bluuebunny/crossref_metadata_2025 huggingface dataset:
Dupuytren's contracture, chronic liver disease and IgA immune complexes
Authors: Houghton Sarah , Holdstock Greg , Cockerell Rosalind , Wright Ralph
Published: August 2010

ABSTRACT— Contrary to previous reports, Dupuytren's contracture was found to be equally common in patients with alcoholic and non‐alcoholic biopsy‐proven liver disease (25% v 28%). Furthermore, in 69 patients with Dupuytren's contracture referred for surgical correction, there was no significant increase in either history of alcohol abuse or abnormality of liver function compared to a matched control group. Patients with Dupuytren's contracture were found to have increased levels of circulating IgA immune complexes compared to those without (p<0.05 for those with liver disease; p<0.001 for those awaiting surgical correction). Circulating immunoglobulins and immune complexes of other classes were similar between the groups with and without Dupuytren's contracture. These results suggest that the importance of alcohol has previously been exaggerated but that IgA immune complexes may be involved in the pathogenesis of the condition.
Cyanamide‐induced liver injury. A predictable lesion
Authors: Vazquez J. J. , Guillen F. J. , Zozaya J. , Lahoz M.
Published: August 2010

ABSTRACT— Cyanamide, a drug frequently used for aversion therapy in chronic alcoholism, induces a liver‐cell lesion consisting of cytoplasmic inclusion bodies, structurally similar to those of Lafora. In order to know how frequently the lesion is associated with the intake of this drug, a prospective study was carried out. A biopsy was performed in ten chronic alcoholic patients who had been treated with Cyanamide. Inclusion bodies were present in all patients (7 cases) whose biopsy was taken when they were on Cyanamide and in two other patients whose biopsies were taken 3 and 7 years after discontinuation of the treatment. Inclusion bodies were absent in one case who was treated for a short time and with a small dose and whose biopsy was performed 3 years after cessation of treatment. On the basis of these findings, the lesion may be considered to be predictable. The absence of inclusions in one patient may be explained by their disappearance after cessation of treatment.
The human liver in extrahepatic cholestasis: ultrastructural morphometric data
Authors: Jezequel A. M. , Librari M. L. , Mosca P. G. , Novelli G.
Published: August 2010

ABSTRACT— The present study reports the data obtained through a quantitative analysis performed on needle liver biopsies of five jaundiced patients with extrahepatic cholestasis. Whatever the duration of jaundice, the surface density of the smooth endoplasmic reticulum remained in the normal range in all subjects. The surface density of the rough endoplasmic reticulum was variable, showing elevated values in three of the five patients. The surface density of peroxisomes was unchanged with respect to controls. All the subjects exhibited an increase of the surface density of mitochondrial cristae without changes of the outer membrane. These data fail to show evidence of hypertrophy of the smooth endoplasmic reticulum in hepatocytes of human liver during extrahepatic cholestasis. Instead, the increased surface density of the mitochondrial cristae, which has also been previously reported in patients with uncomplicated cholelithiasis, appears as an early and constant phenomenon associated with conformational changes of this mitochondrial component. Such a structural modification might represent an elementary response of the liver cells to alterations in the pathways of synthesis and/or excretion of biliary components.
Anti‐actin antibodies of IgM and IgG class in chronic liver diseases detected by fluorometric immunoassay*
Authors: Wiedmann K. H. , Melms A. , Berg P. A.
Published: August 2010

ABSTRACT— Using a sensitive fluoroimmunoassay, anti‐actin antibodies (AA) of the IgM and IgG classes were measured in 240 patients with various chronic liver diseases and in 211 patients with non‐hepatic autoimmune muscle, heart, malignant and inflammatory bowel diseases. Thirty‐two out of 40 patients (80%) with autoimmune chronic active hepatitis (CAH) had AA only of the IgG class (geom. mean X = 1.78, SEM±0.07) and only three patients (8%) had both IgG and IgM AA, the latter in lower titres. In patients with primary biliary cirrhosis (PBC) and AMA‐positive cholestatic CAH, AA of both IgM and IgG classes were equally represented (60% IgG and 64% IgM AA in PBC, 73% IgG and 51% IgM AA in cholestatic CAH) but the titres were very low (geom. mean IgG AA in PBC 1.035, SEM±0.03, in cholestatic CAH 1.18, SEM±0.02). In contrast to autoimmune (lupoid) CAH, AA were rare in HBsAg positive CAH (9/43, 21%) and only present in low titres. However, in six out of 21 patients with anti‐HBs and anti‐HBc‐positive chronic active hepatitis, high AA of IgG class were found, suggesting the autoimmune type of liver disease. In NANB virus‐induced chronic liver disease after blood transfusion, AA were only occasionally found (IgG antibodies 1/19, IgM antibodies 3/19) and none were found in the eight patients with sporadic NANB hepatitis. They were also rare in 30 patients with alcoholic liver disease (3/30, 10%). Of 211 patients with non‐hepatic disorders, only 13 patients (6%) had AA (geom. mean of positive titres 0.076, SEM±0.01). We conclude therefore that high titre AA of the IgG class are reliable serological markers for the diagnosis of an autoimmune liver disease.
Hepatocellular carcinoma and hepatitis B virus infection. Analysis of 75 cases from Switzerland
Authors: Pirovino M. , Heer M. , Joller‐Jemelka H. P. , Altorfer J. , Akovbiantz A. , Schmid M.
Published: August 2010

