bluuebunny/crossref_metadata_2025 huggingface dataset:
Profiles of antinuclear antibodies in chronic active hepatitis, primary biliary cirrhosis and alcoholic liver disease
Authors: Kurki P. , Gripenberg Marianne , Teppo Anna‐Maija , Salaspuro M.
Published: August 2010

ABSTRACT— The profiles of specific antinuclear antibodies were determined in sera from 23 patients with the idiopathic type of chronic active hepatitis (CAH), 15 patients with primary biliary cirrhosis (PBC) and 25 patients with alcoholic liver disease (ALD). The indirect immunofluorescence test for antinuclear antibodies using cultured human embryonic fibroblasts as substrate was positive in 78% in CAH, in 73% in PBC and in 24% in ALD. Seventeen percent of CAH sera and 33% of PBC sera stained small speckles in interphase nuclei. This staining pattern probably represents a new subset of ANA as the centromeres (kinetochores) were not stained. Antibodies to native DNA by the Crithidia luciliae test were found in only one serum from a patient with CAH. In addition, 17 percent of the CAH sera reacted with the saline extract of rabbit thymus by double immunodiffusion. Antibodies to the Sm‐ or RNP‐antigens were not found. SS‐B antibodies could be demonstrated in 39% of the CAH sera by a sensitive immunoenzymatic technique. Patients with CAH also had significantly higher levels of antibodies against denatured, single‐stranded DNA (ss‐DNA) and a synthetic RNA molecule, poly(A) as compared to other groups. Patients with an atypical cholestatic CAH had an antinuclear‐antibody profile resembling that of the other CAH patients, but different from that of PBC patients. Patients with alcoholic cirrhosis had significantly higher levels of ss‐DNA‐ and poly(A)‐antibodies than other patients with ALD. It is concluded that the determination of an antinuclear‐antibody profile using the ELISA seems to be clinically useful in the classification of chronic liver diseases.
Hepatitis B surface antigen (HBsAg) – fibrinogen interaction
Authors: Vanstapel M. J. , De Wolf‐Peeters C. , De Vos R. , Desmet V. J.
Published: August 2010

ABSTRACT— Deparaffinized sections of hepatitis B surface antigen (HBsAg) positive liver biopsies, when incubated in a human fibrinogen solution, reveal a strong labelling of ground‐glass hepatocytes with fibrinogen. This implies an interaction between HBsAg and fibrinogen. The binding of fibrinogen to HBsAg is thought to be mediated by the protein moiety of HBsAg, since its binding capacity is destroyed by trypsin digestion, and to occur through formation of disulphide bridges because the binding can be disrupted by the reducing effect of 2‐mercapto‐ethanol. Not all ground‐glass hepatocytes exhibit fibrinogen binding. The reason for this is at present unclear. No relationship between serum HBeAg positivity and binding of HBsAg to fibrinogen was observed. Preincubation in a fibrinogen solution did not alter the immunoreactivity of HBsAg. We conclude that there is a striking analogy between the interaction of HBsAg with polymerized human serum albumin and its interaction with fibrinogen.
Cytomegalovirus hepatitis in normal and immune compromised hosts
Authors: Ten Napel Chr. H. H. , Houthoff H. J. , The T. H.
Published: August 2010

ABSTRACT— Liver biopsies of six previously normal hosts (Group I, NH), with recent or acute CMV infection, and autopsy liver samples of four immunocompromised hosts (Group II, ICH) with overwhelming CMV infection have been studied in an occasional survey. In both groups, portal tract involvement, bile duct inflammation, liver cell degeneration and parenchymal granulomas were present. In Group I, a randomly distributed hepatitis with predominant involvement of the periportal areas was present, including sinusoidal arrays of lymphocytes and lymphohistiocytic aggregates. In contrast, in Group II liver cell damage was more extensive and the inflammatory infiltration only scarce. Intracellular viral inclusion bodies were found only in Group II, both in liver cells and in bile duct epithelium. Morphologically, the presence of viral inclusion bodies correlated well with the immunohistologic demonstration of CMV specific “late” (CMV‐LA) or structural antigens. In addition, CMV‐specific “early” (CMV‐EA) or non‐structural antigens were present in liver cell nuclei of 2/6 NH and 2/4 ICH.

