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Hepatic Function (hepatic + function)

Distribution by Scientific Domains

Medical Sciences	86%
Life Sciences	13%

Distribution within Medical Sciences

Hepatology	20%
Pharmacology & Pharmaceutical Medicine	9%
12 Other Subdomains	71%

Selected Abstracts

The Influence of Acetylcholinesterase Reactivators on Selected Hepatic Functions in Rats

BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 2 2008
Jaroslav Pejchal
Male Wistar rats were randomly divided to seven groups and intramuscularly administered with saline and acetylcholinesterase reactivators (K027, HI-6 and obidoxime) at doses of 5% LD50 and 50% LD50. Liver tissue samples were taken 24 hr after administration. Histochemical detection of lipid droplets and immunohistochemical detection of multidrug resistance protein 2 (Mrp2) were provided. Lipid droplet count in rat liver did not show any significant differences in animals administered with K027, HI-6 and obidoxime in comparison with the control group. Mrp2 protein expression significantly decreased when animals were administered with K027 at a dose of 50% LD50 and HI-6 and obidoxime at doses of 5% LD50 and 50% LD50, when compared to the controls. No statistical differences of Mrp2 expression were measured when animals were administered with K027 at a dose of 5% LD50 in comparison with control animals. We found impaired hepatic transporter function after administration of HI-6, obidoxime and higher concentration of K027, which might be the underlying mechanism of acetylcholinesterase reactivators' hepatotoxicity. [source]

Primary hepatocyte culture supports hepatitis C virus replication: A model for infection-associated hepatocarcinogenesis,

HEPATOLOGY, Issue 6 2010
Krishna Banaudha
Analysis of progressive changes in hepatic gene expression that underlie hepatocarcinogenesis following hepatitis C virus (HCV) infection require examination of long-term cultures of normally differentiating primary human hepatocytes. We report a culture system of primary hepatocytes that support productive replication of infectious HCV. Hepatic functions were analyzed by reverse-transcription polymerase chain reaction amplification of total cell RNA from cultures maintained in serum-free defined medium for up to 190 days. Sustained hepatic function was assessed by expression of albumin, alpha-fetoprotein, cytochrome P4502E1, cytokeratin-18, type-1 collagen, transforming growth factor-beta 1, matrix metalloproteinase-2 (MMP-2), MMP-13, and interferon alpha-receptors 1 and 2. Normally differentiated human primary hepatocytes supported productive replication of infectious clones of HCV genotypes 1a, 1b, and 2a; virus infection was inhibited by antibodies against CD81 virus entry factor. Virus released into the culture media of HCV-infected primary hepatocytes repeatedly passage to naïve hepatocytes. Replication of the three HCV genotypes shows interferon sensitivity observed in natural infections. Conclusion: Sustained cultures of physiologic host cells for the propagation of infectious HCV strains should accelerate studies of host response to HCV infection and progressive liver disease. Hepatology 2010;51:1922,1932 [source]

Hepatic dysfunction and insulin insensitivity in type 2 diabetes mellitus: a critical target for insulin-sensitizing agents

DIABETES OBESITY & METABOLISM, Issue 9 2008
P. D. Home
The liver plays an essential role in maintaining glucose homeostasis, which includes insulin-mediated processes such as hepatic glucose output (HGO) and uptake, as well as in clearance of insulin itself. In type 2 diabetes, the onset of hyperglycaemia [itself a potent inhibitor of hepatic glucose output (HGO)], alongside hyperinsulinaemia, indicates the presence of hepatic insulin insensitivity. Increased HGO is central to the onset of hyperglycaemia and highlights the need to target hepatic insulin insensitivity as a central component of glucose-lowering therapy. The mechanisms underlying the development of hepatic insulin insensitivity are not well understood, but may be influenced by factors such as fatty acid oversupply and altered adipocytokine release from dysfunctional adipose tissue and increased liver fat content. Furthermore, although the impact of insulin insensitivity as a marker of cardiovascular disease is well known, the specific role of hepatic insulin insensitivity is less clear. The pharmacological tools available to improve insulin sensitivity include the biguanides (metformin) and thiazolidinediones (rosiglitazone and pioglitazone). Data from a number of sources indicate that thiazolidinediones, in particular, can improve multiple aspects of hepatic dysfunction, including reducing HGO, insulin insensitivity and liver fat content, as well as improving other markers of liver function and the levels of mediators with potential involvement in hepatic function, including fatty acids and adipocytokines. The current review addresses this topic from the perspective of the role of the liver in maintaining glucose homeostasis, its key involvement in the pathogenesis of type 2 diabetes and the tools currently available to reduce hepatic insulin insensitivity. [source]

Combination therapy using metformin or thiazolidinediones and insulin in the treatment of diabetes mellitus

