Liver In Normal Subjects Research Articles

Acoustic Radiation Force Impulse Elastometry (ARFI Elastometry) of the Liver in Normal Subjects, after Food Intake and Physical Effort

Purpose: the aim of this study was to assess the values of ARFI elastometry in normal subjects and effects of food intake and physical effort.Material and methods.ARFI elastometry measurements were done in 32 patients (20 (62.5%) volunteers and 12 (37.5%) potential liver fragment donors). Mean age of patients was 26.9 ± 5.3 years. The study was performed in fasting condition in right intercostals approach, while the patients were asked to stop normal breathing for a moment lying in supine position with the right hand placed above the head. For 20 volunteers ARFI elastometry was performed at 30 minutes after food intake (about 350 kcal) and at next day immediately after physical effort (20 squats). The study was performed using Siemens Acuson S2000 ultrasound system with a 6C1 transducer.Results.The stiffness of the right liver lobe in 32 healthy subjects was 1.16 ± 0.12 m/s (95% CI 0.92 ± 1.38), the mean liver stiffness values of 20 volunteers in fasting condition were 1,21±0,09 m/s (95% CI 1.06 ± 1.38), 30 minutes after the meal – 1.22 ± 0.12 m/s (95% CI 1.01 ± 1.43) (р > 0.05). Physical effort didn’t make significant influence on the liver stiffness measurements (1.16 ± 0.12 m/s vs 1.20 ± 0.07 m/s, р > 0.05).Conclusion.Liver stiffness value in healthy subjects was 1.16 ± 0.12 m/s (95% CI 0.92 ± 1.38). There was no significant influence of food intake and physical effort on the liver stiffness measurements.

Assessment of myocardial viability in low signal intensity areas on cine MRI comparison with late gadolinium enhancement imaging in patients with prior myocardial infarction

Background Delayed-enhancement magnetic resonance imaging (DEMRI) is highly effective for the diagnosis of myocardial infarction in both the acute and chronic phases, which is characterized as hyperenhancement after gadolinium injection. The use of gadolinium contrast, however, is limited in patients with advanced renal dysfunction and dialysis. On cine MRI, the signal intensity (SI) of noninfarcted area is equal to that of skeletal muscle and liver in normal subjects. It is well known that the SI of infarcted area is not uniform in patients with prior myocardial infarction. The significance of low SI in infarcted area on cine MRI has not been evaluated. The purpose of this study was to assess the myocardial viability of the area with low SI on cine MRI as compared with DEMRI in patients with prior myocardial infarction. Methods Fifty patients with prior myocardial infarction underwent both cine MRI and DE-MRI to assess the myocardial function and viability. The left ventricle was divided into 17 segments, resulted in a total of 850 segments. On cine MRI, the presence of low SI area and wall motion score (WMS) of each segments were assessed. On DE-MRI, the presence of late gadolinium enhancement (LGE) area, the thickness of LGE area and outer non-enhanced area, and the transmural extension of infarction were evaluated. Results The low SI area on cine MRI was documented in 2.1±2.7 segments per patient and 105 of all 850 segments (12.4%). In DE-MRI, the LGE was detected in 6.6±3.7 segments per patient and 329 of all 850 segments (38.7%). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy to predict the myocardial necrosis by the presence of low SI area on cine MRI were 32%, 100%, 100%, 70% and 74%, respectively. Of 329 segments with LGE on DE-MRI, the segments with low SI showed thinner LGE area (3.0±1.0mm versus 3.3±1.3mm, p=0.037), thinner outer non-LGE area (1.1±1.0mm versus 3.3±2.0mm, p<0.001), greater transmural extent (76±14% versus 53±21%, p<0.001), and lower WMS (3.8±10.5 versus 1.5±0.8, p<0.001) than the segment without low SI. Conclusions Although the sensitivity is relatively low, the presence of low SI area on cine MRI is as igh of prior myocardial infarction. The area with low SI has poor viability. Funding None.

Sci-Fri AM(1): Imaging-08: Improved Diffusion Weighted MR Imaging of Liver in Normal Subjects

