bluuebunny/crossref_metadata_2025 huggingface dataset:
The prognostic significance of bridging hepatic necrosis in chronic type B hepatitis: a histopathologic study
Authors: Chen Tong‐Jong , Liaw Yun‐Fan
Published: August 2010

ABSTRACT—A histopathologic follow‐up study was conducted in 207 consecutive patients to examine the prognostic significance of bridging hepatic necrosis (BHN) in chronic type B hepatitis. One hundred and eight patients showed BHN and the other 99 intralobular spotty necrosis (SN) on initial biopsy. A higher proportion of patients with BHN healed (45.4% vs 26.4%) or developed cirrhosis (18.3% vs 3%) than the patients with SN. In contrast, intralobular inflammation persisted or recurred more frequently in the SN than in the BHN group (40.4% vs 5.6%). These figures were statistically significant (P<0.001). Alternatively, 87% of the patients who developed cirrhosis had had BHN as their initial histologic presentations. The estimated relative risk of cirrhotic progression for the BHN group compared to the SN group was 4:1. We conclude that BHN is a paradoxical prognostic factor, either for healing, or cirrhotic progression.
Acute phase proteins and liver allograft rejection
Authors: Maury C.P.J. , Teppo A‐M. , Höckerstedt K.
Published: August 2010

ABSTRACT—We studied the sequential changes in the positive acute phase reactants orosomucoid, α1‐antichymotrypsin, α1‐antitrypsin, haptoglobin and C‐reactive protein, and in the negative acute phase reactant, prealbumin, as well as in α2‐macroglobulin and β2‐microglobulin in serum following orthotopic liver transplantation in nine adult patients. Synchronous increases in all five positive acute phase reactants were observed in association with acute liver rejection episodes; the elevations were statistically significant for orosomucoid and α1‐antichymotrypsin. In four out of nine well‐documented rejection episodes C‐reactive protein did not increase at all. Marked variations occurred in post‐transplant prealbumin and α2‐macroglobulin levels; both proteins tended to decrease 2–3 days after the rejection was diagnosed. The circulating levels of β2‐microglobulin were raised during the post‐transplant period and markedly increased in association with acute graft rejection episodes. The results demonstrate marked changes in plasma protein concentrations in association with acute liver allograft rejection episodes; the kinetics of serum acute phase reactants is very similar to that found in inflammation and tissue injury in general.
Mass screening of primary hepatocellular carcinoma by alpha‐fetoprotein in a rural area of Taiwan – a dried blood spot method
Authors: Wu Jaw‐Ching , Lee Shou‐Dong , Hsiao Kwang‐Jen , Wang Sun‐Sang , Chou Pesus , Tsao Dean , Tsai Yangte , Lui Wing‐Yiu , Chiang Jen‐Huei , Lo Kwang‐Juei
Published: August 2010

ABSTRACT— A prospective survey of primary hepatocellular carcinoma (PHC) was conducted in a rural area of Taiwan using a two‐site enzyme immunoassay for alphafetoprotein (AFP) in dried blood samples collected on filter paper. Of 1894 men over 40 years of age who were tested, 20 (1%) had AFP levels of greater than 20 ng/ml of blood on screening. Nineteen of these men received ultrasound examinations, and small PHCs were detected in 4 (21%). The remaining 15 cases had other types of hepatobiliary tract diseases, and 6 (40%) were also serum HBsAg positive. They should all be closely followed up by AFP determination and ultrasound examination of the liver. In contrast to the low resection rate of PHC in symptomatic patients who were admitted through the outpatient clinic during the period of this survey, the four cases with small PHC discovered by AFP screening had their tumors successfully removed (5/57 vs. 4/4, p<0.005). Our preliminary results showed that this method is a simple, sensitive and convenient assay for AFP and may be used as a first‐line screening test in mass population surveillance programs for PHC, particularly in areas where PHC is highly prevalent.
Quantitative aspects of the parenchyma‐stroma relationship in experimentally induced cholestasis
Authors: Aronson D. C. , de Haan J. , James J. , Bosch K. S. , Ketel A. G. , Houtkooper J. M. , Heijmans H. S. A.
Published: August 2010

ABSTRACT— In order to quantify changes of the parenchyma/stroma relations in the progression of experimentally induced biliary fibrosis in the rat, localisation of lactate dehydrogenase activity and Sirius Red staining were used as criteria to detect parenchymal cells and collagen fibers, respectively. Blood levels of bilirubin, alkaline phosphatase, anti‐thrombin III activity, α2‐antiplasmin, factor II and factor X were related to the data obtained by histomorphometric measurements in sections gathered 1, 2, 4 and 6 weeks after the onset of cholestasis in three animals and after 8 weeks in one animal. Histophotometry showed a reduction in volume density of the parenchymal cell mass of 96%, 78%, 76%, 62% and 59% of the control values, respectively. During the same period, the collagen increased 5‐fold in 4 weeks time, levelling off afterwards. Newly formed collagen appeared in the portal areas in close association with proliferating ductules, invading with the latter into the parenchymal mass. After 6 weeks, regressive changes were observed in the ductule complexes formed, manifested by a lowering of the epithelium in which extensive apoptotic cell death was observed with the electron microscope. Of the blood parameters analyzed, the clotting factor X showed the best inverse correlation with the Sirius Red readings (r1= ‐0.84), i.e. the volume density of collagenous fibers.
Long‐term administration of toxic doses of paracetamol (acetaminophen) to rats
Authors: Poulsen Henrik E. , Thomsen Per
Published: August 2010

