Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Liver Dysfunction”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,189 records · Page 66Linked to original sources
PubMed2003

[Evaluation of the increasing serum lactate dehydrogenase caused by recombinant human granulocyte-colony stimulating factor].

OBJECTIVE: Increasing serum lactate dehydrogenase (LDH) is often caused by granulocyte-colony stimulating factor (G-CSF) for leukopenia following chemotherapy in patients with lung cancer. To evaluate the increase in LDH, we investigated the significance of its elevation and LDH isozyme during chemotherapy supported by recombinant human G-CSF (rhG-CSF). STUDY DESIGN: To exclude effects of liver diseases and chemotherapy-induced liver dysfunction, only patients in whom laboratory findings concerning liver function were within normal range were entered in this study. If leukocyte or neutrophil counts were less than grade 3, subcutaneous injection of 50 micrograms/m2 of filgrastim was given daily until leukocyte counts increased to more than 10,000/mm3. RESULTS: Sixty patients with unresectable lung cancer were enrolled in this study and the LDH isozyme was evaluable in 54 patients. Increasing LDH was observed in 38 patients(70.4%), and LDH isozyme was measured in these 38 patients. Increases in granulocytes and LDH isozymes were found to have a positive correlation. LDH2, LDH3, LDH4 and LDH5 increased significantly after rhG-CSF administration, although LDH 1 did not increase. CONCLUSION: It was found that a rapid increase in leukocytes by rhG-CSF induced an increase in LDH, especially LDH 3.4. Considering the results of principal component analysis and the distribution ratio of LDH isozymes in neutrophils, it is thought that elevation of LDH is reflected in the rapid production and consumption of neutrophils.

Adult↗
PubMed1991

Effects of anesthetic agents and abdominal surgery on liver blood flow.

The cause of postoperative liver dysfunction is often unclear, but a decrease in liver blood flow during anesthesia and/or major surgery may be important. Plasma half-life and clearance of indocyanine green were therefore measured in 42 patients before, during and after anesthesia and abdominal surgery. In 13 patients, liver blood flow was also estimated from indocyanine green extraction using hepatic vein catheterization. The major finding was an early decrease in estimated liver blood flow after induction of anesthesia, but not later during or after surgery. Mean indocyanine green half-life increased by 26% (p less than 0.005), mean indocyanine green plasma clearance decreased by 19% (p less than 0.01) and mean estimated hepatic blood flow decreased by 36% (p less than 0.005) during the first 30 min of anesthesia. These changes were greater in males and in patients older than 55 yr, but changes were similar with each of three anesthetic groups. Half-life, but not indocyanine green clearance, was also significantly prolonged by mid-operation in the older (greater than 55 yr) patients and in those undergoing lower abdominal surgery. We suggest that this period of reduced liver blood flow during anesthesia is caused by the effects of neuromuscular blocking agents and may contribute to postoperative liver damage.

Abdomen↗
PubMedDate not supplied

Effect of bilateral vasectomy on liver function in langur monkeys (Presbytis entellus entellus Dufresne).

Changes in serum biochemical measures associated with liver dysfunction and biochemical and histological structure of the liver after vasectomy have been studied in langur monkeys. No appreciable changes were observed in the serum SGOT, SGPT, LDH and alkaline phosphatase levels after vasectomy as compared with sham operated controls. Likewise glycogen and cholesterol contents of the liver were found to be unchanged after vasectomy. Histologic structure of liver remained normal. The present investigation has suggested that vasectomy does not cause any adverse effect on liver function in langur monkeys.

Animals↗
PubMed1989

Lithocholate in liver tissue with obstructive jaundice.

The existence of tissue-bound lithocholate in liver tissue was first suggested by Nair et al. (Lipids 1988;12:922-929). Since lithocholate is well known to be cholestatic, we investigated whether tissue-bound lithocholate, if present, can be correlated to liver dysfunction in obstructive jaundice. Tissue-bound lithocholate in liver tissues of 7 patients with obstructive jaundice was analyzed using gas chromatography-mass spectrometry-selected ion monitoring. We found no accumulation of lithocholate, including tissue-bound form, indicating that the role of lithocholate in inducing hepatic dysfunction in obstructive jaundice is minimal, if any.

Cholestasis↗
PubMed2000

Zinc, copper, and metallothionein metabolism after jejunoileal bypass surgery or small bowel resection in rats.