DIABETES OBESITY & METABOLISM, Issue 6 2005
Suzanne M. Strowig
The biguanide, metformin, sensitizes the liver to the effect of insulin, suppressing hepatic glucose output. Thiazolidinediones such as rosiglitazone and pioglitazone enhance insulin-mediated glucose disposal, leading to reduced plasma insulin concentrations. These classes of drugs may also have varying beneficial effects on features of insulin resistance such as lipid levels, blood pressure and body weight. Metformin in combination with insulin has been shown to significantly improve blood glucose levels while lowering total daily insulin dose and body weight. The thiazolidinediones in combination with insulin have also been effective in lowering blood glucose levels and total daily insulin dose. Triple combination therapy using insulin, metformin and a thiazolidinedione improves glycaemic control to a greater degree than dual therapy using insulin and metformin or insulin and a thiazolidinedione. There is insufficient evidence to recommend the use of metformin or thiazolidinediones in type 1 diabetic patients. Although these agents are largely well tolerated, some subjects experience significant gastrointestinal problems while using metformin. Metformin is associated with a low risk of lactic acidosis, but should not be used in patients with elevated serum creatinine or those being treated for congestive heart failure. The thiazolidinediones are associated with an increase in body weight, although this can be avoided with careful lifestyle management. Thiazolidinediones may also lead to oedema and are associated with a low incidence of hepatocellular injury. Thiazolidinediones are contraindicated in patients with underlying heart disease who are at risk of congestive heart failure and in patients who have abnormal hepatic function. The desired blood glucose-lowering effect and adverse event profiles of these agents should be considered when recommending these agents to diabetic patients. The potential for metformin or the thiazolidinediones to impact long-term cardiovascular outcomes remains under investigation. [source]

Hepatotoxicity assay using human hepatocytes trapped in microholes of a microfluidic device

ELECTROPHORESIS, Issue 18 2010
Ju Hun Yeon
Abstract Hepatocytes have been used for in vitro hepatotoxicity assays because of their ability to sustain intact liver-specific functions. Here, we demonstrate a hepatotoxicity assay system using primary human hepatocytes trapped in microholes of a microfluidic device, providing a microscale in vivo liver-like environment. We performed microfluidic hepatotoxicity assays of several drugs, including acetaminophen, verapamil, diclofenac, and benzopyrene, all of which are known to specifically affect hepatic function. The drug sensitivities in hepatocytes and HepG2 cells were measured by calculating the live cell fraction at various drug concentrations. The results indicated that hepatocytes were more sensitive to these drugs than HepG2 cells. The lethal concentration 50 values for all drugs tested were similar to those from the in vitro toxicity data with human hepatocytes obtained from the literature. Furthermore, we developed a mathematical hepatotoxicity model based on the time-dependent cell death profiles measured by our device. This novel assay system enabled us to analyze in vivo -like hepatotoxicity in a microfluidic device by exploiting microstructures to mimic the microenvironment of the liver. [source]

Primary hepatocyte culture supports hepatitis C virus replication: A model for infection-associated hepatocarcinogenesis,

Functional significance of hepatic arterial flow reserve in patients with cirrhosis

HEPATOLOGY, Issue 2 2003
Alexander Zipprich
In cirrhosis, hepatic arterial vasodilatation occurs in response to reduced portal venous blood flow. However, although the hepatic arterial flow reserve is high in patients with cirrhosis, its impact on hepatic function is unknown. This study investigated the effect of adenosine-induced hepatic arterial vasodilatation on different markers of liver function. In 20 patients with cirrhosis (Child-Pugh class A/B/C: n = 2/7/11) adenosine (2-30 ,g · min,1 · kg body wt,1) was infused into the hepatic artery and hepatic arterial average peak flow velocities (APV), pulsatility indices (PI), and blood flow volumes (HABF) were measured using digital angiography and intravascular Doppler sonography. Indocyanine green (ICG), lidocaine, and galactose were administered intravenously in doses of 0.5, 1.0, and 500 mg/kg body weight in the presence of adenosine-induced hepatic arterial vasodilatation and, on a separate study day, without adenosine. ICG disappearance, galactose elimination capacity (GEC), and formation of the lidocaine metabolite monoethylglycinxylidide (MEGX) were assessed. Adenosine markedly increased APV and HABF and markedly decreased PI. Serum MEGX concentrations were 63.7 ± 18.2 (median, 62; range, 36-107) and 99.0 ± 46.3 (82.5; 49-198) ng/mL in the absence and presence of adenosine infusion, respectively (P = .001). Adenosine-induced changes in MEGX concentrations were correlated inversely to changes in APV (r = ,0.5, P = .02) and PI (r = ,0.55, P = .01) and were more marked in Child-Pugh class C compared with Child-Pugh class A patients (57.4 ± 49.9 [44; ,14 to 140] vs. 8.4 ± 16.5 [13; ,11 to 35] ng/mL, P < .01). In conclusion, hepatic arterial vasodilatation provides substantial functional benefit in patients with cirrhosis. The effect does not depend directly on hepatic arterial macroperfusion and is observed preferentially in patients with decompensated disease. [source]

Intrahepatic amino acid and glucose metabolism in a D -galactosamine,induced rat liver failure model

HEPATOLOGY, Issue 2 2001
Kosuke Arai
A better understanding of the hepatic metabolic pathways affected by fulminant hepatic failure (FHF) would help develop nutritional support and other nonsurgical medical therapies for FHF. We used an isolated perfused liver system in combination with a mass-balance model of hepatic intermediary metabolism to generate a comprehensive map of metabolic alterations in the liver in FHF. To induce FHF, rats were fasted for 36 hours, during which they received 2 D -galactosamine injections. The livers were then perfused for 60 minutes via the portal vein with amino acid,supplemented Eagle minimal essential medium containing 3% wt/vol bovine serum albumin and oxygenated with 95% O2/5% CO2. Control rats were fasted for 36 hours with no other treatment before perfusion. FHF rat livers exhibited reduced amino acid uptake, a switch from gluconeogenesis to glycolysis, and a decrease in urea synthesis, but no change in ammonia consumption compared with normal fasted rat livers. Mass-balance analysis showed that hepatic glucose synthesis was inhibited as a result of a reduction in amino acid entry into the tricarboxylic acid cycle by anaplerosis. Furthermore, FHF inhibited intrahepatic aspartate synthesis, which resulted in a 50% reduction in urea cycle flux. Urea synthesis by conversion of exogenous arginine to ornithine was unchanged. Ammonia removal was quantitatively maintained by glutamine synthesis from glutamate and a decrease in the conversion of glutamate to ,-ketoglutarate. Mass-balance analysis of hepatic metabolism will be useful in characterizing changes during FHF, and in elucidating the effects of nutritional supplements and other treatments on hepatic function. [source]

