bluuebunny/crossref_metadata_2025 huggingface dataset:
Portal-systemic shunts for Budd-Chiari syndrome
Authors: Orloff Marshall J.
Published: March 2007

Nine patients with Budd-Chiari syndrome (BCS) were treated by a portal systemic shunt. One had thrombosis of the superior mesenteric vein (SMV) and another had complete obstruction of the retrohepatic inferior vena cava (IVC). All other patients had a marked stenosis of the retrohepatic IVC with caval pressure ranging from 12 to 24 mmHg (mean: 17 mmHg). Seven patients had an interprosition mesocaval shunt using an autologous jugular vein. The patient with a thrombosed SMV had a portoartial shunt. The patient with an obstructed IVC had a cavoatrial shunt after an erroneous portacaval shunt had failed to relieve ascites. There were no operative deaths and no major postoperative complications. One patient died 19 months after operation of acute leukemia complicating polycythemia rubra vera. All other patients were alive and well 8 months to 6 years after operation. None of them had encephalopathy. These results suggest several comments: (1) Portal systemic shunts are a good treatment for BCS and have a low operative risk. (2) the mesocaval shung is an efficient procedure, even when there is stenosis of the IVC with high caval pressure: shunts to the right atrium should be performed only in the case of complete obstruction or inaccessibility of the IVC. (3) The long-term prognosis is excellent, except in patients with potential malignancies. Therfore, portal systemic shunts should be indicated early in patients with symptomatic BCS.
Development of molecular hybridization technology to evaluate albumin and procollagen mrna content in baboons and man
Authors: Weiner Francis R. , Czaja Mark J. , Giambrone Marie-Adele , Wu Catherine H. , Wu George Y. , Zern Mark A.
Published: March 2007

We have developed the methodology for evaluating the effects of pathophysiological conditions on the molecular mechanisms of hepatic protein synthesis and fibrogenesis in baboons and man. Total RNA was extracted from percutaneous liver biopsies of five baboons who were chronically fed an ethanol-rich liquid diet, their pair-fed controls and from humans with a variety of liver abnormalities. Chronic alcohol administration in baboons with liver fibrosis and normal serum albumin levels increased in vitro protein synthesis as measured by [35
S]methionine incorporation, albumin mRNA content and Type I procollagen mRNA content. There was no difference in the β-actin (a constitutive protein) mRNA content. In humans, serum albumin levels correlated with albumin mRNA content as indicated by the intensity of dot blot hybridization and Type I procollagen mRNA levels correlated with the activity of liver fibrosis. The use of RNA-DNA hybridization to investigate procollagen mRNA from human biopsies appears to be a valuable tool for evaluating the potential for collagen synthesis and the future course of liver disease. Besides the use of RNA-DNA hybridization, we describe other methodologies which are useful in delineating the levels of gene expression responsible for hepatic mRNA regulation in normal liver and disease states in man. The use of molecular techniques to evaluate human liver disease provides an opportunity to develop clinically relevant information while at the same time offering the additional advantage of providing fundamental knowledge about fibrogenesis.
Nadolol can prevent the first gastrointestinal bleeding in cirrhotics: A prospective, randomized study†
Authors: Idéo Gaetanô , Bellati Giorgio , Fesce Edoardo , Grimoldi Daniela
Published: March 2007

Propranolol has been reported to prevent the risk of hemorrhage in patients who survived episodes of variceal rupture. Since the first bleeding episode can be lethal, we did a prospective, randomized trial to see whether β-blockers could also prevent the first hemorrhage. Seventy-nine consecutive cirrhotics with large esophageal varices by endoscopy and who had never bled were randomly allocated to one of the following treatments: placebo; ranitidine (300 mg per day), or nadolol (40 to 120 mg per day)—which is not cardioselective, reduces portal hypertension and does not interfere with renal flow. Since no significant differences between ranitidine and placebo treatment were observed, the two groups were combined as the control group and compared with the nadolol group.

After a mean follow-up of 24 months, only 1 of the 30 patients in the nadolol group had bled, while 11 of the 49 patients in the control group had bled. The percentages of patients who had not bled 1 and 2 years after the inclusion-were 100 and 94.4% for the nadolol group and 81.2 and 70.2% for the control group (p < 0.02), respectively. There were no differences in the mortality rate.

In conclusion, nadolol significantly protects against the first gastrointestinal bleeding episode in cirrhotics.
Long-term culture of hepatocytes: Effect of hormones on enzyme activities and metabolic capacity
Authors: Dich John , Vind Constance , Grunnet Niels
Published: March 2007

(i) Hepatocytes isolated from adult rats were cultured for 2 to 3 weeks on collagen in a modified, serum-free Waymouth medium containing fatty acids and varying concentrations of glucocorticoid, insulin and glucagon. (ii) In the presence of all three hormones, it was possible to maintain the content of DNA, the activity of glucokinase, pyruvate kinase, hexokinase and lactate dehydrogenase at initial levels for 2 to 3 weeks. The activity of glucokinase and pyruvate kinase was affected by the concentration of insulin. (iii) The activity of alcohol dehydrogenase was stable for 3 days and declined to about 25% of the initial level after 2 weeks of culture, irrespective of the presence of hormones. (iv) Maintenance of albumin secretion was dependent on the presence of glucocorticoid, and glucocorticoid and insulin showed an additive or, at some time points, a synergistic effect on its secretion. (v) The content of cytochrome P-450 could be kept at 65% of the initial level, provided that a relatively high concentration of dexamethasone was present (10−6
M). (vi) In the absence of hormones, urea synthesis was 70% of initial levels throughout the experimental period. With insulin and glucocorticoid present, a high concentration of glucagon (10−8
M) was required to maintain the synthesis of urea at this level. (vii) It is concluded that hepatocyte cultures as described in the present study may be a useful, well-defined system for long-term metabolic, pharmacologic and toxicologic studies.
Tissue localization and kinetics of pit cells or large granular lymphocytes in the liver of rats treated with biological response modifiers
Authors: Bouwens Luc , Wisse Eddie
Published: March 2007

