bluuebunny/crossref_metadata_2025 huggingface dataset:
Spontaneous and antibody‐dependent cellular immune reactions to ethanol‐altered hepatoma cells
Authors: Poralla T. , Hütteroth T. H. , Knuth A. , Staritz M. , Dienes H. P. , Zum Büschenfelde K.‐H. Meyer
Published: August 2010

ABSTRACT— Spontaneous cell‐mediated cytotoxicity (SCMC), antibody‐dependent cellular cytotoxicity (ADCC) and proliferative lymphocyte stimulation in alcoholic liver disease (ALD) were investigated. Peripheral blood lymphocytes (PBL) from eight patients with advanced ALD and nine normal controls were tested against hepatoma cells (PLC/PRF/5) as targets. Target cells were grown in either normal culture medium or medium supplemented with 1 and 5% ethanol, respectively, for 24 to 48 h. Ethanol‐exposed hepatoma cells exhibited profound and characteristic morphological alterations. Ethanol preincubation, however, proved to be without effect on immune reactions. Provided that hepatoma cells are an appropriate model, we assume that the proposed immune reactions in ALD are based on metabolic interactions operative only in vivo but do not parallel morphological alterations of liver cells directly induced by ethanol.
Kupffer cells and their function
Authors: Wardle E. Nigel
Published: August 2010

ABSTRACT— The intention of this review is to stress new information regarding the quite versatile functions of Kupffer cells. Although their main function is phagocytosis and defence of the liver against bacteria, endotoxaemia and viral infections, they also fulfil other important roles. They will phagocytose and partially degrade bacterial antigens before handing them on to the hepatocytes for excretion into the bile. They handle LDL lipoproteins, whilst the HDL proceed directly into the hepatocytes. They produce lymphokine mediators that direct protein synthesis by the hepatocytes. Also they normally produce prostaglandins that are cyto‐protective for the hepatocytes. Conversely, if they are required to attack infected hepatocytes or cancer cells, then they switch to the production of leukotrienes. Thus they function as specialised macrophages, and it is not surprising that other “activated macrophages” have to be recruited into the liver to support them in inflammatory reactions.
The influence of hepatic insufficiency due to alcoholic cirrhosis on the erythrocyte transketolase activity (ETKA)
Authors: Graudal Niels , Torp‐Pedersen Kirsten , Bonde Jan , Hanel Henrik K. , Kristensen Marie , Milman Nils , Thomsen Åge Chr.
Published: August 2010

ABSTRACT— The erythrocyte transketolase activity (ETKA), the stimulated erythrocyte transketolase activity (ETKAS), and the thiaminepyrophosphate effect (TPPE) were measured in 21 alcoholic patients with cirrhosis and hepatic insufficiency, 13 alcoholic patients without cirrhosis and 21 non‐alcoholic persons before and after oral treatment with 100 mg of thiamine daily for 2 weeks in order to investigate the influence of hepatic insufficiency on these variables. A statistically significant rise in ETKA and fall in TPPE were found in all three groups. ETKA, ETKAS and TPPE did not differ from each other in alcoholic patients with and without cirrhosis, but TPPE was significantly higher in these patients than in the non‐alcoholic persons. The conclusions are that severe cirrhosis does not affect the erythrocyte transketolase apoenzyme, the ability of the tissues to convert thiamine to thiaminepyrophosphate for use in the erythrocytes or the absorption of thiamine from the gastrointestinal tract. Besides alcoholism seems to dispose to thiamine deficiency to a higher degree than cirrhosis, and the role of the liver as a thiamine store appears to be of minor importance in the development of thiamine deficiency. Finally, ETKA, ETKAS, and TPPE are considered to be usable as thiamine deficiency indicators in patients with cirrhosis as well as in patients without cirrhosis.
Effect of chronic administration of taurolithocholate on bile formation and liver ultrastructure in the rat
Authors: Gratton F. , Weber A. M. , Tuchweber B. , Morazain R. , Roy C. C. , Yousef I. M.
Published: August 2010

ABSTRACT— In some cholestatic syndromes, lithocholic acid (LCA) has been identified in serum and bile and might play a role in the pathogenesis of cholestasis. Thus, we examined the effect of chronic LCA administration on hepatobiliary function in rats. The taurine‐conjugate of LCA (TLCA) was given to male rats at the dose of 50 mg/kg body weight i.v. twice daily for 18 days. Bile flow, biliary secretion rate of bile acids, phospholipids and cholesterol, measured 15 h after the last injection, were normal with the exception of phospholipid, which was significantly higher when compared to controls. Individual bile acids measured by GLC showed that the contribution of chenodeoxycholic and muricholic acids increased while that of cholic acid decreased. By electron microscopy, bile canalicular structures appeared normal except for a widening of the pericanalicular ectoplasm. Evaluation of hepatobiliary function 1 h after an additional injection of TLCA to rats that received the bile acid for 18 days, resulted in the typical acute cholestatic response. Thus chronic administration of TLCA does not influence the acute cholestatic effect of TLCA.
Methodological problems in the use of indocyanine green to estimate hepatic blood flow and ICG clearance in man
Authors: Skak Claus , Keiding Susanne
Published: August 2010