The possible relations between the inflammation and the lack of structural antigenic viral expression are discussed. It is concluded that ICH with CMV infection have a prominent cytopathogenic effect and widespread lytic viral infection in the liver in the absence of adequate immunologic reactivity, whereas the opposite is found in NH.
Epidemiology of primary biliary cirrhosis
Authors: Triger D. R. , Berg P. A. , Rodes J.
Published: August 2010

ABSTRACT— A multi‐national survey of the clinical and epidemiological aspects of primary biliary cirrhosis (PBC) has been conducted in 10 countries in Western Europe, surveying a population of over 24 million. The prevalence on 31 December, 1981 was 23/million, but this showed a marked variation from centre to centre for reasons which are not clear. The annual incidence of PBC has remained constant at about 4/million over the past 4 years, while the point prevalence has continued to rise, suggesting that the true prevalence may be rather higher than present figures suggest. The female: male sex ratio is 10:1, but in stages I & II this ratio is 6.5:1 compared with 11.4:1 in stages III & IV. Possible reasons for this are discussed.
Primary portal venopathy in the golden hamster treated with low doses of dimethylnitrosamine
Authors: Ungar Henry
Published: August 2010

ABSTRACT— Ingestion of dimethylnitrosamine in a low dose and for a limited period by hamsters resulted in primary intrahepatic pylephlebitis. The process began at 24 h and progressed within 2–4 weeks to narrowing and, eventually, to partial obstruction of the portal bed. The lesions were characterized by endothelial necrosis followed by infiltrations of lymphoid cells extending into the portal tracts. Superficial lesions of terminal hepatic veins and parenchymal changes occurred only after a lapse of, respectively, 2 and 4 weeks when restrictions of portal blood had been assumed. The parenchymal changes consisted of regional regenerative hyperplasia accompanied by subendothelial prolapse of hepatocytes into the wall of terminal veins. The lesions of the portal veins persisted for a prolonged period of time after the exposure to dimethylnitrosamine had ceased. These findings, associated with characteristic histological aspects, suggested secondary immune reaction following the initial toxic pylephlebitis. The possible relevance of the experimental results to understanding the nature of endemic portal venopathy in man is discussed with regard to pathogenesis and etiology.
Advances in the treatment of porphyria cutanea tarda. Effectiveness of slow subcutaneous desferoxamine infusion
Authors: Gibertini Paolo , Rocchi Emilio , Cassanelli Marco , Pietrangelo Antonello , Ventura Ezio
Published: August 2010

ABSTRACT— The authors present the results of long‐term subcutaneous desferrioxamine (DFX) infusion in 16 porphyria cutanea tarda (PCT) patients who cannot undergo repeated phlebotomies because of severe liver damage, haemolytic anemia, cardiovascular impairment or pulmonary and bone tuberculosis. They employed an automatic, portable syringe pump for subcutaneous infusion (8–10 h) to overcome the short half‐life of the drug. Photodynamic cutaneous lesions and hyperpigmentation quickly disappeared (2–3 months). Uroporphyrin excretion sharply decreased and normalized within 3–12 months. Also, serum iron and ferritin, as well as liver function, showed a significant improvement. The authors therefore propose subcutaneous DFX therapy in PCT treatment when phlebotomy is contraindicated.
Alpha‐1‐antitrypsin (AAT) and its stimulation in the liver of PiMZ phenotype individuals. A “recruitment‐secretory block” (“R‐SB”) phenomenon
Authors: Callea Francesco , Fevery Johan , Massi Guido , Lievens Carl , De Groote Jan , Desmet Valeer J.
Published: August 2010

ABSTRACT— PiMZ individuals in conditions of clinical stimulation show a peculiar immunohistochemical staining pattern for alpha‐1‐antitrypsin (AAT) in the liver: 1) the positivity involves large zones of parenchyma (up to 100% of hepatocytes); 2) in zone 2 and zone 3 hepatocytes the positivity appears in the form of crescents or rectilinear arrays along the sinusoids. This new pattern is designated type II, in contrast to type I which occurs in periportal hepatocytes in the form of inclusions spread over the whole cytoplasm. This peculiar staining pattern is associated with serum elevation of AAT and is considered to be an expression of liver reactivity. Type II positivity marks the hepatocytes which are newly recruited for the synthesis of AAT; owing to its defective export, the Z AAT is retained within the cell and detectable by immunohistochemistry. Thus this staining pattern is an expression of both recruitment for synthesis and block of secretion (“Recruitment‐Secretory Block” “R‐SB” phenomenon). In PiMZ individuals, the secretory block affects selectively and exclusively the Z fraction of AAT. At the EM level the vast majority of the retained protein is found in the RER, which represents the major and the earliest site of storage. Viewed in the framework of present knowledge of glycoprotein biosynthesis, the results of this study shed further light on the nature and cellular site of the Z AAT defect.
Acute liver biopsy lesions in early autoimmune (“lupoid”) chronic active hepatitis
Authors: Lefkowitch Jay H. , Apfelbaum Terri F. , Weinberg Lee , Forester Gary
Published: August 2010