The numbers of Kupffer cells (macrophages) and pit cells (large granular lymphocytes) were counted by light and electron microscopy in perfusion-fixed liver sinusoids. After a single intravenous injection of the biological response modifiers zymosan, Propionibacterium acnes and OK-432, a 4- to 6-fold increase in the number of pit cells and a 2- to 4-fold increase in the number of Kupffer cells were observed within a period of 4 to 7 days. The mechanisms of the pit cell accumulation were further studied by the metaphase arrest method and by selective irradiation of the liver, or of the rest of the body, with a dose of 8.5 Gy. Stimulated pit cells showed mitotic activity in the liver and to a lesser extent in peripheral blood. The zymosan-induced increase in pit cell number was inhibited by irradiation of the liver but not by irradiation of the rest of the body (with shielded liver). It is concluded that the hepatic pit cell population, which has been shown to have natural tumoricidal activity, can be induced to expand by biological response modifiers, and local division of preexisting cells contributes significantly to this expansion.
Hepatic adenine nucleotide metabolism measured in vivo in rats fed ethanol and a high fat-low protein diet
Authors: Miyamoto Kei , French Samuel W.
Published: March 2007

Rats fed a diet high in fat and low in protein continuously infused by intragastric cannula were given ethanol for 2 to 6 months in order to examine the response of liver adenine nucleotides to changes in systemic PO2. Hepatic adenine nucleotides were measured in vivo monthly using liver obtained by biopsy from rats while a high blood alcohol level was maintained. Ethanol decreased hepatic ATP and the total adenylate pool, but did not change the levels of ADP and AMP. Adenylate energy charge showed only a tendency to be decreased. Carotid arterial PO2 was mildly but significantly lower in ethanol-fed rats compared to the pair-fed controls. Pure O2 inhalation for 3 min increased the PO2 four times in the ethanol and control-fed rats, and tended to increase ATP and decrease ADP in ethanol-fed rats as well as pair-fed controls. It restored the energy charge to a normal level in the ethanol-fed rats. Ten per cent O2 + 90% N2 inhalation for 3 min decreased the PO2 to 40 mm Hg in both the ethanol-fed and control rats, and this rapidly decreased ATP. This effect was significantly greater in the ethanol-fed rats compared to the controls. The total adenylate pool and the energy charge were decreased only in ethanol-fed rats. The results show that the reduced energy stores in the rat liver induced by ethanol are rapidly responsive to changes in PO2. Thus, the livers of ethanol-fed rats were more vulnerable to transient hypoxia than were controls.
S -adenosyl-L-methionine synthetase and phospholipid methyltransferase are inhibited in human cirrhosis
Authors: Duce Antonio Martín , Ortíz Pablo , Cabrero Carmen , Mato José M.
Published: March 2007

We have measured the activity S-adenosyl-L-methio-nine synthetase in liver biopsies from a group of controls (n = 17) and in 26 cirrhotics (12 alcoholic and 14 posthepatitic). The activity of this enzyme was markedly reduced in the group of cirrhotics (285 ± 32 pmoles per min per mg protein) when compared with that observed in controls (505 ± 37 pmoles per min per mg protein). No differences in S-adenosyl-L-methionine synthetase was observed between both groups of cirrhotics. Similarly, a marked reduction in the activity phospholipid methyltransferase was also observed in liver biopsies from the same group of cirrhotics (105 ± 12 pmoles per min per mg protein) when compared with the control subjects (241 ± 13 pmoles per min per mg protein). Again, no difference in the activity of this enzyme was observed between both groups of cirrhotics. These results indicated a marked deficiency in the metabolism of S-adenosyl-L-methionine in cirrhosis.
Overestimation of serum concentrations of γ-aminobutyric acid in patients with hepatic encephalopathy by the γ-aminobutyric acid-radioreceptor assay
Authors: Ferenci Peter , Ebner Josef , Zimmermann Christof , Kikuta Christian , Roth Erich , Häussinger Dieter
Published: March 2007

Sera of patients with hepatic encephalopathy strongly inhibit the specific binding of γ-aminobutyric acid to synaptic membranes. In a previous study, this inhibition of specific γ-aminobutyric acid binding was attributed to γ-aminobutyric acid itself, and it was assumed that serum γ-aminobutyric acid is increased 5- to 30-fold in patients with hepatic encephalopathy. The findings of that study, however, were not confirmed by other analytical methods. Therefore, the validity of the γ-aminobutyric acid-radioreceptor assay was tested. In view of the increased serum concentrations of several amino acids in hepatic encephalopathy, the effects of L-α-amino acids on the assay were studied. Five amino acids inhibited specific γ-aminobutyric acid binding at a concentration of 0.5 mM or lower: glutamine; glutamate; taurine; proline, and OH-proline. Equimolar amounts of amino-oxyacetate prevented the inhibition of specific γ-aminobutyric acid binding by glutamine and glutamate but had no effect on that of γ-aminobutyric acid, taurine, proline and OH-proline. Aminooxyacetate had no effect on specific γ-aminobutyric acid binding itself. The inhibitory activity of a serum sample from a patient with hepatic encephalopathy was inhibited by 0.5 mM aminooxyacetate. The γ-aminobutyric acid binding inhibitory activity of a serum sample of a patient with hepatic encephalopathy was purified by gel chromatography and contained several amino acids at concentrations of about 0.1 mM, 3.5 mM glutamine but no detectable γ-aminobutyric acid. Accordingly, the γ-aminobutyric acid binding inhibitory activity is not mediated by γ-aminobutyric acid alone and is most likely due to glutamine. Thus, using the γ-aminobutyric acid-radioreceptor assay serum, “true γ-aminobutyric acid” concentrations in patients with hepatic encephalopathy were overestimated.
Is the hypotension of cirrhosis a GABA-mediated process?
Authors: Minuk Gerald Y. , Maccannell Keith L.
Published: March 2007