ABSTRACT— Liver blood flow (Q) is often measured by constant infusion of ICG (i), concentration measurements in an artery (A) and a hepatic vein (V): Q = (A – V)/A. Some authors use ICG clearance, Cl = i/A, as a measure of Q assuming complete hepatic extraction. During the infusion, the ICG concentration often increases. The importance of this for calculated values of Q and Cl was examined, and the use of Cl as a measure of Q was reevaluated. ICG was given as 0.06–0.20 μmol/min to 52 subjects with liver disease, and about 0.20 μmol/min to 86 subjects with no liver disease. ICG concentration increased steeply during the first 90 min after start of the infusion; thereafter the increment was constant as evaluated in successive 40‐min periods in eleven 320‐min studies (analysis of variance P > 0.5); on average, 6 ± 1% per hour (± SD). Q was not time‐dependent (P > 0.5). ICG clearance decreased significantly, on average 5 ± 2% per hour (± SD). Hepatic extraction fraction, (A‐V)/A, (measurement period 90–130 min) was 0.34 ± 0.21 in liver patients (± SD) and 0.61 ± 0.80 in controls. Cl and Q were positively correlated in both groups but with substantial scatter. Thus, not only is the calculated ICG clearance time‐dependent but the extraction fraction is further so low and variable, that any use of ICG clearance as a measure of liver flow is not justified.
Diagnosis of acute type B hepatitis by a solid phase u‐antibody capture radioimmunoassay for IgM class antibody to hepatitis B core antigen: a diagnostic proposal based on a prospective study
Authors: Chu Chia‐Ming , Liaw Yun‐Fan , Yang Chaur‐Young , Sheen I‐Shyan
Published: August 2010

ABSTRACT— The diagnostic and prognostic significance of IgM anti‐HBc, studied by a solid phase u‐antibody capture radioimmunoassay at a serum dilution of 1:4000, was prospectively evaluated in 73 adult patients with acute hepatitis seropositive for hepatitis B surface antigen (HBsAg). Of the 73 cases, 20 (27.4%) cleared their HBsAg within 6 months, while the remaining 53 (72.6%) did not. HBsAg seroconversion to its antibody occurred in 15 (93.8%) of the 16 patients positive for IgM anti‐HBc with S/N ratios above 5.0, as did 5 (26.3%) of the 19 with S/N ratios between 2.1 to 5.0, and none (0%) of the 38 negative for IgM anti‐HBc (S/N ratios < 2.1). Therefore, a S/N ratio of IgM anti‐HBc above 5.0 is diagnostic for acute type B hepatitis. However, low S/N ratios (2.1–5.0) of IgM anti‐HBc were observed in the early stage of some patients with acute type B hepatitis, and would increase to a level greater than 5.0 when assayed again 1–2 weeks later. It was therefore suggested that repeated testing of anti‐HBc IgM is mandatory for accurate diagnosis of acute type B hepatitis in patients whose initial serum specimens showed low S/N ratios of IgM anti‐HBc. According to this criterion, only 22 (30.1%) of the 73 patients with acute hepatitis seropositive for HBsAg in Taiwan were true acute type B hepatitis, of whom 2 (9.1%) subsequently became chronic HBsAg carriers, while the remaining 51 (69.9%) were chronic HBsAg carriers with other superimposed forms of acute hepatic injury.
Immune electron microscopic demonstration of hepatitis B core antigen (HBcAg) in liver cell plasma membranes
Authors: Kojima Takashi , Bloemen Jozef , Desmet Valeer J.
Published: August 2010

ABSTRACT— Immune light and electron microscopic examinations were carried out to investigate the localization of HBcAg in biopsies from patients with persistent HBs antigenemia. In biopsies with severe intralobular inflammation HBcAg was mainly observed in the cytoplasm of hepatocytes in contrast to nuclear localization in specimens with less severe histological changes. Immune electron microscopic examination demonstrated two different appearances of HBcAg, according to whether it was or was not associated with core particles. In biopsies with more severe parenchymal damage, an increased amoùnt of non‐particulate HBcAg was observed in the cytoplasmic matrix; four such biopsies with intracytoplasmic HBcAg also revealed HBcAg on the plasma membrane of the hepatocytes. These findings support the concept that HBcAg may function as a viral target antigen for the immune response in type B hepatitis.
Leiomyosarcoma of the inferior vena cava presenting as Budd‐Chiari syndrome
Authors: Taylor Richard W. , Sylwestrowicz Thomas , Kossakowska Anna E. , Urbanski Stefan J. , Minuk Gerald Y.
Published: August 2010

ABSTRACT— A case of a 72‐year‐old male with a leiomyosarcoma of the inverior vena cava causing Budd‐Chiari syndrome is described. Percutaneous decompression of the portal system was attempted but with no success. At autopsy, a large tumor arising from and completely obstructing the inferior vena cava was found, histologically proven to be a leiomyosarcoma. Over 50 cases of leiomyosarcoma of the inferior vena cava have been reported in the literature, the majority of which occurred in women and 1/3 of which were associated with the Budd‐Chiari syndrome. Histologically up to two mitotic figures per 10 high power fields have been scored. This case indicates the unreliability of a low mitotic index as an indicator of benign behavior of smooth muscle neoplasms of the venous system.
Lack of effects of Nifedipine on hepatic hemodynamics in patients with HBsAg‐positive cirrhosis
Authors: Lay Chii‐Shyan , Tsai Yang‐Te , Kong Chi‐Woon , Lee Fa‐Yauh , Lee Shou‐Dong , Lo Kwang‐Juei , Chiang Benjamin N. , Chen Kuang‐Y
Published: August 2010

ABSTRACT— The acute effects of Nifedipine on hepatic venous pressure gradient (HVPG) and estimated hepatic blood flow (EHBF) were investigated in six patients with HBsAg‐positive cirrhosis and portal hypertension by simultaneous hepatic venous catheterization. The mean arterial pressure significantly decreased by 18% at 1 h after sublingual administration of 10 mg Nifedipine. Significant increases in heart rate (13%) and cardiac output (20%) were also demonstrated in our patients 1 h after administration of Nifedipine. However, there were no significant changes in HVPG and EHBF after Nifedipine. We conclude that in patients with HBsAg‐positive cirrhosis who receive Nifedipine, EHBF is maintained despite a substantial change in systemic hemodynamics, and that Nifedipine is not effective in acutely reducing HVPG.
Monoclonal antibodies identifying antigens on distinct domains of rat hepatocytes
Authors: Mizuno Motowo , Yamada Gotaro , Sugiyama Toshiro , Vierling John M. , Brown William R.
Published: August 2010

