfusion syndrome.

Reperfusion of support livers after cold preservation produces hemodynamic instability (i.e., postreperfusion syndrome) in the recipient during both orthotopic liver transplantation and extracorporeal liver perfusion. We evaluated the effect of the normal porcine cold-preserved support liver on healthy recipient hemodynamics and in situ liver function during extracorporeal liver perfusion. Support livers were harvested from Yorkshire pigs and reperfused in an extracorporeal circuit with a healthy, anesthetized recipient pig. Correlation analyses were performed between support liver variables of function (oxygen consumption, bile flow, and biliary phospholipid and cholesterol output) and both recipient hemodynamic stability (heart rate, blood pressure, urine output, and vasopressor use) and hepatic function (bile flow and biliary phospholipid secretion). The data indicate that optimally functioning support livers are associated with improved recipient hemodynamic stability manifested by decreased recipient heart rate and vasopressor use and increased recipient urine output. Support livers exhibiting poor biliary secretory function (i.e., bile flow and phospholipid output) were associated with similarly diminished recipient liver biliary secretory function. These data indicate that the functional condition of the support liver after harvest and cold preservation may influence both recipient hemodynamic parameters and the endogenous function of the recipient liver.

Animals↗

Relation between zinc status and hepatic functional reserve in patients with liver disease.

Patients with liver disease may be at risk of zinc depletion. We measured polymorphonuclear cell, mononuclear cell, plasma, and erythrocyte zinc values, and erythrocyte carbonic anhydrase activity to assess zinc status in 17 patients with non-alcoholic liver disease (primary biliary cirrhosis and chronic active hepatitis) and 13 patients with alcoholic liver disease. The plasma zinc concentration was reduced in both patient groups and correlated strongly with the plasma albumin concentration. The mean polymorphonuclear cell zinc value in both groups was similar to that of controls but when results were combined and grouped according to hepatic functional reserve, patients with more severe liver damage (grade C) had a lower polymorphonuclear cell zinc value (mean (SD) 0.86 (0.24) nmol/mg protein) than patients with grade A (1.44 (0.43) nmol/mg protein, p less than 0.01) or grade B liver damage (1.08 (0.30) nmol/mg protein, p less than 0.05), or control subjects (1.26 (0.28) nmol/mg protein, p less than 0.001). The polymorphonuclear cell zinc value did not correlate with other indices of zinc status. The mononuclear cell zinc value was normal in all patients and was unrelated to hepatic damage. The erythrocyte zinc value and carbonic anhydrase activity were raised in alcoholic patients only. Since the polymorphonuclear cell zinc concentration is low in human experimental zinc deficiency and also correlates with tissue zinc, we suggest that our results provide evidence of progressive leucocyte zinc depletion in patients with liver disease.

Adult↗