Systolic and diastolic blood pressures were recorded in 176 ambulant patients with chronic liver disease, including 36 patients with compensated cirrhosis (Group I), 119 patients with noncirrhotic chronic liver disease (Group II) and 21 patients with benign structural or functional liver disease (Group III). Group I patients had significantly lower systolic (113.0 ± 2.2 mm Hg, mean ± S.E.) and diastolic (65.3 ± 1.7 mm Hg) pressures than Group II patients (125.8 ± 3.5 and 76.6 ± 1.5 mm Hg, respectively (p < 0.0001) or Group III patients (125.1 ± 3.4 and 77.5 ± 2.4 mm Hg, respectively) (p < 0.0001). Serum levels of GABA, a potent amino acid neurotransmitter with known vasodilatory effects in vitro, were higher in Group I patients (1.12 ± 0.26 μM, mean ± S.E.) than in Group II patients (0.41 ± 0.05 μM) (p < 0.005) or Group III patients (0.34 ± 0.03 mM) (p < 0.05). A constant infusion of GABA into the systemic circulation of six adult dogs, at rates required to achieve serum GABA levels within one order of magnitude of those observed in humans with cirrhosis, resulted in a 17.0 ± 4.3 mm Hg decrease in systolic pressure (p < 0.05) and a 10.8 ± 3.7 mm Hg decrease in diastolic pressure (p < 0.05). Control amino acids were not vas-oactive. The results of this study suggest that, in addition to other vasoactive compounds, a GABA-mediated process might contribute to the hypotension observed in patients with compensated cirrhosis.
The application of a numerical scoring system for evaluating the histological outcome in patients with chronic hepatitis B followed in long term
Authors: Lindh Gudrun , Weiland Ola , Glaumann Hans
Published: March 2007

A numerical scoring system was applied and compared with conventional histological classification to assess the histological outcome in 42 patients with chronic hepatitis B followed for 16 to 162 months (mean = 75 months). Four histological categories in the biopsies were assessed and scored: (i) piecemeal necrosis; (ii) lobular necrosis; (iii) portal inflammation, and (iv) fibrosis and cirrhosis. The sum of all four categories was defined as the “Histological Activity Index.” Altogether, 102 liver specimens, including 2 to 4 repeats from each patient, were investigated. A good correlation was noted between a high value of the Histological Activity Index score and several liver histology as monitored by conventional terminology for chronic hepatitis. Among patients, with HBeAg persistence, 8 of 14 (57%) deteriorated during follow-up as judged by an increase in the Histological Activity Index score compared to 3 of 13 (23%) of the patients with HBeAg seroconversion (0.5 < p < 0.1). Piecemeal necrosis has been postulated to be a predictive marker for the eventual development of cirrhosis. Here, we found that a low score for piecemeal necrosis in the initial liver biopsy was significantly less predictive of a high fibrosis score in the follow-up biopsy than was a high score for initial piecemeal necrosis (p < 0.001).

It is concluded that the scoring system used can be applied to monitor the histological long-term follow-up, especially when separated into its four constituent categories. It also offers a means of predicting a chronic hepatitis outcome.
Establishment of a new cell line from a woodchuck hepatocellular carcinoma
Authors: Ohnishi Shin , Aoyama Hiromu , Shiga Junji , Itai Yuji , Moriyama Takashi , Ishikawa Takashi , Sasaki Nobuo , Yamamoto Koshi , Koshimizu Kaoru , Kaneko Shuichi , Murakami Seishi , Hattori Nobu , Imawari Michio
Published: March 2007

A new cell line derived from a woodchuck hepatitis surface antigen-positive woodchuck hepatocellular carcinoma has been established and named T3-HEP-W1. This new cell line was established directly from a primary woodchuck hepatocellular carcinoma. Adaptation of the cells to the in vitro culture condition was completed after 3 months, with the doubling time of 24 hr. The morphologic features of the cell by light microscopy were of an epithelial type. The modal chromosome number was 100. Ornithine and tyrosine aminotransferase activities were detected. Production of albumin was negative. Integration of woodchuck hepatitis virus DNA was demonstrated by Southern blot analysis, although the secretion of woodchuck hepatitis surface antigen was not detected. T3-HEP-W1 is quite different from the previously reported WH257GE10 cell line and provides another in vitro model for the study of human hepatocellular carcinoma related to hepatitis B virus.
Selective regulation of intrinsic membrane proteins in HepG2
Authors: Collins Janna C. , Wolkoff Allan W. , Morell Anatol G. , Stockert Richard J.
Published: March 2007

