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At least 163 records · Page 9Linked to original sources
PubMed1982

Autoantibodies to liver antigens in chronic liver disease. I. A radioimmunoassay for antibody to liver membrane antigens.

A radioimmunoassay using a single cell suspension of glutaraldehyde-treated monkey hepatocytes was developed to measure antibody in human serum to liver membrane antigens. Hepatocytes were exposed to doubling dilutions of test sera in microtitre trays and binding of serum IgG was determined by exposure of the washed cells to 125I-labelled staphylococcal protein A. Specificity of binding was established according to several criteria including use of non-hepatic cells such as monkey kidney cells and various cell lines, IgG depletion of serum, absorption of binding activity by pre-exposure of serum to liver cells, and demonstration that binding was mediated by the F(ab) rather than Fc portions of immunoglobulin molecules. This radioimmunoassay distinguished autoimmune-type chronic active hepatitis (CAH) from other categories of liver disease. It should prove useful for diagnosis and classification of cases of CAH, and could facilitate identification of a liver-specific membrane antigen relevant to pathogenesis of autoimmune hepatitis.

Animals↗
PubMed1985

[Liver diseases and pregnancy. II: Liver diseases without causal relation to pregnancy--general principles for treatment of patients with liver disease].

In addition to a previous paper [7] a survey is given of acute viral hepatitis, drug-induced liver-disease, chronic hepatitis, cirrhosis of the liver, hyperbilirubinemia, hepatic porphyria, and obstructive jaundice as hepatobiliary diseases independent of pregnancy. Finally, some questions of treatment of pregnant women suffering from liver disease are stressed.

Chemical and Drug Induced Liver Injury↗
PubMed2003

Decreased liver fatty acid binding capacity and altered liver lipid distribution in mice lacking the liver fatty acid-binding protein gene.

Although liver fatty acid-binding protein (L-FABP) is an important binding site for various hydrophobic ligands in hepatocytes, its in vivo significance is not understood. We have therefore created L-FABP null mice and report here their initial analysis, focusing on the impact of this mutation on hepatic fatty acid binding capacity, lipid composition, and expression of other lipid-binding proteins. Gel-filtered cytosol from L-FABP null liver lacked the main fatty acid binding peak in the fraction that normally comprises both L-FABP and sterol carrier protein-2 (SCP-2). The binding capacity for cis-parinaric acid was decreased >80% in this region. Molar ratios of cholesterol/cholesterol ester, cholesteryl ester/triglyceride, and cholesterol/phospholipid were 2- to 3-fold greater, reflecting up to 3-fold absolute increases in specific lipid classes in the order cholesterol > cholesterol esters > phospholipids. In contrast, the liver pool sizes of nonesterified fatty acids and triglycerides were not altered. However, hepatic deposition of a bolus of intravenously injected [14C]oleate was markedly reduced, showing altered lipid pool turnover. An increase of approximately 75% of soluble SCP-2 but little or no change of other soluble (glutathione S-transferase, albumin) and membrane (fatty acid transport protein, CD36, aspartate aminotransferase, caveolin) fatty acid transporters was measured. These results (i) provide for the first time a quantitative assessment of the contribution of L-FABP to cytosolic fatty acid binding capacity, (ii) establish L-FABP as an important determinant of hepatic lipid composition and turnover, and (iii) suggest that SCP-2 contributes to the accumulation of cholesterol in L-FABP null liver.

Acetyl-CoA C-Acetyltransferase↗
PubMed1986

Cytochrome P-450-dependent monooxygenase activities in prenatal and postnatal human livers: comparison of human liver 7-alkoxycoumarin O-dealkylases with rat liver enzymes.