ABSTRACT—The effect of dosing paracetamol, 4.25 g/kg BW, twice weekly for 18 weeks was assessed in female Wistar rats 24 h after the last dose. Hepatic function, estimated as the prothrombin index, was more depressed in rats given one paracetamol dose than in chronically treated rats. Cytochrome P‐450 and protein concentrations in liver homogenate and microsomes were higher in chronically treated rats. Urinary excretion of paracetamol glucuronide and mercapturate was higher and paracetamol sulfate unchanged after the chronic treatment. Hepatic glutathione was identically depleted after one dose and chronic paracetamol treatment. Histological examination of livers from chronically treated animals showed varying degrees of centrilobular necrosis. We conclude that long‐term treatment with paracetamol in toxic doses leads to partial maintenance of the well‐known protective effect after a few toxic doses. Signs of chronic toxicity consisted of weight loss, progressing to death. We suggest this chronic toxicity to be due to methionine/cysteine deficiency since urinary excretion of sulfur‐containing paracetamol metabolites closely corresponds to calculated dietary intake of sulfur‐containing amino acids.
Bacteriaemia after injection sclerotherapy of oesophageal varices
Authors: Hegnhøj Jens , Andersen Jens Rikardt , Jarløv Jens Otto , Bendtsen Flemming , Rasmussen Henrik Sandvad
Published: August 2010

ABSTRACT— Thirty consecutive alcoholic patients with biopsy‐proven cirrhosis of the liver and oesophageal varices underwent a total of 47 upper intestinal endoscopies. During 31 of the endoscopies paravariceal sclerotherapy of oesophageal varices was performed. Blood cultures were drawn before and after the procedures. Bacteriaemia after endoscopy was detected on seven occasions: six after sclerotherapy and one after endoscopy without sclerotherapy. This difference did not reach statistical significance. The microorganisms cultured belonged to the normal flora of the skin or the oropharynx. Bacteriaemia was transient and had no clinical consequences.
A quantitative evaluation of apoptotic bodies in rat liver
Authors: Benedetti A. , Jezequel A. M. , Orlandi F.
Published: August 2010

ABSTRACT— The aim of the present study was to determine if data on the number and acinar distribution of apoptotic bodies (AB) in normal liver could help in the understanding of cell kinetics in the liver, and the mechanism of early ethanol‐induced liver damage. Normal male Sprague‐Dawley rats were studied. They had free access to Purina chow and drinking water. Ethanol‐treated rats received the drug at increasing concentration in drinking water for 5 weeks. The following parameters were measured: number of AB in the lobule, topographical localization, distance from terminal hepatic veins (THV), i.e. row of hepatocytes concerned, H1 being the closest to the THV. The results show that AB are rare in the normal liver and are always observed in zone 3, next to the THV. Of 149 THV examined, 56 showed one associated AB, exceptionally two. 74% of the AB were confined to the first row of hepatocytes (H1), 21% to H2, 4% to H3, and 1% to H4. In ethanol‐treated rats the mean number of AB was 2 or 3 for each THV. 42% were found in H1, 32% in H2, 15% in H3, 7% in H4, and 4% in H5. The data show that AB are not randomly dispersed in normal liver but show a preferential acinar distribution. In addition, most AB are located in the row of liver cells immediately adjacent to the THV. If apoptosis is indeed an expression of physiological cell renewal, these findings support the concept that zone 3 contains older hepatocytes. In ethanol‐treated animals, besides the O2 lobular gradient and increased rate of formation of intermediate metabolites, the age of pericentral hepatocytes may represent an additional risk factor in ethanol‐induced liver damage.
The streaming liver III. Littoral cells accompany the streaming hepatocyte
Authors: Zajicek G. , Ariel I. , Arber N.
Published: August 2010

ABSTRACT—In previous studies we have shown that hepatocytes stream from the portal tract toward the terminal hepatic vein. The present study provides evidence that littoral cells participate in the same cell stream and that the liver actually streams en masse. Littoral cells stand for sinusoidal endothelia and Kupffer cells. Thirty male adult rats, random bred, were injected with 0.5 μCi [3H]‐thymidine, specific activity 5 Ci/mmol/g body weight. The rats were killed in groups of five, at the following times: 1 h, 14, 30, 60, 90 and 120 days. The livers were processed histologically and dipped into liquid emulsion for autoradiography. In each animal 50 labelled hepatocytes and 50 littoral cells were randomly selected and their distance from the nearest terminal portal tract rim was measured. Both cell populations renew their cells continuously. Each consists of two cell types, progenitors, residing around the portal tract up to the distance of 200 μm. and functional cells, which inhabit the rest of the acinus. The two regions where the different cell types reside are known respectively as progenitor (P) and functional (Q) compartments. Both cells are formed in the P‐compartment and advance jointly along a trajectory, the tissue radius, toward the terminal hepatic vein where they die. They progress at a daily velocity of 2 μm. Since both advance at the same speed, as long as they exist they remain neighbours. Liver parenchyma and stroma thus stream en masse. It is proposed that hepatocytes and littoral cells are displaced as tissue quanta, or proliferons, which are assembled in the progenitor region near the portal tract, and gradually traverse the three acinus zones, changing their metabolic tasks as they go, until at the terminal hepatic vein they disintegrate, probably by apoptosis.
Effect of allopurinol on oxidant stress and hepatic function following ischemia and reperfusion in the rat
Authors: Metzger Jacques , Lauterburg Bernhard H.
Published: August 2010