Recent role of splenectomy in chronic hepatic disorders

HEPATOLOGY RESEARCH, Issue 12 2008
Toru Ikegami
For years splenectomy in hepatic disorders has been indicated only for the treatment of gastro-esophageal varices. However, with recent advances in medical and surgical treatments for chronic hepatic disorders, the use of splenectomy has been greatly expanded, such that splenectomy is used for reversing hypersplenism, for applying interferon treatment for hepatitis C, for treating hyperdynamic portal circulation associated with intractable ascites, and for controlling portal pressure during small grafts in living donor liver transplantation. Such experiences have shown the importance of portal hemodynamics, even in cirrhotic livers. Recent advances in surgical techniques have enabled surgeons to perform splenectomy more safely and less invasively, but the procedure still has considerable clinical outcomes. Splenectomy in hepatic disorders may become a more common procedure with expanded indications. However, it should also be noted that the long-term effects of splenectomy, in terms of improved hematological or hepatic function, is still not guaranteed. Moreover, the impact of splenectomy on immunologic status remains unclear and needs to be elucidated in both experimental and clinical settings. [source]

Pharmacokinetics and pharmacodynamics of prasugrel in subjects with moderate liver disease

JOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 5 2009
D. S. Small PhD
Summary Background and Objective:, Prasugrel is a thienopyridine antiplatelet agent under investigation for the prevention of atherothrombotic events in patients with acute coronary syndrome who undergo percutaneous coronary intervention. Patients with chronic liver disease are among those in the target population for prasugrel. As hepatic enzymes play a key role in formation of prasugrel's active metabolite, hepatic impairment could affect the safety and/or efficacy of prasugrel in such patients. Methods:, This was a parallel-design, open-label, multiple dose study of 30 subjects, 10 with moderate hepatic impairment (Child-Pugh Class B) and 20 with normal hepatic function. Prasugrel was administered orally as a 60-mg loading dose (LD) and daily 10-mg maintenance doses (MDs) for 5 days. Pharmacokinetic parameters (AUC0,t, Cmax and tmax) and maximal platelet aggregation (MPA) by light transmission aggregometry were assessed after the LD and final MD. Results and Discussion:, Exposure to prasugrel's active metabolite was comparable between healthy subjects and those with moderate hepatic impairment. Point estimates for the ratios of geometric least square means for AUC0,t and Cmax after the LD and last MD ranged from 0·91 to 1·14. MPA to 20 ,m ADP was similar between subjects with moderate hepatic impairment and healthy subjects for both the LD and MD. Prasugrel was well tolerated by all subjects, and adverse events were mild in severity. Conclusion:, Moderate hepatic impairment appears to have no effect on exposure to prasugrel's active metabolite. Furthermore, MPA results suggest that moderate hepatic impairment has little or no effect on platelet aggregation relative to healthy controls. Overall, these results suggest that a dose adjustment would not be required in moderately hepatically impaired patients taking prasugrel. [source]

Portosystemic pressure gradient during transjugular intrahepatic portosystemic shunt with Viatorr stent graft: What is the critical low threshold to avoid medically uncontrolled low pressure gradient related complications?

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 1 2008
Hwan-Hoon Chung
Abstract Background:, Inappropriately decreased portosystemic pressure gradient (PSG) during transjugular intrahepatic portosystemic shunt (TIPS) can cause fatal complications but the critical low threshold of PSG is still not clear. The aim of the present study was to evaluate the critical low threshold of PSG during TIPS. Methods:, Sixty-six patients with cirrhosis who successfully underwent de novo TIPS with Viatorr stent grafts were studied. Medically uncontrolled low pressure gradient (LPR) complication was defined as when a patient died, or when acute transplantation or a TIPS reduction procedure was performed due to refractory encephalopathy or the deterioration of hepatic function within 3 months after the procedure. For the determination of the risk group for medically uncontrolled LPR complications, the Child-Pugh score and the model of end-stage liver disease (MELD) score showing a 100% negative predictive value was decided on as a threshold for each score. The risk group was defined when either of both scores was higher than its threshold. For the determination of a critical low post-TIPS PSG, a value of post-TIPS PSG showing the highest discrimination power on the receiver operating characteristic (ROC) curve in the risk group was decided on as a critical low threshold of PSG. The medically uncontrolled LPR complication rates of the patients with the determined threshold or lower were evaluated for the risk group. Results:, Medically uncontrolled LPR complications developed in nine patients (13.6%). Five patients died and four patients had TIPS reduction procedures. Patients with more than 10 on the Child-Pugh score or more than 14 on the MELD score were determined to be the risk group and 34 patients were included. The critical lower threshold of the post-TIPS PSG showing the highest discrimination power on the ROC curve was 5 mmHg (sensitivity 100%, specificity 72%), and the medically uncontrolled LPR complication rates of the patients with 5 mmHg or lower on the post-TIPS PSG were 56.3% (9/16) in the risk group. Conclusions:, The critical threshold of the post-TIPS PSG to avoid the medically uncontrolled LPR complications of TIPS was >5 mmHg. The PSG should not be reduced below this level in the risk group. [source]