ABSTRACT— To aid in evaluating the functional significance of various domains of the hepatocyte plasma membrane, we have developed monoclonal antibodies that react with three different antigens on the surface of rat hepatocytes. One antigen is present on the sinusoidal‐lateral plasma membrane but is absent from the bile canalicular membrane. On the basis of apparent molecular weight and ability to bind a desialylated glycoprotein, this antigen may be the asialoglycoprotein receptor. It was also identified immunocytochemically on the sinusoidal‐lateral plasma membrane of human hepatocytes. The second antigen is present only on the bile canalicular membrane, whereas the third is present on the entire cell surface of rat hepatocytes. Our monoclonal antibodies may be useful in investigations of the sorting mechanisms of hepatocyte membrane proteins and the pathogenesis of certain liver diseases.
Histopathological analysis of chronic hepatitis B virus (HBV) infection in relation to HBV replication
Authors: Suzuki Koyu , Uchida Toshikazu , Shikata Toshio
Published: August 2010

ABSTRACT— The interrelationship among expression patterns of hepatitis B surface and core antigens (HBsAg and HBcAg) in the liver, hepatitis B virus (HBV) DNA in sera, HBeAg/anti‐HBe status and histological features was examined in 189 liver specimens and 106 sera from Japanese patients with chronic HBV infection, utilizing immunoperoxidase methods and a spot hybridization technique. HBsAg and HBcAg were distributed uniformly among the lobules in 8 viral carriers with “normal” liver (NVC) and 30 patients with persistent hepatitis (PH) seropositive for HBeAg. This uniform staining pattern was quite distinct from the non‐uniform and irregular patterns in 137 patients with chronic active hepatitis (CAH) associated with or not associated with cirrhosis. HBcAg was often found to be stained strongly in the cytoplasm as well as in the nucleus of hepatocytes in HBeAg‐positive CAH, in contrast to NVC/PH, in which cytoplasmic HBcAg was very weak. Serum HBV DNA was detected in all 22 cases with HBeAg‐positive NVC/PH, 41 of 46 (89.1%) cases with HBeAg‐positive CAH, 6 of 23 (26.1%) cases with anti‐HBe‐positive CAH and none of 3 cases with anti‐HBe‐positive NVC/PH. The level of serum HBV DNA and staining of HBcAg were in decreasing order in these groups. While the presence of serum HBV DNA and HBcAg staining was always associated with HBeAg seropositivity in NVC/PH, this was not always found in CAH. Moreover, necroinflammatory activity in the liver did not always parallel viral replication in CAH. These findings seem to confirm that NVC/PH and CAH have different biologic processes; viral replication is always concordant in the former, but is sometimes discordant in the latter with HBeAg/anti‐HBe status. The immunologic response of the host seems to suppress and distort replication of the virus to a varying degree among patients and areas of the same liver in CAH differently to that in NVC/PH. The different life cycle of the virus, including integration of viral DNA into the cellular genome, may subsequently result in discordant states of various virus markers in CAH.
Features of chronic hepatitis in alcoholics. A survey in Milan
Authors: Adelasco L. , Monarca A. , Dantes M. , Moioli M. G. , Vinci M. , Croce G. , Tavani E. , Natangelo R. , Lucchelli P. D.
Published: August 2010

ABSTRACT— A study was carried out to confirm the pathogenetic role of ethanol in the development of chronic active hepatitis (CAH) and to assess if previous or current superimposed hepatitis B virus (HBV) infection could be relevant to the course of alcoholic liver disease (ALD). We examined clinical and laboratory reports of 57 alcoholics with biopsy‐proven CAH. Serum and/or tissue HBV markers and the presence or absence of cirrhosis were investigated. Alcohol was the only aetiological factor present in a small group of CAH, with or without histological findings suggestive of alcoholic damage. Age, sex and survival were similar among the subgroups of CAH with and without previous or current HBV infection and among the subgroups of CAH with and without associated histological alcoholic features. Among the laboratory data, the AST/ALT ratio was higher in CAH without previous or current HBV infection. The mean age was comparable in CAH patients with and without cirrhosis, whereas the cumulative 5‐year survival was worse in CAH with cirrhosis (87% vs. 49%). These data suggest a difference in alcohol susceptibility in our subjects.
Prolonged (6 months) treatment of chronic hepatitis B virus infection with recombinant leukocyte A interferon
Authors: Carreño Vicente , Porres Juan C. , Mora Ignacio , Bartolomé Javier , Bas Caridad , Gutiez Julia , Cortés José , Guio Carlos Hernández
Published: August 2010

