bluuebunny/crossref_metadata_2025 huggingface dataset:
A quantitative analysis of the liver following ligation of the common bile duct
Authors: Gall John A. M. , Bhathal Prithi S.
Published: August 2010

ABSTRACT— A quantitative analysis of the liver was performed at intervals of 24, 48, 72 and 96 h and 7, 21 and 50 days following total biliary obstruction (TBO) in the Sprague‐Dawley rat. During this period, the liver weight increased from 7.72±0.51 g (mean±SEM) in controls to 24.57±1.66 g (p<0.0005) at 50 days. There was a concomitant reduction in the volume proportion of the liver occupied by liver cells, from 71.37±1.36% to 21.54±3.27% (p<0.0005), but there were increases in the volume proportions of biliary epithelial cells (BEC) from 0.14±0.02% to 16.39±1.12% (p<0.0005), of other cell and tissue types from 5.50±4.89% to 30.73±2.42% (p<0.0005) and of vascular and biliary channel spaces from 22.99±1.17% to 31.35±0.87% (p<0.0025). In control animals, the liver cell and BEC volume was estimated to be 6240±360 μm3 and 100±10 μm3, respectively. Following TBO, the liver cell volume was significantly greater than control only from 48–96 h, whereas the BEC increased significantly in volume from 24 to 72 h and then remained approximately 6 times the control value until the end of the period of study. Contrary to the histological appearance and decrease observed in volume proportion, the total liver cell population did not significantly differ from the control value of 8.83 × 108±0.80 × 108 cells, other than at 21 days when it increased to 14.90 × 108±1.04 × 108 cells (p<0.05). When expressed as the number of liver cells/100 g b.wt., an increase from the control value of 4.37 × 108±0.32 × 108 cells was observed only at 7 (5.66 × 108±0.42 × 108 cells; p<0.05) and 21 days (6.94 × 108±0.48 × 108 cells; p<0.05). This maintenance of liver cell population, following biliary obstruction, at or above the control values matches the clinical observation of preserved liver cell function. The total BEC population in control livers was 1.11 × 108±0.20 × 108 cells. A significant increase in this population was observed at 7 days (3.82 × 108±0.62 × 108 cells; p<0.05) with further increases to 57.90 × 108±6.42 × 108 cells (p<0.05) at 50 days, 52 times the control value. When expressed as cells/100 g b.wt., similar changes were observed. The results reported here indicate the importance of taking into account the change in the entire organ size and total mass of the cells in question when assessing alterations in their number.
Polyamines — potential nucleating factors in bile
Authors: Konikoff Fred , Goldman Gideon , Halpern Zamir , Somjen Giora J , Gilat Tuvia
Published: August 2010

ABSTRACT— Lithogenicity of human bile is dependent not only on cholesterol saturation, but also on the presence of nucleating and antinucleating factors. Most of the research in this field is directed toward biliary proteins, particularly glycoproteins. In the present study we have shown that spermine, spermidine, cadaverine and putrescine have a nucleating effect in model bile as well as in native human bile. These findings are based on 183 mixing experiments using biles from 10 patients and model biles. The effect seems to be dose dependent at concentrations up to 10 mmol/l. It is not accompanied by a shift in cholesterol distribution between its vesicular and micellar carriers. It is at present uncertain whether these effects are pharmacologic or physiologic. These findings emphasize, however, the potential importance of non‐protein compounds in the cholesterol nucleation process in bile.
Acute exacerbation in patients with liver cirrhosis: a clinicopathological study
Authors: Liaw Yun‐Fan , Chen Jyh‐Jou , Chen Tong‐Jong
Published: August 2010

ABSTRACT— The incidence, clinicopathologic features and etiology of acute exacerbation occurring in patients with liver cirrhosis were assessed prospectively among 332 hepatitis B surface antigen (HBsAg) positive and 71 HBsAg negative patients. During an 11‐year period and a mean follow‐up duration of 26.8 months, 148 acute exacerbation occurred in 107 HBsAg positive patients and 32 episodes occurred in 18 HBsAg negative patients. The calculated annual incidence was 11.5%. The clinical, laboratory and histologic features were similar to those in patients with chronic hepatitis. Confluent hepatic necrosis and alphafetoprotein elevation over 100 ng/ml occurred frequently, particularly in HBeAg positive patients. In general, acute exacerbations in HBsAg negative patients were less severe than their HBsAg positive counterparts. Of the exacerbations in HBsAg positive patients, 54.8% of the HBeAg positive ones and 38.6% of the HBeAg negative ones were attributable to hepatitis B virus reactivation, while 4.8% and 7.9%, respectively, were due to hepatitis delta virus superinfection. The others might be the results of hepatitis non‐A, non‐B virus superinfection or increased piecemeal necrosis. The immediate outcome of acute exacerbations in cirrhotic patients was usually good, although 13.8% developed hepatic decompensation and 4.4% died. Further follow‐up study is required to evaluate the long‐term effect of the frequent occurrence of bridging hepatic necrosis, high elevation of alphafetoprotein and hepatic decompensation during acute exacerbation in cirrhotic patients.
Inhibitory effects of hepatitis B virus antigen on induction of lymphokine‐activated killer cell activity
Authors: Shirai Mutsunori , Watanabe Seishirou , Nishioka Mikio
Published: August 2010