Hepatic resection compared to percutaneous ethanol injection for small hepatocellular carcinoma using propensity score matching

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 10 2007
Yong Beom Cho
Abstract Background:, Several surgical and non-surgical therapeutic modalities have been used for the treatment of hepatocellular carcinoma (HCC). There have been several studies comparing hepatic resection (HR) and percutaneous ethanol injection (PEI) for the treatment of HCC. However, there is still disagreement about the best treatment modality. Methods:, From 130 patients undergoing HR, 116 patients were individually matched to 116 controls from 249 patients undergoing PEI using propensity score matching to overcome possible biases in non-randomized study. Survival analyses were undertaken to compare these propensity score-matched groups. Results:, After matching by propensity score, the major clinical outcomes in the HR (n = 116) and the PEI (n = 116) groups were found to be similar. The 1-, 3- and 5-year overall survival rates were higher in the HR group (94.8%, 76.5% and 65.6%) compared to the PEI group (95.7%, 73.5% and 49.3%) (P = 0.059). The cumulative 1-, 3- and 5-year disease-free survival rates showed the same trend (HR: 76.1%, 50.6% and 40.6%; PEI: 62.6%, 25.5% and 19.1%) (P < 0.001). However, when stratified by Child,Pugh classification, it was no longer the case in the Child B patients. Single intrahepatic recurrence was the most common pattern of tumor recurrence after both treatments. Conclusions:, Patients undergoing HR had a better survival profile than those undergoing PEI. However, when considering which technique to use for optimal HCC management, the individual patient's hepatic function must be considered. [source]

Evaluation of hernia repair operation in Child,Turcotte,Pugh class C cirrhosis and refractory ascites

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 3 2007
Joo Kyung Park
Abstract Background and Aim:, Abdominal wall hernia is a common feature of decompensated liver cirrhosis and frequently causes life-threatening complications or severe pain. However, there have been no data reported on postoperative mortality, hepatic functional deterioration and recurrence rate according to Child,Turcotte,Pugh (CTP) class and to the presence of refractory ascites. Methods:, The study population comprised 53 liver cirrhosis patients who underwent hernia repair operation. Comparisons were made of 30-day mortality among the different CTP classes, and between those with or without refractory ascites. Liver function was also analyzed just before the operation, in the immediate postoperative period, and in the remote postoperative period. Results:, Seventeen patients were in CTP class A, 27 patients in class B, and 9 patients in class C. The median follow-up duration was 24 months. There was single 30-day postoperative mortality in class C, and no CTP class deterioration after 30 days of operation. There was no mortality or recurrences in 17 patients with medically refractory ascites. The difference in 30-day mortality according to CTP class and the presence of refractory ascites did not show statistical significance (P = 0.17 and 0.97, respectively). Conclusion:, Hernia operation could be done safely in CTP class A and B with low rate of recurrences, and there was no definitive increase in the operative risk in class C. In addition, refractory ascites did not increase operative risk and recurrence rate. Therefore, surgical repair might be recommended even in patients with refractory ascites and poor hepatic function to prevent life-threatening complications or severe pain. [source]

Pharmacokinetics of roxatidine acetate in patients with chronic liver disease

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 8 2001
Mikihiro Tsutsumi
Abstract Background and Aim: Patients with liver disease are prone to develop peptic ulceration and often receive H2 -receptor antagonists. Therefore, it is important to clarify whether the pharmacokinetics of H2 -receptor antagonists is affected by hepatic function. However, pharmacokinetics of a new H2 -receptor antagonist, roxatidine acetate, in chronic liver disease has not been well known. In this study, we analyzed the pharmacokinetics of roxatidine in patients with liver disease. Methods: Blood samples were obtained from 11 patients with chronic hepatitis, 11 patients with cirrhosis and six healthy subjects. Under fasting conditions, 75 mg of roxatidine acetate was administered orally, and plasma roxatidine levels were determined sequentially from 3 to 12 h. Relationships between pharmacokinetic variables and each parameter related to hepatic functions were also investigated. Results: There was no difference in the pharmacokinetic variables and serum levels of roxatidine between chronic hepatitis and healthy controls. In contrast, in cirrhosis, serum roxatidine levels were significantly higher than those in chronic hepatitis and normal control. Half-life, the area under the plasma concentration,time curve and clearance in cirrhosis were also significantly longer, bigger and smaller than those in chronic hepatitis and healthy controls, respectively. The half-life became longer and the clearance became smaller in parallel with the progression of liver disease. Serum levels of hyaluronate and ,-glutamyl transpeptidase showed a good correlation with half-life, clearance and elimination rate. A good correlation between creatinine clearance and elimination rate was found. Conclusion: Pharmacokinetics of roxatidine acetate is affected by hepatic function, and the dosage of roxatidine acetate for patients with liver disease, especially cirrhosis, should be modified. [source]

Toxicity in Doberman Pinchers with Ventricular Arrhythmias Treated with Amiodarone (1996,2005)

JOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 1 2009
M.S. Kraus
Background: Asymptomatic Doberman Pinschers with dilated cardiomyopathy (DCM) often die suddenly owing to ventricular tachycardia that degenerates into ventricular fibrillation. A safe and effective antiarrhythmic drug treatment is needed. This will require a large, well-controlled, prospective study. Hypothesis: Amiodarone toxicity is common in Dobermans with occult DCM and ventricular tachyarrhythmias refractory to antiarrhythmia therapy. Infrequent monitoring of hepatic function is inadequate. Frequent monitoring may be useful to determine dogs in which the dosage should be decreased or the drug withdrawn. Methods: Medical records from the University of Georgia and Cornell University were searched for Doberman Pinschers diagnosed with preclinical DCM that received amiodarone for severe ventricular arrhythmias refractory to other antiarrhythmic agents. Echocardiographic data, Holter recording data, hepatic enzyme serum activity, and serum amiodarone concentrations were recorded. The presence of clinical signs of toxicity was recorded. Serum amiodarone concentrations were obtained in some dogs. Results: Reversible toxicity was identified in 10 of 22 (45%) dogs. Conclusion and Clinical Importance: Adverse effects from amiodarone were common and were, in part, dosage related. Patients should be monitored for signs of toxicity and liver enzyme activity should be measured at least monthly. [source]

Preclinical experiment of auxiliary partial orthotopic liver transplantation as a curative treatment for hemophilia

LIVER TRANSPLANTATION, Issue 5 2005
Saiho Ko
The cause of hemophilia is deficiency of coagulation factor VIII production in the liver, which can be cured by liver transplantation. Because the hepatic function of hemophilia patients is quite normal except for production of factor VIII, auxiliary partial orthotopic liver transplantation (APOLT) is beneficial in that patient survival is secured by preserving native liver even in the event of graft loss. However, it is not known whether the graft of APOLT would be enough to cure hemophilia. We evaluated the efficacy and feasibility of APOLT for hemophilia in a canine hemophilia A model that we established. Partial left liver graft was taken from the normal donor (blood factor VIII activity > 60%). The graft was transplanted to the hemophilia beagle dog (blood factor VIII activity < 5%) after resection of the left lobe preserving native right lobe. Changes in time of blood factor VIII activity and liver function parameters were observed after APOLT. APOLT and perioperative hemostatic management were successfully performed. The blood factor VIII activity increased to 30% after APOLT, and was sustained at least 6 weeks throughout the observation period without symptoms of bleeding. The result demonstrated sustained production of factor VIII in the hemophilia recipient after APOLT. Transplantation of approximately one third of whole liver resulted in cure of hemophilia. In conclusion, it is suggested that APOLT would be feasible as a curative treatment of hemophilia A to improve quality of life of the patients. (Liver Transpl 2005;11:579,584.) [source]

Surgical treatment of Budd-Chiari syndrome

LIVER TRANSPLANTATION, Issue 9 2003
Andrew S. Klein
Shunting and transplantation are satisfactory methods of treating Budd-Chiari syndrome (BCS). Selection of treatment is based on the degree of hepatic injury (clinical settings), liver biopsy results, potential for parenchymal recovery, and pressure measurements. Shunting is recommended in cases of preserved hepatic function and architecture. In the presence of fulminant forms of BCS, in cases of established cirrhosis or frank fibrosis, or for patients with defined hepatic metabolic defects (e.g., protein C or protein S deficiency), liver transplantation is the treatment of choice. Nonsurgical alternatives, although encouraging, have limited long-term outcome results at the present time. In most cases of BCS, a thrombophilic disorder can be identified. However, it is important to note that postoperative vascular thrombosis has been identified in patients with BCS who do not have a definable hypercoagulable predisposition. It therefore is our practice to recommend early (<24 hours postoperatively) initiation of intravenous heparin therapy in all patients with BCS, who then undergo life-long anticoagulation with coumadin. (Liver Transpl 2003;9:891-896.) [source]

Pathophysiology of renal disease associated with liver disorders: Implications for liver transplantation.

LIVER TRANSPLANTATION, Issue 2 2002
Part I
Renal and hepatic function are often intertwined through both the existence of associated primary organ diseases and hemodynamic interrelationships. This connection occasionally results in the chronic failure of both organs, necessitating combined liver-kidney transplantation (LKT). Since 1988, more than 850 patients in the United States have received such transplants, with patient survival somewhat less than that for patients receiving either organ alone. Patients with renal failure caused by acute injury or hepatorenal syndrome have classically not been included as candidates for combined transplantation because of the reversibility of renal dysfunction after liver transplantation. However, the rate and duration of renal failure before liver transplantation is increasing in association with prolonged waiting list times. Thus, the issue of acquired permanent renal damage in the setting of hepatic failure continues to confront the transplant community. The following article and its sequel (Part II, to be published in vol 8, no 3 of this journal) attempt to review the problem of primary and secondary renal disease in patients with end-stage liver disease, elements involved in renal disease progression and recovery, the impact of renal disease on liver transplant outcome, and results of combined LKT; outline the steps in the pretransplantation renal evaluation; and provide the beginnings of an algorithm for making the decision for combined LKT. [source]

In situ splitting of a liver with middle hepatic vein anomaly

LIVER TRANSPLANTATION, Issue 9 2001
Alessandro Genzone MD
In situ liver splitting provides a way to expand the graft pool, minimize cold ischemia time, and improve hemostasis at the cut surface of the graft. Vascular anomalies of the liver may make the splitting procedure very difficult or even impossible to perform. The in situ splitting procedure, performed on a liver with a middle hepatic vein (MHV) anomaly, is described here. The MHV drained directly into the segment III vein within the hepatic parenchyma instead of draining into the left hepatic vein to form the common trunk. In situ splitting was performed during multiorgan procurement from a 33-year-old man who died of isolated cerebral trauma. The MHV was reconstructed on the back table to secure right graft venous drainage using an iliac vein graft. The resultant right graft, segments I and IV to VIII, and left graft, segments II and III, were transplanted successfully into an adult and a child, respectively. The 2 transplant recipients are currently alive with normal hepatic function 20 months after transplantation. [source]