Human liver samples from 17 embryos, 5 fetuses, 5 infants and 4 adults were used to investigate human liver cytochrome P-450-dependent 7-alkoxycoumarin O-dealkylase activities, and their drug-metabolizing activities were compared to those of rat livers. The O-dealkylase activities in human embryos and fetuses were very low, although detectable, similar to those in fetal rats. Both male and female rats showed a postnatal increase of hepatic O-dealkylase activities with a maximum at about 30-40 days after birth and then a decline in the activities which was marked in female rats. Adult female rats showed a marked decrease in the hepatic enzyme activity observed in the O-depropylation reaction rather than the O-demethylation and O-deethylation reactions. During the developmental period of human infants, the O-demethylase activity, but not O-depropylase activity, increased gradually. Enzymes in adult human livers metabolize the O-methyl derivative of 7-hydroxycoumarin in preference to the O-ethyl and O-propyl derivatives. The metabolic activities of human adult enzymes for 7-alkoxycoumarin resembled those in adult female rats and were quite different from those in male rats. The study demonstrated that caution must be exercised in extrapolating pharmacological results from animal to man in the field of drug metabolism.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1995

Hypertriglyceridemia and fatty liver: clinical diagnosis of fatty liver and lipoprotein profiles in hypertriglyceridemic patients with fatty liver.

Fatty liver has prevailed by 14% in the healthy population of this country. The factors contributing genesis of fatty liver were gender (male), obesity, high alcohol consumption, glucose intolerance and hypertriglyceridemia. And hypertriglyceridemia seems to be the common underlying factor to all other causes. The mechanism for accumulation of triglycerides in the liver can be explained at least by increased HTGL activities and elevated apo A-II levels, a postulated co-factor of HTGL. An hypertriglyceridemic patients with fatty liver had the insulin resistance.

Adult↗
PubMed2000

Nutritional pharmacotherapy of chronic liver disease: from support of liver failure to prevention of liver cancer.

Many patients with liver cirrhosis are in a state of protein and energy malnutrition and require careful nutritional support. Our research has revealed that approximately 30% of the patients have protein-energy malnutrition, 40% protein malnutrition, and 10% energy malnutrition; 20% are in a normal nutritional state. Supplementation with branched-chain amino acids alleviates chronic liver failure, improves the protein nutritional state, and subsequently prolongs survival. In contrast, therapeutic modalities for energy malnutrition have not yet been fully elucidated and await further studies. Improved survival of the cirrhotic patients essentially brings a higher incidence of hepatocellular carcinoma (HCC). A synthetic analogue of vitamin A (acyclic retinoid or 4,5-dehydrogeranyl geranoic acid) prevents at least the development of second primary tumors after curative treatment of preceding HCC. The mechanism of this cancer chemo-prevention is clonal deletion of premalignant and latent malignant cells by the retinoid. We describe our clinical experiences with these two nutritional pharmacotherapies of chronic liver diseases and review their basic mechanisms.

Amino Acids, Branched-Chain↗
PubMed2003

Bridging a patient with acute liver failure to liver transplantation by the AMC-bioartificial liver.

Recently a phase I clinical trial has been started in Italy to bridge patients with acute liver failure (ALF) to orthotopic liver transplantation (OLT) by the AMC-bioartificial liver (AMC-BAL). The AMC-BAL is charged with 10 x 10(9) viable primary porcine hepatocytes isolated from a specified pathogen-free (SPF) pig. Here we report a patient with ALF due to acute HBV infection. This patient was treated for 35 h by two AMC-BAL treatments and was bridged to OLT. There was improvement of biochemical and clinical parameters during the treatment. No severe adverse events were observed during treatment and follow-up of 15 months after hospital discharge. Possible porcine endogenous retrovirus (PERV) activity could not be detected in the patient's blood or blood cells up to 12 months after treatment.

Adult↗
PubMed1991

Scintigraphic right-to-left liver lobe ratio and liver-to-spleen ratio in cirrhosis and non cirrhotic liver diseases.