ABSTRACT— The prevalence of serological markers of hepatitis B virus (HBV) infection was investigated in 75 patients with histologically confirmed hepatocellular carcinoma (HCC). Hepatitis Bs‐antigen (HBs‐Ag) was found in 30.8% and evidence of present or past infection in 61.5%. In a control group of 115 patients with liver cirrhosis of various etiologies in whom evidence of a coexistent HCC was lacking, the corresponding numbers were significantly lower (16.5% and 41.7% resp., p<0.05). Below the age of 65 years, markers of present or past HBV‐infection were significantly more frequent than in patients above 65 years of age (p<0.025). All patients positive for HBs‐Ag had an underlying cirrhosis; in seven cases, HCC was found in a non‐cirrhotic liver. Alpha‐fetoprotein measurements failed to identify patients with HCC in up to 43.6% of the HBs‐Ag negative cases. It is concluded that HBV‐infection does represent a cofactor in the malignant transformation of the liver, even in areas of lower incidence. Alpha‐fetoprotein measurements need to be complemented by other investigations if early recognition of HCC is to lead to better survival.
Hepatitis B virus and host cell membrane antigens on a primary hepatocellular carcinoma cell line
Authors: De Koning R. W. , Goodall A. , Varghese Z. , Thomas H. C.
Published: August 2010

ABSTRACT— We have defined some membrane antigens of the cultured hepatocellular carcinoma cell line PLC/PRF/5, which contains the integrated genome of hepatitis B virus. Using fluoresceinated antibodies, we identified HLA Class 1 glycoprotein and HB surface antigen on the membrane. Only in a minority of cells was physical association of these antigens demonstrated by co‐capping. The presence of a “division” antigen was indicated by reactivity of the cells with the murine monoclonal antibody OKT9.
Relative incidence of primary liver cancer in cirrhosis in Austria. Etiological considerations
Authors: Ferenci Peter , Dragosics Brigitte , Marosi Leo , Kiss Fritz
Published: August 2010

ABSTRACT— The incidence of primary liver cancer (PLC) was assessed in 652 patients (429 male, 223 female) with liver cirrhosis. By the end of the study 416 (64%) of all patients had died. The autopsy rate was 65%. PLC developed in 73 patients. Histologically, 67 cases were classified as hepatocellular (HCC), one as mixed hepatocellular‐cholangiocellular and five as cholangiocellular carcinoma. In 30 cases, HCC was confirmed within a year of diagnosis of cirrhosis, and in the remaining 37 cases HCC developed 2–13 years later. At autopsy, the frequency of HCC was almost twice as high in males (27%) as in females (15%) (p<0.025). This difference occurred in alcoholic and posthepatitic cirrhosis but not in cryptogenetic cirrhosis. HBsAg was detected in 19.0% of male and 9.2% of female patients (p<0.01). Comparison of patients with and without HCC revealed no significant differences in the prevalence of HBsAg. These data indicate that HCC is common in Austrian patients with cirrhosis, representing 60% of all malignant tumors in this group. In view of the high HBsAg carrier rate and the prevalence of chronic alcoholism in patients with cirrhosis, it is suggested that the two factors together lead to an increased risk of cirrhosis followed by an increased incidence of HCC.
Perinodular arteriolar plexus in liver cirrhosis. Scanning electron microscopy of microvascular casts
Authors: Yamamoto T. , Kobayashi T. , Phillips M. J.
Published: August 2010

ABSTRACT— The blood supply to regenerative nodules in liver cirrhosis was studied by scanning electron microscopy of microvascular casts. Cirrhotic nodules are surrounded by many arterioles with rich anastomoses that form a perinodular arteriolar plexus: these arterioles connect with sinusoids in the nodules. The portal vein branches, on the contrary, are distorted and compressed by connective tissue. These findings illustrate how the regenerative nodules in liver cirrhosis are mainly nourished by hepatic arterial blood via a perinodular arteriolar plexus.
Manifestations of nonsuppurative cholangitis in chronic hepatobiliary diseases: morphologic spectrum, clinical correlations and terminology
Authors: Ludwig Jurgen , Czaja Albert J. , Dickson E. Rolland , LaRusso Nicholas F. , Wiesner Russell H.
Published: August 2010

ABSTRACT— The features of nonsuppurative cholangitis were studied in liver biopsy specimens from 185 patients with chronic active hepatitis (CAH), 280 patients with primary biliary cirrhosis (PBC), and 55 patients with primary sclerosing cholangitis (PSC). Specimens from patients with other liver diseases in which the presence of nonsuppurative cholangitis had been recorded were also studied. We identified four types of nonsuppurative cholangitis: granulomatous cholangitis, lymphoid cholangitis, fibrous cholangitis, and pleomorphic cholangitis. Granulomatous cholangitis almost always seemed to be destructive; the other types were either destructive or nondestructive. Granulomatous cholangitis was, for all practical purposes, diagnostic of PBC and the obliterative form of fibrous cholangitis was similarly diagnostic for the hepatic manifestations of PSC in adults and paucity of intrahepatic bile ducts in infants. All other types of cholangitis were found in CAH, PBC, PSC, and other liver diseases. Thus, the term “nonsuppurative cholangitis” describes a spectrum of morphologic lesions that differ in incidence, morphogenesis, usefulness for liver biopsy diagnosis, and, probably, pathogenesis.
Delta agent infection: an unfavourable event in HBsAg positive chronic hepatitis
Authors: Sagnelli Evangelista , Piccinino Felice , Pasquale Giuseppe , Di Costanzo Maria Giovanna , Franzese Rosa , Peinetti Patrizia
Published: August 2010

ABSTRACT— To investigate the clinical value of delta agent infection in HBsAg positive chronic hepatitis, we detected anti‐delta antibody (anti‐δ) in serum and delta antigen (δ‐Ag) on sequential liver biopsies of nine patients with HBsAg‐positive CPH and 45 patients with HBsAg‐positive CAH without cirrhosis observed for at least 2 years. The initial group of patients with CAH was composed of 54 patients who were consecutively either left untreated or treated with 15 mg of prednisolone daily. Nine patients dropped out. δ‐Ag was searched by the direct immunofluorescence technique. HBsAg, anti‐δ, HBeAg and anti‐HBe were detected by RIA.