Treatment of invasive candidiasis with echinocandins

MYCOSES, Issue 6 2009
Andreas Glöckner
Summary Blood stream infections by Candida spp. represent the majority of invasive fungal infections in intensive care patients. The high crude mortality of invasive candidiasis remained essentially unchanged during the last two decades despite new treatment options that became available. The echinocandins, the latest class of antifungals introduced since 2001, exhibit potent activity against clinically relevant fungi including most Candida spp. In several randomised multicentre phase III trials, anidulafungin, caspofungin and micafungin showed convincing efficacy when compared with standard treatment regimens. In all trials, echinocandins were at least non-inferior to standard treatments. Anidulafungin was shown to be superior to fluconazole. Echinocandins have a favourable tolerability profile and exhibit a minimal potential for drug interactions since their pharmacokinetics is independent of renal and , largely , hepatic function. As a result of these properties, echinocandins are appropriate drugs of choice for invasive candidiasis in intensive care where many patients experience organ failure and receive multiple drugs with complex interactions. [source]

Comparison of plasma , glutathione S-transferase concentrations during and after low-flow sevoflurane or isoflurane anaesthesia

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 10 2001
H. Higuchi
Background: We evaluated the effect of low-flow sevoflurane anaesthesia, in which compound A is generated, and isoflurane anaesthesia, in which compound A is not generated (n=13 in each group), on hepatocellular integrity using , glutathione S-transferase (GST). , GST is a more sensitive and specific marker of hepatocellular damage than is aminotransferase activity and correlates better with hepatic histology. Methods: Sevoflurane or isoflurane were delivered without nitrous oxide with a fresh gas flow of 1 l/min. Concentrations of compound A in the circuit were measured hourly, and plasma , GST concentrations were measured perioperatively. Results: Mean duration of anaesthesia was 338±92 min in the sevoflurane group and 320±63 min in the isoflurane group. Mean compound A concentration in the sevoflurane group was 28.6±9.0 ppm. There was no significant difference in , GST concentrations between the sevoflurane and isoflurane groups during or after anaesthesia. Conclusion: These results indicate that low-flow sevoflurane and isoflurane anaesthesia have the same effect on hepatic function, as assessed by plasma , GST concentrations. [source]

Effect of Photocrosslinkable Chitosan Hydrogel and Its Sponges to Stop Bleeding in a Rat Liver Injury Model

ARTIFICIAL ORGANS, Issue 4 2010
Takuya Horio
Abstract This study examined the hemostatic efficacy of photocrosslinkable chitosan hydrogel-mixed photocrosslinked chitosan sponges (PCM-S) after hepatic injury in rats. The left lobe of the liver was penetrated with a dermal punch to produce a penetrating wound in heparinized and nonheparinized rats. Treated rats either had PCM-S applied into the wound and then were immediately ultraviolet irradiated, or they had TachoComb (TC) inserted into the wound. Blood loss, hemostasis, and survival were quantified after the hepatic injury. Measurements on serum alanine aminotransferase in nonheparinized rats and hemoglobin concentrations and histologic examinations in heparinized rats were performed to assess hepatic function. Although the hemostatic effect in the PCM-S-treated nonheparinized rats was identical to that of the TC-treated group, PCM-S-treatment has higher hemostatic effect in heparinized rats. No adverse events related to the use of PCM-S were detected in blood and histologic examinations. [source]

Mechanical Dissociation of Swine Liver to Produce Organoid Units for Tissue Engineering and In Vitro Disease Modeling

ARTIFICIAL ORGANS, Issue 1 2010
Katayun Irani
Abstract The complex intricate architecture of the liver is crucial to hepatic function. Standard protocols used for enzymatic digestion to isolate hepatocytes destroy tissue structure and result in significant loss of synthetic, metabolic, and detoxification processes. We describe a process using mechanical dissociation to generate hepatic organoids with preserved intrinsic tissue architecture from swine liver. Oxygen-supplemented perfusion culture better preserved organoid viability, morphology, serum protein synthesis, and urea production, compared with standard and oxygen-supplemented static culture. Hepatic organoids offer an alternative source for hepatic assist devices, engineered liver, disease modeling, and xenobiotic testing. [source]

Application of Multivariate Analysis to Optimize Function of Cultured Hepatocytes

BIOTECHNOLOGY PROGRESS, Issue 2 2003
Christina Chan
Understanding the metabolic and regulatory pathways of hepatocytes is important for biotechnological applications involving liver cells, including the development of bioartificial liver (BAL) devices. To characterize intermediary metabolism in the hepatocytes, metabolic flux analysis (MFA) was applied to elucidate the changes in intracellular pathway fluxes of primary rat hepatocytes exposed to human plasma and to provide a comprehensive snapshot of the hepatic metabolic profile. In the current study, the combination of preconditioning and plasma supplementation produced distinct metabolic states. Combining the metabolic flux distribution obtained by MFA with methodologies such as Fisher discriminant analysis (FDA) and partial least squares or projection to latent structures (PLS) provided insights into the underlying structure and causal relationship within the data. With the aid of these analyses, patterns in the cellular response of the hepatocytes that contributed to the separation of the different hepatic states were identified. Of particular interest was the recognition of distal pathways that strongly correlated with a particular hepatic function. The hepatic functions investigated were intracellular triglyceride accumulation and urea production. This study illustrates a framework for optimizing hepatic function and a possibility of identifying potential targets for improving hepatic functions. [source]

Systemic toxicity of tacrolimus given by various routes and the response to dose reduction

