摘要:

AbstractThe role of vitamin D in hepatic osteodystrophy was examined. Eleven unselected patients with primary biliary cirrhosis (PBC) were assessed for disorders of mineral and vitamin D metabolism. Six were not receiving supplementary vitamin D, and five were being treated with oral vitamin D (50,000 IU daily). Serum levels of 25‐hydroxyvitamin D were normal in all patients receiving oral therapy and in 4 of 6 untreated patients. Levels of serum 1,25‐dihydroxy vitamin D and 24,25‐dihydroxyvitamin D were normal or near normal in all patients. Studies were repeated after 6 months of therapy with parenteral vitamin D2(100,000 IU i.m. monthly) in 7 patients. Initial bone histomorphometry revealed no evidence of osteomalacia or osteoporosis. However, the bone resorption surface of trabecular bone was increased. This abnormality was no longer present on repeat bone biopsies obtained after parenteral vitamin D therapy, and bone formation had decreased. In addition, trabecular bone volume remained normal in the face of the lower rate of bone formation. Increased bone resorption surface in the absence of osteoporosis or osteomalacia has not been previously described in PBC. Improvement in this bone parameter, associated with the finding of a decrease in the formation of bone and in hydroxyproline excretion in urine after parenteral vitamin D, suggests that increased turnover may be an early feature of the bone disease which complicates PBC and that parenteral vitamin D may retard the rate at which hepatic osteodystrophy develops in chronic cholestatic liver di

ISSN:0270-9139    

DOI:10.1002/hep.1840040101

出版商:W.B. Saunders    

年代:1984

数据来源: WILEY

摘要:

AbstractTotal complement activity was normal in 18 patients with primary biliary cirrhosis using two hemolytic assays capable of distinguishing between defects in classical and alternative pathways. Activation of the classical pathway was demonstrated in all patients by formation of complexes between C1r, C1s, and C1 inactivator. Large amounts of free C1q, not in complex with C1r and C1s, were demonstrated in the majority of patient sera. Furthermore, C4 levels were within the normal range or slightly subnormal. No evidence for alternative pathway activation was found. Increased mean levels of several complement components, in particular C1 inactivator, C2, C3, factor B, factor H, were noted. A significant correlation between these complement factors, derived mainly from the liver, and ceruloplasmin suggests that this elevation might be secondary to cholestasis. In contrast, no significant correlations with levels of early reacting acute phase reactants, immunoglobulins, or circulating immune complex‐like material were observed. It is concluded that activation of the complement system by the classical pathway is common in patients with primary biliary cirrhosi

ISSN:0270-9139    

DOI:10.1002/hep.1840040102

出版商:W.B. Saunders    

年代:1984

数据来源: WILEY

摘要:

AbstractTwo immunosuppressive serum factors, serum inhibition factor (SIF) and rosette inhibitory factor (RIF), were studied in sera from patients with acute and chronic viral hepatitis. In a study of 30 patients with acute viral hepatitis, an association was found between RIF, SIF, and biochemical and virological parameters in 27 patients (90%), 25 of whom recovered completely; two had a protracted course. In three patients, the clinical course was not reflected by the immunosuppressive factors. In 26 patients with chronic persistent hepatitis, 3 had RIF and 7 had SIF of low activity. In patients with HBsAg‐positive and ‐negative chronic active hepatitis, 32 of 47 had RIF and 24 had SIF. SIF activity was significantly increased in HBsAg positive as compared to ‐negative cases. There was no correlation between RIF and SIF activity at any stage of viral hepatitis. Although SIF was demonstrated in patients with various infectious and other inflammatory diseases, RIF was infrequently detected in nonviral liver disorders, and was not present in any of the nonhepatic diseases tested. It was confirmed that RIF is associated with the β‐lipoprotein fraction. RIF was easily separated from SIF by density gradient ultracentrifugation. The evaluation of SIF and RIF may be helpful in determining the outcome of acute viral hepatitis. In chronic hepatitis, RIF was a better indicator of disease activity than was SIF. These clinical data support previous findings that SIF may be related to the immune response whereas RIF is associated with liver cel

ISSN:0270-9139    

DOI:10.1002/hep.1840040103

出版商:W.B. Saunders    

年代:1984

数据来源: WILEY

摘要:

AbstractLiver sections from 18 patients positive for hepatitis B surface antigen (HBsAg), and from 12 negative patients, were examined for the presence of hepatitis B virus (HBV) DNA using anin situhybridization assay that would identify only those hepatocytes containing more than 10 to 15 HBV genome equivalents per cell. Such cells are likely to be undergoing active viral replication, rather than latent infection. The findings were correlated with results of tissue immunofluorescence for HBV antigens and the presence of serum hepatitis B e antigen (HBeAg), together with histologic assessment of each liver. HBV DNA detected in the above assay was predominantly cytoplasmic; it was associated with the presence of hepatitis B core antigen (HBcAg) in hepatocytes and HBeAg in serum, and to a lesser extent with cirrhosis and immunosuppression, but not with the presence of HBsAg in hepatocytes, nor with histological evidence of disease activity judged by the presence of piece‐meal necrosis and lobular and portal tract inflammation. These findings support the view that liver HBcAg and serum HBeAg are markers of virus replication, and demonstrate that active liver disease in HBsAg‐positive patients may occur with or without such markers of replication. It is proposed that alternative mechanisms for hepatocyte injury may apply in different chronic HBV patients, one related to virus replication and one dependent on immunological fact