Expression of three hepatocellular membrane proteins—the asialoglycoprotein receptor (hepatic binding protein) the insulin receptor and organic anion binding protein—have been studied in the HepG2 cell line. HepG2 grown in minimal essential medium supplemented with 10% fetal bovine serum maximally expressed hepatic binding protein and insulin receptor only at confluence while organic anion binding protein appeared independent of the state of cellular proliferation. When cells were grown in medium supplemented with dialyzed fetal bovine serum, adult bovine serum or in chemically defined medium, expression of hepatic binding protein and insulin receptor but not organic anion binding protein was reduced by 60 to 80%. Immunoblotting techniques revealed that cells grown in dialyzed fetal bovine serum contained virtually no mature, glycosylated 45 kD hepatic binding protein, but a small amount of 36 kD protein. Metabolic labeling of cells grown in dialyzed fetal bovine serum with [35
S] methionine indicated reduced synthesis of the 45 kD hepatic binding protein and the absence of the 36 kD protein. Restoration of normal expression of hepatic binding protein and insulin receptor was achieved by addition to dialyzed fetal bovine serum of: fetal bovine serum; 2,000 dalton ultrafiltrate of fetal bovine serum, or 300 to 350 dalton fraction of the ultrafiltrate. The normal concentration of organic anion binding protein demonstrable in cells grown in dialyzed fetal bovine serum indicates that the low molecular weight factor(s) is not a generalized modulator of plasma membrane biogenesis. However, its effect on the steady-state level of the hepatic binding protein and insulin receptor, characteristic of mature hepatocytes, suggests a role for this fetal serum factor in hepatocellular differentiation.
Impaired release of vitamin a from liver in primary biliary cirrhosis†
Authors: Nyberg Anders , Berne Berit , Nordlinder Hans , Busch Christer , Eriksson Ulf , Lööf Lars , Vahlquist Anders
Published: March 2007

In 44 patients with primary biliary cirrhosis serum levels of vitamin A, retinol-binding protein and transthyretin (prealbumin) were found to be significantly lower than in 25 sex- and age-matched controls. Liver biopsies were available for chemical analyses in 28 of the patients. Their mean liver vitamin A concentration (2.8 ± 2.0 μmoles per gm wet weight) did not differ significantly from that in 22 cases of sudden death which served as controls (2.0 ± 1.5 μmoles per gm wet weight). Immunohistochemical investigation showed a normal distribution of serum retinol-binding protein in the patients’ livers, whereas the staining pattern of cellular retinol-binding protein, believed to be involved in the intrahepatic transport of vitamin A, was abnormal. Thus, the number size and cellular retinol-binding protein staining intensity of fat-storing (Ito) cells were clearly higher in the patients as compared with controls. The results suggest that the low serum vitamin A levels in primary biliary cirrhosis are not a consequence of vitamin A deficiency but instead reflect a defective mobilization of vitamin A from the liver.
Serum hyaluronate in primary biliary cirrhosis—A biochemical marker for progressive liver damage
Authors: Nyberg Anders , Engström-Làurent Anna , Lööf Lars
Published: March 2007

To evaluate serum hyaluronate as a marker for progressive liver injury in patients with primary biliary cirrhosis, a longitudinal study including 48 patients was conducted with a mean follow-up time of 40 months. The patients were examined every 6 months with a standardized set of conventional liver function tests, and a liver biopsy was performed every year. The hyaluronate concentration correlated significantly (p < 0.001) with albumin, t 1/2 galactose tolerance test, bilirubin and prothrombin time but not to serum variables reflecting inflammatory activity. Furthermore, there was a close correlation between serum hyaluronate levels and histopathological changes in the liver. The hyaluronate concentration increased significantly over time in all clinical stages of primary biliary cirrhosis (p < 0.01), whereas the conventional liver function tests only changed in the advanced cases. The present data indicate that serum hyaluronate may be a sensitive marker for progressive liver damage in primary biliary cirrhosis. Serial determinations of hyaluronate are therefore of potential value for monitoring liver function during clinical management of the condition.
Primary biliary cirrhosis and the crest syndrome: New terminology?
Authors: Epstein Owen
Published: March 2007

The syndrome of primary biliary cirrhosis and limited scleroderma (the CREST syndrome) is described in 22 patients. The syndrome is expanded to include a serologic marker—the anticentromere antibody—and keratoconjunctivitis sicca. The acronym “PACK” (primary biliary cirrhosis, anticentromere antibody, CREST syndrome, and keratoconjunctivitis sicca) with “syndrome” is suggested to facilitate recall of the various components of this entity.
Elevation of acetylpolyamine levels in mouse tissues, serum and urine after treatment with radical-producing drugs and lipopolysaccharide
Authors: Sugimoto Hiroyuki , Yamada Shoji , Arai Takayuki , Kobayashi Setsuo , Hamana Koei , Matsuzaki Shigeru
Published: March 2007

Polyamines and acetylpolyamines were analyzed in the liver, spleen, lung, kidney, serum and urine by high-performance liquid chromatography on a column of cation-exchange resin after administering various cytotoxic substances to male mice. All of the compounds tested more or less affected the tissue levels of polyamines, including putrescine, spermidine, spermine and acetylpolyamines (N
1-acetylspermidine and N
1-acetylspermine). It was found that they were classified into two groups of substances: one group (including radical-producing drugs and lipopolysaccharide) which elevated the tissue levels of N
1-acetylspermidine, especially in the liver, while another group of drugs (such as D-galactosamine and DL-ethionine) had little effect on the acetylpolyamine levels. When the acetylpolyamine levels rose, the levels of spermidine and spermine declined, and then putrescine levels were elevated. N
1-Acetylspermine was detected only when N
1-acetylspermidine levels were very high after treatment with radical-producing drugs and lipopolysaccharide. Halogenated carbon, such as carbon tetrachloride and halothane, elevated the levels of acetylpolyamines especially in the liver, while paraquat elevated them in all tissues examined.
Uptake and processing of [3h]retinoids in rat liver studied by electron microscopic autoradiography
Authors: Hendriks Henk F. J. , Elhanany Edith , Brouwer Adriaan , de Leeuw Margreet A. , Knook Dick L.
Published: March 2007