ABSTRACT—Reactive oxygen species generated by xanthine oxidase during reperfusion of ischemic liver might in part be responsible for ischemic organ injury. Therefore, the effect of allopurinol, an inhibitor of xanthine oxidase, on the oxidant stress associated with reperfusion and on hepatic function 24 h after ischemia was assessed in a model of partial hepatic ischemia in rats. The increase in circulating glutathione disulfide (GSSG) was used as an index of oxidant stress. Hepatic function was assessed using a breath test to quantitate the demethylation of aminopyrinein vivo.In control animals the plasma concentration of GSSG 1 h after onset of reperfusion increased from 0.9 μmol/1 in sham‐operated controls to 4.2, 5.5, and 8.0 μmol/1 following 45, 90 and 120 min of ischemia, respectively. The percent of the administered dose of (dimethylamine‐14C)‐aminopyrine appearing in breath as14CO2was not significantly different from sham‐operated controls (40.2%) 24 h after 45 min of ischemia (34.1%), but decreased progressively to 26.0% (p<0.05) and 20.6% (p<0.05) after 90 and 120 min of ischemia, respectively. Allopurinol, administered at a dose of 50 mg/kg 18 h and 1 h prior to ischemia, did not prevent the rise in plasma GSSG, did not alleviate the release of transaminases, and did not improve the demethylation of aminopyrine 24 h after ischemia, suggesting that reactive oxygen species generated by xan thine oxidase during reperfusion of ischemic liver do not contribute significantly to ischemic injury.
Prolonged cholestasis and disappearance of interlobular bile ducts following chlorpropamide and erythromycin ethylsuccinate. Case of drug interaction?
Authors: Geubel A. P. , Nakad A. , Rahier J. , Dive C.
Published: August 2010

ABSTRACT— A 52‐year‐old man, having been treated for 4 months with chlorpropamide for diabetes mellitus type II, developed severe cholestatic hepatitis following a short course of erythromycin ethylsuccinate. Despite prompt withdrawal of both drugs, the cholestatic picture worsened and was associated with morphological evidence of disappearing interlobular bile ducts. After a 2‐year course of profound cholestasis complicated by steatorrhea and striking hyperlipidemia, the patient died of ischemic cardiomyopathy. It is believed that this is the first published case of irreversible cholestasis with disappearance of ducts potentially related to a metabolic interaction between erythromycin ethylsuccinate and chlorpropamide.
Effect of interferon α, γ, and tumor necrosis factor α on the HLA‐A, B, C expression of cell lines derived from human liver
Authors: Yoshioka Kentaro , Kakumu Shinichi , Tahara Hirofumi , Arao Motohiro , Fuji Akihiko
Published: August 2010

ABSTRACT— Our study was undertaken to determine whether human recombinant interferon α(rIFNα), γ(rIFNγ), and tumor necrosis factor α(rTNFα) exert an effect on the HLA‐A, B, C expression of human liver cell lines. The HLA‐A, B, C expression was assayed by immunoperoxidase staining and enzyme‐linked immunosorbent assay. rIFNα and γ enhanced the HLA‐A, B, C expression of the three cell lines tested, Chang cells, SK‐Hep‐1, and PLC/PRF/5. The activity of rIFNγ proved more than 8000 times more potent than that of rIFNα in Chang cells, 30 times in SK‐Hep‐1, and 20 times in PLC/PRF/5, respectively. rTNFα also enhanced the HLA‐A, B, C expression of the three cell lines. The enhancement of HLA‐A, B, C expression by rIFNα and γ reached a peak on day 3, and that by rTNFα on day 5. These findings suggest that IFNα, IFNγ, and TNFα may play similar roles in enhancement of HLA‐A, B, C expression of hepatocytes in hepatitis and hepatoma cells.
Relation of sinusoidal stenoses following hepatocyte swelling to hepatic vascular resistance in experimental liver cirrhosis
Authors: Shibayama Yuro , Nakata Katsuji
Published: August 2010

ABSTRACT— To investigate the significance of sinusoidal stenoses and a decrease in the sinusoidal bed due to hepatic cell swelling as a factor increasing hepatic vascular resistance in liver cirrhosis, hepatic vascular resistance in choline‐deficient diet‐induced cirrhotic rats was measured by an isolated liver perfusion method. In the cirrhotic rats, the swollen hepatic cells resulting from accumulation of fat droplets narrowed the sinusoids and decreased the sinusoidal bed. Consequently, the hepatic vascular resistance was increased by 2.7 times normal (8.60 ± 2.32 mm H2Oml‐1.min; controls, 3.13 ± 0.67 mm H2Oml‐1.min), and portal hypertension was also recognized (188.1 ± 26.3 mm H2O; controls, 114.2 ± 12.8 mm H2O). In the cirrhotic rats fed with ordinary rat pellets for 2 months, however, the sinusoidal stenoses and the decreased sinusoidal bed recovered to nearly normal as a result of disappearance of the fat droplets in the hepatic cells. The increased hepatic vascular resistance was decreased to 1.5 times normal (4.68 ± 0.82 mm H2Oml‐1.min), and the elevated portal vein pressure was reduced (141.5 ± 17.4 mm H2O). These findings clearly demonstrate that an important factor leading to an increase in hepatic vascular resistance is sinusoidal stenoses and a decrease in the sinusoidal bed resulting from swollen hepatic cells.
Detection of proteins encoded by the pre‐S region of hepatitis B virus in the sera of HBsAg carriers: relation to viral replication
Authors: IBARRA MIREN ZURIN̄E , MORA IGNACIO , BARTOLOMÉ JAVIER , PORRES JUAN CARLOS , CARREN̄O VICENTE
Published: August 2010