ABSTRACT—We studied two female patients with autoimmune (“lupoid”) chronic active hepatitis whose liver biopsies at initial presentation showed the unusual features of an acute hepatitis. Centrilobular hepatocyte swelling and multinucleation, acidophilic degeneration, cholestasis, mild fatty change and bile duct damage in one case resembled lesions of non‐A, non‐B hepatitis. Lobular and portal infiltrates of plasma cells with piecemeal necrosis suggested transition to chronicity as well as an autoimmune component. This was additionally supported by the presence of hypergammaglobulinemia and auto‐antibodies in both patients. We conclude that liver biopsy features in the acute presentation of lupoid hepatitis may be difficult to distinguish from those seen in acute hepatitis due to virus or drugs.
Murine monoclonal antibodies against „liver specific lipoprotein” (LSP) defining three antigenic sites which differ in tissue‐ and species‐distribution and subcellular location
Authors: KENNA J. G. , MAJOR G. N. , LAMBERT K. J. , MCFARLANE I. G. , WILLIAMS R.
Published: August 2010

ABSTRACT— The tissue and species cross‐reactivity of three monoclonal antibodies against human liver‐specific lipoprotein (LSP), as well as the subcellular locations of the respective target antigens, has been investigated using an enzyme‐linked immunosorbent assay (ELISA). Antibody D6 was widely tissue cross‐reactive and bound to human and rabbit but not rat, mouse or guinea pig tissues. This antibody bound to a particulate antigen localized in the microsomal fraction of rabbit liver, and distinct from enzyme markers for plasma membrane (5′‐nucleotidase) and endoplasmic reticulum (glucose‐6‐phosphatase) in its sedimentation properties on sucrose density gradients. Antibody A9/63 bound to human liver and pancreas, but not kidney, spleen, adipose tissue, skeletal muscle, small intestine or heart, and also bound only to human and rabbit tissues. This antibody bound to a particulate antigen in pancreas, but a soluble antigen in liver. Antibody B20 bound to all tissues from all species tested, with the exception of guinea pig, and bound to particulate antigens in adipose tissue and pancreas but soluble antigens in other tissues (including liver). In addition to emphasizing the immunochemical complexity of LSP, these experiments demonstrate the suitability of monoclonal antibodies for analysis of its constituent antigens.
Cytoprotective effect of prostaglandins on isolated rat liver cells
Authors: GUARNER FRANCISCO , FREMONT‐SMITH MAURICE , PRIETO JESUS
Published: August 2010

ABSTRACT— In vitro studies were carried out on isolated rat hepatocytes to examine further the proposed cytoprotective actions of prostaglandins (PG) using carbon tetrachloride (CCl4) as the toxic agent. Isolated hepatocytes, prepared by collagenase, were cultured in Leibowitz‐15 medium. Following preincubation, CCl4(300 or 150 μg/ml) was added to the hepatocytes. Treatment with Indomethacin (INDO), 16, 16‐dimethyl‐PGE2(PGE2) and prostacyclin (PGI2) was assayed in the cultures. Cell damage was measured by lactic dehydrogenase (LDH) release. 6‐keto‐PGF1α was measured in the supernatant by direct radioimmunoassay. The results showed PGI2 (30.0 ng/ml) treatment 30 min after CCl4(300 μg/ml) addition to be highly protective (p<0.001 versus CCl4 control). PGE2(3 ng/ml) showed similar protection (p<0.001). INDO (2 μg/ml) following CCl4(150 μg/ml) demonstrated increased cell death (p<0.001). INDO (0.5 μg/ml) reduced 6‐keto‐PGF1α production (p<0.05). Low dose ethanol (1.5 μg/ ml) increased 6‐keto‐PGF1α production (p<0.05). Ethanol (1.5 μg/ml), added to stimulate endogenous PG production, was cytoprotective when added prior to CCl4 (p<0.01). This protection was suppressed by INDO. Ethanol added after CCl4 was not protective. We conclude that exogenously added PGI2and PGE2 are cytoprotective in this in vitro model and that endogenous PG production may play a protective role in the initial stages of cellular damage.
Association of hepatitis Be antigen (HBeAg) with the core of the hepatitis B virus (HBcAg)
Authors: SLUSARCZYK J. , HESS G. , BOSCHENFELDE K.‐H. MEYER ZUM
Published: August 2010