The aim of this study was to perform reliable measurements of the diffusion (D) and perfusion ( D * ) coefficients and perfusion fraction (f) for normal liver using IVIM model. Six volunteers considered to have normal liver underwent DW imaging at 1.5 Tesla. A respiratory triggered diffusion‐weighted single‐shot echo‐planar MRI sequence was performed. The diffusion gradients were applied in the slice select direction and the b values used in the protocol were: 0, 50, 100, 150, 200, 250, 300, 350, 400, 450, 500, 650 and 800 s / mm 2 . Diffusion decays for all regions of interest (ROIs) were analyzed using a Levenberg‐Marquardt nonlinear least‐squares fit to the IVIM model equation and the parameters D, f, and D * were obtained. Diffusion coefficients and perfusion fraction maps were calculated on a pixel‐by‐pixel basis as well and color overlaid onto the corresponding anatomical images ( b =0 s / mm 2 ). No significant difference in results was observed between the whole‐liver ROIs and the peripherally located 100 pixel ROIs. To within experimental error, all patients had the same values of D ( 1.041±0.105 mm 2 / s ), D * ( 54.97±14.92 mm 2 / s ), and f (43.11±4.06 %). This shows that there are no gradual variations across the liver, as long as areas that contain large blood vessels are excluded. By increasing both the number and the range of b‐values used in the protocol we were able to get more consistent results than previously reported in the literature. Correct values for D, D * and f for normal liver are critically necessary when evaluating any distribution of patients, normal or abnormal.

Mast cell subpopulations in chronic inflammatory hepatobiliary diseases.

In various hepatobiliary diseases mast cells have been found to be associated with fibrogenesis. However, mast cell subpopulations have not been investigated in the human liver in normal subjects or in disease. Human mast cells are categorized into mast cells positive for tryptase (MC(T)) only and mast cells positive for both tryptase and chymase (MC(TC)). In this study we investigated mast cell subpopulations (MC(T) and MC(TC)) by double immunostaining for mast cell tryptase and chymase as well as by a computer-aided quantitative morphometry in 13 normal livers and in 193 liver tissue specimens comprising of primary biliary cirrhosis (n=43), autoimmune hepatitis (n=11), chronic hepatitis B (n=37), chronic hepatitis C (n=41), alcoholic liver disease (n=40) and hepatolithiasis (n=21). The densities of MC(T) and MC(TC) per 1 mm2 stroma were low in normal livers but high in chronic liver diseases, and correlated positively with the degree of fibrosis. The percentages of MC(T) and MC(TC) subpopulations were 25% and 75%, respectively. The percentage was almost the same in normal livers and various hepatobliliary diseases, as well as between less fibrotic cases and more fibrotic cases in liver diseases. These results suggest that MC(T) and MC(TC) subpopulations in healthy and diseased livers do not change during liver fibrosis of any etiology.

Difference in global hepatic enhancement assessed by dynamic CT in normal subjects and patients with hepatic metastases.

Our goal was to determine if there are differences in liver densitometry parameters using helical CT between normal subjects and subjects with liver metastases. One-hundred fifty subjects (64 with normal livers and 86 with CT-visible hepatic metastases) underwent dual phase helical scanning of the liver. Images were obtained in the "arterial" (early) and "venous" (late) phases of hepatic enhancement. Densitometry measurements were obtained from the liver (distinct from obvious lesions or vessels) and aorta at 25, 40, 75, and 90 s. Enhancement values at the same time points were calculated in 73 subjects in whom noncontrast images of the liver were available. A peak liver densitometry value was also determined. Several ratios were determined for each time point: the liver/aortic ratio (L/A), liver/liver peak ratio (L/P), liver enhancement/aortic enhancement ratio (LE/AE), and liver enhancement/liver peak enhancement ratio (LE/LPE). The degree of tumor burden in the hepatic metastatic group was assessed in each case. Values for L/A, L/P, LE/AE, and LE/LPE at 25 and 40 s were significantly (p < 0.05) higher in the liver metastases group than the normal liver group. Enhancement ratios were even more elevated in breast cancer, which can have hypervascular metastases. These CT parameters did not show significant differences when analyzed according to the degree of hepatic metastatic tumor burden. All densitometry parameters and ratios obtained at 75 and 90 s were not significantly different between the two groups. In the early phase of bolus intravenous contrast agent administration, the visually normal portion of the liver parenchyma in patients with hepatic metastases enhances to a greater degree than the liver in normal subjects. This may reflect generalized increased hepatic arterial flow in tumor-bearing livers and has the potential to increase the sensitivity of CT for detection of hepatic metastases.