The role of rat liver cell organelles in retinoid uptake and processing was studied by electron microscopic autoradiography. [3H]Retinoids were administered either orally, to make an inventory of the cell organelles involved, or intravenously as chylomicron remnant constituents to study retinoid processing by the liver with time. No qualitative differences were observed between the two routes of administration. Time-related changes in the distribution of grains were studied using chylomicron remnant [3H]retinoids. The percentages of grains observed over cells and the space of Disse at 5 and 30 min after administration were, respectively: parenchymal cells, 72.6 and 70.4%; fat-storing cells, 5.0 and 18.1%, and the space of Disse, 14.4 and 8.9%. Low numbers of grains were observed over endothelial and Kupffer cells. The percentages of grains observed over parenchymal cell organelles were, respectively: sinusoidal area., 59.6 and 34.4%; smooth endoplasmic reticulum associated with glycogen, 13.8 and 13.4%; mitochondria, 5.4 and 13.6%; rough endoplasmic reticulum, 4.2 and 7.3%, and rough endoplasmic reticulum associated with mitochondria, 3.7 and 6.5%. It is concluded that chylomicron remnant [3H]retinoids in combination with electron microscopic autoradiography provide a good system to study the liver processing of retinoids in vivo. These results, obtained in the intact liver under physiological conditions, further substantiate that retinoids are processed through parenchymal cells before storage occurs in fat-storing cell lipid droplets, that retinoid uptake is not mediated through lysosomes and that the endoplasmic reticulum is a major organelle in retinoid processing.
Interactions between isolated hepatocytes and kupffer cells in iron metabolism: A possible role for ferritin as an iron carrier protein
Authors: Sibille Jean-Claude , Kondo Hitoshi , Aisen Philip
Published: March 2007

Like the rat peritoneal macrophage, the isolated Kupffer cell is capable of processing and releasing iron acquired by phagocytosis of immunosensitized homologous red blood cells. When erythrophagocytosis is restrained to levels which do not affect cell viability, about one red cell per macrophage, close to 50% of iron acquired from red cells is released within 24 hr in the form of ferritin. Immunoradiometric assay of the extracellular medium indicates that 160 ng ferritin are released by 106 Kupffer cells after 24-hr incubation at 37°C. Iron release is temperature-dependent, the rate at 37°C being nearly 5-fold greater than at 4°C. As estimated by sucrose-gradient ultracentrifugation, ferritin released by the erythrophagocytosing Kupffer cell averages 2,400 iron atoms per molecule.

When reincubated with isolated hepatocytes, this released ferritin is rapidly taken up by the cells. Via this process, hepatocytes may accumulate more than 160,000 iron atoms per cell per min. Such accumulation is not impeded by the presence of iron-loaded transferrin in the culture medium, but is markedly depressed by rat liver ferritin. In contrast to the conservation of transferrin during its interaction with hepatocytes, the protein shell of the ferritin molecule is rapidly degraded into trichloroacetic acid-soluble fragments. Ferritin-mediated transfer of iron from Kupffer cells to hepatocytes may help explain the resistance of the liver to iron deficiency as well as the liver’s susceptibility to iron overload.
Liver disease in children with pizz α1-antitrypsin deficiency
Authors: Ghishan Fayez K. , Greene Harry L.
Published: March 2007

We present our experience with 18 pediatric patients with α1-antitrypsin deficiency of the PiZZ phenotype. Fifteen patients (83%) presented with neonatal cholestatic jaundice at a mean age of 2 ± 0.6 months (±S.D.). The male:female ratio was 15:3, indicating a male predominance. All metabolic, infectious and obstructive causes of jaundice were ruled out by appropriate tests in the patients with neonatal cholestasis. Liver biopsy in 14 patients with neonatal cholestasis showed a histological picture of cholestasis in all biopsies; neonatal giant cell hepatitis appeared in seven, increased fibrosis in appeared five and established liver cirrhosis appeared in two biopsies. Patients were followed for a mean of 3.7 ± 2.4 years (±S.D.). Of the 15 patients with neonatal cholestasis, 3 under went liver transplantation because of decompensated liver cirrhosis at 3, 3 1/2 and 7 years. Two patients died at 4 months and 3 years from complications of liver cirrhosis. Of the remaining 10 patients, 3 had histological evidence of liver cirrhosis, and the remaining 7 patients continue to have enlarged liver and spleen with abnormal liver function tests. Of the three patients without history of neonatal cholestasis, only one had enlarged liver and spleen, and the remaining two are healthy with normal liver function tests. Our experience indicates serious liver disease is highly likely to develop in patients with PiZZ α1-antitrypsin deficiency who present with neonatal cholestatic jaundice. Our experience differs from more recent reports on such patients.
Cytochrome p-450 gene expression in the functional units of the fetal liver
Authors: Chianale Jose , Dvorak Caroline , Farmer Donna L. , Michaels Linda , Gumucio Jorge J.
Published: March 2007