All CPH patients were δ‐Ag negative in the 1st liver biopsy and anti‐δ negative in serum. Out of these nine patients, seven remained δ‐Ag negative CPH throughout the observation and the remaining two became δ‐Ag positive, anti‐δ positive and developed CAH.

The 73% of patients with CAH were δ‐Ag positive on the 1st biopsy and anti‐δ positive in serum. The patients in the δ‐Ag positive group (24 were always δ‐Ag positive and two became δ‐Ag positive during the observation) more frequently than those in the δ‐Ag negative group (10 were always δ‐Ag negative and nine became δ‐Ag negative during the study) showed deterioration or died (77 vs. 16%; P<0.001). Neither in the δ‐Ag positive group nor in the δ‐Ag negative group did prednisolone modify the course of the disease. The δ‐Ag positive compared to the δ‐Ag negative patients were anti‐HBe positive more frequently and circulated HBeAg less frequently. The presence or absence of HBeAg and anti‐HBe in serum was not correlated to a type of outcome.
Hepatitis B virus DNA (HBV‐DNA) in anti‐HBe positive sera
Authors: Negro Francesco , Chiaberge Elisabetta , Oliviero Salvatore , Hammer Marlene , Berninger Mark , Canese Maria Grazia , Bonino Ferruccio
Published: August 2010

ABSTRACT— HBV‐DNA measured by the spot hybridization technique, was found in the sera of 28 of 106 (26.4%) anti‐HBe positive carriers of HBsAg. Dane particle‐associated HBeAg, HBcAg and HBV‐specific DNA‐polymerase activity were found in the sera of nine (8.5%), five (4.7%) and two (1.9%) of these patients, respectively. All carriers with serum HBV‐DNA had chronic liver disease and 18 had intrahepatic δ‐Ag and serum anti‐δ at titers higher than 1/5000. Intrahepatic HBcAg was detected in the nuclei of 90% of delta negative individuals; 50% of them also had cytoplasmic fluorescence. Only two of the 18 patients with intrahepatic δ‐Ag (11%) had HBcAg in the liver.

Viral nucleic acid was not found in the sera of 15 other patients with chronic hepatitis, seven of whom had intrahepatic δ‐Ag. Serum HBV‐DNA was also negative in the remaining 63 symptomless carriers of HBsAg lacking markers of delta infection.

Interestingly, although DNA‐polymerase negative, some sera gave autoradiographic spots of high optical density. HBV‐DNA was detected in them at concentrations typical of sera which are usually both DNA‐polymerase and HBeAg positive. Detection of HBV‐DNA in serum represents the most direct and sensitive in vitro assay for assessing HBV infectivity and characterizes HBsAg carriers with HBV‐related liver damage and ongoing HBV replication independently from the state of HBeAg/anti‐HBe system. In the Mediterranean area, the majority of anti‐HBe positive carriers with serum HBV‐DNA have chronic liver disease and delta infection.
Monoclonal gammopathy in chronic active hepatitis
Authors: Heer M. , Joller‐Jemelka H. , Fontana A. , Seefeld U. , Schmid M. , Ammann R.
Published: August 2010

ABSTRACT— Immunoelectrophoresis was performed in 31 of 272 patients with chronic active hepatitis (CAH) because of an M‐spike component (seven patients, 2.6%) or hypergammaglobulinemia (24 patients) revealing a monoclonal gammopathy (MG) in 11 patients. In addition, 50 randomly selected patients with CAH and no evidence for an M‐spike component were tested by immunoelectrophoresis. In 13 patients (26%), an MG was found. The mean age of the 24 patients with MG was 57.4 years (range: 23–76). HBsAg was present in nine patients (37.5%), no HBV‐marker was detected in ten patients (41.7%). The immunoglobulin class of MG was IgG in ten patients (41.7%), IgA in one patient (4.2%) and IgM in 11 patients (45.8%). In two patients, Bence Jones protein was found in either serum or urine. In only one patient was the MG associated with multiple myeloma, whereas none of the other 23 patients developed a malignant lymphoproliferative disease within the median observation period of 6 years. We conclude that there is an unexpectedly high prevalence of benign MG in patients with CAH.
Immunohistochemical characterization of inflammatory infiltrates in primary biliary cirrhosis
Authors: Van Den Oord J. J. , Fevery J. , De Groote J. , Desmet V. J.
Published: August 2010