ISSN:0270-9139    

DOI:10.1002/hep.1840040104

出版商:W.B. Saunders    

年代:1984

数据来源: WILEY

摘要:

AbstractThe status of the excitatory glutamatergic neurotransmitter system in hepatic encephalopathy has been studied. Synaptic membranes (SM) were prepared from the brains of normal rabbits, hyperammonemic normal rabbits, and rabbits with fulminant hepatic failure. Data on the specific binding of glutamate to SM indicated that fulminant hepatic failure was associated with a decrease in the number of glutamate receptors on SM from cerebral cortex, cerebellum, and particularly the hippocampus, without any associated change in the affinity of these receptors. In contrast, hyperammonemia was associated with an increase in the affinity and no decrease in the number of glutamate receptors on SM from the hippocampus. These findings indicate that the effects of hyperammonemia and fulminant hepatic failure on cerebral glutamate receptors are fundamentally different. The decreased number of glutamate receptors in hepatic encephalopathy might reflect a decreased sensitivity of glutamatergic neurons to glutamate‐mediated neural excitation, a phenomenon that could contribute to the neural inhibition of hepatic encephalopath

ISSN:0270-9139    

DOI:10.1002/hep.1840040105

出版商:W.B. Saunders    

年代:1984

数据来源: WILEY

摘要:

AbstractEstradiol‐17β‐D‐glucuronide (E‐17G), a metabolite of natural estrogen, is a potent cholestatic agentin vivo.We, therefore, studied the mechanisms of E‐17G cholestasis usingin vitroperfused rat liver system. Furthermore, since it has been postulated that sodium taurocholate (TC) may interfere with either uptake or biliary excretion of other steroid agents, we tested whether E‐17G cholestasis could be modified by TC administration. During a constant infusion of TC at a physiological rate (0.50 μ mole per min), a dose‐dependent decrease of bile flow was observed after E‐17G addition from 1.5 to 5 x 10−5M. E‐17G decreased bile acid excretory rate but not bile acid concentration in bile. In separate experiments, TC was infused at different rates (0, 0.25, 0.50, and 0.75 μ mole per min) into the perfusate over the entire experimental period, and E‐17G was added at 1.75 x 10−5M. In this setting, E‐17G cholestasis was diminished by increasing TC infusion rate and was prevented by TC at 0.75 μ mole per min. Infusion of sodium dehydrocholate (0.75 μ mole per min), a nonmicelle‐forming bile acid, did not prevent E‐17G cholestasis. During E‐17G cholestasis, an increased biliary permeability to14C‐sucrose was observed. This effect was also prevented by TC, but not by sodium dehydrocholate which was infused at 0.75 μ mole per min. The perfusate disappearance curves of3H‐E‐17G at the different TC infusion rates showed no changes in the initial uptake phase, but a profound dose‐dependent difference in the excretory phase. The amount of E‐17G left in perfusate at the end of experiments was 34% when no TC was infused and decreased to 28%; 22 and 7% at 0.25; 0.50 and 0.75 nmole per min TC rate, respectively. Measurement of3H‐E‐17G excreted in bile as well as its biliary concentration in the four TC groups showed that TC significantly increased E‐17G excretion. Small amounts of E‐17G were recovered in liver plasma membranes. However, these amounts were directly proportional to changes of bile flow induced by estrogen at different TC infusion rates. In these same liver membrane preparations, neither Na+,K+− nor Mg++−ATPases were altered. The data suggest that alterations of canalicular membrane permeability may be critical in the development of E‐17G cholestasis. Prevention of E‐17G cholestasis by TC infusion may occur through increased micellar solubilization and facilitated biliary excre

ISSN:0270-9139    

DOI:10.1002/hep.1840040106

出版商:W.B. Saunders    

年代:1984

数据来源: WILEY

摘要:

AbstractThe effects of liver disease on caffeine plasma clearance (CI) and on exhalation of14CO2following i.v. injection of 2 μCi of [ 3‐methyl‐14C]caffeine together with 125 mg of the unlabeled compound were measured in 15 patients with cirrhosis, 11 subjects with miscellaneous liver disease, and 10 normal volunteers. Compared to mean values for CI (2.02 ± S.D. 0.68 ml per min per kg) and t½ (3.8 ± 0.9 hr) in normal volunteers, cirrhotics were characterized by highly significant reductions in CI (to 0.76 ± 0.40) and prolongation in t½ (to 13.7 ± 13.0), whereas the volume of distribution (VD) remained relatively unchanged (0.57 ± 0.16 vs. 0.64 ± 0.13 liter per kg in normals). Cumulative14CO2production and specific activity of14CO2in breath decreased in parallel (r = 0.83) with Cl. Patients with miscellaneous liver disease exhibited only small changes in Cl and t½; however,14CO2parameters in breath appeared more sensitive in indicating the slight functional derangement. In view of the correlation (Rs= 0.83) of cumulative14CO2excretion with the initial disappearance constant for bromosulfophthalein, the caffeine breath test may be considered as a quantitative measure of hepatic microsomal activity; based on a surprisingly close, hyperbolic relationship between Cl and fasting caffeine plasma concentrations, the latter might serve as a simple guide to severity of