In order to determine the relationship between the presence of pre‐S1 and pre‐S2 proteins and the level of hepatitis B virus (HBV) replication, a study of 94 HBsAg chronic carriers, 15 anti‐HBe positive patients who suffered a viral reactivation and 12 HBeAg, HBV‐DNA positive cases under antiviral therapy, has been carried out. Pre‐S1 and pre‐S2 antigens were detected by RIA using polystyrene beads coated with anti‐preS1 or anti‐preS2 (Dr W. Gerlich, Göttingen) and 125I‐anti‐HBs as tracer. The presence of pre‐S1 and pre‐S2 antigens was detected in 74 (79%) and 85 (90%), respectively, out of the 94 HBsAg chronic carriers included. The level of these antigens was significantly higher in HBeAg, HBV‐DNA positive patients than in the other patients (p<0.05). Among anti‐HBe positive patients suffering a reactivation, a significant increase of pre‐S1 and pre‐S2 levels was observed, concurring with ALT exacerbation and HBV‐DNA positivity. After reactivation, the level of pre‐S antigens returned to the basal values. A significant decrease in pre‐S antigen levels (p<0.05) among patients who respond to recombinant interferon therapy was observed, while no changes were detected among non‐responder cases. The detection of pre‐S1 and pre‐S2 antigens in serum is more frequent in those patients with high viral replication. Furthermore, among anti‐HBe carriers with a viral reactivation, synthesis of pre‐S antigens takes place again.
Development of cavernous vasculatures in livers with hepatocellular carcinoma. An autopsy study
Authors: TERADA TADASHI , HOSO MASAHIRO , NAKANUMA YASUNI
Published: August 2010

The incidence and morphology of cavernous vasculatures in livers with hepatocellular carcinoma were examined. These vasculatures were grossly or microscopically found in 64% of 102 autopsied livers with hepatocellular carcinoma, though the incidence of grossly visible vasculatures was only 7%. These vasculatures were preferentially found within the portal tracts in the vicinity of portal veins obstructed by tumor emboli, especially in the cases with marked tumor emboli of the portal venous system. A majority of these vasculatures showed histochemical and immunohistochemical characteristics of blood vessels. Our findings suggest that these vasculatures frequently develop as collaterals of portal veins obstructed by the tumor emboli in hepatocellular carcinoma.
The source of serum alkaline phosphatases in liver‐tumour‐bearing rats
Authors: Hultcrantz Rolf , Eriksson Lennart C.
Published: August 2010

ABSTRACT— Patients with hepatic tumours have increased serum activities of alkaline phosphatases. In order to clarify the origin of the increased enzyme activity, two experimental models of rat liver carcinogenesis were studied. In one model, the resistant hepatocyte model, the process was initiated by diethylnitrosamine (DEN, 200 mg/kg), and preneoplastic liver nodules were selected for by 2 weeks of 2‐acetylaminofluorene (2‐AAF, 0.02%) feeding and partial hepatectomy (PH). High activities of serum alkaline phosphatases were found in these rapidly growing nodules harvested at the peak time of nodular mass expansion. In the other model in which nodules were induced with long‐term intermittent feeding of a diet containing 0.05% 2‐AAF and harvested in a late stage with a low increase of nodular liver cell mass, no such increase in serum alkaline phosphatase activity was found. A similar difference was also noted when measuring the activities of the enzyme in the nodular tissue. Thus the first model showed high activities of the enzyme in the nodular tissue, while the second model had similar activities to those of the control animals. The serum levels reflected the nodular enzyme activity in both models. The tissue surrounding the nodules did not show increased enzyme activity. No difference was noted in the serum or tissue activity of transaminases. In both models the liver nodules occupied 30–50% of the liver volume. The experimental models were selected to emphasize the importance of the rate of intrahepatic mass expansion for the levels of serum alkaline phosphatase activities. Our findings indicate that the increase in serum activities of alkaline phosphatase was caused by induction and release of the enzyme in the nodules themselves rather than by tissue compression and a following cholestasis of the surrounding liver tissue.
Detection of HBV DNA in HBsAg‐positive sera after amplification using the polymerase chain reaction
Authors: Theilmann L. , Fischer M. , Galle P. R. , Nassal M.
Published: August 2010

ABSTRACT— The presence of hepatitis B virus (HBV) DNA in serum as detected by molecular hybridization is considered the most reliable marker for the presence of complete virions and, therefore, infectivity. This technique, however, has a lower limit of detection of 0.1 pg HBV DNA. Using the polymerase chain reaction (PCR), a technique by which DNA sequences can be amplified selectively, we investigated sera from 30 HBsAg carriers, 6 also positive for HBeAg and 24 negative for HBeAg. After PCR followed by Southern blot, 27 sera were found to be positive for HBV DNA, whereas only 7 sera were positive for HBV DNA in the conventional dot blot. PCR followed by Southern blot analysis lowered the limit of detection to 0.5 fg HBV DNA. Amplified HBV DNA fragments from some samples were directly sequenced without previous cloning. We conclude that PCR is a suitable method to amplify parts of viral genomes present in human sera, and that PCR with subsequent Southern blot analysis allows the detection of hepatitis B virions in the majority of HBsAg‐positive sera.
Ultrastructural heterogeneity of glycogen in human liver
Authors: Chamlian A. , Benkoel L. , Minko D. , Njee T. , Gulian J. M.
Published: August 2010

ABSTRACT— The ultrastructure of the lobular patterns of hepatic glycogen was studied in four human liver surgical biopsies, obtained 14 h after the last meal. In centrilobular hepatocytes, glycogen particles were regularly dispersed with elements of SER between the particles. Periportal hepatocytes showed dense glycogen deposits with SER restricted to the periphery of the glycogen masses. The ultrastructural heterogeneity of the lobular distribution of glycogen in our human cases is similar to that found in control‐fed rats and mice. The metabolic signification of these findings is as yet unclear.
Sirius Red histophotometry and spectrophotometry of sections in the assessment of the collagen content of liver tissue and its application in growing rat liver
Authors: James J. , Bosch K. S. , Aronson D. C. , Houtkooper J. M.
Published: August 2010