Liver dysfunction is a frequent complication of jejunoileal bypass (JIB) surgery, a procedure commonly used until recently to treat morbid obesity. It has been suggested that liver failure in JIB patients is due to bacterial overgrowth and translocation from the bypassed intestine. Because invading microorganisms cause hepatic inflammation these experiments evaluated zinc, copper, and metallothionein (MT) in two experimental rat models of intestinal surgery to determine whether their distribution in plasma and tissues was similar to the highly characteristic pattern observed during an inflammatory response. In the JIB rat model 90 per cent of the small intestine was isolated from the flow of digesta but remained viable in the abdominal cavity. In the small bowel resection (SBR) model 90 per cent of the small intestine was removed and the remaining intestine was resected. Data collected 21 days after surgery showed decreased growth rate and plasma zinc in the SBR and JIB rats that was significantly improved by supplemental zinc. All other measures of zinc, copper, and MT metabolism in the SBR rats were similar to those of controls. In JIB rats, however, liver copper, MT protein, and MT mRNA were significantly elevated, and a high proportion of the intracellular zinc and copper was associated with MT. The pattern of zinc, copper, and MT distribution in systemic circulation and liver of JIB rats suggests hepatic inflammation superimposed on low zinc and copper status. Lack of a similar response in the SBR rats confirms the involvement of the bypassed intestinal segment and supports the hypothesis that bacterial overgrowth and translocation are responsible for liver inflammation and dysfunction in JIB patients.

Animals↗
PubMed1994

Erythromycin ototoxicity in liver transplant patients.

We report on three liver transplant patients who developed erythromycin-related ototoxicity. This complication has been described in renal transplant patients and in patients with liver dysfunction, but to our knowledge it has not yet been reported in liver transplant patients. The influence of hepatic dysfunction, common renal failure, and the interaction between cyclosporin and erythromycin in the development of erythromycin ototoxicity are discussed.

Adult↗
PubMed2006

An Australian experience with the molecular adsorbents recirculating system (Mars).

The molecular adsorbents recirculating system (MARS) is a form of artificial extracorporeal liver support which has the potential to remove substantial quantities of albumin-bound toxins postulated to contribute to the pathogenesis of liver cell damage, hemodynamic instability and multi-organ failure in patients with acute liver failure and acute-on-chronic liver failure (AoCLF). We assessed the efficacy of MARS therapy in a cohort of patients with severe liver damage unresponsive to intensive medical therapy. MARS therapy was instituted late in the clinical course of six patients with severely impaired liver function refractory to intensive medical therapy, including four with AoCLF precipitated by sepsis and two with liver dysfunction due to sepsis in the absence of pre-existing chronic liver disease. Outcome measures included markers of hemodynamic stability, renal function, serum bilirubin and bile acid levels, arterial ammonia levels, the arterial ketone body (acetoacetate/beta-hydroxybutyrate) ratio, hepatic encephalopathy grade and the plasma disappearance rate of indocyanine green. The rates of discharge from the intensive care unit and in-hospital mortality were determined. Our findings suggest that MARS treatment might be associated with some clinical efficacy even in patients with advanced multi-organ dysfunction occurring in the setting of severe liver damage and in whom treatment is instituted late in the clinical course. However, the overall survival rate (1/6; 17%) was poor. More data obtained from larger cohorts of patients enrolled in randomized controlled studies will be required in order to identify categories of liver failure patients who might benefit most from MARS treatment and to ascertain the most appropriate timing of intervention.

Adult↗
PubMed1994

Assessment of the cytokine response in liver donors at the time of organ procurement and association with allograft function after orthotopic transplantation.

BACKGROUND: The cause of allograft liver dysfunction after transplantation is unresolved. We tested the hypothesis that human donor liver may be predisposed to ischemia reperfusion injury, and graft dysfunction subsequent to ongoing inflammatory processes during donor hospitalization. STUDY DESIGN: A prospective study of organ donors and transplant recipients of allograft livers from these donors was conducted. Portal venous, inferior vena caval, and superior vena caval blood samples were obtained from 16 clinical organ donors at the time of organ procurement (one to 12 days post-trauma) to characterize the hepatic cytokine and acute phase protein response, to determine whether or not this response resulted from bacterial or endotoxin translocation to the portal circulation, and to assess whether or not transplant outcome was associated with plasma levels of cytokines in the donor. RESULTS: In comparison with systemic blood samples from ten healthy persons, all 16 donors exhibited significantly (p < 0.05) elevated plasma concentrations of interleukin-6, interleukin-8, soluble p55 tumor necrosis factor receptor type I (sTNFr-I), and C-reactive protein. No concentration differences existed among portal venous, inferior vena caval, and superior vena caval blood samples for any cytokine or acute phase protein measured. Donor levels of endotoxin, TNF-alpha, soluble intercellular adhesion molecule-1 (sICAM-1), alpha 1-acid glycoprotein, alpha 1-antitrypsin, and haptoglobin were comparable with those in the healthy persons. Bacterial cultures of portal blood were negative. There was no association between the causation of donor trauma and either donor cytokine response or function and quality of the allograft liver after transplantation. Nor could an association between donor cytokine response and either early allograft function (less than 96 hours) or eventual transplant outcome in the recipients be detected. CONCLUSIONS: These results indicate that, although an ongoing inflammatory response to injury was evident in these donors at the time of organ procurement, there were no apparent adverse effects arising from these inflammatory processes on the function and quality of the donor liver after transplantation. Bacterial translocation does not seem to be a component of the pathogenesis of inflammation. Whether or not the presence of inflammation in the donor alters the metabolic responses of the allograft liver and recipient to transplant operation is unknown.