ABSTRACT— Ten liver biopsy specimens from nine patients with PBC stages II to IV were studied immunohistochemically with a broad panel of monoclonal antibodies. In areas of bile‐duct proliferation, many BA1+ B‐lymphocytes and OKT4+/Leu3a+ helper/inducer T‐cells were observed, admixed with some C3b‐receptor positive, mono‐and polymorphonuclear OKM1+ cells. Numerous IgM‐containing plasma cells were seen in portal tracts showing bile‐duct proliferation. In contrast, areas of piecemeal necrosis and intralobular spotty necrosis consisted mainly of OKT4+/Leu3a+ helper/inducer, and OKT8+ suppressor/cytotoxic T‐cells, admixed with some OKM1+ polymorphonuclear granulocytes. Almost no BA1+ B‐lymphocytes or Ig‐containing plasma cells were observed in areas of piecemeal necrosis and spotty necrosis. Major histocompatibility complex (MHC)‐class I antigens (i.e. HLA‐A,B,C) were demonstrated either on the liver cell membrane, or on sinusoidal lining cells. The latter also expressed MHC‐class II antigens (i.e. HLA‐DR). In two liver biopsies, an increased expression of HLA antigens was observed near areas of piecemeal and spotty necrosis. Our results indicate that several immune mechanisms each with a particular topographical distribution, are operative in PBC. Inflammatory cells, involved in humoral immunity, are present mainly in areas of bile duct proliferation. In contrast, the effector cells of antigen‐specific cellular cytotoxicity are present in areas of piecemeal necrosis and spotty necrosis. In the latter areas, a pronounced expression of MHC products representing the afferent limb of the cell‐mediated immune response, may permit an optimal T‐cell‐mediated immune effect or, eventually, result in adverse effects.
Ultrasound determination of liver size and assessment of patients with malignant liver disease
Authors: Raeth U. , Johnson P. J. , Williams Roger
Published: August 2010

ABSTRACT— The value of ultrasound‐measured liver volume in assessing response to therapy in patients with malignant liver disease was determined by the method originally described by Carr, which was modified and validated. Volumes measured in five cadavers by ultrasound and, after removal, by water displacement agreed to within 8% and the wide range of volumes in 20 normal subjects (800–2400 ml) was closely correlated with body weight. In 20 patients with non‐malignant diffuse liver disease (cirrhosis or fatty liver) and 33 with malignant liver disease, initial volumes ranged from 1000 to 4900 ml and did not correlate with body weight. Changes in response to therapy in 15 patients with malignant liver disease were monitored by serial measurements with demonstrable changes in volume which, in those with alpha‐fetoprotein tumours, were in parallel with changes in serum alpha‐fetoprotein levels.
Fulminant hepatic and renal failure complicating Wilson's disease
Authors: Rector William G. , Uchida Toshikazu , Kanel Gary C. , Redeker Allan G. , Reynolds Telfer B.
Published: August 2010

ABSTRACT— We report a case of fatal fulminant liver failure complicating Wilson's disease that is unique in several respects. The illness supervened after several years of medical noncompliance in a patient who had been previously diagnosed and successfully treated with penicillamine. Re‐institution of penicillamine therapy 2 weeks prior to the fulminant decompensation failed to prevent it. Renal failure in this patient was apparently secondary to rhabdomyolysis. Addition of penicillamine to a peritoneal dialysis solution allowed chelation and removal of over 14 mg per day of copper but without apparent benefit. Exchange transfusion and high dose dexamethasone therapy (24 mg/day) were equally ineffective in reversing the liver failure. Other reported cases have also been fatal. The best treatment for fulminant Wilson's disease is prevention by diagnosis in a pre‐symptomatic stage and institution of carefully supervised lifelong therapy with penicillamine.
The diagnostic value of α1‐antitrypsin globules in liver cells as a morphological marker of α1‐antitrypsin deficiency
Authors: Clausen Per P. , Lindskov Jørgen , Gad Inger , Kreutzfeldt Mogens , Orholm Marianne , Reinicke Vagn , Larsen Helmer Ring , Strøm Peter
Published: August 2010

ABSTRACT— In order to determine the diagnostic value of α1‐antitrypsin (AAT) globules as a morphological marker of AAT‐deficiency of the Pi‐Z type, liver needle biopsies from a prospective series of 600 patients were stained with PAS after pretreatment with diastase and by indirect immunoperoxidase staining for AAT deposits. Serum AAT phenotypes of the patients were determined by means of isoelectric focusing. Thirty‐two biopsies were from patients with the Pi‐Z allele (31 MZ, 1 Z), and 568 biopsies from patients without the Pi‐Z allele. AAT globules larger than 3 μm were found in 16 biopsies of which 15 were from patients with the Pi‐Z allele (diagnostic specificity 0.94), whereas 20 of 26 biopsies with AAT globules larger than 1 μm were from Pi‐Z patients (diagnostic specificity 0.77). Only 47% of the biopsies from patients with the Pi‐Z allele contained AAT globules larger than 3 μm. Thus, although AAT globules larger than 3 μm are highly specific as a morphological marker of the Pi‐Z allele, their rather infrequent occurrence in carriers of the Pi‐Z allele indicates that all investigations concerning the correlation between AAT deficiency of the Pi‐Z type and liver disease should be based on phenotyping of sera from all the patients.
Differential diagnosis of jaundice: a pocket diagnostic chart
Authors: Matzen Peter , Malchow‐Møller Axel , Hilden Jørgen , Thomsen Carsten , Svendsen Lars Bo , Gammelgaard Jens , Juhl Erik ,   The Copenhagen Computer Icterus Group
Published: August 2010

ABSTRACT— Based on extensive clinical and clinical chemical information (107 different items) from 1002 jaundiced patients, we developed a diagnostic algorithm which was evaluated on a test sample of another 110 jaundiced patients. A primary classification into categories of obstructive jaundice (probability of obstruction ≥0.80), non‐obstructive jaundice (probability of obstruction ≤0.20), and of doubtful causes of jaundice (probability of obstruction: 0.20–0.80) was attempted. Among 234 patients in the data base who were classified as obstructive, 220 (94%) proved to be so, as did 36 (97%) of 37 in the test sample. The corresponding figures for non‐obstructive jaundice were 463 (96%) of 483 patients correctly classified in the data base and 47 (92%) of 51 patients in the test sample. Altogether 69% of the patients in the data base and 75% of those in the test sample were correctly classified, in 27% and 20% the cause of jaundice was doubtful, and only 4% and 5%, respectively, were misclassified. A slight majority of the patients in whom the algorithmic diagnoses were doubtful proved obstructive. A close correlation was found between the preliminary diagnoses made by the algorithm and by the clinicians. A secondary classification of the patients by the algorithm into benign versus malignant causes of obstructive jaundice performed equally well in the data base and the test sample.
Discrimination between organic and hepatic encephalopathy by means of continuous reaction times
Authors: ELSASS P. , CHRISTENSEN S.‐E. , MORTENSEN E. L. , VILSTRUP H.
Published: August 2010