ABSTRACT— Twelve hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), hepatitis B virus DNA polymerase (HBV‐DNAp) and hepatitis B virus DNA (HBV‐DNA) positive patients with chronic active hepatitis (CAH) were treated with doses of either 20 times 106 IU/m2 or 10 times 106 IU/m2 body surface of recombinant interferon (rIFN)‐alpha‐2A, I.M., twice a week, during a period of 6 months. No appreciable differences with respect to clinical history, liver function tests and markers of HBV replication between the two groups were apparent at the time of entry into the trial. At the third month of treatment HBV‐DNAp became negative in 10 out of 12 patients (83%). After a 15‐month follow‐up, HBV‐DNAp, HBV‐DNA and HBeAg were negative in 7 out of 12 patients (38%) (responders). Furthermore, at 24 months, 2 non‐responder patients became HBV‐DNA and HBV‐DNAp negative and one responder lost serum HBsAg. In addition, HBsAg concentration, GPT level and histological Knodell's index decreased significantly in the responder patients, while no changes were observed in non‐responders. Five out of six patients who received a low rIFN dose responded to the treatment, and only 2 out of 6 with a higher dose. No unacceptable toxicity was noted in any of the 12 patients. All of them completed the course of treatment. The results suggest that long‐term rIFN‐alpha‐2A therapy has an antiviral effect in CAH due to HBV infection and is well tolerated.
Serum aminoterminal type III procollagen peptide and the 7S domain of type IV collagen in patients with alcohol abuse Relation to ultrastructural fibrosis in the acinar zone 3 and to serum hyaluronan
Authors: Bentsen Kirsten D. , Horn Thomas , Risteli Juha , Risteli Leila , Engström‐Laurent Anna , Hørslev‐Petersen Kim , Lorenzen Ib ,   The Copenhagen Study Group on Fibrotic Diseases
Published: August 2010

ABSTRACT— Serum concentrations of the aminoterminal propeptide of type III procollagen and of the 7S domain of type IV collagen, presumed to reflect fibrotic activity in liver tissue, and of the glycosamonoglycan hyaluronan, were obtained from 40 alcohol abusers, at the time of liver biopsy. The serological results were related to morphological findings in liver tissue, i.e. no fibrosis, fibrosis without cirrhosis, micronodular cirrhosis and macronodular cirrhosis, and to ultrastructural indications of perisinusoidal fibrosis in the acinar zone 3. All patients with fibrosis and cirrhosis on light microscopy had elevated serum levels of the type III procollagen peptide as well as of the 7S domain of type IV collagen. However, due to a considerable overlap between the groups, no relations could be demonstrated to the severity of the fibrosis, supporting the assumption that these serological markers reflect the current fibrotic activity and not the amount of fibrotic tissue previously deposited. Among patients without fibrosis on light microscopy, a relation between the propeptide levels and ultrastructural perisinusoidal zone 3 fibrosis was observed, suggesting that type III procollagen peptide may be valuable in detecting very early liver fibrosis. A positive correlation was demonstrated between the serum concentrations of type III procollagen peptide and hyaluronan. As hyaluronan is degraded in the liver endothelial cells, it is suggested that the liver is involved, not only in the synthesis, but also in the degradation of the propeptide.
Ultrastructural findings on polymorphonuclear leucocyte infiltration and acute hepatocellular damage in alcoholic hepatitis
Authors: Takahashi Toru , Kamimura Tomoteru , Ichida Fumihiro
Published: August 2010

ABSTRACT— Ultrastructural examination was carried out in 13 liver biopsies from patients with alcoholic hepatitis, with special reference to the relationship between alcoholic hyaline (AH)‐containing hepatocytes and inflammatory cell infiltration. In as many as one third of the cases, polymorphonuclear leucocyte (PMN) migration into the cytoplasm of AH‐containing hepatocytes was noted. The migrating PMNs often had discontinuous cell membranes and their primary and secondary granules were demonstrated to be released into the liver cell cytoplasm. Finally, migrating PMNs appeared collapsed and dying. These PMNs appeared to gather around AH, presumably due to the strong chemoattractive action of AH. The hepatocytes invaded by PMNs revealed various degrees of degeneration and cell necrosis. Occasionally, some lymphocytes infiltrated into hepatocytes and had a direct contact with AH. However, the occurrence of lymphocyte migration was much less than that of PMNs. Kupffer cells were also intermingled with these PMNs and often possessed AH in degraded forms in their phagosomes or phagolysosomes. Based on these results, it is postulated that acute hepatocellular damage in patients with alcoholic hepatitis might be caused by this peculiar type of degranulation and collapse of migrating PMNs against AH‐containing hepatocytes in addition to the various causes previously studied.
The detection of acetaldehyde/liver plasma membrane protein adduct formed in vivo by alcohol feeding
Authors: Barry R. E. , Williams A. J. K. , McGivan J. D.
Published: August 2010

ABSTRACT— In order to assess whether acetaldehyde adducts with liver plasma membrane proteins are formed in vivo during alcohol ingestion, liver plasma membranes were prepared from control rats and rats fed on 10% ethanol from weaning and the amino acid constituents of liver plasma membrane proteins were assessed by reversed phase liquid chromatography of an acid hydrolysate of the membranes. The retention time of acetaldehyde/lysine adduct after stabilisation through reduction was determined by chromatography of an acid hydrolysate of polylysine pretreated with acetaldehyde. The presence of a peak with identical retention time to the acetaldehyde/lysine adduct was detected in liver plasma membranes isolated from alcohol‐fed rats indicating adduct formation in vivo. The adduct was detectable only when the membranes were prepared by a rapid (Percoll) method, suggesting that the adduct may be unstable. The findings are consistent with the hypothesis that the inflammation of acute alcoholic liver disease may be initiated by the product of acetaldehyde/membrane binding in vivo.
Histological changes in the liver and portal hypertension subsequent to repeated intraportal injections of killed E. coli in the dog
Authors: Sugita Shujiro , Ohnishi Kunihiko , Iida Shinji , Nomura Fumio , Okuda Kunio
Published: August 2010