Acute-Phase Proteins↗
PubMed1999

Astilbin selectively induces dysfunction of liver-infiltrating cells--novel protection from liver damage.

The present study aimed to examine the effect of astilbin, a flavanoid, on liver injury. When administered during the effector but not induction phase, astilbin significantly decreased the liver injury induced by delayed-type hypersensitivity to picryl chloride in mice. The pretreatment of nonparenchymal cells but not hepatocytes with astilbin in vitro caused a concentration- and time-dependent inhibition against the damage. Nonparenchymal cells isolated from astilbin-administered mice also showed a significant incompetence of hepatotoxicity, correlated with the inhibition of serum transaminase elevation. However, astilbin did not protect from CCl4-induced liver damage. Furthermore, the flavanoid markedly promoted the apoptosis of nonparenchymal cells from liver-injured mice, whereas did not influence those from naive mice. These results suggest that astilbin provides improvement against liver injury through a selective dysfunction of liver-infiltrating cells rather than by protecting the hepatocyte membrane. Such characteristics will be of significance to pave a new way for treating immunologically related liver diseases and for developing new drugs.

Animals↗
PubMedDate not supplied

Valproate (VPA) metabolites in various clinical conditions of probable VPA-associated hepatotoxicity.

Of a cohort of 470 epileptic patients in whom valproate (VPA) serum metabolites had been measured, 170 subjects without symptoms or signs of hepatic side effects were chosen as a reference group to establish the usual metabolic pattern. A wide interindividual variation of VPA metabolite concentrations was noted. Infants receiving VPA monotherapy and comedication with other antiepileptic drugs (AEDs) showed lower concentrations of the potential hepatotoxin 4-ene-VPA than did older children. In 11 patients with early symptoms and signs of possible fatal VPA-associated hepatotoxicity, the following spectrum of benign clinical conditions was observed: unusually severe side effect during initiation of VPA therapy (1 patient), high VPA dosage (2 patients), reversible impairment of coagulation with bleeding manifestations in association with a slight increase in transaminase levels (1 child), and reversible liver dysfunction associated with febrile illness (7 patients). Reversible or irreversible fulminant liver failure had occurred in 5 children. Three of the 4 children with a fatal outcome had massive lactic acidosis. In all patients with probable VPA-associated hepatotoxicity, some aspects of VPA metabolism differed distinctly from that of the reference group, but the inter-individual profile of metabolites varied considerably, even in the subgroup of 4 children who died. Impairment of VPA beta-oxidation and increase of metabolites of alternative metabolic pathways (omega- and omega 1-hydroxylation, dehydrogenation reactions) were the most frequent findings. Increased values of 2-n-propyl-4-pentenoic acid metabolite of VPA (4-ene-VPA), could be detected only in 1 of the 5 patients with fulminant liver failure and in one other child with a slight hepatic dysfunction, indicating that this VPA metabolite is not the decisive hepatotoxin or indicator of hepatotoxicity. Because we cannot distinguish between benign and life-threatening hepatic adverse reactions on the basis of VPA metabolites, all identified changes are considered secondary to an as-yet-unknown primary metabolic event. The most toxic compound could be VPA itself, which may unmask an inborn or an acquired metabolic defect in the processing of fatty acids.

Chemical and Drug Induced Liver Injury↗
PubMed2003

Differential induction of hepatic dysfunction after intraportal and intravenous challenge with endotoxin and Staphylococcal enterotoxin B.