Abstract— We investigated the inhibitory effects of purified recombinant hepatitis B virus (HBV) surface antigen (rHBsAg) and core antigen (rHBcAg) on lymphokine‐activated killer cell (LAK) activity. Either peripheral blood mononuclear cells (PBMCs) or CD16+CD3‐ LAK precursors, both of which were pre‐incubated with interleukin‐2 (IL‐2) and rHBsAg or rHBcAg for 72 h, showed a significant decrease in LAK cytotoxicity against Daudi cells, in comparison to the results recorded in the presence of IL‐2 alone, or IL‐2 and E. coli extracts. This inhibitory effect was dose‐dependent and was observed to be time‐dependent from 24 to 72‐h‐cultures with these HBV antigens. This influence was not mediated with either adherent cells or other accessory cells. The proliferative reaction of either PBMCs or the LAK precursors after being cultured with IL‐2 and rHBsAg or rHBcAg for 72 h was significantly diminished compared with the levels of reaction of those cells after a 72‐h culture with IL‐2 alone or with IL‐2 and E. coli extracts. The levels of IL‐2‐driven IL‐2 receptor (p55) expression of either PBMCs or the LAK precursors in the presence of rHBsAg or rHBcAg were higher than the levels seen in the absence of these HBV antigens. These results suggest that HBsAg and HBcAg may inhibit the induction of LAK activity by interfering with the proliferative reaction of the LAK precursors to IL‐2 without inhibiting the IL‐2 receptor expression of the cells. Cytofluorographic analysis of PBMCs, cultured with rIL‐2, showed lower percentages of CD3+ and CD16+ cells in the presence of these HBV antigens than those in the absence of antigens.
Cholic acid and chenodeoxycholic acid transport in the hepatic acinus in rats: Effect of necrosis of zone 3 induced by bromobenzene
Authors: DIONNE S. , RUSSO P. , TUCHWEBER B. , PLAA G. L. , YOUSEF I. M.
Published: August 2010

ABSTRACT— The transport of cholic acid (CA) and chenodeoxycholic acid (CDC) and their influence on bile formation was investigated in rats treated with bromobenzene (BZ), a toxicant which selectively destroys zone 3 of the hepatic acinus. The necrosis equals 27–31% of the acinus cells. The absence of zone 3 in rats reduced the secretory rate maximum of CA and CDC by 18% (NS) and 25% (p<0.05), respectively. The maximum bile flow was not different from control during CA infusion but was lower during CDC infusion in BZ‐treated animals. Although the bile acid concentration was lower in BZ‐treated rats, only values obtained during the basal period and the beginning of the infusion reached the level of statistically significant difference. The bile salt‐independent flow (BSIF) was not affected by the absence of zone 3. Our data suggest that zones 1 and 2 of the hepatic acinus can compensate for the secretion of CA and elaboration of BSIF when zone 3 is destroyed. However, necrosis of zone 3 reduces CDC secretion. Thus, the capacity for bile acid transport of the hepatocytes of different zones in the hepatic acinus may differ according to the circulating bile acid.
Expression of pre‐S1, pre‐S2, S and X peptides in relation to viral replication in livers with chronic hepatitis B
Authors: SUZUKI KOYU , UCHIDA TOSHIKAZU , SHIKATA TOSHIO , MORIYAMA MITSUHIKO , ARAKAWA YASUYUKI , MIZOKAMI MASASHI , MIMA FUSAAKI
Published: August 2010

ABSTRACT— The expression of large (pre‐S1), middle (pre‐S2), major S (S) polypeptides of the envelope (HBs) and X peptides of hepatitis B virus (HBV) was investigated in 37 liver specimens with chronic hepatitis B by indirect immunoperoxidase staining. Primary antisera utilized were polyclonal ones against HBs (poly‐HBs), core (HBc) and X and monoclonal ones against pre‐Sl, pre‐S2 and S with (particle‐S) or without (peptide‐S) conformational structure. The localization of HBs proteins in hepatocytes was classified into three types: diffuse, membranous and inclusion. The peptide‐S and pre‐S2 were expressed at nearly the same frequency as poly‐HBs in all types, whereas particle‐S was found less frequently (18/29 cases) in the inclusion type, and pre‐S1 was recognized relatively rarely (9/33 cases) in the membranous type. As for staining intensity, peptide‐S and pre‐S2 were almost identical to poly‐HBs which stained the most strongly among all three staining types. Particle‐S was similar to poly‐HBs in the membranous type, but was weak in the inclusion type in the majority. While pre‐S1 was stained in a similar intensity to poly‐HBs in the diffuse and inclusion types, it was weak or negative in the membranous type. Thus, envelope particles indicated by particle‐S staining appeared to be located most frequently in the membranous type, but their assembly might be suppressed in the inclusion type where pre‐S1 was well expressed. The X peptide was more frequently detected in the liver with serum HBe antigen and/or HBV DNA. The X peptide was stained exclusively in the cytoplasm of hepatocytes and was correlated with the cytoplasmic HBc antigen. The X peptide was not observed differently between cases with and those without cirrhosis. This suggests that the expression of X peptide tends to occur with virus replication but not with disease progression.
Interferon γ modulates production of interleukin 1 and tumor necrosis factor by murine Kupffer cells
Authors: Kawada Norifumi , Mizoguchi Yasuhiro , Kobayashi Kenzo , Morisawa Seiji , Monna Takeyuki , Yamamoto Sukeo
Published: August 2010

ABSTRACT— When mononuclear phagocytes, including Kupffer cells, are activated by various agents, they synthesize and release cytokines such as interleukin 1 (IL‐1) and tumor necrosis factor (TNF). In this study, we examined the effect of in vitro Kupffer cell activation by recombinant murine interferon γ (IFNγ) on IL‐1 and TNF secretion. IFNγ enhanced TNF production in the presence or absence of lipopolysaccharide (LPS), but suppressed IL‐1 production by Kupffer cells. Because IFNγ also stimulated prostaglandin E2 (PGE2) production, the effect of indomethacin, which is an inhibitor of cyclooxygenase and which inhibits PGE2 biosynthesis, on IL‐1 and TNF production by Kupffer cells was examined. As a result, indomethacin enhanced TNF production by Kupffer cells, but had no effect on IL‐1 synthesis. These results suggested that IFNγ modulates the production of IL‐1 and TNF by Kupffer cells through different mechanisms.
Duck hepatitis B virus infection of non‐hepatocytes
Authors: Walter E. , Teubner K. , Blum H. E. , Offensperger W. B. , Offensperger S. , Gerok W.
Published: August 2010