ABSTRACT— Measurement of continuous reaction times (CRT) was applied to 105 hospitalized controls, 65 patients with brain damage and 47 patients with hepatic encephalopathy. One hundred and fifty reaction times were measured in every patient. The best discrimination between controls and patients with organic brain damage was obtained with the 10 percentile of the reaction time distribution (86% correct classification). The 90 percentile discriminated best between controls and patients with hepatic encephalopathy (86% correct classification). Furthermore, the ratio between the 50 percentile and the difference between the 10 and 90 percentile made it possible to discriminate between the two groups of patients (91% correct classification), which indicates that the CRT test is suitable as a screening device for discrimination between organic brain damage and hepatic encephalopathy.
Antinecrotic effect of 3‐palmitoyl‐(+)‐catechin against liver damage induced by galactosamine or ethanol in the rat
Authors: Perrissoud D. , Maignan M. F. , Dumont J.‐M.
Published: August 2010

ABSTRACT— The antinecrotic potential of a new drug, 3‐palmitoyl‐(+)‐catechin (PC), which is a derivative of (+)‐cyanidanol‐3, was studied in two different experimental models of necrosis of the liver in the rat: acute hepatitis induced by galactosamine and liver damage induced by a combination of chronic ethanol feeding and hypoxia. The extent of liver damage was assessed by histological examination and by measuring blood hepatic enzyme and bilirubin levels. Intraperitoneal and oral treatments with PC were carried out at different dosages and times, before acute galactosamine intoxication. PC treatment decreased the extent of diffuse necrosis and inflammation in liver tissue and reduced galactosamine‐induced biochemical deterioration. The lowest active doses of PC were 25 mg/kg, i.p. and 500 mg/kg by mouth. In experiments with ethanol, we confirmed that a 6‐h period of hypoxia produced necrosis of the liver in rats undergoing chronic treatment with ethanol. Simultaneous treatment with PC (80 mg/kg/day) for 21 days during ethanol feeding gave significant protection against histological and biochemical deterioration induced by ethanol and hypoxia. The antinecrotic effect of PC in two models, which are recognized as producing part of the biochemical and/or histological deterioration induced by viruses and ethanol in man, indicates that it is a potentially useful agent for the treatment of necrosis of the human liver.
The cellular infiltrate in the liver in auto‐immune chronic active hepatitis: analysis with monoclonal antibodies
Authors: Frazer I. H. , Mackay I. R. , Bell J. , Becker G.
Published: August 2010

ABSTRACT— The mononuclear cell infiltrate in the liver was analyzed, using a panel of monoclonal antibodies (MAbs) of known specificity, in 10 patients with auto‐immune chronic active hepatitis and, for contrast, in 14 with other types of chronic parenchymal liver diseases. In all cases, the mononuclear cell (MNC) infiltrate in the liver consisted mostly of T lymphocytes. Helper (Th) cells were more frequent than suppressor/cytotoxic T cells (Tsc) in the portal tracts and cirrhotic scar tissue, while Tsc were more common in the hepatic parenchyma. The number of Tsc cells in the parenchyma was greatest in patients with histologically active CAH and least in patients with quiescent cirrhosis. “Plasmacytoid” cells with the morphology of plasma cells, a hallmark of the MNC infiltrate in auto‐immune CAH, were more frequent in histologically active CAH than in quiescent cirrhosis. These plasmacytoid cells were T200 + ve, and hence of bone marrow origin, but the majority expressed neither membrane nor cytoplasmic immunoglobulin nor any lineage‐specific marker antigens, and hence did not fulfil criteria for B lymphocytes; however, these cells were positive for OKT10 and HLA DR. No difference was evident between the MNC infiltrate in the liver in auto‐immune CAH and that in the other acute or chronic liver diseases studied, including HBV‐associated CAH; hence immunohistological studies do not point to any pathological processes uniquely responsible for the pattern of hepatocyte damage seen in auto‐immune CAH.
Correlation between liver morphology and haemodynamics in alcoholic liver disease
Authors: Krogsgaard Kim , Gluud Christian , Henriksen Jens H. , Christoffersen Per
Published: August 2010

ABSTRACT— In 32 alcoholic patients the degree of hepatic architectural destruction was graded (preserved architecture, nodules alternating with preserved architecture, totally destroyed architecture) and related to portal pressure. A significant positive correlation was found between degree of architectural destruction and wedged‐to‐free hepatic vein pressure (W‐FHVP) (p < 0.001). The degree of necrosis, fatty change and inflammation showed no correlation with portal pressure, whereas a significant positive correlation was found between the occurrence of Mallory bodies and W‐FHVP (p < 0.01) and between degree of fibrosis and W‐FHVP (p < 0.001). In 22 of the patients, hepatic blood flow (HBF) was measured and in these patients hepatic resistance was calculated (W‐FHVP/HBF). A significant positive correlation was found between fibrosis and hepatic resistance (p < 0.01). Further, hepatic architectural destruction (p < 0.01) was positively correlated to hepatic resistance. Necrosis, fatty change, occurrence of Mallory bodies or inflammation showed no significant correlation with hepatic resistance. Mean hepatocyte volume was calculated in 29 patients, but no correlation was found with haemodynamic variables. The present data substantiate the concept that established portal hypertension in alcoholic liver disease is mainly accomplished by a derangement in hepatic architecture, whereas parenchymal changes, including hepatocyte size, are of less importance.
Tru‐cut and Menghini needles: different yield in the histological diagnosis of liver disease
Authors: Vargas‐Tank L. , Martinez V. , Jirón M. I. , Soto J. R. , Armas‐Merino R.
Published: August 2010