ABSTRACT— Three substances (pronase E, sodium dodecylsulfate (SDS) and guanidine hydrochloride) with different chemical actions partially convert HBcAg to HBeAg. This process retains the integrity of the HBcAg particle, which was not different between HBcAg subpopulations, and does not generate HBcAg or HBeAg sub‐units. DNA polymerase activity was destroyed by SDS and guanidine hydrochloride, but not by pronase E. Serum HBeAg could not be converted into HBcAg, suggesting that this might be an irreversible process. The data are consistent with the assumption that HBcAg and HBeAg are coded for by the same gene (C gene of the HBV‐DNA).
Chronic hepatitis: a possible etiology of fatty liver
Authors: Bruguera M. , Zambón1 D. , Ros E. , Tápias J. M. Sánchez , Rodés J.
Published: August 2010

ABSTRACT— In a survey of the etiology of hepatic steatosis, none of the known causes of fatty liver was identified in 12 of 137 patients with severe fatty changes (more than 50% of hepatic cells containing fat vacuoles) diagnosed over a 4‐year period. The retrospective analysis of the clinical records of these patients disclosed the absence of symptoms, liver biopsy being performed because of persistent hypertransaminasemia, which had been discovered fortuitously in 10 cases and after acute hepatitis in two. None had HBsAg in serum. In addition to fatty changes, lobular necrosis was found in 11 cases and chronic inflammation of portal tracts in eight. Patients remained asymptomatic and had raised transaminases during a follow‐up ranging from 1 to 3 years. The clinical, biochemical and follow‐up features of these patients closely resemble those of patients with chronic hepatitis in Mediterranean countries. Thus it can be suggested that in some cases fatty liver may be a prominent feature of chronic hepatitis.
Immune mechanisms for hepatic fibrogenesis. T‐lymphocyte‐mediated stimulation of fibroblast collagen production in chronic active hepatitis
Authors: Casini Alessandro , Ricci Oriano Elvio , Paoletti Francesco , Surrenti Calogero
Published: August 2010

ABSTRACT— Lymphocytes can produce soluble factors capable of enhancing fibroblast proliferation and collagen synthesis. T‐lymphocytes, adherent cells and undifferentiated peripheral blood mononuclear cells from patients with HBsAg‐positive chronic active hepatitis and from HBsAg healthy carriers were triggered with purified HBsAg and tested for their ability to enhance collagen production by human dermal fibroblast cultures. Purified HBsAg did not induce any proliferative response in the mononuclear cell cultures. Addition of patient T‐lymphocyte supernates to monolayers of fibroblast consistently resulted in a significant enhancement of collagen production. On the contrary, supernates harvested from adherent cell cultures did not demonstrate any stimulatory activity. We therefore assumed that the observed enhancement of collagen production was probably the result of lymphokine(s) produced by T‐lymphocytes. This fibrogenic factor (or factors), which is released by T‐cells independently of the presence in vitro of HBsAg, is stable at –80°C, not dialyzable and, by Sephadex G‐100 gel filtration, is present in a fraction which collects substances of a molecular weight between 50000 and 100000. Mononuclear cell supernates from HBsAg healthy carriers did not influence fibroblast collagen accumulation. These data emphasize the possible role that lymphokines may play in the pathogenesis of fibrosis during the natural history of chronic liver disease.
Subclinical encephalopathy after portosystemic shunts in patients with non‐cirrhotic portal fibrosis
Authors: Sarin S. K. , Nundy S.
Published: August 2010

ABSTRACT— Cerebral function was studied in patients with non‐cirrhotic portal fibrosis who had no clinically detectable neurological abnormality, 14 before and 29 after a proximal lienorenal shunt operation. In each patient electroencephalography (EEG) and psychometric tests (the number connection test, construction of a five‐pointed star and the reverse counting test) were performed. Psychometric tests were also done in an equal number of matched, healthy controls. Subclinical encephalopathy was diagnosed when any of these tests was abnormal. In the unoperated group the EEG was normal in all patients and there was no difference in the psychometric test results between patients and healthy controls. After portosystemic shunt operations, the EEG was abnormal in 10%, the number connection test in 38%, construction of a five‐pointed star in 19% and the reverse counting test in 30% of the patients. Detection of subclinical hepatic encephalopathy in such a high proportion of operated patients with non‐cirrhotic portal fibrosis suggests that the surgical procedure and its haemodynamic consequences per se could have been responsible.
Biliary elimination of beta‐lactam antibiotics by the isolated perfused rabbit liver
Authors: Brogard Jean‐Marie , Pinget Michel , Dorner Marc , Blickle Jean‐Frédéric
Published: August 2010