ABSTRACT— One hundred and seventeen ducklings, 42 inoculated with duck hepatitis B virus (DHBV) 2 days after hatching and 55 connatally infected, were studied over a 6‐month period in parallel with 20 ducklings without DHBV infection. Using immunohistochemical, in situ and blot hybridization analyses, the natural course of hepatic and extrahepatic infection was examined. DHBV infection started in the liver 2–4 days post‐inoculation. There, DHBV was found not only in hepatocytes, but also in bile duct epithelial cells. Further, DHBV infection occurred in exocrine and endocrine pancreas (beginning 6–10 days and 20 days post‐inoculation, respectively) and in germinal centers of the spleen (beginning 8 weeks post‐inoculation). Occasionally viral DNA was also found in kidney glomeruli. Using strand‐specific RNA probes, viral DNA in pancreas and spleen was clearly demonstrated to be replicating intermediates. Hepatic and extrahepatic infection with DHBV was not associated with histologic inflammation or pathologic changes in these tissues or the liver. These data indicate that DHBV can infect cells other than hepatocytes. The biological significance of non‐hepatocyte infection for the life‐cycle of the virus and its potential significance for viral persistence remain to be determined.
Appearance of α‐smooth‐muscle‐actin‐positive cells in hepatic fibrosis
Authors: Nouchi Toshihiko , Tanaka Yujiro , Tsukada Toyohiro , Sato Chifumi , Marumo Fumiaki
Published: August 2010

ABSTRACT— The appearance of α‐smooth‐muscle‐actin (α‐smA)‐positive cells during hepatic fibrosis was studied immunohistochemically in rat and human livers. In the normal rat liver, α‐smA was observed only in vascular smooth muscle cells. With the progression of fibrosis induced by CCl4 injection, α‐smA‐positive cells appeared in the perisinusoidal space and the fibrous septa, and ultimately surrounded regenerative nodules. An increase of desmin‐positive cells was recognized in the fibrotic areas and the perisinusoidal area. In the human liver, α‐smA‐positive cells appeared in the fibrotic area, whereas no desmin‐positive cells were observed, except in vascular walls of the central vein and the portal tract. α‐smA is a good marker for the detection of myofibroblast‐like cells, and the appearance of α‐smA in liver mesenchymal cells seems closely related to the process of hepatic fibrosis in both rat and man.
Ruffle formation in the evaluation of stimulatory state of hepatic macrophages in rats
Authors: Ohno Akihiko , Hirata Keiichi , Ohta Yasuhiko , Yamada Shinwa , Mochida Satoshi , Fujiwara Kenji
Published: August 2010

ABSTRACT— Morphological changes in hepatic macrophages after stimulation were observed with a transmission electron microscope in rats. In the normal liver ruffle formation occupied less than 30% of the cell surface facing the sinusoidal space in 21 of 25 macrophages. When the rats received a dose of carbon tetrachloride, hepatic macrophages I day later showed ruffle formation to the same extent as in normal rats. In contrast, in rats 6 days after a dose of Corynebacterium parvum, ruffle formation was intensified, and in 19 of 25 macrophages it was seen to occupy more than 30% of the cell surface (p<0.01); 9 of 10 macrophages with more than 70% of the cell surface affected belonged to these rats. Considering that hepatic macrophages at I or 6 days after treatment with carbon tetrachloride or Corynebacterium parvum are at the responsive or primed stages, respectively, measurement of the extent of ruffle formation in hepatic macrophages with a transmission electron microscope may provide a useful tool in estimating their stimulatory stage.
Prevalence of antibody to hepatitis C virus in prospectively followed acute non‐A, non‐B hepatitis, from different epidemiological categories
Authors: Rodríguez Manuel , Riestra Sabino , Romån Fernando San , Pérez Ramón , Suárez Adolfo , Sánchez José L. , Rodrigo Luis
Published: August 2010

ABSTRACT— We have studied the prevalence of antibody against hepatitis C virus (anti‐HCV) and its relation to the time of onset of the symptoms in 57 patients with acute non‐A, non‐B hepatitis: 16 post‐transfusion, 25 drug addicts and 16 sporadic cases. In the 1st month after the onset of illness, anti‐HCV was positive in 25% of patients with post‐transfusion hepatitis, 44% of drug addicts and 25% of sporadic hepatitis. In the 3rd month this antibody was detected in 75%, 88% and 31.2%, and in the 6th month in 87.5%, 96% and 31.2%, respectively. The prevalence in the 3rd and 6th months was significantly higher in post‐transfusion patients and drug addicts than in sporadic cases. In the 6th month the prevalence of anti‐HCV in patients who progressed towards chronicity was also significantly higher than in those with acute resolving non‐A, non‐B hepatitis (94% vs 50%, p<0.001). These results show that HCV is probably the main agent in acute post‐tranfusion non‐A, non‐B hepatitis and in those occurring in drug addicts, and that in a high proportion of these patients the anti‐HCV can be detected in the 3rd month after the beginning of the symptoms. On the other hand, the relation of hepatitis C virus with sporadic acute non‐A, non‐B hepatitis may be doubtful.
Histological changes of the liver in experimental graft‐versus‐host disease across minor histocompatibility barriers. V. A light and electron microscopic study of the intralobular changes
Authors: Nonomura Akitaka , Kono Naoko , Yoshida Kazuharu , Mizukami Yuji , Nakanuma Yasuni , Matsubara Fujitsugu
Published: August 2010