ABSTRACT— An evaluation of the information obtained by percutaneous liver biopsy performed with Travenol Tru‐cut® (“Tru‐cut”), Menghini's 1.9 and 1.6 needles, was done using cadavers. All needles used had a similar, low number of “failures”. Recognition of diffuse liver lesions, excluding fibrosis, was very high regardless of the needle used. Identification of cirrhosis was significantly more frequent in biopsies performed with the Tru‐cut needle.
Mechanically isolated hepatocytes are unsuitable to detect antibodies directed against plasma membrane determinants
Authors: LENZI M. , PREDA PAOLA , BIANCHI F. B. , BIAGINI GRAZIELLA , CASSANI F. , VOLTA U. , PISI E.
Published: August 2010

ABSTRACT— The ultrastructural morphology of mechanically and enzymatically isolated hepatocytes was compared. Plasma membrane integrity was evaluated by electron microscopy, both in the absence and in the presence of ruthenium red, which stains cell coat glycoproteins and makes it possible to identify even partially permeable cells, and by indirect immunofluorescence using experimental antibodies directed against epithelial submembranous components (prekeratin, actin). In order to evaluate the antigenic integrity of the hepatocellular plasma membrane after the isolation procedures, an immuno‐electronmicroscopical technique (Staph. pA‐colloidal gold) was applied using the IgG fraction from two liver‐kidney microsomal antibody (LKM) positive sera, known to react with both plasma membranes and smooth endoplasmic reticulum (SER). Enzymatic procedure made it possible to isolate hepatocytes with a good preservation of both plasma membranes and subcellular organelles. Ruthenium red staining was confined to plasma membranes, thus indicating the preservation of both cell‐coat glycoproteins and plasma membrane. Most cells were negative after exposure to experimental antibodies. After exposure to LKM positive sera colloidal gold was strictly confined to the plasma membrane. On the other hand, mechanically isolated hepatocytes showed wide interruptions of the plasma membrane and gross alterations of subcellular organelles. Most cells were stained by ruthenium red, thus confirming the plasma membrane permeability. In addition, a linear peripheral positivity was found in the vast majority of the cells tested with anti‐prekeratin and anti‐actin antibodies. LKM‐colloidal gold complexes were found at the level of both residual plasma membrane and SER. Cytoplasmic structures of mechanically isolated hepatocytes can therefore be reached by a variety of antibodies, commonly found in liver patients' sera. Thus, mechanically isolated hepatocytes are not a reliable substrate for the immunopathological demonstration of antibodies to plasma membrane constituents.
Human hepatocellular carcinoma is associated with quantitative and qualitative changes in glycolipids
Authors: OKADA YOSHIO , ARIMA TERUKATSU , HADA HAJIME , FUKUSHIMA MASAKI , WATANABE JUN‐ICHI , NAGASHIMA HIDEO
Published: August 2010

ABSTRACT— Changes of glycolipids in the naturally occurring human hepatocellular carcinoma tissues were studied. Neutral glycolipids (two fractions) and gangliosides from human hepatocellular carcinoma tissues and their adjacent uninvolved liver tissues from ten patients were purified and analyzed by high‐performance thin‐layer chromatography. Human hepatocellular carcinoma was shown to be associated with the extensive changes of the thin‐layer chromatography patterns of both neutral glycolipids and gangliosides. Changes in neutral glycolipids were: (a) increased dihexaosylceramide with the concomitant decrease of trihexaosylceramide and globoside, (b) increased ratio of the lower band of globoside to the upper band, and (c) increased expression of at least two “upper‐phase” neutral glycolipids. Changes in gangliosides were: (a) increased expression of gangliosides migrating slower than GM3, on thin‐layer chromatography with relative decrease of GM3, and (b) expression of tumorassociated new gangliosides, i.e., “neogangliosides”.
The streaming liver
Authors: ZAJICEK G. , OREN R. , WEINREB M.
Published: August 2010

ABSTRACT— Twenty male adult rats weighing 200 g were injected with tritiated thymidine (3HTdR). The animals were then killed in groups of five, at the following times: 1 h, 1, 3 and 5 weeks. Autoradiograms of sections through the liver were prepared. The distances between labelled cells and the portal space rim were measured. One hour after labelling most labelled cells were confined to a region extending from the portal space rim up to a distance of 700 μm, which roughly corresponds to Rappaport's hepatic acinus zones‐1 and ‐2. Throughout the experiment lasting 5 weeks labelled cells entered zone‐3 and advanced toward the terminal hepatic vein. Hepatocytes travelled at a daily velocity of 1.44 μm, covering daily 0.324% of the acinus diameter. During the experiment acinus size did not change appreciably. The estimated mean hepatocyte cell cycle time was 37 days and its life expectation, 201 days. These experiments show that the liver is essentially a slowly renewing cell population. Hepatocytes nascent at the portal space gradually stream toward the terminal hepatic vein where they are probably eliminated by apoptosis. Their journey lasts 201 days. Since hepatocytes are glued together with tight junctions, all have to advance toward their terminal hepatic veins en masse. During their voyage, they traverse the three acinus zones, and since in each they produce different enzymes, each zone represents a differentiation state of the advancing cell. It is suggested further that the streaming hepatocyte carries with it its nerve supply and is accompanied by sinusoidal endothelium and Kupffer cells.
Histopathological changes in rat liver following repeated vespine envenomation
Authors: BARR‐NEA L. , NEUMAN M. G. , ESCHAR J. , ISHAY J. S.
Published: August 2010