Various criteria are used together for the scintigraphic diagnosis of cirrhosis as no single criterion may be reliable. However, low right-to-left hepatic lobe uptake ratio has been reported to be sensitive and specific for alcoholic cirrhosis. A low liver-to-spleen uptake ratio has also been reported in various hepatocellular disorders. We tested these ratios in patients with cirrhosis and non cirrhotic causes of portal hypertension. The right-to-left lobe uptake ratio was significantly lower (1.59 +/- 1.23 vs 2.36 +/- 0.63 in normals; p = 0.037) in only Child's C alcoholic cirrhosis, but the sensitivity of this ratio was low (40%) even in this subgroup of cirrhosis (mean +/- SD 1.72 +/- 1.08) as against 1 of 10 patients with non cirrhotic portal hypertension (3.57 +/- 1.33; p = 0.0005). We conclude that the right-to-left hepatic lobe uptake ratio is not a discriminatory scintigraphic sign in liver disease. A low liver-to-spleen uptake ratio can distinguish cirrhosis from non cirrhotic causes of portal hypertension.

Diagnosis, Differential↗
PubMed1988

[Liver metabolism of indocyanine green and aminopyrine in liver cirrhosis: relations with functioning liver cell mass].

Hepatic clearance of indocyanine green, a drug with a high hepatic extraction rate, and breath tests with aminopyrine, a drug with a low hepatic extraction ratio, were calculated in 26 patients with liver cirrhosis. In addition galactose elimination capacity was calculated as an index of functional liver cell mass. All these parameters resulted significantly correlated with each other. These results confirm the view that during liver cirrhosis, metabolism of drugs with high and low hepatic extraction rates can be described according to the intact hepatocyte theory.

Adult↗
PubMed1988

[Chemistry of swine liver and products of liver processing. 1. Carbohydrate content of swine liver in relation to thermal stress].

Glucose can be extracted from the carbohydrates of pig liver by water, but glycogen only by boiling alkalies. The last one can be precipitated with ethanol. The boiling of an aqueous liver suspension causes a decrease in glucose quantity as expected. Thereby the influence of the liver proteins on carbohydrate concentration becomes apparent as well as the interaction between both substances within the reaction of non-enzymatic browning. A series of storing experiments confirmed that neither freezing nor boiling temperatures can completely stop this reaction.

Animals↗
PubMed1990

N-acetylglutamate content in liver and gut of normal and fasted mice, normal human livers, and livers of individuals with carbamyl phosphate synthetase or ornithine transcarbamylase deficiency.

N-acetylglutamate (NAG) content was measured in homogenates of liver and small intestine obtained from normal and 24-h starved syngeneic mice. Subsequently, NAG was determined in normal, and in carbamyl phosphate synthetase I and ornithine transcarbamylase enzyme-deficient human liver tissue homogenates. The method used in this study, which is direct and highly specific, used anion exchange extraction, gas chromatographic separation, and mass spectrometric detection and quantitation. Hepatic NAG content in the fed animals was 94.8 +/- 19.8 nmol/g tissue or 602.5 +/- 168.4 nmol/g protein (mean +/- SD, n = 5), whereas it was much lower in the fasted mice (49.4 +/- 13.0 nmol/g tissue or 330.1 +/- 113.9 nmol/g protein, mean +/- SD, n = 5). The magnitude of the difference was much smaller for intestinal NAG content, 19.8 +/- 5.4 nmol/g tissue or 205.3 +/- 70.3 nmol/g protein (mean +/- SD, n = 5) in the fed mice and 14.2 +/- 4.3 nmol/g tissue or 168.1 +/- 80.8 nmol/g protein (mean +/- SD, n = 5) in the fasted mice. The concentrations of hepatic NAG in normal human livers (controls) ranged from 19.3 to 67.1 nmol/g tissue (41.6 +/- 19.3, mean +/- SD, n = 5) or from 193 to 764.3 nmol/g of protein (437.5 +/- 233.4, mean +/- SD, n = 5).(ABSTRACT TRUNCATED AT 250 WORDS)

Ammonia↗
PubMed1981

A new method in differential diagnosis of the liver: identification of liver pulsating activities by spectral analysis of radio-isotope counts during liver scan. Comparative studies by ultrasonography.