ABSTRACT— By means of staining with Sirius Red F3BA in a saturated picric acid solution, the collagen contents of rat livers with varying degrees of fibrosis have been measured quantitatively in fixed and sectioned material, using both histophotometry in situ and extraction of bound dye with colorimetric analysis. These findings have been correlated with chemical assays of the hydroxyproline content in homogenates from the same livers. It appears that a highly significant correlation exists between both section‐based analysis methods and the hydroxyproline content, the Spearman‐Rank correlation coefficients being virtually identical. For analysis of collagen accumulation in rat liver, both section‐based methods seem to be useful and reliable, the extraction method giving the quickest results for large‐scale screening, and the histophotometric method being more appropriate to take readings in selected areas. With human liver material, indications have been obtained for the existence of large sampling errors due to inhomogeneous distribution of collagen deposits. Using the extraction method, no significant changes could be observed in the volume density of collagen during postnatal growth from 1 week to 21 months in rat liver: only on the third day after birth was a higher value of collagen/total protein obtained, possibly due to a higher water content of the hepatocytes. Partial hepatectomy was found to have no influence at all on the collagen content of rat liver during the period of restorative growth or after it.
Immuno‐light and electron microscopic features of chronic hepatitis D
Authors: Kojima Takashi , Callea Francesco , Desmyter Jan , Sakurai Isamu , Desmet Valeer J.
Published: August 2010

ABSTRACT— A morphologic study with immunohistochemical detection of the viral antigens of hepatitis B and Delta was performed on 36 liver specimens from patients with delta positive chronic viral hepatitis B. Electron microscopy was performed in 9 cases. No light microscopic or ultrastructural features specific for hepatitis D were observed. Lymphocytic infiltration occurred more often close to hepatocytes containing either hepatitis Delta antigen or hepatitis B core antigen in the cytoplasm, suggesting an involvement of cellular immune mechanisms in chronic hepatitis D as well as in hepatitis B. The simultaneous expression of both HBcAg and Delta antigen in occasional specimens over longer time periods indicates the possible co‐existence of both viruses without mutual inhibition.
Comparative sequential changes in serum and biliary levels of bile acid components after a single dose of D‐galactosamine or partial hepatectomy in the rat
Authors: Tsuda Hiroyoki , Wada Shigetsugu , Masui Tsuneo , Inui Masahiko , Ito Nobuyuki , Katagiri Kenji , Hoshino Makoto , Inaguma Hideki , Miyaji Makoto , Takeuchi Toshihiko
Published: August 2010

ABSTRACT— In order to characterize changes in bile acid profile during liver cell damage and regeneration, levels of bile acids in serum and bile were determined by high performance liquid chromatography (HPLC) in F344 rats treated with a single dose of D‐galactosamine (galactosamine, 300 mg/kg, i.p.) or subjected to two‐thirds partial hepatectomy (PH). In the serum, galactosamine caused elevation of conjugated bile acids such as taurocholic acid (TCA) and tauro‐ß‐muricholic acid (TßMCA) at the 24 and 48‐h time points, whereas unconjugated bile acids including cholic acid (CA) at 24 h and hyodeoxycholic acid (HDCA) at 48 h were increased after PH. In the bile, elevation of TCA showed most remarkable elevation at the 24‐h time point in the galactosamine‐treated group. All components of biliary bile acids showed rapid decreases from 24 to 48 h. The results demonstrated that while liver tissue damaged by galactosamine is able to conjugate bile acids it allows leakage into the blood stream. In contrast, the results for rats subjected to PH indicated that liver cells during DNA synthesis are not capable of conjugating all free bile acids with taurine although a similar leakage occurs. It is concluded that obvious elevation of serum TCA or CA and biliary TßMCA could be a useful indicator of hepatocellular proliferation.
Distribution of Lipiodol in hepatocellular carcinoma
Authors: Park Chanil , Choi Soo Im , Kim Hoguen , Yoo Hyung Sik , Lee Yoo Bock
Published: August 2010

ABSTRACT— Intrahepatic distribution of Lipiodol and I‐131 Lipiodol infused via the hepatic arteries was evaluated in six patients with HCC who had undergone hepatic lobectomy or segmentectomy. CT scan and gamma camera radiograph confirmed that the oily contrast material or I‐131 radioactivity accumulated selectively in the tumor over a long period. One to two thirds of the tumor mass appeared necrotic, although the extent tended to be larger in the case of radioactive Lipiodol infusion. The tumor cells contained numerous lipid globules within the cytoplasm. Also, oil red 0 stain demonstrated that the individual tumor cells had non‐globular lipid on their surface. In conclusion, Lipiodol leaks out of the vascular spaces to attach to the cancer cell membrane as a non‐globular lipid as well as to enter the cancer cells as a globular lipid. This phenomenon specific to cancer cells suggests a biochemical membrane change which may have occurred during carcinogenesis, causing alteration of membrane transport and cell death.
The role of acinar zone 3 hepatocytes in bile formation: influence of bromobenzene treatment on bile formation in the rat
Authors: Dionne Serge , Russo Pierre , Tuchweber Béatriz , Plaa Gabriel L. , Yousef Ibrahim M.
Published: August 2010

ABSTRACT—The role of zone 3 hepatocytes in bile formation was determined when they were selectively destroyed by 3.8 mmol/kg b.w. of bromobenzene injected i.p. for 48 h, as compared to appropriate controls. Bromobenzene treatment resulted in 29±4.4% hepatic lobule necrosis localized in the zone 3 hepatocytes. Although bile flow and bile salt‐independent flow were not affected, this treatment was associated with a significant reduction in bile salt, and phospholipid secretion. The bile salt pool and bile salt synthesis were also significantly decreased. These results suggest that necrosis of zone 3 hepatocytes induced by bromobenzene reduced bile acid synthesis which decreased bile salt pool and affected bile salt and phospholipid secretion rates. However, necrosis of zone 3 hepatocytes did not affect bile flow or the bile salt‐independent flow, suggesting that hepatocytes of zones 1 and 2 maintained the normal bile salt‐independent flow when zone 3 hepatocytes were damaged.
Immunocytochemical studies on cholestatic factor in human liver with or without cholestasis
Authors: Yamada Shoji , Takehara Ken , Arai Takayuki , Takezawa Jiro , Kobayashi Setsuo , Mizoguchi Yasuhiro , Morisawa Seiji , Yamamoto Sukeo , Nagura Hiroshi
Published: August 2010