ABSTRACT— Intralobular changes of the liver in experimental graft‐versus‐host disease (GVHD) across minor histocompatibility barriers were investigated for up to 14 months after bone marrow transplantation. Sinusoidal lymphocyte infiltration, and necrosis and degeneration of hepatocytes were evident by day 4 and reached a maximum level at 2 weeks after transplantation, then gradually decreased, but they persisted during the entire period of observation, indicating that more or less hepatocyte injury may persist continuously in hepatic GVHD. Piecemeal necrosis was transiently observed around 2 weeks after transplantation, in parallel with the peak of lymphocyte infiltration into the portal area. Similarly, central vein endothelialitis (attachment of lymphocytes to endothelial cells) was transiently observed with a peak activity at 2 weeks after transplantation. Mild centrilobular and portal fibroplasia were evident by 2 weeks after transplantation, but they hardly progressed and no cases developed liver cirrhosis. Frequently lymphocytes were found located beneath endothelial cells and attached to hepatocytes. Ultrastructural observation revealed that sinusoidal lymphocytes were occasionally in contact with endothelial cells by means of cytoplasmic pseudopods. Also lymphocytes were frequently in close contact with hepatocyte plasma membranes over short distances. Lymphocytes occasionally accompanied other inflammatory cells, such as eosinophilic leukocytes and mononuclear phagocytic cells. Hepatocytes in close contact with lymphocyte and other inflammatory cells showed a varying degree of degenerative changes, including condensation of cytoplasm and nucleus with irregular nuclear contours, dilatation of endoplasmic reticulum and mitochondria, formation of cytoplasmic vacuoles, and loss of microvilli. Although the distribution and the degree of morphologic abnormalities of hepatocytes were not so prominent as the bile duct lesions seen in the present mouse hepatic GVHD, hepatocyte injury was observed consistently for up to 14 months after transplantation, indicating that lymphocytes, together with concomitant non‐lymphocytic cells, may play an important role in the induction of hepatocyte injury. Hepatocyte injury may be an inherent part of pathologic changes of hepatic GVHD.
Angiomyolipoma of the liver: immunohistochemical study of a case
Authors: Linton Patrick L. , Ahn Woo Sung , Schwartz Myron E. , Miller Charles M. , Thung Swan N.
Published: August 2010

ABSTRACT— Angiomyolipoma, a not uncommon tumor of the kidney, is rarely encountered in the liver. We report a case of angiomyolipoma of the liver in a 68‐year‐old woman, in which immunohistochemical study was performed.
Portal pressure in patients with exudative ascites in the course of acute hepatitis B
Authors: Calvet Xavier , Bruix Jordi , Bosch Jaume , Rodes Joan
Published: August 2010

ABSTRACT— We describe three patients who developed ascites during the course of acute viral hepatitis B. Two of them had exudative ascites, with a high protein and cell content, and the other transudative ascites, with low protein and cell content. Both patients with exudative ascites had a benign clinical course, and their liver disease was milder than in the patient with transudative ascites, who had signs of severe liver failure and a submassive hepatic necrosis on liver biopsy. Moreover, the patient with transudative ascites had evidence of portal hypertension (as indicated by a hepatic vein pressure gradient of 12.5 mmHg, normal 1–6 mmHg), whereas patients with exudative ascites did not (hepatic vein pressure gradient of 5 and 5.5 mmHg, respectively). These data support our previous suggestion that “exudative” ascites during acute viral hepatitis B represents a self‐limited immunopathic sign that is not related to portal hypertension or severe hepatic disease.
Evidence for enhanced secretory function of hepatic macrophages after long‐term ethanol feeding in rats
Authors: Yamada Shinwa , Mochida Satoshi , Ohno Akihiko , Hirata Keiichi , Ogata Itsuro , Ohta Yasuhiko , Fujiwara Kenji
Published: August 2010

ABSTRACT—Rats were pair‐fed nutritionally adequate liquid diets, containing ethanol as 36% of energy or an isocaloric amount of carbohydrate for 4–6 weeks. Ruffle formation of hepatic macrophages in the periportal area observed with a transmission electron microscope (which reflects their extent in activation) was more remarkable in ethanol‐fed rats than in control rats. The ability of hepatic macrophages to produce superoxide anions assessedin situby formazan deposition after liver perfusion with nitro‐blue tetrazolium and phorbol myristate acetate was enhanced after such ethanol feeding. A similar result was seen 24 h after withdrawal of ethanol feeding. These findings suggest that long‐term ethanol consumption may activate hepatic macrophages in secretory function.
Clinicopathological analysis of alcoholic liver disease complicating chronic type C hepatitis
Authors: Noguchi Osamu , Yamaoka Kazuaki , Ikeda Takaaki , Tozuka Shinichi , Sakamoto Shigemi , Kanayama Masaaki , Uchida Toshikazu
Published: August 2010

ABSTRACT— Seventy‐six chronic alcoholics in Japan were evaluated for histological changes of liver needle biopsies, Chiron C100 antibody (C‐100) for hepatitis C virus, as well as clinical and laboratory data. In biopsies, the presence of necroinflammations within the parenchyma, lymphocytic reaction in the portal tracts, or both, might indicate non‐A, non‐B (NANB) chronic hepatitis. Using these histological criteria, the patients were previously classified into two groups: alcoholic liver disease (ALD) alone and ALD complicating NANB chronic hepatitis. The C100‐positive ratio was found to be 12% in the former group and 69% in the latter. Further clinical and laboratory comparison revealed that there were significant differences in gamma‐glutamyl transpeptidase, gamma‐globulin, and adenosine deaminase levels in the sera between the ALD alone and the ALD complicating NANB chronic hepatitis groups. Since some chronic alcoholics are also affected by chronic type C hepatitis, detailed evaluations of the liver biopsy and C‐100 assay are required for the differentiation of these hepatic disorders.
Transplantation studies on human and duck hepatocytes in athymic nude mice
Authors: Hanawa‐Shimizu Mie , Maéno Mitsugu , Shikata Toshio
Published: August 2010