ABSTRACT— Biliary elimination of 15 beta‐lactams was studied using a model of isolated perfused rabbit liver. During the perfusion period, the main liver functions were well preserved. The highest biliary concentrations were reached by antibiotics of the penicillin group, and the highest biliary recovery was observed with metampicillin, apalcillin and mezlocillin (46.5, 30.7 and 20.3%, respectively, of the dose administered). This technique was also suitable for estimating the degree of bio‐transformation in the liver of the antibiotics studied.
Functional status of the liver during chronic renal failure: an experimental study in the rabbit
Authors: TVEDEGAARD ERLING , POULSEN HENRIK ENGHUSEN , VILSTRUP HENRIK , THOMSEN HENRIK KLEM
Published: August 2010

ABSTRACT— Quantitative and qualitative measures of liver function were investigated in rabbits with chronic renal failure (CRF) induced 3 months earlier by surgical reduction of renal mass, and compared with a sham‐operated control group. In the CRF group the galactose elimination capacity (GEC) was significantly decreased by 25%, but when related to liver weight the difference was not statistically significant. The clearance of antipyrine was unaffected. The serum activities of alanine aminotransferase, lactate dehydrogenase and alkaline phosphatase were similar in the two groups. The prothrombin index was increased by 20%, and the serum albumin concentration decreased by 9%. By light microscopy no significant morphological changes were found in the livers of the CRF rabbits. The results do not indicate significant changes of the hepatic functional status during moderate chronic renal insufficiency.
The liver in biliary obstruction due to chronic pancreatitis
Authors: DI BISCEGLIE A. M. , PATERSON A. C. , SEGAL I.
Published: August 2010

ABSTRACT— Biliary obstruction is an important complication of chronic calcifying pancreatitis. In this study, liver biopsies were examined to determine the nature and severity of hepatic complications in 23 such cases. The most striking changes were portal tract expansion due to oedema and fibrosis, with proliferation of bile ducts. Although common, these changes were not severe, and no patient had developed secondary biliary cirrhosis. Other features of note were intrahepatic cholestasis, iron overload (56.5%), copper‐associated protein stained with the orcein technique (34.7%) and mild fatty change or perivenular sclerosis in 13%. It is concluded that no serious, irreversible pathological changes occurred in the liver despite clinically marked biliary obstruction.
One sample antipyrine clearance after 90% partial hepatectomy in the rat
Authors: POULSEN HENRIK E.
Published: August 2010

ABSTRACT— Antipyrine clearance was estimated by a one‐sample saliva technique before and after 90% partial hepatectomy in nine rats. For comparison, the hepatic contents of cytochrome P450 and serum alanine amino transaminase activity were determined in vitro. Antipyrine clearance and hepatic cytochrome P450 were reduced according to the reduction in liver weight following hepatectomy. During hepatic regeneration, antipyrine clearance and liver weight increased identically, whereas total cytochrome P450 recovered more slowly, being 71% of initial values at the time when antipyrine clearance and liver weight had recovered. Serum alanine amino transferase activity increased 10–20 times 24 h after hepatectomy, and normalized after 52 h. The hepatic glutathione content per gram liver weight was unchanged during the regeneration, suggesting intact detoxification during hepatic regeneration. This study demonstrates that, although the assessment requires some time, and that a value cannot be attached to a fixed time‐point, the one‐sample antipyrine saliva clearance is a quantitative in vivo estimate of ‘functional hepatic mass’. The test can easily be applied in animal studies where such a measure is requested.
Detection of two forms of HBeAg (free‐and IgG‐bound HBeAg) in patients with HBe antigenemia using staphylococcus bearing protein A
Authors: SAGNELLI EVANGELISTA , TRIOLO GIOVANNI , CHIARAMONTE MARIA , PEINETTI PATRIZIA , FELACO FRANCESCA MARIA , PIETRO FILIPPINI , VERNACE SALVATORE J. , NACCARATO REMO , PARONETTO FIORENZO
Published: August 2010