Liver scanning with 99mCi 99Tc sulphur-colloid was practiced in 50 patients: 30 suffering from malignant tumors, 10 from hepatic cirrhosis and 10 from pyrexia of unknown origin. Liver radioactivity was recorded by a gamma-camera connected to a computer, 1 frame each 10 seconds for 15 minutes. The spectral analysis of the radioactivity counts taken in different region of interest, showed evidence of a periodic fluctuation, with a period value around 1 minute. Comparative ultrasonographic dynamic study showed evidence of the same phenomena in 16 examined patients. The period of pulsation was found different in each of the following groups: normal liver, cirrhotic, metastatic and infectious diseases.

Diagnosis, Differential↗
PubMed1992

The results of reduced-size liver transplantation, including split livers, in patients with end-stage liver disease.

We initiated a policy of using RSLT in critically ill patients in June of 1988. Since that time we have performed 30 RSLTs in 29 patients, including 28 children and 1 adult. The mean age of the children was 27 months (range 1 month to 10 years) with 14 (52%) being 1 year of age or less. The mean weight was 11.3 kg (range 2-50 kg) with 20 being 10 kg or less. A total of 22 patients were in the intensive care unit at the time of RSLT including 9 who were intubated. Of the 30 RSLTs, 23 were performed as a primary transplant while 7 were retransplants. Indications for primary transplantation included biliary atresia (n = 11), fulminant hepatic failure (n = 5), neonatal hepatitis (n = 4) and others (n = 3). The RSLT was used in retransplantation for primary nonfunction (n = 2), hepatic artery thrombosis (n = 2), chronic rejection (n = 2), and herpetic hepatitis (n = 1). The size reductions included 18 left lobes, 7 left lateral segments, and 5 right lobes. This group includes the use of the split-liver technique, which was applied to 10 patients (5 livers). The median donor/recipient weight ratio for left lobe transplants was 2:1; left lateral segments was 7.3:1; and right lobes 1.6:1. One year actuarial patient and graft survivals were 68 and 65%, respectively, with a mean follow-up of 10.6 months. The number of children dying awaiting transplantation has been significantly reduced following the introduction of RSLD (3 of 115, 2.6% vs. 12 of 95, 13%; P less than 0.02).

Adult↗
PubMed2005

Preconditioning by extracorporeal liver support (MARS) of patients with cirrhosis and severe liver failure evaluated for living donor liver transplantation -- a pilot study.

PURPOSE: The aim of this prospective study was to evaluate the effectiveness of preconditioning molecular adsorbent recirculating system (MARS) treatment on patients with acute-on-chronic liver failure (AoCLF), who were awaiting living donor liver transplantation (LDLT). PATIENTS AND METHODS: Between January and December 2001, 10 consecutive AoCLF patients (with progressive hyperbilirubinemia (>20 mg/dl) and hepatic encephalopathy grade > or =2) were studied. MARS was used in eight of these patients who were evaluated for LDLT during 2001. Three AoCLF patients who received LDLT before clinical use of MARS were used as historical controls. RESULTS: Because of a shortage of donors, only five out of 10 patients considered for LDLT could receive transplants. Three patients were treated with MARS for 8 h the day before receiving LDLT, and all three survived. The remaining two patients who received transplants, and who were not pretreated with MARS, died from sepsis and multi-organ failure within 2 weeks. Four of the patients who did not receive transplants because of donor shortage died despite 1 or 3 MARS treatments, however bilirubin levels and grade of encephalopathy were significantly reduced in these patients. CONCLUSIONS: Results of this small pilot study suggest that MARS, by reducing the severity of jaundice and encephalopathy, might be effective as a bridging option in AoCLF patients awaiting LDLT.

Adult↗
PubMed1985

Antibody to liver-specific lipoprotein in acute and chronic liver diseases. Its quantitative assay with monoclonal antibody, but without the use of liver-specific lipoprotein.