CLINICAL & EXPERIMENTAL OPHTHALMOLOGY, Issue 1 2005
Laboratory Science
Abstract Purpose:,To evaluate the long-term systemic toxicity of tacrolimus (FK-506) administered by various routes, and to assess the effect of dose reduction on toxicity. Methods:,The study animals were 120 experimentally naïve adult female Wistar rats weighing 200,250 g each. The rats were randomly divided into 10 equal groups (n = 12 in each) and treated with tacrolimus administered topically (in drops, 0.3%, q.i.d.), intravitreally (0.5 mg/kg bodyweight/week), intramuscularly (1 mg/kg bodyweight/week), low-dose intravenously (1 mg/kg bodyweight/week) and in high-dose intravenously (2 mg/kg bodyweight/week) for 3 months. The rats in the control groups (one for each different route of administration) were treated with 0.9% NaCl. The blood concentration of tacrolimus, complete blood count and biochemistry parameters were measured each month for the 3-month study period. Results:,The rats in the control groups and experimental groups administered topical and intravitreal tacrolimus did not demonstrate any systemic toxic effects. The rats that developed certain toxic effects (hyperglycaemia, hyperkalaemia and nephrotoxicity) in the groups given low-dose or high-dose i.v. tacrolimus responded well to dose reduction. Following dose reduction, blood glucose concentrations decreased from 247.4 ± 42.3 mg/dL to 189.6 ± 37.9 mg/dL (P < 0.05), and from 237.4 ± 41.1 mg/dL to 182.3 ± 22.7 mg/dL (P < 0.05) in the low- and high-dose i.v. tacrolimus-treated rats, respectively. The rats that developed impaired hepatic function after high-dose tacrolimus did not respond to dose reduction. Baseline cholesterol concentrations for the intramuscular and low- and high-dose i.v. tacrolimus-treated groups, demonstrated decreases, respectively, from 87.4 ± 14.0 mg/dL, 86.4 ± 14.0 mg/dL and 90.4 ± 14.3 mg/dL to 53.6 ± 9.8 mg/dL, 52.1 ± 12.5 mg/dL and 63.5 ± 11.7 mg/dL by the end of the second month. The differences were found to be statistically significant (P < 0.05 for each result). Conclusion:,Topical or intravitreal administration of tacrolimus seems to be systemically safe whereas parenteral administration can cause some systemic haematological changes such as dose-dependent decreased serum cholesterol concentrations. Dose reduction may prevent such adverse effects. [source]

PATIENT AGE IS A STRONG INDEPENDENT PREDICTOR OF 13C-AMINOPYRINE BREATH TEST RESULTS: A COMPARATIVE STUDY WITH HISTOLOGY, DUPLEX-DOPPLER AND A LABORATORY INDEX IN PATIENTS WITH CHRONIC HEPATITIS C VIRUS INFECTION

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 4 2006
Arne RJ Schneider
SUMMARY 1Noninvasive tests for the staging of chronic hepatitis C virus (HCV) infection would be an attractive alternative to liver biopsy. The 13C-aminopyrine breath test (ABT) has been proposed for the noninvasive assessment of hepatic function and partly correlates with fibrosis. We aimed to investigate causes for the lack of discriminatory power for different degrees of hepatic fibrosis. 2Eighty-three patients (median age 49 years (28,78 years)) with chronic HCV infection underwent the ABT after an oral load of 75 mg N,N-dimethyl- 13C-aminopyrine. Portal vein flow was assessed by duplex-Doppler and a laboratory index (aspartate aminotransferase to platelet ratio index or APRI) was calculated. Parameters were compared with liver histology. 3The cumulative 13C-recovery differed significantly between patients without relevant fibrosis (fibrosis score 0,2) and cirrhosis (5,6), beginning after 30 min of sampling (P < 0.05). The ABT did not discriminate patients with fibrosis scores 3,4 from the remaining two patient groups. Sensitivity and specificity for the prediction of cirrhosis was 73.4,82.8% and 63.2,68.4%, depending on the sampling time. Compared with the fibrosis score (P = 0.04), patient age was a highly significant independent predictor for the 13C-recovery (P < 0.0001). Aspartate aminotransferase to platelet ratio index and duplex-Doppler predicted cirrhosis with 76.6%vs. 87.5% sensitivity and 63.2%vs. 68.4% specificity. 4Our data suggest an age-dependent decrease of cytochrome P450 activity which probably accounts for the large overlap of ABT results that preclude clear differentiation. This is also consistent with former pharmacodynamic trials. Age-adapted reference ranges could improve ABT results. [source]

Chronic Liver Disease Impairs Bacterial Clearance in a Human Model of Induced Bacteremia

CLINICAL AND TRANSLATIONAL SCIENCE, Issue 3 2009
Alix Ashare M.D., Ph.D.
Abstract Sepsis often causes impaired hepatic function. Patients with liver disease have an increased risk of bacteremia. This is thought to be secondary to impaired reticuloendothelial system function. However, this has not been demonstrated clinically. Since transient bacteremia occurs following toothbrushing, we hypothesized that subjects with cirrhosis would have impaired bacterial clearance following toothbrushing compared with subjects with pulmonary disease and healthy controls. After baseline blood was drawn, the subjects underwent a dental examination to determine plaque index and gingival index. Following toothbrushing, blood was drawn at 30 seconds, 5 minutes, and 15 minutes. Bacteremia was measured using quantitative real-time PCR with primers that amplify all known bacteria. We found greater than 75% incidence of bacteremia following toothbrushing. While control and pulmonary subjects were able to clear this bacteremia, subjects with cirrhosis had prolonged bacteremia. Baseline and peak bacterial load correlated with plaque index, suggesting that dental hygiene predicts the degree of bacteremia. However, only the severity of cirrhosis was predictive of bacterial clearance at 15 minutes, suggesting that liver function is important in clearing bacteremia. In this study, we demonstrate clinically that cirrhosis results in impaired bacterial clearance. This suggests that cirrhotic patients may be more susceptible to sepsis because of ineffective bacterial clearance. [source]