ABSTRACT— For determination of the most suitable tissue for heterotopic transplantation of exogenous hepatocytes, dissociated hepatocytes or small pieces of liver tissue were transplanted into the spleen, adipose tissue and inside the capsule of the kidney of BALB/c mice. Survival of syngeneic grafts of dissociated hepatocytes was highest in the spleen and that of pieces of liver tissue in the adipose tissue, but only the latter system was suitable for xenogeneic transplantation. Histological examination showed that a total of 50% of the human or duck liver tissue implants survived in the inguinal fat pad of athymic nude mice (BALB/c‐nu). Histochemical analyses revealed that most hepatocytes transplanted into the fat pad gave positive reactions for glucose‐6‐phosphatase and with periodic acid‐Schiff reagent at least 28 days after transplantation. Electron microscopic observation showed that these cells also maintained characteristic cellular organelles. This xenogeneic transplantation into adipose tissue should be useful in the studies on replication and infection of human hepatotropic viruses such as hepatitis B and C viruses.
An automated microassay for enzyme inhibitory effects of M2 antibodies in primary biliary cirrhosis
Authors: Teoh Khay‐Lin , Rowley Merrill J. , Mackay Ian R.
Published: August 2010

ABSTRACT— In primary biliary cirrhosis (PBC), autoantibodies are produced to the M2 group of mitochondrial antigens, of which a major constituent is the E2 subunit of the pyruvate dehydrogenase complex (PDC). These antibodies, in addition to conventional reactivities with PDC, characteristically inhibit the catalytic function of PDC in vitro, as judged by a macroinhibition assay based on spectrophotometry. We describe a microinhibition assay adapted for microtitre plates and for an automated readout of results by an ELISA plate reader. We show that this microassay has a sensitivity similar to that of the macroassay. In a study of 83 sera, from PBC and other diseases, the inhibitory microassay proved specific for PBC. This automated inhibitory microassay for PBC sera could become a primary laboratory procedure for the diagnosis of PBC, particularly because it may identify antibodies to the actual autoepitope on the PDC‐E2.
Second evaluation of HEPAR, an expert system for the diagnosis of disorders of the liver and biliary tract
Authors: Lucas P. J. F. , Janssens A. R.
Published: August 2010

ABSTRACT— HEPAR is an expert system which can be used as a supportive tool in the diagnosis of disorders of the liver and biliary tract. When consulted for a particular patient, the system assesses the patient's disorder in two stages. In the first stage, data of medical history, physical examination and routine laboratory tests are used to determine whether the disorder is hepatocellular or biliary obstructive, and whether benign or malignant features are present. In the second stage, the system produces a differential diagnosis out of a set of 80 disease categories, using the conclusions of the first stage of the assessment and the results of a restricted number of supplementary investigations, i.e. serological tests and ultrasonography. The conclusions of the two stages are ordered by the amount of evidence computed by HEPAR. The system is not yet suitable for clinical use. The system has been evaluated using data of 181 patients selected from a population of 214 consecutively admitted patients with jaundice. The patients were classified by the system as having a hepatocellular or biliary obstructive, and a benign or malignant disorder in 96% and 100% of the cases, respectively. When comparing the conclusions with strongest evidence with the final clinical diagnoses, the patients were classified correctly in 86% and 83% of the classified cases, respectively. A differential diagnosis was produced in 87% of the patients. A correspondence between the diagnosis with strongest evidence and the final clinical diagnosis was found in 78% of the classified patients.
Analysis of hepatitis B virus DNA, liver disease and influence of antibody to hepatitis C virus in anti‐HBe chronic carriers
Authors: Moraleda Gloria , Bartolomé Javier , Molina Josefina , Castillo Inmaculada , Carreño Vicente
Published: August 2010

ABSTRACT— Hepatitis B virus DNA (HBV‐DNA) in serum was studied in 67 anti‐HBe patients using dot‐blot hybridization, a modified technique and polymerase chain reaction (PCR). All patients had abnormal aminotransferase (ALT) levels. Serum HBV‐DNA was detected in 14/67 cases by dot‐blot and in 39/67 (DNA probe) and 45/67 (RNA probe) using the modified technique. The RNA probe was more sensitive than the DNA probe when they were compared, using serial dilutions of HBV‐DNA of known concentration (0.1 pg vs 1 pg, respectively). HBV‐DNA was found by PCR in 57/67 patients. Ten patients were negative to serum HBV‐DNA. The ALT level was significantly higher in patients with serum HBV‐DNA by dot‐blot as compared to those who had serum HBV‐DNA by the modified technique and PCR. With respect to the presence of anti‐HCV, 6/67 had anti‐HCV confirmed by RIBA test. These 6 patients had serum HBV‐DNA. The route of acquisition of HBV infection in anti‐HCV positive patients was by parenteral exposure in 67% of the cases and 15% in HCV negative (p<0.05). All patients were negative to nonorganic specific autoantibodies. In summary, most of the anti‐HBe patients (85%) had viral replication. HCV superinfection plays a minor role in the activity of liver disease.
IgM anti‐preS2 monitoring during combined corticosteroid/interferon‐alpha 2b therapy in chronic hepatitis B
Authors: Fei G. Z. , Sylvan S. P. E. , Hellström U. B. , Yao G. B.
Published: August 2010