Hepatocytes of the right and left lobes of the fetal liver are surrounded by different microenvironments. The right and left lobes of the fetal liver are perfused by vascular systems carrying different concentrations of oxygen and constitute distinct functional units. The aim of this study was to assess the expression of the phenobarbital-inducible cytochrome P-450 b,e genes in hepatocytes of the right and left fetal liver lobes in mice. Northern-blot analysis using [32P]cDNAs and quantitative dot-blot hybridization were performed to assess the size and levels of these mRNAs in the right and left fetal liver lobes. In fetal mice, the levels of cytochrome P-450, b,e mRNAs were higher in the left than in the right fetal liver lobe. During the last days of gestation and in the immediate postnatal period, the levels of liver cytochrome P-450 b,e mRNAs increased predominantly in the left liver lobe. In contrast, the levels of albumin and α-fetoprotein mRNAs (genes studied to assess the specificity of these findings) were similar in each of functional units of the fetal liver. Phenobarbital induction of cytochromes P-450 b,e mRNAs was not observed in either of the fetal liver lobes. Postnatally, phenobarbital induced these cytochromes similarly in the right and left liver lobes. Therefore, the microenvironment surrounding fetal hepatocytes seems to influence the expression of the cytochrome P-450 b,e genes. This lobar heterogeneity of expression disappears as the pattern of adult liver circulation is attained.
Determination of parameters effecting proton relaxation of hepatic and gallbladder biles in dogs
Authors: Bakan Douglas A. , Barnhart James L.
Published: March 2007

The parameters which are important in causing changes in the Tl and T2 proton magnetic relaxation times of dog bile were investigated. Three factors were found to be important in causing relaxation in bile: (i) total bile salt concentration; (ii) total protein concentration, and (iii) viscosity. The T1 and T2 values of hepatic and gallbladder biles were found to be independent of specific gravity, osmolarity and electrolyte concentrations. In vitro experiments were conducted with taurocholic acid, bovine serum albumin and porcine stomach mucin to examine the effects of intermolecular interactions on proton relaxation. Relative to each of the molecules alone, various combinations of the bile salt and proteins exhibit relaxation rates of 20 to 60% below theoretically expected values. This influence of in vitro molecular interactions on T1 and T2 is also likely to occur in hepatic and gallbladder biles in vivo. Thus, the effects of complex intermolecular interactions associated with the gallbladder microenvironment complicate but likely will not preclude direct assessment of physiologic data with magnetic resonance imaging.
Clinical value of the guanase screening test in donor blood for prevention of posttransfusional non-A, non-B hepatitis
Authors: Ito Susumu , Tsuji Yasuhiro , Kitagawa Naoyuki , Akihiko Ishihara , Syundo Jyoji , Tamura Yoshiyuki , Kishi Seiichiro , Mori Hiroyoshi
Published: March 2007

We adopted an automated method for measuring guanase in donor blood and examined the incidence of posttransfusional non-A, non-B hepatitis when donor blood with high guanase activities was excluded. Sixty-seven (2.4%) of 2,826 units were excluded from use in transfusion because they had guanase activities above 1.71 units per liter. Of 112 recipients, 8 (7%) developed posttransfusional non-A, non-B hepatitis. The incidence of posttransfusional non-A, non-B hepatitis was 17% before adoption of the guanase screening test and 7% after its adoption. Thus, the incidence of posttransfusional non-A, non-B hepatitis was significantly decreased after adoption of this screening test.

This study shows that, for prevention of posttransfusional non-A, non-B hepatitis, it is important to screen donor blood for guanase activity and discard blood with high activities.
Postliver biopsy hepatic hematomas: Are routine ultrasonograms needed?
Authors: Spinzi Glancarlo , Terruzzi Vittorio , Minoli Giogio
Published: March 2007

Percutaneous liver biopsies were performed in 40 adult patients with acute or chronic liver disease. Real-time sector scan ultrasound of the right upper quadrant was obtained just before biopsy, 1 day after biopsy, and in 10 randomly selected cases 7 days after biopsy. Twenty patients were randomized, by sealed envelope, to 6-h and 20 patients to 24-h postbiopsy bed rest. Nine patients (23%) had ultrasound-detected hematomas 1 day after liver biopsy (7 intrahepatic, 2 subcapsular). Five of these patients had been randomized to 6-h and 4 to 24-h bed rest. Follow-up ultrasound at 7 days in the 10 randomly selected patients failed to reveal any hematomas not seen on day 1 (n = 6) and showed complete or partial resolution of those that had been detected previously (n = 4). Significant drops in systolic and diastolic blood pressures and increases in pulse rate were common postbiopsy findings, and were unrelated to hematoma formation. The results of this study indicate that intrahepatic and subcapsular hematomas are common after percutaneous liver biopsy. The length of postbiopsy bed rest (6 vs. 24 h) does not appear to influence the frequency of this complication.
Safe splenoportography: Objective confirmation is still needed
Authors: Burcharth Flemming
Published: March 2007

The records of 37 patients who had undergone splenoportography, including one group of 12 who were studied before 1976 and a second group of 25 who were studied after 1977, were reviewed. The primary difference was that in the second group, the tract in the spleen was occluded with absorbable gelatin sponge (Gelfoam) plugs as the needle was withdrawn. In addition, there were minor changes in technique, such as changes in the needle puncture angle and entry site. When the new technique was used, there was a significant decrease in the complications traditionally associated with splenoportography. This procedure is safe and deserves to be considered the procedure of choice in patients in whom precise anatomic information is needed preoperatively that cannot be obtained with noninvasive procedures such as ultrasound or magnetic resonance imaging.
The development of cirrhosis in patients with chronic type B hepatitis: A prospective study
Authors: Liaw Yun-Fan , Tai Dar-In , Chu Chia-Ming , Chen Tong-Jong
Published: March 2007