ABSTRACT— The histopathological picture of rat liver was studied after repeated envenomation with hornet (Vespa orientalis) venom sac extract (VSE). Light microscopical and histochemical investigation showed foci of necrosis of the hepatocytes, a decrease in glycogen content and in succinic dehydrogenase activity, some fat infiltration and an increase in alkaline phosphatase activity. Electron microscopy showed a decrease in the number of mitochondria per cell as well as a decrease in their cristae, enlargement of bile canaliculi, and destruction of the endothelium of the sinusoids bringing the cytoplasm of the necrotic hepatocytes in contact with the lumen of the sinusoid. The rat liver is proposed as a model for the study of pathological effects of animal toxins.
Double infections with hepatitis A and B viruses
Authors: TASSOPOULOS NICOLAOS , PAPAEVANGE‐LOU GEORGE , ROUMELIOTOU‐KARAYANNIS ANASTASIA , KALAFATAS PETER , ENGLE RONALD , GERIN JOHN , PURCELL ROBERT H.
Published: August 2010

ABSTRACT— Ten (2.8%) asymptomatic carriers of HBsAg and four (1.1%) patients with acute hepatitis B virus (HBV) infection were detected among 356 adults with acute viral hepatitis A (HAV) consecutively admitted to the Athens Hospital for Infectious Diseases from May 1981 to March 1984. These patients did not differ in clinical, epidemiologic (except in age), biochemical or serologic characteristics from patients acutely infected with HAV alone. Transient suppression of the HBV replication and disappearance of the HBV DNA accompanied by seroconversion from HBeAg positive to anti‐HBe positive were detected in one and two carriers respectively. The titer of non‐class‐specific anti‐HBc was low (>10‐2) in all cases. These data suggest that superinfection of HBsAg carriers with HAV does not cause more severe disease or influence adversely the course of chronic hepatitis B disease. However, accurate diagnosis of double infections is necessary for prognosis of the liver disease and appropriate management of the patient's environment. This is quite important in areas with a high prevalence of HBV infections, like Greece, where double infections are relatively common.
Long‐term follow‐up of 60 patients with chronic hepatitis B. I. Seroconversion in the hepatitis B e‐system, frequency of delta infection and histological outcome
Authors: Lindh G. , Weiland O. , Svedmyr A. , Glaumann H. , Hansson B. G.
Published: August 2010

ABSTRACT— Sixty patients with liver biopsy documented chronic hepatitis B attending Roslagstull Hospital for Infectious Diseases, Stockholm, Sweden, were followed during a mean period of 53 months (range 7–133 months) in order to evaluate the frequency of delta infection and HBeAg seroconversion as well as the histological outcome as assessed by liver biopsy. Spontaneous HBeAg clearance and development of anti‐HBe occurred among 17 of 36 initially HBeAg positive patients (47%), corresponding to an annual seroconversion rate of 11%. Biochemical improvement was noted in 7/17 patients (41%) after seroconversion as against in 2/19 patients (10.5%) with HBeAg persistence. Superinfection with the delta agent was seen to be associated with severe liver injury among drug addicts and immigrants with chronic hepatitis B. In the absence of a delta infection, progressive liver disease seemed to be associated with persistence of HBeAg. Although none of the homosexual men studied were delta superinfected, 71% developed chronic active hepatitis (CAH) with or without cirrhosis (CI).
Nodular regenerative hyperplasia and focal nodular hyperplasia of the liver associated with severe cholestasis. Report of a case with autopsy findings
Authors: De Otazu R. Diaz , Garcia‐Campos F. , Basterra G. , Lopez‐Barbarin J. M.
Published: August 2010

ABSTRACT— Nodular regenerative hyperplasia of the liver was found at liver biopsy and at autopsy in a 61‐year‐old woman with severe cholestasis. Increased bilirubin levels persisted over a follow‐up period of 4 years. Microscopic findings included hyperplastic hepatocytic nodules, interlobular bile duct lesions, fibrous medial and intimal thickening of small arterial branches and portal veins, and recanalization of a thrombus in a major portal branch related to an area of focal nodular hyperplasia of the liver. Bile duct and small vessel changes were prominent in the present case. Their role as contributing factors to the development of nodular regenerative hyperplasia of the liver is discussed.
Perfusion fixation of hepatic needle biopsies for scanning electron microscopy. A methodological study
Authors: HORN T. , CHRISTOFFERSEN P.
Published: August 2010

ABSTRACT— Perfusion fixation is essential for the examination of the hepatic microvasculature by scanning electron microscopy. No detailed study has previously been done on the perfusion of human hepatic needle biopsies. The present paper demonstrates two modifications of a simple technique by which needle biopsies can be perfused. Perfusion was performed either manually (n = 33) or with a constant perfusion pressure of 10–15 mm H2O (n = 54). No significant difference in the ultrastructural preservation was observed in the two groups. Manual perfusion, however, when done gently, was superior in cleaning the sinusoids, and thus larger areas could be investigated by this method. Topographical orientation was possible, allowing the identification of terminal hepatic veins and portal tracts.
Alpha‐fetoprotein changes in the course of chronic hepatitis: relation to bridging hepatic necrosis and hepatocellular carcinoma
Authors: LIAW YUN‐FAN , TAI DAR‐IN , CHEN TONG‐JONG , CHU CHIA‐MING , HUANG MIAU‐JU
Published: August 2010