ABSTRACT— Protein A‐bearing Staphylococcus aureus organisms (STA) were used to separate free HBeAg from IgG‐bound HBeAg. Free HBeAg was detected in the supernate while IgG‐bound HBeAg could be liberated from the pellets using MgCl2 or a glycine buffer. HBeAg was determined by radioimmunoassay and the results expressed as patient's cpm/normal control's cpm ratio (S/N ratio). This ratio was demonstrated to be proportionate to the antigen concentration and used as a titer of HBeAg. Sera of 40 HBsAg‐negative healthy volunteers and 82 HBeAg‐positive patients who were either asymptomatic HBsAg carriers or had various diseases including chronic persistent hepatitis (CPH), chronic active hepatitis (CAH), and renal disease undergoing hemodialysis, were tested for free HBeAg and IgG‐bound HBeAg. Patients with CAH from two different countries were compared. Free HBeAg was detected in all patients but one, IgG‐bound HBeAg was detected with similar prevalences (from 56% to 67%) in HBsAg asymptomatic carriers, hemodialysis patients, CPH and Italian CAH patients. In contrast, all CAH patients from New York, who had frequently been exposed to HBV infection, had detectable levels of IgG‐bound HBeAg, with the highest S/N ratios observed in the study, and frequently showed an unfavorable outcome. In AVH due to HBV and delta agent co‐infection, IgG‐bound HBeAg was detected in two of four patients only in the initial stage of the disease. The data reported indicate that a separate determination of free‐ and IgG‐bound HBeAg may have clinical value.
Percutaneous measurement of portal blood flow in the piglet by continuous thermodilution
Authors: BAURET P. , MIROUZE D. , BORIES P. , THUILE J. , RIQUE J. L. , MARCHAL G. , MICHEL H.
Published: August 2010

ABSTRACT— The continuous thermodilution method was applied to the percutaneous measurement of portal blood flow in the piglet by inserting a thermodilution probe into the portal vein via the transhepatic transvenous route. The method was compared to electromagnetic flowmetry in three piglets; the two methods yielded statistically identical results. The coefficient of variation of the continuous thermodilution measurements was 4%. The method allows portal blood flow measurements that are instantaneous, reliable, reproducible, and repetitive. It was applied to a study of rapid flow variations in piglets receiving an infusion of posterior pituitary extract.
Hepatitis B virus antigen and antibodies in alcoholics. Etiological role of HBV in liver diseases of alcoholic patients
Authors: INOUE KYOICHI , KOJIMA TAKASHI , KOYATA HIROHISA , MATSUI SHINJIRO , AOYAMA KEIICHI , KONDA TAKEHIKO , ICHIDA TAKAFUMI , SASAKI HIROSHI
Published: August 2010

ABSTRACT— A study was carried out to clarify the pathogenetic role of HBV in alcoholic patients with liver diseases. The incidence of serological markers of HBV infection was investigated in these patients and the histological characteristics were compared among the alcoholic patients with and without HBV markers. A high percentage of patients were positive for either HBsAg, anti‐HBs or anti‐HBc. In six of eight patients with positive HBsAg, liver histology showed viral features, but in 23 of 39 patients with positive anti‐HBs and/or low titre anti‐HBc and in 12 of 18 patients with negative HBV markers liver histology showed alcoholic features. From these results it is concluded that HBV presumably plays a major role in the pathogenesis of liver disease in alcoholic patients with persistent HBV infection but not in patients with positive antibodies.
Myeloid metaplasia, perisinusoidal fibrosis, and nodular regenerative hyperplasia of the liver
Authors: DEGOTT CLAUDE , CAPRON JEAN‐PIERRE , BETTAN LOUIS , MOLAS GEORGES , BERNUAU DOMINIQUE , POTET FRANCOIS , FELDMANN GERARD , BENHAMOU JEAN‐PIERRE
Published: August 2010

ABSTRACT— We describe two patients with myeloid metaplasia in whom portal hypertension resulted, not from infiltration of the liver sinusoids by myeloid cells, but from perisinusoidal fibrosis and nodular regenerative hyperplasia of the liver. We hypothesize that myeloid metaplasia induced the development of perisinusoidal fibrosis, which resulted in heterogeneous hepatic tissue blood perfusion, with atrophy of the liver cells in the underperfused areas and nodular regenerative hyperplasia in the normally perfused areas.
Deletion of hyperplastic biliary epithelial cells by apoptosis following removal of the proliferative stimulus
Authors: BHATHAL PRITHI S. , GALL JOHN A. M.
Published: August 2010