ABSTRACT— The localization of the cholestatic factor (CF) was immunocylochemically investigated in liver biopsy specimens obtained from patients with various liver diseases. CF was detected in seven of nine patients with drug‐induced liver injury, three of four with acute viral hepatitis, three of five with alcoholic liver injury and in the two patients with autoimmune hepatitis. Fourteen of these 15 CF‐positive patients had jaundice in their clinical courses. CF was stained diffusely in the cytoplasm of hepatocytes throughout the lobules in a granular pattern. Electron‐microscopically, it was localized on the ribosomes and polysomes as well as on the filamentous structures around the bile canaliculi. However, CF was not detected in liver specimens from normal controls and patients with primary biliary cirrhosis and extrahepatic biliary obstruction. These findings suggest that CF plays an important role in intrahepatic cholestasis in various liver diseases.
Are there diagnostic histologic features of porphyria cutanea tarda in liver biopsy specimens?
Authors: Campo Elias , Bruguera Miguel , Rodés Joan
Published: August 2010

ABSTRACT— In a blind review of 485 consecutive liver biopsy specimens, 16 from patients with porphyria cutanea tarda (PCT) and 469 from patients with other diseases, we have evaluated the frequency of the following features: a) needle‐shaped cytoplasmic inclusions in liver cells, b) lobular aggregates of histiocytes laden with ceroid and iron, and c) the simultaneous presence of portal inflammation, hemosiderosis and fatty change, in order to ascertain their usefulness in the diagnosis of PCT. Cytoplasmic inclusions and lobular aggregates of macrophages were only found in two specimens, both of them from patients with PCT. The simultaneous presence of portal inflammation, hemosiderin and fat was found in nine patients (56%) with PCT and in nine (1.9%) of those without PCT. The localization of hemosiderin deposits differed between the two groups, being observed in periportal hepatocytes in cases with PCT, whilst it was predominantly found in Kupffer cells with a diffuse lobular distribution in cases without PCT. Thus, the finding in a liver biopsy specimen of hemosiderin in periportal hepatocytes, fatty changes and portal inflammation should alert one to the possible diagnosis of PCT and encourage the utilization of tests to confirm this diagnosis.
Streaming liver VI: streaming intra‐hepatic bile ducts
Authors: Arber N. , Zajicek G.
Published: August 2010

Abstract— Thirty male adult rats, weighing 250–300 g, were injected with 0.5 μCi [3H]‐thymidine. The rats were killed in groups of five, at the following times: 1 h, 14, 30, 60, 90 and 120 days. The livers were fixed in formalin, embedded in paraffin and cut into 5‐μm‐thick sections, which were then dipped into liquid emulsion for autoradiography. Bile ducts were evaluated in all portal tracts of a section. Obliquely cut bile ducts were excluded. The number of cells paving the duct lumen was defined as bile duct class. Class is roughly proportional to bile duct size. One hour after labelling, labelling index was 3.39 ± 0.06% (the second number is one standard error of the mean). With time it declined, reaching 0.22 ± 0.15 on day 60. Initially labelled cells were found in narrow bile ducts and the mean labelled cell was located at class 7.48 ± 0.63. With time, labelled cells proceeded into wider bile ducts advancing daily 0.122 ± 0.025 classes. Intra‐hepatic bile duct epithelium renews its cells continuously in the same way as epidermis or gastro‐intestinal mucosa do. It consists of two kinetic compartments, a progenitor (P) and a functional (Q) compartment. P feeds Q with cells.
Antibody to the hepatitis C virus in acute hepatitis and chronic liver diseases in Japan
Authors: Nishioka Kusuya , Watanabe Junnosuke , Furuta Seiichi , Tanaka Eiji , Suzuki Hiroshi , Iino Shiro , Tsuji Takao , Yano Michitami , Kuo George , Choo Qui‐Lim , Houghton Michael , Oda Toshitsugu
Published: August 2010

ABSTRACT— In a 6‐month follow‐up study of acute hepatitis in Japan, 31 out of 41 (75.6%) cases of post‐transfusion non‐A and non‐B hepatitis (NANB‐PTH) and 14 out of 40 (35.0%) cases of sporadic non‐A non‐B hepatitis (NANB‐SPO) were found to be positive for antibody to the hepatitis C virus (HCVAb). After 12 months of follow‐up, 30 cases (81.1%) became chronic among 37 HCVAb positive acute NANB hepatitis cases. This figure shows a significantly higher rate of chronicity as compared with HCVAb negative acute NANB hepatitis. The prevalences of HCVAb in hepatitis B surface antigen (HBsAg) negative cases of chronic hepatitis and liver cirrhosis were 76.3% (200/262) and 66.7% (106/159), respectively, which were significantly different from the values of 5.1% (13/255) and 10.6% (13/123) observed in HBsAg positive cases. Of chronic liver disease cases positive for HCVAb, 45.8% (152/332) had a history of blood transfusion, in contrast to the value of 3.7% (13/352) observed in HBsAg positive cases of chronic liver disease that were negative for HCVAb.
Histological changes in the liver in experimental graft‐versus‐host disease across minor histocompatibility barriers. VI. A light and electron microscopic study of the periportal changes
Authors: Nonomura Akitaka , Kono Naoko , Mizukzmi Yuji , Nakanuma Yasuni , Matsubara Fujitsugu
Published: August 2010