ABSTRACT— The etiology of idiopathic portal hypertension (IPH) is not known. To obtain clues to the pathogenesis, an attempt was made to produce a hepatic lesion similar to that in IPH by repeated injections of aggregated killed non‐pathogenic E. coli directly into the portal vein. In the treated dogs, histology of the liver showed dense fibrosis in the portal tract and an aberrant vasculature around the portal area after 1 month. Portal pressure was elevated and middle‐to‐small‐sized portal branches were decreased in number as studied by portography. These changes closely mimic those seen in human IPH. The possibility is discussed that chronic entrance of an antigen such as bacteria from the intestine to the portal venous system plays an etiologic role in IPH.
Inflammatory pseudotumor of the liver
Authors: Kessler E. , Turani H. , Kayser S. , Bar‐ziv J. , Chaimoff CH.
Published: August 2010

ABSTRACT— Inflammatory lesions in the liver simulating tumor formation are rare. Eleven cases have so far been reported in the literature, most of them in recent years. We present an additional case of an “inflammatory pseudotumor” in a 17‐year‐old male. The inflammatory pseudotumor should be kept in mind in the differential diagnosis of hepatic space‐occupying lesions.
Acute phase proteins in chronic and malignant liver diseases
Authors: Meliconi R. , Parracino O. , Facchini A. , Morselli‐Labate A. M. , Bortolotti Flavia , Tremolada F. , Martuzzi M. , Miglio F. , Gasbarrini G.
Published: August 2010

ABSTRACT— Six acute phase proteins (haptoglobin, α 1‐acid glycoprotein, α 1‐antitrypsin, α2‐macroglobulin, C reactive protein and transferrin) have been measured in the sera of chronic liver disease (CLD) patients with different aetiology (viral, autoimmune and alcoholic) and histology (steatosis, chronic persistent hepatitis, chronic active hepatitis, cirrhosis), and in patients with liver cancer. 1) The most striking changes concerned α2‐macroglobulin (increased) and haptoglobin (decreased) levels. 2) Transferrin was lower in alcoholic liver disease than in viral CLD, CRP was lower in autoimmune than in viral or alcoholic CLD, and α 1‐acid glycoprotein was lower in viral and alcoholic CLD than in autoimmune CLD. Acute phase protein assay may prove useful in differential diagnosis, particularly when specific markers are not available (autoimmune, non A, non B, alcoholic liver diseases). 3) No significant differences related to aetiology (B, non A non B, D viruses) were observed in viral CLD. 4) Patients who progressed to CLD after acute viral hepatitis type B or non A non B did not show different APP levels from those who had recovered when tested 8–12 months after the acute phase. 5) The pattern of APP changes observed in primary liver cell carcinoma was different from both the cirrhotic pattern and the pattern presented by other tumours with or without liver metastasis.
On the pathogenesis of portal hypertension in cirrhosis of the liver
Authors: Shibayama Yuro
Published: August 2010

ABSTRACT— To investigate the localization of increased vascular resistance in the cirrhotic liver, blood pressures at key points in hepatic vascular pathways were measured in the cirrhotic rat produced by carbon tetrachloride injections. Blood pressures in the portal vein, the terminal portal venule, the terminal hepatic venule and the inferior vena cava were 110, 68, 28 and 20 mm H2O respectively in normal rats, and 211, 112, 34 and 24 mm H2O respectively in rats with liver cirrhosis. These values suggested that the increased vascular resistance in the cirrhotic liver was in the intrahepatic portal vein and the sinusoids, and not in the intrahepatic hepatic vein, although marked distortion of the intrahepatic hepatic vein branches was found in the cirrhotic liver. The increase in sinusoidal vascular resistance was associated with sinusoidal stenoses and a decrease in the sinusoidal space due to the hepatic cell swelling, and that in the intrahepatic portal vein might result from distortion of the peripheral branches of the vein.
Activities of the interferon system in patients with HBsAg‐positive chronic hepatitis B during short‐term steroid withdrawal therapy
Authors: Hirai Nobuyuki , Shimizu Motoshige , Morioka Takeshi , Hinoue Yoshinobu , Tanaka Nobuyoshi , Kobayashi Kenichi , Hattori Nobu , Hashimoto Takuma
Published: August 2010

ABSTRACT— Changes in the host interferon system during short‐term steroid hormone (prednisolone) withdrawal therapy in seven patients with HBeAg‐positive chronic hepatitis B were investigated by estimating the in vitro interferon‐α production in peripheral blood lymphocytes and 2–5 oligoadenylate synthetase activity in the serum. The interferon‐α production induced by the Sendai virus and estimated in lymphocyte cultures was rapidly and significantly (p < 0.01) reduced by prednisolone administration and subsequently followed by a recovery corresponding to its withdrawal. The serum 2–5 oligoadenylate synthetase activity showed a similar tendency to diminish under prednisolone administration and to revive during its withdrawal. In all four patients who developed an acute and transient post‐prednisolone withdrawal exacerbation a significant initial increase in serum HBV‐DNA levels was noted in accordance with the reduction in the host interferon system activity. The results suggest that the changes in the host interferon system activity, i.e. an initial fall and subsequent recovery as caused by a short‐term steroid administration with gradual withdrawal, appear to promote viral replication in the early phase and the development of acute and transient exacerbation of hepatitis in the post‐steroid withdrawal phase, which may lead to HBeAg/anti‐HBe seroconversion in HBeAg‐positive chronic hepatitis B patients.
Natural and activated cytotoxic lymphocytes reactivity to human hepatocellular carcinoma cell lines in hepatocellular carcinoma patients
Authors: Chu Ming‐huey H. , Chien Shu‐chen , Hu Cheng‐po , Wang Ching‐yu , Lee Shou‐dong , Tsai Yang‐te , Wu Jaw‐Ching , Han Shou‐Hwa , Chang Chungming
Published: August 2010