ABSTRACT— Regression of bile ductular hyperplasia following elimination of the proliferative stimulus is widely recognised but the mode of deletion of the excess biliary epithelial cells (BEC) is not understood. Apoptosis, a process of cell death distinct from coagulative necrosis, is known to be involved in both atrophy and physiological involution of various organs. Therefore, a time course histological study was made of the frequency of apoptosis among BEC following removal of the proliferative stimulus in two rat models of BEC hyperplasia produced by the feeding of α‐naphthyl isothiocy‐anate (ANIT) for 6 weeks or the ligation of the common bile duct for 5 weeks. In the former, the rats were returned to a normal diet after 6 weeks and in the latter, the total biliary obstruction (TBO) was relieved by a Roux‐en‐Y choledochojejunostomy. As it has been reported that apoptotic bodies in glandular tissues may be extruded into acinar lumina to be lysed or washed away, thereby reducing chances of their detection in histological preparations, in a third experiment bile was collected for 22 h following relief of TBO of 7 days' duration. The centrifuged pellet of bile was studied by electron microscopy. In both models, throughout the 21 days of observation following removal of the stimulus, apoptotic bodies were found between or as phagocytosed bodies within BEC. The frequency of apoptotic bodies peaked at 3 days corresponding with a rapid reduction in the number of BEC during the first 3 days followed by a much slower rate of deletion in the succeeding 18 days of observation. Electron microscopy of the centrifuged pellet of bile revealed apoptotic bodies. It is concluded that deletion of excess BEC during regression of BEC hyperplasia occurs principally by apoptosis.
Hepatocellular carcinoma in Italy: report of a clinical trial with intravenous doxorubicin
Authors: COLOMBO MASSIMO , TOMMASINI MAURIZIO A. , del NINNO ERSI‐LIO , RUMI MARIA GRAZIA , De FAZIO CRISTINA , DIOGUARDI MARIA LAURA
Published: August 2010

ABSTRACT— Sixty‐six patients with hepatocellular carcinoma (HCC) in various stages of hepatic involvement were studied prospectively. Of these, 50 (75%) had associated cirrhosis and 19 (28%) had serum hepatitis B surface antigen (HBsAg). Six (9%) patients were eligible for tumor resection, 34 were selected for doxorubicin chemotherapy (60 mg/m2, i.v., given every 3 weeks, up to a maximum dose of 550 mg/m2), and 26 were followed up without treatment. Untreated patients survived 1–18 months (median 1) after diagnosis. Surgically treated patients survived 1–14 months (median 4.5). In the doxorubicin group, six patients died soon after the first course of treatment, leaving 28 patients to be evaluated. Seven (24.5%) responded to therapy, surviving 2–26 months (median 8.0). Twenty‐one (75.5%) did not respond to chemotherapy and had a median survival of 3.5 months (range: 2–12). Initial performance status and the degree of hepatic impairment were found to be covariates of prognostic significance. The type and severity of drug‐related side‐effects appeared to be comparable to those reported by others. In accordance with previous reports, our patients with HCC often had non‐resectable tumors or responded poorly to chemotherapy. The association between this tumor and cirrhosis might partially account for treatment failure.
Cianidanol therapy for HBe‐antigen‐positive chronic hepatitis: a multicentre, double‐blind study
Authors: Suzuki Hiroshi , Yamamoto Sukeo , Hirayama Chisato , Takino Tatsuro , Fujisawa Kiyoshi , Oda Toshitsugu
Published: August 2010

ABSTRACT— The effect of cianidanol on the HBeAg/anti‐HBe system in 338 patients with HBeAg‐positive chronic hepatitis was studied in a double‐blind, randomised, placebo‐controlled, multicentre clinical trial. 174 patients received cianidanol in a daily dose of 1.5 g for 2 weeks, followed by 2.25 g for a further 14 weeks. 164 patients received a placebo for the same period: patients were followed up for a further 8 weeks. HBeAg and anti‐HBe antibody titers were measured by R.I.A. at 4‐week intervals and the results were expressed as a “cut‐off index” and “inhibition percent”, respectively. Liver function tests were also monitored at the same intervals. The HBeAg titer decreased by at least 50% in 44 of 144 cases treated with cianidanol (21 of 140 cases treated with placebo). The difference was significant (p<0.01). The HBeAg disappeared in 16 of the cianidanol cases and four of the placebo (p<0.05) and a seroconversion was observed in six cianidanol patients and three placebo patients. The mean HBeAg titer in the cianidanol group was significantly lower than that in the placebo group at the end of the 16 weeks of therapy (p<0.05). The patients whose HBeAg titer was lowered were largely those with chronic active hepatitis and had higher initial values of SGPT, SGOT and γ‐globulin than the patients whose HBeAg titers remained unchanged. The mean values for these liver function tests also fell significantly in the former sub‐group. The drug was well tolerated, the only notable side effect being a transient febrile reaction in 13 patients. It is concluded that cianidanol is a useful and well‐tolerated drug for improving the HBeAg/anti‐HBe system in patients with HBeAg‐positive chronic active hepatitis.
Experimental anaerobic liver abscess: observations on treatment
Authors: LUCORE C. L. , McDONALD M. I. , WHARTON M. , DURACK D. T.
Published: August 2010