ABSTRACT— Periportal changes of the liver in experimental graft‐versus‐host disease (GVHD) across minor histocompatibility barriers were investigated electron‐microscopically for up to 14 months after bone marrow transplantation (BMT). In GVHD mice, periportal changes affecting the limiting plate of hepatocytes were relatively mild and, in general, classical piecemeal necrosis was rarely observed. However, around 2 weeks after transplantation disruption of the limiting plate of hepatocytes was transiently observed. At that time, lymphocytes invaded directly into the hepatic parenchyma and were in close contact with hepatocytes mainly through a number of point‐contacts of cell membranes. Hepatocytes in close contact with lymphocytes showed minor degenerative changes under electron microscopy. On the other hand, periportal bile ductules and canals of Hering were constantly injured by inflammatory cells during the entire observation period up to 14 months after BMT. They were abutted by lymphocytes, together with other inflammatory cells including eosinophils, neutrophils, plasma cells and monocytes. Infiltration of inflammatory cells into the epithelial layer of the bile ductules and canals of Hering through the basement membrane was frequently found. Inflammatory cells were in contact with duct epithelial cells mainly through a number of point‐contacts of cell membranes. Epithelial cells in contact with inflammatory cells exhibited a number of degenerative changes, including condensation of cytoplasm, irregular contour of nucleus, dilatation of endoplasmic reticulum, formation of cytoplasmic vesicles, focal cytoplasmic degeneration, and so on. These results suggest that classical piecemeal necrosis of the limiting plate of hepatocytes is not characteristic for hepatic GVHD, whereas the smaller and smallest periportal bile ductules or canals of Hering are frequently injured by lymphocytes and other inflammatory cells, similar to those seen in the interlobular and septal bile ducts, indicating that not only the interlobular and septal bile ducts but also the smaller or smallest periportal bile ductules and canals of Hering are the major targets in hepatic GVHD, and thus hepatic injury in GVHD may progress along the biliary tree.
Pathogenesis of liver cirrhosis in alcoholic patients: histological evidence for hepatitis C virus responsibility
Authors: Halimi C. , Dány P. , Gotheil C. , Trinchet J. C. , Mal F. , Scavizzi M. , Beaugrand M.
Published: August 2010

ABSTRACT— Hepatitis C virus (HCV) has been proposed to be a cofactor in the pathogenesis of cirrhosis in patients with chronic alcoholism. The demonstration of a different liver histological pattern in anti‐HCV positive patients might provide additional evidence. We studied 164 patients with chronic alcoholism, and histologically proven cirrhosis. For all of them, serum samples were collected at the time of a liver biopsy and stored at –80°C. Testing for anti‐HCV antibodies was done using the Ortho Diagnostic Systems Anti‐HCV ELISA test. Only reproducible results were considered positive. A semi‐quantitative assessment of seven histological parameters was made independently on liver biopsy samples. In the study group, 29 patients (18%) had anti‐HCV antibodies. When compared with anti‐HCV negative patients, both groups had similar ALT and AST seric activities. Anti‐HCV positive patients had a greater score of mononuclear cells infiltrate (0.71±0.57 vs 0.41 ±0.52; p<0.05) and a lesser score of alcoholic hepatitis (0.19 ±0.57 vs 0.74 ±0.74; p<0.005). The scores for steatosis, perisinusoidal and perinodular fibrosis, and hepatocellular necrosis were similar in the two groups. In anti‐HCV positive patients, with a clearly positive recombinant immunobinding assay (RIBA, Chiron‐Ortho Diagnostic Systems), a greater score for hepatic necrosis and a lesser one for fibrosis were demonstrated. Among the seven patients with active cirrhosis, six were anti‐HCV positive. Therefore, HCV is likely to play a role in the pathogenesis of liver damage in a few patients with alcoholic cirrhosis, especially, those with active cirrhosis.
Bacteremia in patients with cirrhosis of the liver
Authors: Kuo Chung‐Huang , Changchien Chi‐Sin , Yang Chaur‐Young , Sheen I‐Shyan , Liaw Yun‐Fan
Published: August 2010

ABSTRACT— Infections are frequent in patients with liver cirrhosis, as their defenses against infectious agents are altered. But bacteremia occurring in cirrhotic patients has seldom been reported in the literature. From 1981 to 1986, we collected 197 cases with 228 episodes of bacteremia for this retrospective study. The incidence of bacteremia in cirrhotic patients was 8.8%; no significant difference was noted between cirrhotic patients with variant etiologies of HBV(+), HBV(–) and alcohol. But the incidence increased with the severity of the disease (1%, 4.8%, 17.1% in Child's A, B, C groups, respectively). Gram‐negative bacteria were the predominant microorganisms of bacteremia (75.6%). Among them, Escherichia coli, Klebsiella pneumoniae and Aeromonas hydrophilia were the three most commonly detected microorganisms. Gram‐positive bacterias were detected in 21.2% of patients with bacteremia, with predominance of the Streptococcus group and Staphylococcus aureus. In about 26.3% of cases the infectious sources were the same by bacteria cultures as from blood. The most common sources were spontaneous bacterial peritonitis, urinary tract infection, pneumonia and biliary tree infection. In cirrhotic patients with and without bacteremia, the mortality rate increased significantly in the bacteremia group (54.8% vs 23.2%, P<0.05). By Child's classification, the mortality of patients with classes B and C increased significantly after onset of bacteremia. There was no significant difference in mortality between bacteremic patients in the HBV(+), HBV(–) and alcohol groups. In conclusion, bacteremia is a severe complication of liver cirrhosis and a sign of a poor prognosis.
Effects of epinephrine on urea synthesis in vivo in rats
Authors: Heindorff Hans , Almdal Thomas , Vilstrup Hendrik
Published: August 2010