ABSTRACT— The biological significance of antibody reactivities towards the preS2 gene encoded proteins of HBV is not yet well known. We investigated the pretreatment IgM anti‐preS2 (1–55) ad reactivity in 22 Chinese and 11 Swedish patients with active HBV disease. Significantly enhanced IgM anti‐preS2 levels (titers >1/1000) were observed in 48% (16/33) of these patients. The OD405 values for sera from patients with indolent HBsAg carriership were within the range of that obtained for “normal” control‐sera when tested at dilutions from 1/1000 to 1/128000. Five Chinese patients were treated with a short course of corticosteroids, followed by alpha‐interferon 2b (IFN‐α2b) treatment for 16 weeks. The IgM anti‐preS2 response was consecutively monitored during treatment. A beneficial effect on the outcome of the combined treatment was associated with rising titers of IgM anti‐preS2 during the prednisolone cycle. The IgM anti‐preS2 levels fell dramatically upon steroid withdrawal and were followed by a second peak response of IgM anti‐preS2 reactivity during the IFN‐α2b treatment. No sustained loss of HBV‐DNA or DNA polymerase with concomitant HBe/anti‐HBe seroconversion was observed in treated patients, who lacked detectable pretreatment levels of IgM anti‐preS2 in circulation.
Monokine gene expression in normal human liver: selective involvement of the portal compartment
Authors: Emilie Dominique , Navratil Emmanuelle , Devergne Odile , Reynes Michel , Crevon Marie‐Claude , Samuel Didier , Galanaud Pierre
Published: August 2010

Abstract: Monokines play a major role in the regulation of hepatocyte functions. To document a possible in situ production of these mediators under physiological conditions, expression of IL‐1β and of IL‐6 genes was analyzed by in situ hybridization in four histologically normal human livers. We detected cells containing IL‐1β mRNA or IL‐6 mRNA in all cases. Cells expressing either the IL‐1β gene or the IL‐6 gene were found with equal frequency and were similarly distributed. Although present in all liver compartments, they were selectively enriched in portal areas, in which they were detected both in endothelial positions and in perivascular connective tissues. Few positive cells were observed in hepatic lobules, most of them being located in the walls of centrolobular veins, in an endothelial position. Subcapsular cells were also shown to express monokine genes. The location of positive cells and their pattern of labelling suggested that macrophages, fibroblasts and endothelial cells were the main cell populations expressing monokine genes. In contrast, Kupffer cells, biliary epithelial cells and hepatocytes did not express monokine genes. No marker of immune activation other than monokine gene expression was detected in these histologically normal livers. The expression of the IL‐1β gene and of the IL‐6 gene may be induced by gut‐derived LPS, and could play a role in the modulation of hepatocyte function in normal liver.
Hepatocellular carcinoma in porphyria cutanea tarda: frequency and factors related to its occurrence
Authors: Siersema Peter D. , Ten Kate Fiebo J. W. , Mulder Paul G. H. , Wilson J. H. Paul
Published: August 2010

Abstract: Thirty‐eight patients with porphyria cutanea tarda (PCT) have been seen in the last 18 years. Five of these patients (13%) developed hepatocellular carcinoma (HCC) during follow‐up. We analyzed the differences in clinical, laboratory and liver histology findings at presentation, between patients who developed HCC during follow‐up (HCC‐group, n = 5) and those who did not (PCT‐group, n = 33). Of the clinical features the duration of skin‐symptoms was longer in the HCC‐group (mean: 10.4±1.1 years) than in the PCT‐group (mean: 1.4±1 years) (p > 0.001). No differences in routine laboratory findings were found. Although 11/38 (29%) patients had serologic evidence of a past hepatitis B virus infection and 7/38 (18%) patients had antibodies against hepatitis C virus, no differences in these parameters were found between the PCT‐group and the HCC‐group. In all 34 liver biopsies a variable degree of siderosis was found (PCT‐group vs. HCC‐group: NS). Only piecemeal necrosis (p>0.01) and advanced fibrosis or cirrhosis (p>0.001) were more common in liver biopsies in the HCC‐group. In conclusion, factors related to an increased risk of HCC in PCT are: a) a long symptomatic period before start of treatment and b) the presence of chronic active hepatitis and/or advanced fibrosis or cirrhosis in liver biopsies.
Increased steady‐state levels of alpha‐fetoprotein mRNA in hepatocellular carcinoma: an analysis by in situ hybridization
Authors: Varagona G. , Brown D. , Haase A. , Dusheiko G.
Published: August 2010

Abstract: The molecular basis for the augmented production of alpha‐fetoprotein is unknown. We have used in situ hybridization of alpha‐fetoprotein cDNA to malignant hepatocytes to establish if increased serum alpha‐fetoprotein concentrations are related to detectable steady‐state levels of alpha‐fetoprotein mRNA in hepatocytes. Tumor tissue from four patients with histologically confirmed hepatocellular carcinoma were examined, and the results compared to fetal liver. Northern blot hybridization for alpha‐fetoprotein mRNA in tumor tissue was also analyzed. As expected a high number of grains was observed in fetal liver tissue, indicative of high levels of alpha‐fetoprotein mRNA physiologically present during pre‐natal development. Sections from all patients with high serum concentrations of alpha fetoprotein showed appreciable hybrid formation, which correlated semi‐quantitatively with the serum concentrations. However, hybrids were not detected in a patient with a normal serum alpha‐fetoprotein. The high alpha‐fetoprotein mRNA levels in fetal and neoplastic liver suggest that gene transcription is the mechanism of alpha‐fetoprotein production in malignancy, although the control of this mechanism remains speculative.
A method for sequential excision biopsies of rat liver in an isolated perfused system
Authors: Clavien Pierre‐Alain , Sanabria Juan R. , Cywes Robert , Robert P. , Harvey C. , Strasberg Steven M.
Published: August 2010