We have previously shown that systemic infusion of the bacterial toxins Staphylococcal enterotoxin B (SEB) and endotoxin (LPS) induces hepatic dysfunction as measured by decreased biliary indocyanine green (ICG) excretion. In this study, we compare the effects of these bacterial toxins after infusion into the portal and systemic circulation and directly measure biliary bile acid excretion as a measure of cholestasis. We hypothesized that bacterial toxins infused into the portal vein would induce greater hepatic dysfunction than toxins infused into the systemic circulation. Using a chronically catheterized rat model, biliary bile acid excretion was directly measured after infusion of LPS at 10 and 100 microg/kg with and without 50 microg/kg SEB into the portal vein (IPV) or inferior vena cava (IV) at baseline, and at 6 and 24 h. We found that when LPS was infused alone, only IPV administration caused a significant decrease in bile acid excretion at 6 h. There was no change in bile acid excretion after IV administration of LPS. In contrast, when the combination of LPS and SEB was infused, both IV and IPV administration significantly decreased bile acid excretion at 6 and 24 h. At 6 h post-LPS and -SEB administration, the decrease in bile acid excretion was significantly greater after IPV than IV administration. There was no site-specific difference in IFN-gamma release after infusion of toxins. However, peak TNFalpha release was decreased in IPV-infused rats [10 microg/kg (P < 0.05) or 100 microg/kg (P = ns) LPS with SEB] compared with the same doses in IV-infused rats. These data question the role of systemic TNF-alpha and IFN-gamma in regulating hepatic dysfunction and suggest a differential functional response of the liver to systemic and gut-derived septic events. This study also further explains the frequent development of liver dysfunction in patients with sepsis, multisystem organ failure, and other diseases with altered intestinal permeability.

Animals↗
PubMed2003

Reproducible hepatic dysfunction following separate anesthesia with sevoflurane and desflurane.

Both desflurane and sevoflurane have individually been reported to induce hepatic dysfunction; however hepatic dysfunction after administration of both of them separately in a single patient has not previously been reported. As their metabolites differ in nature, we considered that it would be unlikely that their combined use would cause sensitization and induce hepatic dysfunction. We report on the first patient with reproducible liver dysfunction after sevoflurane and desflurane. This 54-year-old man sequentially received 3 anesthetics over a 1-year period. The first anesthetic was isoflurane, and the course was uneventful. The second anesthetic was sevoflurane, and this resulted in fever with chills and elevated aspartate aminotransferase (543 U/l) 17 days later. The third anesthetic was desflurane which resulted in a similar clinical picture after 17 days. The symptoms improved, and the serum transaminase level returned to normal after conservative therapy. The similar time interval between the operation date and the onset of hepatic dysfunction, after excluding other possibilities, made us highly suspicious that the hepatic dysfunction was induced by sevoflurane on 1 occasion and desflurane on the other. We suggest that inhaled anesthetics should be totally replaced by intravenous anesthetics for future operations in patients with such a diagnosis.

Anesthetics, Inhalation↗
PubMed1998

Hepatic extraction of tacrolimus in rats with experimental liver diseases.

Tacrolimus, an immunosuppressive agent, is metabolized mainly in the liver and has shown large intra- and interindividual pharmacokinetic variability. We investigated the effect of liver dysfunctions on the pharmacokinetics of tacrolimus in rats with experimental liver diseases. Experimental hepatic failure was induced by CCl4-treatment or bile duct ligation. Tacrolimus (1 or 0.3 mg/kg) was administered intravenously or intraportally to the rats (n = 5-6 per group), and blood samples were collected over a 240-min period. The tacrolimus concentrations in the blood were then measured by a high-performance liquid chromatography-enzyme immunoassay. In the normal rats, the hepatic extraction ratio of tacrolimus (EH) was dose-independent, ranging from 0.556-0.598 at 0.3 and 1.0 mg/kg doses. The EH were dose-dependent in the CCl4-treated rats and in the bile duct-ligated rats: the EH at 1.0 mg/kg dose were 0.158-0.170 and those at 0.3 mg/kg dose were 0.329-0.394. The intermediate EH of tacrolimus suggested that the clearance of tacrolimus depends not only on hepatic intrinsic clearance but also on hepatic blood flow. The present pharmacokinetic study also suggested that the decrease of EH and the dose-dependence of EH contribute to the elevation of blood tacrolimus concentrations and to the large variability in the pharmacokinetics of tacrolimus after oral administration in hepatic dysfunctions.

Animals↗
PubMedDate not supplied

Changes in albumin, alpha-fetoprotein and collagen gene transcription in CCl4-induced hepatic fibrosis.