ABSTRACT— The status of cellular cytotoxic activity in Hepatocellular Carcinoma (HCC) patients was compared to that in normal individuals by testing the cytotoxicity against K562 and five established HCC cell line targets. Natural killer (NK) activity of fresh peripheral blood mononuclear (PBM) cells in HCC patients to K562 cell line target was lower than that in normal donors. NK activity of unstimulated PBM cells from either source was minute against all five HCC cell line targets. Three different activation systems were employed to examine the cellular cytotoxicity of activated PBM cells: (1) conventional mixed lymphocyte culture (MLC), (2) allogeneic mixed lymphocyte tumor culture (MLTC), and (3) lymphokine‐activated killer (LAK) cell culture. The cytotoxic effects of PBM cells in all three activation conditions were significantly lower in HCC patients than in normal donors (P<0.05 to P<0.01). These results suggest that, in addition to naturally present NK cells, the degree of in vitro activation of PBM cells may also have decreased in HCC patients.
Expression of oncogenes in human liver disease
Authors: Himeno Yasuo , Fukuda Yoshihiro , Hatanaka Masakazu , Imura Hiroo
Published: August 2010

ABSTRACT— To elucidate the role of oncogene expression in hepatocarcinogenesis, we examined the expression of 8 cellular oncogenes by dot blot and/or northern blot analysis in neoplastic, cirrhotic and non‐cirrhotic human liver tissues obtained at surgery. Significantly higher levels of c‐myc gene expression were observed in tissues of hepatocellular carcinoma (HCC) and adjacent cirrhotic tissues than in apparently normal liver tissues or those of chronic hepatitis (normal‐chronic hepatitis). There was a tendency to higher c‐myc mRNA levels in HCC than in liver cirrhosis. However, when tumorous and adjacent cirrhotic tissues from the same patient were compared, c‐myc mRNA levels were not consistently higher in HCC. No significant differences in mRNA levels of c‐fos, N‐myc, N‐ras, Ha‐ras, c‐erbA, c‐erbB and c‐abl were observed among the HCC, cirrhosis and normal‐chronic hepatitis groups. Although the significance of increased c‐myc gene expression in liver cirrhosis and HCC is still not known, it is conceivable that the persistent elevation of c‐myc gene expression in cirrhosis contributes to the development of HCC.
The effect of oral testosterone on serum TBG levels in alcoholic cirrhotic men
Authors: Becker Ulrik , Gluud Christian , Bennett Paul ,   The Copenhagen Study Group for Liver Diseases
Published: August 2010

ABSTRACT— Seventy‐three euthyroid male patients with alcoholic cirrhosis of the liver were randomly allocated to oral testosterone (200 mg t.i.d.) or placebo and followed for up to 36 months. Triiodothyronine (T3), tetraiodothyronine (T4), thyroxine binding globulin (TBG) and T4/TBG ratio were determined before entry and during follow‐up. No significant differences were observed before entry or during follow‐up between the two treatment groups. T3, T4 and T4/TBG ratio did not change significantly during follow‐up, while TBG concentrations decreased (P<0.05). Using a multivariate test, it is demonstrated that testosterone treatment significantly reduced TBG concentrations in cirrhotic men with preserved liver function, like normal men, but not in patients with moderate liver dysfunction. The lack of effect of testosterone in patients with more advanced cirrhosis may be due to a decreased function of sex hormone receptors in their liver.
Change of hepatitis B virus DNA distribution associated with the progression of chronic hepatitis
Authors: Michitaka Kojiro , Horiike Norio , Nadano Seijin , Onji Morikazu , Ohta Yasuyuki
Published: August 2010

ABSTRACT— Hepatitis B virus (HBV) DNA was detected by in situ hybridization in 53 out of 74 liver specimens from patients with chronic HBV infection. The distribution of HBV DNA was classified into three patterns: diffuse (HBV DNA distributed diffusely, within the section of specimen), lobular (HBV DNA was present in 1/3–2/3 of the section) and spotty. All three specimens from asymptomatic HBV carriers showed the diffuse pattern. In the advanced stage of liver disease (chronic active hepatitis with severe activity and liver cirrhosis), a decreased number of specimens showed the diffuse pattern, whereas the number of specimens with the lobular pattern increased. From these data, we conclude that HBV may replicate diffusely in the liver in the early stage of chronic liver disease, and the site of HBV replication becomes localized in the advanced stage of the disease. The main target cells of immunocytes may be hepatocytes undergoing HBV replication, because HVB DNA was frequently detected in areas of focal, piecemeal and bridging hepatic necrosis.
Liver cirrhosis in histiocytosis X
Authors: Pirovino Mauro , Jeanneret Christina , Läng R. Hubert , Luisier Jean , Bianchi Leonardo , Spichtin Hanspeter
Published: August 2010

ABSTRACT— Cirrhosis of the liver was diagnosed in an 18‐year‐old man with histiocytosis X. Electron microscopy and immunohistochemistry revealed infiltration of the liver by the typical cellular elements of histiocytosis X. Endoscopic retrograde cholangiography showed alterations resembling those of sclerosing cholangitis. Sixteen months later, the patient died of recurrent variceal bleeding and cholangiosepsis. Autopsy confirmed that cirrhosis was the main manifestation of the underlying disease. Thus, cirrhosis of liver can be a main and potentially fatal manifestation of histiocytosis X beyond the pediatric age range. Histiocytosis X may lead to parenchymal infiltration of the liver and to changes of the major bile ducts resembling sclerosing cholangitis. The diagnosis of hepatic histiocytosis X can easily be missed without relying on appropriate electron microscopic and immunohistochemical investigations.
Effect of ornithine on transferrin secretion of rat and human hepatocyte cultures
Authors: Lescoat G. , Loreal O. , Desvergne B. , Pasdeloup N. , Deugnier Y. , Brissot P.
Published: August 2010