Role of the Splanchnic Tissues in the Pathogenesis of Altered Carbohydrate Metabolism in Patients with Chronic Renal Failure

To evaluate the contribution of the splanchnic area to the carbohydrate abnormalities associated with chronic uremia, the splanchnic exchange of glucose and gluconeogenic substrates was quantitated basally and after an iv glucose load in nine uremic patients with impaired glucose tolerance and seven control subjects. In the basal state, blood glucose and splanchnic glucose production were similar in the two groups. During glucose infusion (33 mumol/kg.min for 90 min), blood glucose reached significantly higher levels in the uremic patients than in controls (P less than 0.02). Plasma insulin increased slightly more in uremic patients than in controls (P less than 0.05 at 15 min). Both basal and postglucose glucagon levels were 2- to 3-fold higher in uremic patients than in normal subjects (P less than 0.05-0.02). In both groups, splanchnic glucose balance switched from net output in the basal state (-9.4 +/- 0.5 and -8.0 +/- 1.1 mumol/kg.min in normals and uremics, respectively) to net uptake with glucose infusion. However, this response was less marked in the uremic patients than in normal subjects (P less than 0.05-0.02 at 30 and 90 min). The cumulative net splanchnic glucose balance over the 90-min study period was 538 +/- 55 mumol/kg in normal subjects and 279 +/- 89 in uremic subjects (P less than 0.05). A net splanchnic lactate uptake was present in the basal state in normal (4.2 +/- 0.5 mumol/kg.min) and uremic subjects (3.4 +/- 0.5). During glucose infusion, in normal subjects splanchnic lactate exchange switched to a net output (-4.0 +/- 1.6 mumol/kg.min), whereas in the uremic group it remained as a net uptake (1.1 +/- 0.7) throughout the study period. Splanchnic gluconeogenic amino acid uptake was similar in the two groups in the basal state (1.8 +/- 0.1 mumol/kg.min and 2.2 +/- 0.2 in normal and uremic subjects, respectively). Glucose infusion caused a marked fall in amino acid uptake by liver in normal subjects, whereas no change was observed in the uremic group (0.9 +/- 0.3 and 1.9 +/- 0.2 mumol/kg.min, respectively). Splanchnic glycerol uptake was not different in the two groups in the basal state (0.75 +/- 0.2 and 1.1 +/- 0.2 mumol/kg.min) and decreased to a similar extent during glucose infusion. We conclude the following. 1) In uremic patients with glucose intolerance but normal fasting glycemia, the splanchnic metabolism of glucose and gluconeogenic substrates is normal in the postabsorptive state.(ABSTRACT TRUNCATED AT 400 WORDS)

Pharmacokinetics of Benzodiazepine Antagonist Ro 15-1788 in Cirrhotic Patients With Moderate or Severe Liver Dysfunction

Ro 15-1788, a benzodiazepine antagonist, has been advocated as a new treatment for hepatic encephalopathy. This drug is extensively metabolized by the liver in normal subjects. In the present study, we examined Ro 15-1788 disposition in eight healthy controls (Group I), eight cirrhotic patients with moderately impaired liver function (Pugh score less than 10, Group II) and eight patients with severe liver dysfunction (Pugh score greater than 10, Group III). The subjects of each group were age and sex matched. After an intravenous infusion of 2 mg Ro 15-1788 over 5 min, blood samples were taken at fixed intervals up to 7 hr after the infusion. Plasma levels of the drug were determined by capillary gas chromatography. In controls, Ro 15-1788 had a high plasma clearance [16.3 +/- 2.6 ml per min per kg (mean +/- S.D.)], a short half-life (45.7 +/- 8.5 min), a large volume of distribution (0.62 +/- 0.09 liter per kg) and a low plasma protein binding (45 +/- 6%). Plasma clearance was reduced markedly in both groups of cirrhotic patients (-57 and -74%, respectively); the volume of distribution was unchanged in Group II and moderately increased in Group III (+37%). The elimination half-life was markedly prolonged in Groups II and III (+66 and +210%, respectively). Plasma clearance and Pugh score were highly correlated in cirrhotic patients (r = 0.830, p less than 0.001). The plasma protein binding of Ro 15-1788 was lower in cirrhotics, resulting in a significant increase in the free fraction of the drug (+16% in Group II; +44% in Group III).(ABSTRACT TRUNCATED AT 250 WORDS)

Noninvasive assessment in vivo of hepatic drug metabolism in health and disease.

Despite the availability of techniques and concepts for examining the physiologic processes of drug disposition and clearance by the liver in normal subjects and in patients with liver disease, important questions remain in this field. Major problems include high inducibility of hepatic drug-metabolizing enzymes, even in patients with liver disease (normal drug clearances can occur in liver disease patients who chronically ingest drugs that induce these enzymes); poor correlation between routine liver function tests, such as SGOT, SGPT, alkaline phosphatase, and bilirubin, and alterations of hepatic drug metabolism in hepatocellular disease; failure of all drugs to be similarly affected in liver disease, even for drugs with similar metabolic pathways. Nevertheless, certain test drugs, such as antipyrine and aminopyrine, whose clearances from plasma or saliva closely reflect their hepatic metabolism, may serve as probes to explore under normal and disease conditions how drugs are handled in the liver. Nevertheless, limitations in the use of antipyrine and aminopyrine metabolism as tests of hepatic function must be recognized: special conditions of patients may render results of these tests by themselves impossible to interpret. Utilizing additional drug substrates and measuring rates of formation of individual metabolites, as well as disappearance of parent drug, investigators may be able to research more effectively and in greater detail for interrelationships between liver disease and the processes of hepatic drug metabolism, hepatic blood flow, and even other, as yet unidentified, processes that influence liver and drugs interactions.