The incidence and contributing factors of cirrhosis developing in patients with chronic type B hepatitis were assessed prospectively in 684 clinicopathologically verified patients, of which 509 were HBeAg positive and 175 were anti-HBe positive at entry into the study. During an average follow-up period of 35.3 months, cirrhosis occurred 6 to 64 months after entry in 35 HBeAg-positive and 7 anti-HBe positive patients with a calculated annual incidence of 2.4 and 1.3%, respectively (p > 0.05). The incidence increased significantly with the increasing age at entry. Patients who had experienced (a) hepatic decompensation, (b) repeated episodes of severe acute exacerbation (with α-fetoprotein > 100 ng per ml and/or bridging hepatic necrosis), (c) severe acute exacerbation not accompanied by subsequent HBeAg seroconversion and (d) hepatitis B virus reactivation (particularly those with HBeAg reappearance) were found to develop cirrhosis much more frequently (p < 0.001). Contrary to general belief, patients who had hepatitis delta virus superinfection and patients with chronic active hepatitis were not particularly prone to develop cirrhosis. We conclude that in addition to age factor, the extent, severity, duration, frequency and etiology of the hepatic lobular alterations are important factors for the development of cirrhosis in patients with chronic type B hepatitis.
Experimental duck hepatitis B virus infection: Pathology and evolution of hepatic and extrahepatic infection
Authors: Freiman John S. , Jilbert Allison R. , Dixon Robert J. , Holmes Marlis , Gowans Eric J. , Burrell Christopher J. , Wills Edward J. , Cossart Yvonne E.
Published: March 2007

Seventy, 1-day-old ducklings inoculated intraperitoneally with duck hepatitis B virus and 30 controls have been studied over a 2-year period. Infection with duck hepatitis B virus occurred in all inoculated ducks, although this was not associated with clinical morbidity. Duck hepatitis B virus DNA was first detected in liver on Day 3, in pancreatic acinar cells on Day 4, serum on Day 6, splenic red and white pulp on Day 7 and in the renal glomurulus on Day 14, using a combination of dot, Southern blot and in situ hybridization techniques. Peak levels of circulating virus, as determined by DNA polymerase levels, occurred 1 to 4 weeks postinoculation. Mild degrees of portal inflammation were seen in sections of liver tissue in both infected and control ducks. However, moderately severe inflammatory changes were present in 8 of 22 infected birds compared with 0 of 18 controls (p < 0.025). Appearance of this inflammatory infiltrate 6 weeks postinoculation coincided with a decrease in levels of duck hepatitis B virus DNA in hepatocytes and within the pancreatic acinar cells. At the same time, duck hepatitis B virus DNA became increasingly localized to the splenic germinal centers, and viral DNA was first detected in pancreatic islet cells. No histological changes accompanied the extra-hepatic tissue infection. The sequence and significance of duck hepatitis B virus infection in liver and extra-hepatic tissues is discussed in relation to the pathogenesis of hepatitis B virus infection in man.
Nuclear antigens reacted with sera and ascites of hepatocellular carcinoma patients
Authors: Chen Yi-Ming , Hu Cheng-Po , Chen Pao-Huei , Chu Ming-Huey H. , Tsai Yang-Te , Lee Shou-Dong , Chang Chungming
Published: March 2007

In order to study hepatocellular carcinoma-associated antigens, screening of sera and ascites was done from hepatocellular carcinoma patients having antibodies reactive with three hepatocellular carcinoma cell lines (PLC/PRF/5, Hep 3B and HA22T/VGH). The indirect immunofluorescent antibody test was used. Ten of 86 (11.6%) sera and 3 of 14 (21.4%) ascites from hepatocellular carcinoma patients showed positive bindings, whereas only 1 of 35 (2.8%) sera, none of 4 (0%) ascites from chronic hepatitis patients and 3 of 60 (5%) normal human sera had positive immunofluorescent antibody activity. The binding specificities of these positive specimens were further defined by other human cancer cell lines and mouse NIH/3T3 fibroblasts. The antinuclear antibody test against mouse liver sections was also performed. The results suggested that antigens identified by the two tests may not be identical. The nature of nuclear antigens reactive with one of the serum samples, S83, and ascites A83 were characterized. These antigens were sensitive to trypsin but not to RNase A and DNase I. Further studies by radioimmunoprecipitation and two-dimensional gel electrophoresis with serum S83 and ascites A83 showed two acidic phosphorylated antigens with molecular weights of 77 and 79 kd, which had a pI around pH 5.2. The presence of a large amount of these two phosphorylated proteins in 5 of 7 human hepatocellular carcinoma cell lines suggests that these two antigens might play some roles in the carcinogenesis or progression of human hepatocellular carcinoma.
The role of alcoholism and liver disease in the appearance of serum antibodies against acetaldehyde adducts
Authors: Hoerner Martin , Behrens Ursula J. , Worner Theresa M. , Blacksberg Ileen , Braly Lawrence F. , Schaffner Fenton , Lieber Charles S.
Published: March 2007

We recently presented preliminary data indicating the presence of antibodies against acetaldehyde adducts in sera of over 70% of alcoholic patients. To assess the respective roles of liver disease and alcohol consumption as well as the specificity of this immune response, 141 patients in various stages of alcoholic and nonalcoholic liver diseases were tested by a hemagglutination assay. Sixty-three (73%) of 86 alcoholics had antibody titers above control levels (p < 0.0001). Alcohol consumption of these individuals was significantly higher (p < 0.001) than that of those alcoholics with normal titers. Twentytwo patients (39%) with nonalcoholic liver diseases also had elevated levels of antibodies against acetaldehyde adducts (p < 0.0005); of these, 8 had primary biliary cirrhosis (7 in Stages III and IV), 9 had chronic active hepatitis (6 with cirrhosis) and 5 had acute (virus- or drug-induced) hepatitis. Antibody titers did not correlate with levels of transaminase or alkaline phosphatase activity, nor with bilirubin, and albumin. However, in 52 alcoholics and in nonalcoholic patients with biopsy-confirmed liver disease, the highest titers were seen in the more advanced stages of liver damage. Thus, in addition to alcohol consumption, severity of liver disease may play a role in the appearance of circulating antibodies against acetaldehyde adducts.
Influence of smoking on caffeine elimination in healthy volunteers and in patients with alcoholic liver cirrhosis
Authors: Joeres Rolf , Klinker Hartwig , Heusler Hermann , Epping Johannes , Zilly Walter , Richter Ernst
Published: March 2007