ISSN:0270-9139    

DOI:10.1002/hep.1840040107

出版商:W.B. Saunders    

年代:1984

数据来源: WILEY

摘要:

AbstractPhenacetin, a high‐clearance drug, was labeled as [14C‐ethyl]phenacetin and used in a breath test of hepatic function.14CO2appeared rapidly in breath such that more than 30% of the administered radioactivity was expired in 2 hr. For all means of expression used to describe the appearance of14CO2in breath, normal controls and hospitalized patients without liver disease were clearly separated from cirrhotic subjects with moderate and severe liver damage.The phenacetin breath test was validated by the close correlation of14CO2appearance with the disposition of the parent compound examined after its intravenous administration, and by demonstration that the rate‐limiting step in14CO2generation from labeled phenacetin occurred proximal to14CO2generation from [14C]acetate given intravenously. Correcting for the actual volume of CO2exhaled by control and cirrhotic subjects did not increase the sensitivity of the test. The phenacetin breath test has potential as a simple procedure to quantitate hepatic metabolism of drugs, particularly those mediated by cytochrome

ISSN:0270-9139    

DOI:10.1002/hep.1840040108

出版商:W.B. Saunders    

年代:1984

数据来源: WILEY

摘要:

AbstractThe reticuloendothelial system phagocytic activity, estimated by the plasma elimination rate constant of99mtechnetium‐sulfur colloid, was studied in 41 decompensated cirrhotics and 10 normal subjects. The results were related to the incidence and type of bacterial infections occurring during hospitalization and follow‐up, and to survival. The elimination rate constant of99mtechnetium‐sulfur colloid was lower in cirrhotic patients (0.168 ± 0.007) (x ± S.E.) than in normal subjects (0.220 ± 0.005) (p<0.01). Cirrhotics were divided into two groups. Group I (16 patients) and Group II (25 patients) had normal or reduced elimination rate constant of99mtechnetium‐sulfur colloid, respectively. Both groups were similar in relation to clinical and biochemical data, hepatic blood flow, and wedged hepatic venous pressure. However, the liver scan and the elimination rate constant of indocyanine green were more altered in Group II. Patients in Group II developed acute bacterial infections more frequently than did patients in Group I. During hospitalization (24 ± 2 days), bacteremia occurred in six patients in Group II and in none in Group I (p<0.05). During follow‐up (28 ± 3 months), 5 patients in Group II and none in Group I developed bacteremia (p<0.05). The cumulative survival rate of Group I patients was higher (p<0.05) than that of Group II patients at 3 months (100 vs. 80%), 6 months (94 vs. 68%), 24 months (74 vs. 42%), and 48 months (68 vs. 34%). We suggest that decompensated cirrhotics with depressed reticuloendothelial system phagocytic activity are at great risk to acquire bacteremia, and that reticuloendothelial system phagocytic activity has prognostic valu

ISSN:0270-9139    

DOI:10.1002/hep.1840040109

出版商:W.B. Saunders    

年代:1984

数据来源: WILEY

摘要:

AbstractWe studied the influence of posterior pituitary extract, vasopressin, and somatostatin on hepatic elimination function. Hepatic clearance and its two biological determinants, hepatic blood flow and metabolic activity (clearance Vmax/Km), were determined from hepatic indocyanine green elimination at steady‐state in cirrhotic patients. Intravenous infusion of posterior pituitary extract (oxytocin, 59%; vasopressin, 41%) at the constant rate of 0.3 unit per kg per hr decreased hepatic clearance (p<0.05) and Vmax/Km(p<0.05) but did not change hepatic blood flow. Intravenous infusion of vasopressin (0.3 unit per kg per hr) decreased hepatic clearance (p<0.05), Vmax/Km(p<0.05) and hepatic blood flow (p<0.05). Intravenous infusion of somatostatin (250 μg per hr following a bolus i.v. injection of 250 μg) decreased hepatic clearance (p<0.05), Vmax/Km(p<0.05), and hepatic blood flow (p<0.05). This study shows that the vasoactive agents used in the management of upper digestive bleeding in cirrhotic patients may have deleterious effects on the metabolic activity of the liver in addition to their effects on hemodynamics. The results suggest that the vasoactive substances either increased the fraction of total hepatic blood which bypassed intact hepatocytes or directly impaired metabolic activity of hepatocytes. Reduction in the metabolic activity of the liver produced by vasoactive agents may have important implications in therapy of portal hypertens

ISSN:0270-9139    

DOI:10.1002/hep.1840040110

出版商:W.B. Saunders    

年代:1984

数据来源: WILEY