Pulmonary hypertension complicating portal hypertension.

We report 9 patients with pulmonary hypertension complicating portal hypertension. The cause of portal hypertension was cirrhosis in 7 patients, nodular regenerative hyperplasia of the liver in 1, and portal vein obstruction in 1. Six patients had been treated by portal-systemic shunting before the clinical onset of pulmonary hypertension. The interval between the first manifestation of portal hypertension and the recognition of pulmonary hypertension ranged from 2 to 15 years. Histologic examination in 1 of these patients revealed medial hypertrophy, concentric intimal proliferation, and plexiform lesions affecting the small pulmonary arteries. Pulmonary hypertension might result from the effect of a vasoconstrictive agent on the small pulmonary arteries or of a substance toxic to the walls of these vessels that is produced in the splanchnic territory, destroyed by the liver in normal subjects, and reaches the pulmonary arteries through portal-systemic shunts in these patients.

Determination of human liver cytochrome P-450 level by electron paramagnetic resonance of liver biopsies

Human liver cytochrome P-450 level has been determined by direct electron paramagnetic resonance spectroscopy at 77° K of liver specimens obtained by surgical biopsy. A preliminary experiment with rat livers was performed in order to calibrate the intensity of the cytochrome P-450 EPR signal as a function of the cytochrome concentration obtained by the classical spectrophotometric method. 44 subjects have been examined. We found a cytochrome P-450 value of 21.5 ± 11.2 nmoles per gram of liver in normal subjects. Variations of this level in some pathological liver states are discussed.

STUDIES ON GLUCOSE AND POTASSIUM METABOLISM OF LIVER

Studing on the relationship between Glucose (G) and potassium (K) metabolism of liver in normal subjects, hepatitis and cirrhosis etc., following results were obtained.1) In cases with liver disease, fasting arterial plasma potassium level (PKA) was somewhat lower than in normal subjects.2) In fasting state, hepatic mobilization of G and K was admitted in control subjects, but in hepatitis and cirrhosis, to less degree. Significant correlation was observed between the amount of G mobilized from liver and that of K.3) After intravenous injection of glucose (0.5gm per Kg), hepatic uptake of G and K occured, resulting in arterial blood sugar (GA) fall and PKA decrease in normal subjects, but the effect was lesser in hepatitis and cirrhosis. The rate of GA fall was significantly correlated with the decrease of PKA. Furthermore GA fall and PKA decrease seemed to be proportional with the grade of hepatic G and K uptake respectively.4) After intravenous injection of insulin (0.1unit per Kg), hepatic uptake of K and reduction of hepatic G mobilization occured, resulting in the decrease of GA and PKA in normal subjects, but the effect was lesser in hepatitis and cirrhosis. Significant correlation was observed between the decrease of GA and that of PKA. Furthermore the decrease of GA and PKA seemed to be proportional with the grade of reduction of hepatic G mobilization and the grade of hepatic K uptake respectively.5) Subcutaneous injection of adrenaline (0.01mg per kg) in normal subjects, caused GA increase and PKA decrease simultaneously, but had a lesser effect in cirrhosis. There was no close relationship between GA increase and PKA decrease, and for PKA decrease, apparent hepatic uptake of K was not observed. Intravenous rapid injection of adrenaline (0.02gm) to normal dogs, caused hepatic mobilization of G and K, resulting in the increase of GA and PKA, but had a lesser effect in dogs injured with CCl4. The increase of GA was significantly correlated with the increase of PKA. Furthermore the increase of GA and PKA seemed to be proportional with the grade of hepatic mobilization of G and K respectively. The change of K always preceded that of G.6) After the oral administration of KCl (5gm), slight increase of GA was observed in normal subjects, and the effect was quite similar in hepatitis and cirrhosis. After intravenous injection of KCl (20mg per kg as K), hepatic mobilization of G and K occured, resulting in the increase of GA. There was no close relationship between the increase of GA and the change of PKA, but the increase of GA seemed to be proportional with the grade of G mobilization from liver. The effect was lesser in dogs injured with CCl4, but the rate of K disappearance from arterial blood was not altered.7) In two cases with familial periodic paralysis, striking abnormality in G and K metabolism was observed. In them, the uptake of G and K after intravenous injection of glucose or insulin was more apparent in peripheral tissues than liver.