A double-antibody radioimmunoassay was developed to detect antibody to human liver-specific membrane lipoprotein (anti-LSP antibody) in patients' serum. Anti-human LSP monoclonal antibody was labeled with 125I and anti-anti-LSP antiserum raised in rabbits was used as the first antibody in the assay. Anti-LSP antibody level was quantitatively measured and the assay was shown to be specific. Anti-LSP antibody was found in 5/8 patients with type B acute viral hepatitis (AVH), 3/7 patients with type A AVH, 1/6 patients with non-A, non-B AVH, 10/17 patients with chronic active hepatitis (CAH), 6/16 patients with chronic persistent hepatitis, 13/16 patients with active cirrhosis of the liver and 7/19 patients with primary nonhepatic autoimmune diseases such as glomerulonephritis, systemic lupus erythematosus and rheumatoid arthritis. The mean levels of anti-LSP were increased in patients with cirrhosis of the liver (p less than 0.01), CAH (p less than 0.05) and AVH (p less than 0.05) when compared with that of normal individuals. However, the frequencies of anti-LSP did not depend on HBsAg status. The data showed that anti-LSP antibody can be detected without the use of LSP preparation although it is also found in patients with primary nonhepatic autoimmune diseases.

Animals↗
PubMed2000

[Therapy of recurrent hepatitis B infection after liver transplantation. A retrospective analysis of 200 liver transplantations based on hepatitis B associated liver diseases].

BACKGROUND: Before introduction of passive immunoprophylaxis and new antiviral nucleoside analogues the course of hepatitis B recurrence after liver transplantation could hardly be influenced. The result was a inferior graft survival. In the present retrospective analysis of the efficacy of hepatitis B therapy after liver transplantation was analysed retrospectively. PATIENTS AND METHODS: Between 1988 and 1998 in total 179 patients were transplanted due to hepatitis B related liver failure at our centre. All patients received passive immunoprophylaxis with hepatitis B immunoglobulin. In case of reinfection after 1993 an antiviral therapy with famciclovir 1500 mg daily was initiated (n = 26), since 1996 lamivudine (100-150 mg daily) was used (n = 12). In case of viral breakthrough under famciclovir treatment or prophylaxis therapy was switched to lamivudine (n = 22). In case of ineffectiveness of lamivudine an antiviral combination therapy with lamivudine and interferon (n = 4) or lamivudine and famciclovir (n = 4) was initiated. Before availability of antiviral agents or in case of viral breakthrough in total 12 patients were retransplanted due to acute or chronic reinfection. RESULTS: With passive immunoprophylaxis reinfection rate was 33%, 43% and 44% after 1, 3 and 5 years respectively. Without antiviral treatment 52% of patients died within the first year after reinfection. Antiviral therapy with lamivudine or famciclovir improved the one year survival after reinfection to 79%. Suppression of viral replication was more effective with lamivudine. Under lamivudine 26 patients (76%) became HBV-DNA negative, 9 patients HBsAg negative (26%). In contrast no patient became HBsAg negative during famciclovir therapy. Lamivudine was effective also after famciclovir breakthrough in 94% of patients. In case of lamivudine resistant reinfection viral replication could be suppressed with an antiviral combination therapy up to negative HBV-DNA in the hybridization assay. Severe side effects were not observed during any of the antiviral therapies. The graft survival after retransplantation for hepatitis B reinfection was 42% and 25% after one and 3 years. CONCLUSION: Whereas it is generally accepted, that passive immunoprophylaxis lowers the reinfection rate it could be shown in the present study, that antiviral treatment lowers mortality of hepatitis B reinfection. The major problem of lamivudine and famciclovir is viral resistance formation. In this case an antiviral combination therapy might be useful, whereas retransplantation for hepatitis B reinfection should be considered carefully due to inferior graft survival rates.

2-Aminopurine↗
PubMed1991

[Splitting liver transplantation. Orthotopic liver transplantation in two recipients with a single donor liver].

Surgical reduction of donor livers to treat small children has been performed successfully in several centers. While this procedure improves the allocation of livers, it does not increase the organ supply. Since either lobe can be used in preparing a reduced-size graft, both lobes can become grafts, if acceptable vascular pedicles and bile ducts can be established for each one. We report and demonstrate a technique, in which a donor liver has been split and was used to transplant in two recipients.

Anastomosis, Surgical↗