ABSTRACT— Fetal rat or neonatal human hepatocytes and a human hepatoma cell line were cultured in an arginine‐free medium, supplemented or not with L‐ornithine. This amino‐acid improved survival of hepatocytes and strongly enhanced their transferrin secretion. Moreover, this increase observed in transferrin production was well correlated with a higher corresponding mRNA level. Thus, it may be postulated that the mechanism involved in the increased transferrin secretion by L‐ornithine is of pretranslational origin.
Protective effect of prostaglandin E1 (PGE1) on energy metabolism and reticuloendothelial function in the ischemically damaged canine liver
Authors: Ueda Yuji , Matsuo Kenichi , Kamei Takashi , Kayashima Kohji , Konomi Kohki
Published: August 2010

ABSTRACT— The protective effects of PGE1 on ischemia‐related liver damage were evaluated in dogs. Ninety minutes warm hepatic ischemia was induced by the total clamping of hepatic inflow vasculatures with portal bypassing. The survival rate improved up to 62.5% when PGE1 was administered intravenously prior to ischemia, while no dog survived for longer than 1 week in the nontreated group. Hepatic ATP content was restored up to 80% of preischemic level 2 h after reflow in the PGE1 pretreated group, compared to 55% recovery in the nontreated group. Complete normalization of hepatic energy charge and rapid decrease of lactate were also seen in the PGE1 group. The clearance rate of intravascular lipid emulsion remained fairly normal in the PGE1 group, thereby suggesting well‐preserved hepatic reticuloendothelial functions. The serum activities of β‐glucuronidase, GOT and GPT were suppressed in the PGE1‐pretreated group, thereby implying a well‐protected hepatic integrity. The histology revealed well‐preserved hepatic architecture. The remarkable cytoprotective effect of PGE1 on hepatic ischemia shown in this study indicates that PGE1 warrants further study for protection of ischemically compromised hepatic allografts.
Influence of HDV infection on clinical, biochemical and histological presentation of HBsAg positive chronic hepatitis
Authors: Sagnelli E. , Felaco F. M. , Filippini P. , Pasquale G. , Peinetti P. , Buonagurio E. , Aprea L. , Pulella C. , Piccinino F. , Giusti G.
Published: August 2010

ABSTRACT— In an attempt to identify some characteristics of HDV infection in the different forms of HBsAg positive chronic hepatitis (CH), we evaluated numerous clinical, biochemical and histological aspects in 203 consecutive HBsAg positive CH patients. The presence of hepatitis delta antigen (HD–Ag) in the liver tissue was the criterion used to identify HDV infection. HD–Ag was observed in none of the 7 patients with non‐specific reactive hepatitis, in 14.6% of the 48 with chronic persistent hepatitis (CPH), in 36.4% of the 44 with chronic lobular hepatitis (CLH), in 36% of the 25 with mild chronic active hepatitis (CAH), in 52% of the 36 with severe CAH and in 30.2% of the 43 with inactive or moderately active cirrhosis. Compared with the 139 HD–Ag negative patients in this study, the 64 HD–Ag positive patients more frequently had severe CAH (29.7 vs. 12.2%, p < 0.01) and less frequently CPH (10.9 vs. 29.5%, p < 0.01). Of the 139 HD–Ag negative patients, 80 were anti‐HD positive and 59 anti‐HD negative. The 59 patients with no HD–Ag or anti‐HD showed severe CAH less frequently than the 64 HD–Ag positive patients (6.8 vs. 29.7, p < 0.01) and CPH more frequently (44.1 vs. 10.9, p < 0.001). Both in CPH and CLH the presence of HD–Ag in the hepatocytes identified subgroups of patients who frequently showed high serum levels of aminotransferases and gammaglobulins and more extended areas of circumscribed lobular necrosis. HD–Ag positive CAH was characterized by a more frequent occurrence of eosinophilic degeneration of hepatocytes without peripolesis (p < 0.05). Patients with HD–Ag positive cirrhosis were younger than the HD–Ag negative patients (p < 0.05). The data suggest that HDV replication is responsible for a more extended necrosis or degeneration of the hepatocytes and for a more active disease in CPH, CLH and CAH. These Findings per se seem to indicate an unfavourable course of the disease due to HDV infection.
Human hepatic sinusoidal endothelial cells in culture produce von Willebrand factor and contain Weibel‐Palade bodies
Authors: Harrison Robert L. , Boudreau Raymond
Published: August 2010

ABSTRACT— Human hepatic sinusoidal endothelial cells were derived from cadaveric human livers. Cells were grown in culture for several weeks to produce small patches of confluent endothelial cells. The ultrastructure of sinusoidal endothelial cells was examined, cell monolayers were stained immunocytochemically for von Willebrand factor antigen, and antigen in cell culture media was measured by enzyme‐linked immunosorbent assay. Human hepatic sinusoidal endothelial cells contained von Willebrand factor antigen and Weibel‐Palade bodies, were fenestrated, and released von Willebrand factor antigen into media in a time‐dependent manner. Although in some respects human hepatic endothelial cells were different from vascular cells, there was no evidence that there were qualitative differences in their capacity to produce von Willebrand factor.
Perisinusoidal cells (Ito‐cells) enlargement in a family with myotonic dystrophy
Authors: Poynard Thierry , Bedossa Pierre , Naveau Sylvie , Lemaigre Guy , Martin Etienne D. , Chaput Jean‐Claude
Published: August 2010