ABSTRACT— To examine the frequency and significance of alpha‐fetoprotein (AFP) elevation, radioimmunoassay for AFP was performed every 3–6 months in a prospective follow‐up study on 432 hepatitis B surface antigen (HBsAg)‐positive and 105 HBsAg‐negative patients with clinicopathologically proven chronic hepatitis. In a period of 6–85 months (mean 26.9±16.8), AFP elevation (>20 ng/ml) was recorded in 45.6% of the HBsAg‐positive patients. In addition, 19.4% of the HBsAg‐positive patients had AFP levels greater than 100 ng/ml, with a highest level of 2520 ng/ml in the absence of hepatocellular carcinoma (HCC). All these figures were much greater than those for HBsAg‐negative patients (P<0.001). Most episodes of AFP elevation were transient, with parallel moderate SGPT elevation (>200 IU/L). The AFP levels in such episodes correlated closely with the presence of bridging hepatic necrosis, only weakly with peak SGPT levels, but not with age, sex or hepatitis B e antigen/antibody status. None of the transient episodes was followed by subsequent development of HCC. On the other hand, AFP elevation (> 100 ng/ml) without parallel SGPT elevation could predict the presence of HCC with very high specificity (98.7%). However, the sensitivity was not high enough (66.7%) for one to rely solely on AFP for the detection of HCC at its earlier stage.
Preparation and characterization of human monoclonal antibodies directed against the hepatitis B virus surface antigen
Authors: COLUCCI G. , KOHTZ D. S. , WAKSAL S. D.
Published: August 2010

ABSTRACT— The hepatitis B surface antigen (HBsAg) is highly immunogenic and induces an antibody response which is protective in vivo against hepatitis B virus (HBV) infection. Human monoclonal antibodies specific for HBsAg were produced, which could have potential therapeutic applications. Lymphocytes obtained from a vaccinated donor were stimulated in vitro and fused with the human myeloma cell line GM 4672, and eight hybridomas were obtained. Three of these clones, which reacted in an ELISA against the HBsAg vaccine, were expanded, subcloned and further analyzed. The subclones E7C2, C4C10, and D5B2 were able to bind to different HBsAg preparations, which express various subtypes, and recognized the major HBsAg peptides in Western blot analysis. Cross‐inhibition experiments showed that E7C2, C4C10 and D5B2 are directed against the same epitope and have an affinity constant ranging from 5 times 107 to 3.3 times 109 M. Furthermore, these antibodies stained the surface and cytoplasm of the HBsAg‐secreting cell lines PLC/PRF/5 and 4.10. The production of immunoglobulins varies from 0.3 to 1.3 μg/ml/106 and has remained stable over a period of 8 months. These human monoclonal antibodies, which appear to be directed against an antigenic determinant common to all HBsAg subtypes, could be useful in the study of HBV‐related liver diseases as well as in their diagnosis and experimental therapy
The distribution of metastases of different primary tumors in the liver
Authors: STROHMEYER T. , SCHULTZ W.
Published: August 2010

ABSTRACT— The distribution of the number and volume of liver metastases in both lobes of the liver was investigated. The density of the metastases and their volume were analyzed. The study of 71 human metastatic livers revealed an almost homogeneous pattern of metastatic distribution. There was no difference whether the spread of the tumor cells had occurred via the portal vein or the hepatic artery. Both sides of the liver were affected similarly.
Cross‐circulation in experimental hepatic failure in the pig
Authors: Tønnesen Klaus
Published: August 2010

ABSTRACT— In experimental liver failure (pigs with totally devascularized liver) the effect of different types of extracorporeal hepatic assistance was evaluated. Group I (N = 6) were untreated controls, Group II (N = 6), simple cross‐circulation, Group III (N = 6), cross‐circulation with inflow in the donor directly into the portal vein and Group IV (N = 4), cross‐perfusion with isolated perfused liver. The cross‐circulation was started 20 h after devascularization. There was no change in survival time. Bilirubin was decreased by a factor of 2 and the prothrombin index increased by a factor of 2 after initiation of the cross‐circulation due to the dilution. In contrast to this, ammonia was unchanged. During the perfusion no significant changes were found. In Group V (N = 4), extended cross‐perfusion with isolated perfused liver for 20 h, starting just after exclusion of liver function in the recipient and with a new liver in the perfusion system every 6th hour, the survival time was significantly increased. Furthermore, changes in the biochemical variables were prevented. It is concluded that with a supply of quantitatively sufficient hepatic assistance it is possible to extend the survival time in experimental liver failure.
Ultrasound‐guided fine‐needle aspiration biopsy in the diagnosis of hepatic hemangioma
Authors: Caturelli Eugenio , Rapaccini Glan Ludovica , Sabelli Carlo , De Simone Filiberto , Fabiano Alfredo , Romagna‐Manoja Emanuele , Anti Marcello , Fedeli Giuseppe
Published: August 2010

ABSTRACT— Fine‐needle biopsy of hepatic hemangioma is discussed on the basis of a series of 10 biopsies performed on eight patients. The fine needle biopsies were executed because of the atypical sonographic pattern of some lesions, or in order to exclude malignancy for others (five patients were known to have neoplasms). No complication presented during or after the punctures. In six cases cytologic samples included capillary vessels or endothelial cells, supplying the diagnosis of hemangioma. It is concluded that fine‐needle biopsy of a hepatic hemangioma is not loaded with complications, and moreover can yield true positive information in 60% of cases.