Abstract: We describe a simple method of performing sequential excision biopsies during liver reperfusion in the isolated perfused rat liver. After hepatectomy, four ligatures (5.0 silk) tied with a slip knot are placed around the pedicles of: (1) the inferior and (2) the superior parts of the caudate lobe, as well as (3) the inferior and (4) the superior parts of the right lateral lobe. At the time of biopsy, the prepared 5.0 silk ties are tightened with sufficient force to occlude the vascular pedicle, preventing leakage of circulating perfusate. The procedure provides four biopsies of more than 350 mg each without alteration of perfusate transaminases and tissue ATP contents. The total tissue removed by this method comprises 20–25% of the whole liver weight.
Space‐occupying lesions of the liver detected by ultrasonography and their relation to hepatocellular carcinoma in cirrhosis
Authors: Benvegnu Luisa , Cecchetto Attilio , Noventa Franco , Tremolada Federico , Ruol Arturo , Alberti Alfredo
Published: August 2010

Abstract: Fifty‐four patients with cirrhosis, found to have a space‐occupying lesion in the liver by ultrasound (US), underwent US‐assisted biopsy of the lesion and were then followed prospectively to define outcome and survival. Histologic examination revealed hepatocellular carcinoma in 26 patients, while five had liver cell dysplasia without hepatocellular carcinoma and 23 had no evidence of tumor or of dysplasia. All five patients with an initial diagnosis of dysplasia developed hepatocellular carcinoma during follow‐up and their survival curve was similar to that of patients with liver cancer and significantly worse than that of patients without dysplasia or tumor. There were five false‐negative cases of hepatocellular carcinoma among the patients with negative histology. Overall, US‐assisted liver biopsy diagnosed malignancy with a sensitivity of 72%, which increased to 86% when dysplasia was considered a pre‐neoplastic lesion.
Long‐term follow‐up of anti‐hepatitis C virus antibodies in patients with acute nonA nonB hepatitis and different outcome of liver disease
Authors: Giuberti Tiziana , Ferrari Carlo , Marchelli Silvia , Antoni Anna Maria Degli , Schianchi Claudia , Pizzaferri Paelo , Fiaccadori France
Published: August 2010

Abstract: We screened 74 patients with nonA nonB acute hepatitis (37 of post‐transfusion PTH, and 37 of non‐post‐transfusion, NPTH, origin) for the presence of anti‐HCV by tests detecting either C100–3 antibodies alone (ELISA I) or C100–3 plus C33c plus C22–3 antibodies (ELISA II). Samples were taken at the onset of disease and then serially for a period of time ranging from 12 to 60 months. An increased number of anti‐HCV positive cases (86% vs 69%) and an earlier seroconversion were observed with the second compared to the first generation ELISA. Positive samples were confirmed by recombinant immunoblot assay (RIBA), which was also used to study the kinetics of the antibody response to individual HCV antigens. Anti‐C33c and anti‐C22–3 antibodies were the first detectable markers of HCV infection in 80% and 20% of the patients, respectively. Thirty‐two percent of the patients studied showed complete and persistent biochemical recovery, whereas 68% maintained a chronic elevation of the transaminase values. Among the 20 patients who showed early and persistent normalization of the transaminase values, complete disappearance of all antibody reactivities was limited to five of them, whereas in four cases only anti‐C100–3 and anti‐5–1‐1 became negative.
Argyrophilic nucleolar organizer regions in neoplastic and non‐neoplastic hepatocytes bearing Mallory bodies
Authors: Hoso Masahiro , Nakanuma Yasuni
Published: August 2010

ABSTRACT— The proliferative activity of Mallory bodies (MB)‐positive hepatocytes (neoplastic and non‐neoplastic) was examined by counting the argyrophilic nucleolar organizer regions (AgNORs). Among 19 cases of hepatocellular carcinoma, the mean number of AgNORs was lower in the MB‐positive carcinoma cells than in the negative ones in nine cases, higher in six, and there was no difference in four. In non‐neoplastic cases (seven cases of advanced primary biliary cirrhosis and seven cases of alcoholic or nutritional liver injury), the mean number of AgNORs was lower in the MB‐positive hepatocytes than that in the negative ones in eight cases, and approximately equal in number in six cases. These findings imply that MB formation does not directly represent the level of proliferative activity of hepatocytes, regardless of whether they are malignant or not.
Effect of thermal injury on transfer of IR22 IgA myeloma protein into bile in the rat
Authors: Cappeller Wolf A. , Bloch Kurt J. , Fagundes Julie , Carter Edward A. , Sullivan David , Harmatz Paul R.
Published: August 2010

ABSTRACT— We previously observed a 75–90% decrease in concentration of biliary IgA after thermal injury to rat skin. Decrease in biliary IgA might result from an alteration in supply of polymeric IgA delivered to the hepatocyte or from an alteration in hepatocyte transfer of polymeric IgA into bile. In the present study, we examined the transfer of intravenously administered 125I‐IgA into bile. Purified IR22 rat IgA myeloma protein consisting of both monomeric and polymeric IgA was labelled with 125I. Sprague‐Dawley rats (140–180 g) received a 20–30% body surface area scald‐burn or sham treatment. The bile duct was cannulated 18–24 h later and 125I‐IgA preparations were injected into the tail vein. Bile was collected under light ether anesthesia for 3 h. In rats injected with 125I‐IR22 IgA myeloma protein there were no significant differences in total, TCA‐precipitable, or immunoprecipitable radioactivity in bile from burn‐injured or sham‐treated animals. On Bio‐Gel A‐1.5 m gel permeation, the radioactivity in bile from sham‐treated animals eluted in the region of polymeric IgA as expected; the radioactivity in the bile from burn‐injured animals eluted equally in the same regions as polymeric IgA and monomeric IgA. In sham‐treated rats injected with isolated polymeric IgA only, bile contained primarily polymeric IgA. In burn‐injured rats injected with polymeric IgA only, bile contained a mixture of polymeric IgA and monomeric IgA. These findings suggest that hepatocyte processing of polymeric IgA is altered after thermal injury, resulting in the transformation of some polymeric IgA into its monomeric form.
Detection of proliferating hepatocytes by immunohistochemical staining for proliferating cell nuclear antigen (PCNA) in patients with acute hepatic failure
Authors: Kayano Kozo , Yasunaga Mitsuru , Kubota Masafumi , Takenaka Kazuyuki , Mori Kenji , Yamashita Aogu , Kubo Yoshitsugu , Sakaida Isao , Okita Kiwamu , Sanuki Kazutoshi
Published: August 2010