Liver dysfunction in Turner's syndrome: prevalence, natural history and effect of exogenous oestrogen

CLINICAL ENDOCRINOLOGY, Issue 2 2008
Olympia Koulouri
Summary Objectives, Raised liver enzymes are a common feature of Turner's syndrome (TS), but the cause remains unclear. We studied the hepatic function in a large cohort of women with TS and tested the effect of increasing doses of hormone replacement therapy (HRT) on liver function tests (LFTs). Design and patients, LFTs were assessed in three studies. A cross-sectional review of liver function of 125 women (median age: 31 years), a longitudinal study of 30 women (mean follow-up period: 8 years) and a dose,response study of 14 women with TS and 11 controls with hypogonadism, who received oral 17-,-oestradiol (E2) 1, 2 and 4 mg daily in a cyclical formulation for 12 weeks each. Measurements, Clinical features, oestrogen use and metabolic parameters were compared to liver enzymes (,-glutamyl transferase (GGT), alanine aminotransferase (ALT) and alkaline phosphatase (ALP)), albumin and bilirubin. LFTs were also measured during each treatment interval of the dose,response study. Hepatic autoimmunity was sought in the cross-sectional study. Results, When compared to the control population, as opposed to reference ranges, 91% of women with TS demonstrated liver enzyme elevation, with a yearly incidence of 2·1%. LFTs correlated positively with cholesterol (P < 0·001), BMI (P = 0·004) and type of oestrogen therapy (P = 0·04). Increasing doses of HRT resulted in a significant decrease in GGT, ALT, bilirubin and albumin. No evidence of excessive hepatic autoimmunity was found. Conclusion, The prevalence of raised liver enzymes in TS may have been underestimated by the use of reference ranges rather than matched controls. Obesity and hyperlipidaemia are associated with raised LFTs, as well as the use of HRT compared to the oral contraceptive pill (OCP). Exogenous oestrogen both as OCP and HRT improves liver function. Liver dysfunction in TS is likely to be a form of hepatic steatosis and intervention trials are now indicated. [source]

13C-breath tests for clinical investigation of liver mitochondrial function

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 9 2010
Ignazio Grattagliano
Eur J Clin Invest 2010; 40 (9): 843,850 Abstract Background, Mitochondria play a major role in cell energetic metabolism; therefore, mitochondrial dysfunction inevitably participates in or even determines the onset and progression of chronic liver diseases. The assessment of mitochondrial function in vivo, by providing more insight into the pathogenesis of liver diseases, would be a helpful tool to study specific hepatic functions and to develop rational diagnostic, prognostic and therapeutic strategies. Design, This review focuses on the utility of breath tests to assess mitochondrial function in humans and experimental animals. Results, The introduction in the clinical setting of specific breath tests may allow elegantly and noninvasively overcoming the difficulties caused by previous complex techniques and might provide clinically relevant information, i.e the effects of drugs on mitochondria. Substrates meeting this requirement are alpha-keto-isocaproic acid and methionine that are both decarboxylated by mitochondria. Long-and medium-chain fatty acids that are metabolized through the Krebs cycle, and benzoic acid which undergoes glycine conjugation, may also reflect the function of mitochondria. Conclusions, Breath tests to assess in vivo mitochondrial function in humans represent a potentially useful diagnostic and prognostic tool in clinical investigation. [source]

Upregulation of the tumor suppressor gene menin in hepatocellular carcinomas and its significance in fibrogenesis,

HEPATOLOGY, Issue 5 2006
Pierre J. Zindy
The molecular mechanisms underlying the progression of cirrhosis toward hepatocellular carcinoma were investigated by a combination of DNA microarray analysis and literature data mining. By using a microarray screening of suppression subtractive hybridization cDNA libraries, we first analyzed genes differentially expressed in tumor and nontumor livers with cirrhosis from 15 patients with hepatocellular carcinomas. Seventy-four genes were similarly recovered in tumor (57.8% of differentially expressed genes) and adjacent nontumor tissues (64% of differentially expressed genes) compared with histologically normal livers. Gene ontology analyses revealed that downregulated genes (n = 35) were mostly associated with hepatic functions. Upregulated genes (n = 39) included both known genes associated with extracellular matrix remodeling, cell communication, metabolism, and post-transcriptional regulation gene (e.g., ZFP36L1), as well as the tumor suppressor gene menin (multiple endocrine neoplasia type 1; MEN1). MEN1 was further identified as an important node of a regulatory network graph that integrated array data with array-independent literature mining. Upregulation of MEN1 in tumor was confirmed in an independent set of samples and associated with tumor size (P = .016). In the underlying liver with cirrhosis, increased steady-state MEN1 mRNA levels were correlated with those of collagen ,2(I) mRNA (P < .01). In addition, MEN1 expression was associated with hepatic stellate cell activation during fibrogenesis and involved in transforming growth factor beta (TGF-,),dependent collagen ,2(I) regulation. In conclusion, menin is a key regulator of gene networks that are activated in fibrogenesis associated with hepatocellular carcinoma through the modulation of TGF-, response. (HEPATOLOGY 2006;44:1296,1307.) [source]