Abstract: Three hours after hysterectomy the rate of urea synthesis doubles in rats. At the same time the increase in catecholamines is at a maximum, suggesting that catecholamines might be of regulatory importance. The effect of exogenous epinephrine on the rate of urea synthesis was studied in rats receiving epinephrine at rates of 2 and 20 μg/kg/h. The low dose increased plasma concentration of catecholamines two‐fold over control values (p>0.01), comparable with the increase seen after surgery, and the high dose of epinephrine increased the concentration fivefold. The high dose increased the rate of urea synthesis by 30% (p>0.05), whereas the low dose had no effect. Following a high dose of epinephrine, alanine decreased from 358 ± 29 to 254 ± 17 mmol/1 (p>0.05), indicating that the increase in urea synthesis was due to an effect on the liver rather than on extra‐hepatic tissues, in that more aminonitrogen was eliminated from plasma than released into it. In conclusion, epinephrine in physiological concentrations cannot by itself account for the increase of urea synthesis seen in vivo after surgery.
Free fatty acids have nucleating effects in model biles
Authors: Halpern Z. , Goldman G. , Peled Y. , Konikoff F. , Rattan J. , Lichtenberg D. , Gilat T.
Published: August 2010

ABSTRACT— Nucleating factors are thought to be responsible for the more rapid nucleation of gallbladder bile from patients with gallstones as compared to controls. Biliary proteins and, in particular, mucus and non‐mucus glycoproteins are the focus of current research. Non‐protein nucleating factors were not extensively investigated. In this study we studied the role of free fatty acids (FFA) as possible nucleating factors. Palmitic, oleic and linoleic acid were added to model biles in increasing concentrations from 0 to 20 μmol/ml. The nucleation time of model biles decreased to 45%‐60% of the initial following the addition of 0.5 to 1 μmol/ml of each of the three fatty acids. Only a small further decrease in the nucleation time was noted with higher concentrations of up to 20 μmol/ml. The pronucleating effect of FFA added to whole model bile was also examined in the isolated vesicular and non‐vesicular fractions. The decrease in the nucleation time at each concentration of the three fatty acids was in the following order of magnitude: whole bile > vesicular phase > non‐vesicular phase. The addition of each of the three fatty acids resulted in a partial solubilization of vesicles, with transfer of their lipid contents to the non‐vesicular fraction. The effect was more marked with oleic acid and least marked with linoleic acid. The vesicular cholesterol to phospholipid ratio did not change following the addition of exogenous free fatty acids. Studies with labeled FFA showed that they migrated with the non‐vesicular fraction on gel chromatography. The three fatty acids exerted their nucleating effect at low concentration, which may be close to the physiologic range. Free fatty acids may thus be nucleating factors in human bile. Their pathophysiologic importance and mechanism of action remain to be elucidated.
Prospective controlled study of posttransfusion hepatitis after cardiac surgery in a large referral hospital in India
Authors: Dasarathy S. , Misra S. C. , Acharya S. K. , Irshad M. , Joshi Y. K. , Venugopal P. , Tandon B. N.
Published: August 2010

ABSTRACT— We studied the risk of post‐transfusion hepatitis (PTH) in recipients of blood collected from voluntary donors screened for HBsAg. Two hundred and fifty patients without any previous history of liver disease or transfusion were followed up for 12 months subsequent to cardiac surgery. Thirty‐five of them had closed‐heart surgery without receiving transfusion and served as controls. The remaining 215 patients received single‐point transfusions (mean 4 ± 2.4 units). None of the controls and 15 (6.9%) blood recipients developed PTH. Three (20%) patients had hepatitis‐B‐virus‐induced hepatitis while the remainder (80%) had non A, non B (NANB) hepatitis. The number of units of blood transfused and surrogate markers for development of PTH (donor alanine aminotransferase, anti‐HBc and anti‐HBs antibody) were not associated with the occurrence of PTH (p>0.05). Nine (60%) of the 15 patients developing PTH were asymptomatic. All the patients recovered from the PTH, except one who died of fulminant hepatitis. At the end of 1 year of follow‐up, none of the patients had evidence of chronic hepatitis. Only three (25%) of the patients with NANB‐PTH developed anti‐hepatitis C virus (HCV) antibody during the follow‐up. We conclude that the incidence of PTH in India is similar to other parts of the world and NANB virus was the major cause of the PTH. The absence of chronicity and lack of seroconversion to anti‐HCV antibody in the majority of the patients after 1 year of follow‐up may suggest the possibility of a NANB virus other than HCV as the major cause of PTH in India.
Role of the spleen in endotoxin‐induced hepatic injury in chronic alcohol‐fed rats
Authors: Tanaka Shimpei , Kumashiro Ryukichi , Tanikawa Kyulchi
Published: August 2010

ABSTRACT— The present experiments were designed to study the role of the spleen in endotoxin‐induced hepatic injury in chronic alcohol‐fed rats. Administration of 2 mg/kg body weight of endotoxin caused severe hepatic injury in chronic alcohol‐fed rats as compared with controls. This injury was significantly less in those whose spleens had been resected 1 week prior to endotoxin administration. There were no differences in plasma endotoxin levels 16 h after intravenous injection of endotoxin between sham‐operated control rats, and chronic alcohol‐fed rats with and without splenectomy. The plasma tumor necrosis factor (TNF) level 1 h after intravenous injection of endotoxin was significantly higher in chronic alcohol‐fed rats than in controls. However, TNF levels were significantly lower in those with splenectomy. Neutrophil infiltration was seen in the liver sinusoid of sham‐operated chronic alcohol‐fed rats as early as 1 h after injection of endotoxin, and was observed even 15 h later. These results suggest that endotoxin‐induced liver injury is closely related to factors derived from the spleen and induced by plasma endotoxin, especially when Kupffer cell function is reduced by chronic alcohol feeding. In addition, TNF and neutrophils may play an important role in this type of liver injury.