ABSTRACT— This study evaluated whether liver regeneration could take place after massive or submassive necrosis of liver cells in 25 patients with several kinds of hepatic failure by immunohistochemical staining for proliferating cell nuclear antigen (PCNA). PCNA positivity was significantly higher (P<0.01) in the patients who survived than in the patients who died. Furthermore, PCNA‐positive hepatocytes were recognized diffusely in the lobule of the liver in survivors. There was positive correlation between PCNA positivity and plasma concentration of AFP (α‐fetoprotein), (r = 0.77, P<0.01). These results show that liver regeneration could take place after massive necrosis of liver cells in survivors from acute hepatic failure and that immunohistochemical staining for PCNA is useful for prognostic evaluation.
Bile duct hemorrhage: a biopsy finding after cholangiography or biliary tree manipulation
Authors: Hartshorne Nikolas , Hartman Grace , Markin Rodney S. , Demetris A. J. , Ferrell Linda
Published: August 2010

ABSTRACT— We report on 13 patients with a distinctive bile duct lesion that presented histologically as erythrocyte engorgement of the epithelium of the small bile ducts, resulting in a red‐beaded appearance. In ten of our cases, the lesion was associated with a recent history of cholangiography, and in two of our cases with vigorous manipulation of the distal biliary tree, raising the possibility that the hemorrhage might have been caused by increased pressure within the ducts during cholangiography or as a result of mechanical trauma to the biliary system.
Variations in human liver fucosyltransferase activities in hepatobiliary diseases
Authors: Jezequel‐Cuer Maryvonne , Dalix Anne‐Marie , Flejou Jean‐François , Durand Geneviève
Published: August 2010

ABSTRACT— The hyperfucosylation of a number of glycoconjugates observed in liver diseases involves the action of several specific fucosyltransferases (F.T.) notably responsible for synthesizing histo‐blood group antigens. We determined the activities of α3, α2 and α3/4 F.T. in 35 liver biopsy samples from patients with fatty liver, alcoholic or post‐hepatic liver cirrhosis, primary or secondary biliary cirrhosis, acute hepatitis or a normal liver. F.T. activities were measured by transfer of GDP [14C] fucose to asialotransferrin for α3 F.T, to phenyl β‐D‐galactoside for α2 F.T. and to 2′ fucosyllactose for α3/4 F.T. The diseased liver extracts showed an early increase in non‐Le gene‐associated α3 F.T. activity (p = 0.001), which was related to the number of steatosic hepatocytes and the degree of intralobular inflammatory infiltration. Overexpression of this α3 F.T. provides an explanation for the strong expression of 3‐fucosyl lactosamine structures described in several hepatobiliary diseases. α2 F.T. levels were significantly elevated in the two groups of liver cirrhosis and acute hepatitis (p = 0.05), but not enough to consider α2 F.T. as a sensitive feature of mesenchymal cell injury. All Lewis‐positive biopsies displaying biliary alterations showed increased Le gene‐encoded α3/4 F.T. activity (p = 0.001), which was related to the intensity of neoductular proliferation. Elevated levels of α3/4 F.T may be a very early sign of biliary regeneration.
Breakdown of mucosal defences in congestive gastropathy in cirrhotics
Authors: Guslandi M. , Foppa L. , Sorghi M. , Pellegrini A. , Fanti L. , Tittobello A.
Published: August 2010

ABSTRACT— The gastric mucus‐bicarbonate barrier, the first line of mucosal defence, has been evaluated in patients with congestive gastropathy and cirrhosis of the liver. Fourteen cirrhotic patients of both sexes (Child's class A or B), with or without oesophageal varices, but with endoscopic signs of congestive gastropathy, and a matched group of healthy controls were studied. The amount of luminal mucoproteins, a Mucoprotective Index as a qualitative assessment of mucus secretion and the output of gastric bicarbonate were determined in basal conditions. In patients with congestive gastropathy a significant (p<0.01) reduction in all the above parameters was observed, suggesting a substantial impairment of the gastric mucus‐bicarbonate barrier. Whether this is an independent phenomenon or a consequence of altered local microcirculation remains to be determined.
An immunohistochemical study of the blood vessels within primary hepatocellular tumours
Authors: Dhillon Amar P. , Colombari Romano , Savage Kay , Scheuer Peter J.
Published: August 2010

ABSTRACT— We studied the blood vessels in routinely formalin‐fixed and paraffin‐processed tissue from 18 hepatocellular carcinomas, three “small” hepatocellular carcinomas, and 15 benign nodular lesions representing a spectrum of conditions with which liver cell carcinomas may be confused. These were stained for a basement membrane component (collagen IV) and endothelial markers (Factor VIII‐related antigen, Ulex europaeus lectin binding, and QBEnd10). The staining pattern of normal and cirrhotic liver was also examined in tissue removed with these tumours. There was an increased expression by small blood vessels for collagen IV in carcinomas and benign lesions compared with cirrhotic nodules. All endothelial markers (Factor VIII‐related antigen, QBEnd10, and Ulex europaeus binding) were best expressed in liver cell carcinomas. These differences were of degree and pattern, and no single marker distinguished benign from malignant lesions. The differences in staining pattern taken together with other clinical and pathological information should be useful in diagnosis particularly of small liver cell carcinoma. The differences between benign and malignant lesions support the idea that malignant neoplastic blood vessels in the liver are of a different basic biological type from normal hepatic sinusoids, and this difference could be exploited further in future therapy.