In efforts to understand mechanisms of liver dysfunction in cirrhosis, transcription of specific genes important to liver function has been measured in the rat model of CCl4-induced hepatic fibrosis. The relative transcription rates of albumin, alpha-fetoprotein and pro-alpha 1-collagen genes were studied during development of fibrosis and after fibrosis was established. During the initial phase of CCl4 administration, there was a decrease in albumin transcription associated with increased alpha-fetoprotein transcription, indicative of active liver regeneration. However, later during development of fibrosis, the response pattern of these genes was different, as albumin gene transcription was normal or increased and alpha-fetoprotein gene transcription was no longer increased. Three weeks after completion of CCl4 treatment (fully established cirrhosis), albumin genes responded normally or hypernormally to an acute regenerative stimulus, but the alpha-fetoprotein gene was again not measurably responsive. Pro-alpha 1-collagen gene transcription increased during the entire fibrogenic process and remained elevated after cirrhosis was established. These studies suggest that a switch from albumin to alpha-fetoprotein gene transcription can serve as a marker of liver regenerative capacity, and that this process is altered during and after development of hepatic fibrosis. The fibrogenic process is also associated with elevated transcription of collagen genes.

Animals↗
PubMed1990

Hepatic efflux and renal extraction of plasma glutathione: marked differences between healthy subjects and the rat.

Hepatic efflux of glutathione accounts for almost 85% of the plasma level in the rat. However, the expected high concentration in the hepatic vein in man has not been demonstrated as yet. Our findings in ten patients without liver dysfunction reveal that substantial translocation of glutathione from the liver to the plasma does not occur. The removal rate of circulating glutathione by the kidney is far lower in man than in the rat (49.5% vs 84.6%). Moreover, the inferior vena cava in man contains more circulating glutathione than the artery, which is not consistent with the results obtained in the rat. Furthermore, the plasma concentration in man is about one tenth of that in the animals. These results clearly indicate that species-specific differences in the overall biosynthesis and metabolism of the tripeptide occur, resulting in marked variations in its plasma concentration.

Adult↗
PubMed2005

Coumadin-induced hepatitis.

The diagnosis of "coumadin-induced hepatitis" is compatible with the time relationship between the start of the drug and the onset of hepatopathy, the rapid improvement following discontinuation of the drug, recurrence of liver dysfunction after re-exposure to the drug and liver histology. Although liver damage induced by coumadin derivatives is rare, it is important to be aware of the hepatotoxic potential of these drugs, which, in most cases, mimic the clinical presentation of viral hepatitis.

Journal Article↗
PubMed1999

Liver damage induced by coumarin anticoagulants.

Except for bleeding complications, relevant adverse effects of coumarin anticoagulants are comparatively rare considering the widespread use of these substances. Here we present the case of a 56-year-old woman who developed recurrent episodes of severe hepatitis following repeated exposure to phenprocoumon (Marcumar; Roche, Grenzach-Wyhlen, Germany) and warfarin (Coumadin; DuPont Pharma, Bad Homburg, Germany) after replacement of the mitral valve with a mechanical prosthesis. The diagnosis of "coumarin-induced hepatitis" is compatible with the time relationship between start of the drug and the onset of hepatopathy (first episode 8 months, second episode 4 weeks, and third episode 7 days), the rapid improvement following discontinuation of the drug, recurrence of liver dysfunction after re-exposure to the drug, and liver histology. After anticoagulant therapy was changed to heparin and acenocoumarol (Sintrom; Ciba-Geigy, Basel, Switzerland), the patient's general state was markedly improved and her liver values became almost normal. This case will be discussed and compared with other reports of coumarin-induced hepatic lesions. Although liver damage induced by coumarin derivates is rare, it is important to be aware of the hepatotoxic potential of these drugs, which, in most cases, mimics the clinical presentation of viral hepatitis.

Anticoagulants↗
PubMed1995

Fungal liver infection in marrow transplant recipients: prevalence at autopsy, predisposing factors, and clinical features.

To determine the prevalence of fungal liver infection at autopsy in marrow transplant recipients, we reviewed autopsy results for the period 1980-1989. Cases were compared to randomly chosen autopsied controls without fungal infection. Fungal liver infection was found in 67 (9%) of 731 patients. Fungal cultures of liver lesions were positive for 34 of 67 patients, most of whom had been culture-positive for the same fungal species (largely Candida) during life. Multivariate analysis revealed that independent predictors of fungal liver infection were deep fungal infection after transplantation (RR, 35), colonization or superficial infection after transplantation (RR, 13), and severe liver dysfunction caused by veno-occlusive disease of the liver and/or graft-versus-host disease (RR, 7). Clinical and laboratory findings during the last month of life revealed no differences between cases and controls. Liver imaging studies performed during the last 15 days of life had a sensitivity of only 18% for detecting fungal liver lesions.

Adult↗