The effect of smoking on caffeine elimination was measured in 7 healthy volunteers and in 18 smoking and in 30 nonsmoking patients with alcoholic liver cirrhosis following oral application of 366 mg caffeine. In an intraindividual experiment in smoking healthy probands, caffeine clearance decreased from 118 ± 33 to 77 ± 22 ml per min (p < 0.05) after abstaining cigarette smoking for 3 weeks. In a control group without liver disease (8 smokers, 15 nonsmokers), we found a caffeine clearance of 114 ± 40 ml per min in smokers and 64 ± 20 in nonsmokers (p < 0.05).

Smoking and nonsmoking patients with alcoholic liver cirrhosis did not differ with respect to clinical and laboratory data and hexobarbitone elimination. However, caffeine clearance was 63 ± 63 ml per min in smoking patients compared to 34 ± 49 ml per min in nonsmokers (p < 0.05).

Fasting plasma concentrations of caffeine were higher in nonsmokers (5.1 ± 6.2 μg per ml) than in smokers (2.1 ± 4.5 μg per ml, p < 0.05). We conclude that smoking habits have to be taken into account if caffeine is used as a model compound for measuring quantitative liver function.
Early midzonal cell death during low-flow hypoxia in the isolated, perfused rat liver: Protection by allopurinol
Authors: Marotto Mark E. , Thurman Ronald G. , Lemasters John J.
Published: March 2007

Trypan blue uptake and lactate dehydrogenase release were measured as indices of irreversible cell damage in isolated, perfused rat livers during low-flow hypoxia. In livers from fasted rats perfused in the anterograde direction, trypan blue uptake took place beginning at about 45 min of hypoxia. Cells which took up trypan blue first were located in narrow bands at the border between anoxic pericentral areas and normoxic periportal regions of the liver lobule. After longer periods of hypoxia, trypan blue uptake progressed towards the central vein until after 120 min virtually all cells in the pericentral regions were stained. Under these conditions, cells in periportal regions were spared. In perfusions in the retrograde direction, cell death began in midzonal regions and spread towards the portal vein. Release of lactate dehydrogenase into the effluent paralleled trypan blue uptake, beginning at about 40 min of low-flow hypoxia and peaking at 80 min. In contrast to livers from fasted rats, trypan blue was not taken up, and lactate dehydrogenase was not released in livers from fed rats exposed to low-flow hypoxia for as long as 120 min. To test the hypothesis that xanthine oxidasemediated oxygen-free radical formation was involved in cell injury at the border between anoxic and normoxic regions (anoxic edge), allopurinol, an inhibitor of xanthine oxidase, was studied. Allopurinol (0.2 to 5 mM) delayed the release of lactate dehydrogenase during low-flow hypoxia in a dose-dependent fashion (e.g., 5 mM allopurinol delayed hypoxia-induced lactate dehydrogenase release by about 30 min). Allopurinol also delayed loss of cell viability as assessed by trypan blue uptake. The results indicate that cells located at the anoxic edge are more susceptible to irreversible hypoxic injury than totally anoxic cells, and we conclude that xanthine oxidase-mediated free radical formation is involved in the mechanism of damage.
Amiodarone-induced hepatic phospholipidosis: Correlation of morphological and biochemical findings in an animal model
Authors: Pirovino Mauro , Müller Otfried , Zysset Thomas , Honegger Ueli
Published: March 2007

Morphological and biochemical investigations were performed in guinea pigs after 1, 3, 5 and 16 weeks of amiodarone feeding. The most prominent morphological finding was an increase in dense bodies in hepatocytes, Kupffer cells and in bile duct epithelia, reaching a maximum after 5 weeks of treatment according to morphometric analysis. Similar time courses were observed for the serum and liver tissue concentrations of amiodarone and desethylamiodarone and the—albeit minimal—extent of hepatocellular necrosis. Phospholipids in the liver homogenate were unchanged after 1 week, but significantly increased after prolonged amiodarone treatment. There was no significant alteration in the pattern of individual phospholipids. Serum and tissue concentrations as well as the extent of phospholipidosis do not appear to be a function of the duration of drug application. A very close correlation, however, was observed between the liver tissue concentration of amiodarone and the amount of dense bodies as a morphological expression of phospholipidosis.
Induction of heat shock proteins in short-term cultured hepatocytes derived from normal and chronically griseofulvin-treated mice†
Authors: Zatloukal Kurt , Sohar Ruth , Lackinger Elisabeth , Denk Helmut
Published: March 2007

Freshly isolated mouse hepatocytes were tested with respect to the induction of heat shock (stress) proteins by elevated temperature, sodium arsenite and ethanol treatment. With heat, arsenite and ethanol treatments, the synthesis of a protein with a molecular weight of 68 kD (heat shock protein 68) was predominantly elevated; arsenite and ethanol exerted their effects on heat shock protein synthesis in a dose-dependent manner. Hepatocytes derived from livers of chronically griseofulvin-pretreated mice differed in their response from normal hepatocytes in that ethanol was ineffective in these cells. These results indicate that different modes and pathways of the stress response exist, depending on the nature of the inducing agent but also on pretreatment conditions. In vivo, pathologic alterations of cells and organs (e.g., in the course of chronic diseases) can, therefore, be expected to modulate the stress response.