ABSTRACT— Two cases are reported, a daughter and her mother who both have myotonic dystrophy with abnormalities of liver function tests and an important perisinusoidal cell enlargement without other pathologic features. In both cases, the myotonic dystrophy was clinically obvious and confirmed by electromyography. No other causes of perisinusoidal cell enlargement were found including vitamin A intake, psoriasis, viral disease or alcoholism. These observations suggest a genetic linkage and that serum test abnormalities could be associated with a perisinusoidal cell change.
Diagnosis of hepatic hemangioma with 99mTc‐labeled red cells: single photon emission computed tomography (SPECT) versus planar imaging
Authors: Langsteger W. , Lind P. , Eber B. , Költringer P. , Beham A. , Eber O.
Published: August 2010

ABSTRACT— This paper reports the results of a prospective study carried out to demonstrate the most important advantages of 99mTc‐blood pool single emission computed tomography (SPECT) versus the established method of planar scintigraphy (PS) in the non‐invasive diagnosis of liver hemangiomas. The study group comprised 40 patients in whom positive evidence of 56 hemangiomas, detected incidentally in the course of screening examinations, was established via SPECT and PS. The sensitivity of SPECT was 51/56 (91%), of PS 22/56 (39.3%); for lesions smaller than 30 mm in diameter, the sensitivity of SPECT was 31/38 (81.6%), of PS 6/38 (15.8%). All lesions with diameters of more than 30 mm were detected by both PS and SPECT. However, the SPECT method proved to be clearly superior in the identification of lesions which were smaller than 30 mm and located in unfavourable topographical sites (dorsal or subphrenic). The study proves that SPECT with 99mTc‐labeled erythrocytes is the ideal complement to ultrasonography in the detection of liver hemangionas; its major advantage over TCT (transmission computed tomography) is its safe application in cases with contrast agent intolerance and hyperthyroid patients. Moreover, liver biopsies are dangerous and ill‐suited for the verification of diagnosis.
Role of lysosomal enzymes in tissue damage during hepatic amoebiasis. An experimental study
Authors: Virk K. J. , Ganguly N. K. , Dilawari J. B. , Mahajan R. C.
Published: August 2010

ABSTRACT— Two key lysosomal enzymes, N‐acetyl‐β‐glucosaminidase and β‐glucuronidase of Kupffer cells and blood monocytes were studied in guinea pigs infected intramesenterically with E. histolytica. The animals were sacrificed on days 0, 2, 5 and 8 post‐infection. The enzyme levels in the cell lysate and supernatants of both Kupffer cells and blood monocytes were significantly higher (P < 0.01) in the infected animals compared with the controls. This increase was more marked on the 5th and 8th days post infection (P < 0.001). The alteration in enzyme levels was higher in Kupffer cells than in blood monocytes (P < 0.05). The enzyme levels increased exponentially with the severity of the hepatic lesions. A direct correlation was observed between the enzyme levels and the severity of the hepatic lesions (P < 0.01). Hence, the role of lysosomal enzymes, released by activated mononuclear phagocytic cells, in the pathogenesis of hepatic amoebiasis is postulated.
HBV‐DNA by in situ hybridization. A method to improve sensitivity on formalin‐fixed, paraffinembedded liver biopsies
Authors: Infantolino Domenico , Pinarello Antonella , Ceccato Renzo , Barbazza Renzo
Published: August 2010

ABSTRACT— In situ hybridization of hepatitis B virus DNA by means of biotinylated probes is a rapid specific histochemical method but it is not very sensitive in formalin‐fixed, paraffin‐embedded material. The specificity and sensitivity of a new method using a digitonin solution and hydrolytic bath before cytohybridization in 19 formalin‐fixed, paraffin‐embedded liver biopsies was evaluated and a noticeable increase in staining intensivity observed. Digitonin and hydrochloric acid at low concentration increase the permeability and the diffusion of the bio‐probe, improving significantly the sensitivity of reaction. Hepatocytes containing few copies of HBV‐DNA were revealed by this method and microscopic visualization of specimens with numerous viral episomes was considerably improved. Therefore cytohybridization can be a specific and sensitive method, even for formalin‐fixed, paraffin‐embedded material, revealing active HBV replication even in HBcAg negative hepatocytes.
Analysis of the deterioration rates of liver function in cirrhosis, based on galactose elimination capacity
Authors: Marchesini G. , Fabbri A. , Bugianesi Elisabetta , Bianchi G. P. , Marchi Elisabetta , Zoli M. , Pisi E.
Published: August 2010

ABSTRACT— The prognosis of cirrhotic patients may depend on their liver function, but very few data are available to predict life expectancy in individual subjects on the basis of their liver function tests. The yearly changes in liver function, based on galactose elimination capacity (GEC), were retrospectively analyzed in 76 cirrhotic patients. The first GEC measurement had always been performed at the time of diagnosis. From that time on, mean GEC changes (in mmol/min per year) were +0.13 [SD 0.60] in the 1st year (range: +1.42/ –1.35), and –0.03 [0.30] in the 2nd year (P = ns). Only after 36 months could a significant deterioration in liver function be demonstrated, but GEC changes still ranged from +0.14 to –0.35. The trend in liver function was similar in patients with alcoholic and non‐alcoholic cirrhosis, but in alcoholics a favourable effect of abstinence was proved. In individual subjects, 2 consecutive GEC measurements, at least 6 months apart, failed to predict the following GEC values. The coefficients of determination between expected and measured GEC or ΔGEC were 0.13 and 0.36, respectively (n = 58). When forecasting was limited to 2 years (n = 38), still only 31% and 55% of GEC values and ΔGEC variance was predictable on the basis of preceding GEC values. The study shows that no definite trends in liver function deterioration rates can be observed in cirrhosis. This limits the usefulness of liver function tests in predicting prognosis in cirrhotic patients.