ABSTRACT— Various treatment modalities for solitary anaerobic liver abscesses were evaluated in a recently‐described rabbit model. In the first phase of the experiment, 35 rabbits with liver abscesses induced with Bacteroides fragilis and Fusobacterium necrophorum were randomized into four groups: surgical drainage alone, drainage plus clindamycin 150 mg IM 8‐hourly, clindamycin alone, and untreated controls. Serum clindamycin concentrations in rabbits were similar to those achieved in humans. The survival of rabbits receiving antibiotic chemotherapy alone was significantly better than controls, whereas the survival of those having surgical drainage with or without chemotherapy was not. However, successful surgical drainage was followed by weight gain in surviving rabbits. In the second phase of the experiment 18 rabbits with abscesses were randomized into the same groups. Aspirates of pus from all rabbits receiving clindamycin were sterile by day 7 of treatment, but high bacterial counts were still present in the abscess cavities of control rabbits and of those undergoing drainage alone. These findings illustrate the application of a new model for pyogenic liver abscess in laboratory investigation. Their relevance to management of human pyogenic liver abscesses remains to be assessed.
Hepatitis B virus infection in porphyria cutanea tarda
Authors: ROCCHI EMILIO , GIBERTINI PAOLO , CAS‐SANELLI MARCO , PIETRANGELO ANTONELLO , JENSEN JAN , VENTURA EZIO
Published: August 2010

ABSTRACT— Serum markers of hepatitis B virus (HBV) infection were determined in 82 patients with porphyria cutanea tarda (PCT). Pathogenetic factors (alcohol, thalassemia minor, drugs) and clinical and histologic findings of PCT were taken into account. The prevalence of HBV infection was very high (70.7%). Hepatitis B surface antigen (HBsAg) was positive in 14 patients (17%). Eight patients had HBV infection as the only documented acquired factor. The clinical picture and histologic findings were aggravated by HBV infection; primary hepatic carcinoma occurred in four patients with HBV infection. Liver siderosis was histologically documented in 82.6% of cases, serum ferritin was pathologically increased in 91%, confirming the role of iron overload in PCT. A correlation (p<0.02; chi‐squared method) was found between increased serum ferritin levels and HBV infection, suggesting a possible relationship between liver siderosis and HBV clearance. HBV infection appears to be a relevant additional factor in the pathogenesis of PCT liver disease.
Cost‐effectiveness of introducing a third‐generation test for HBsAg in Danish blood donors
Authors: WANTZIN P. , SKOVGAADR L. , TYGSTRUP N. , NIELSEN J. O. , SOERENSEN H. , DYBKJAER E.
Published: August 2010

ABSTRACT— Owing to the low incidence of hepatitis B in Denmark, screening of blood donors for HBsAg has mostly been done by immunoelectroosmophoresis (IEOP). The purpose of the present study was to carry out a cost‐effectiveness analysis prior to the introduction of a third‐generation test for HBsAg in Danish blood donors. The analysis was performed on data from a subsequent screening of 48 750 blood units by radioimmunoassay (RIA) 3 weeks after donation. The RIA‐pos., IEOP‐neg. blood donors identified in the study were evaluated by a follow‐up examination, and the recipients of RIA‐pos., IEOP‐neg. blood units were monitored for up to 9 months as to the development of acute hepatitis B. The study shows that the estimated cost for each prevented case of transfusion‐associated hepatitis B in Denmark is US$ 1100 when screening donors not previously tested by a third‐generation technique, and US$ 240 000 when screening donors tested before by this technique.
Significance of IgM antibody to hepatitis B core antigen in a Greek population with chronic hepatitis B virus infection
Authors: Tassopoulos Nicolaos C. , Sjogren Maria H. , Ticehurst John R. , Engle Ronald E. , Roumeliotou‐Karayannis Anastasia , Gerin John L. , Purcell Robert H. , Papaevangelou George
Published: August 2010

ABSTRACT— IgM antibody to hepatitis B core antigen (IgM anti‐HBc) may indicate an active immune response to persistent infection with hepatitis B virus (HBV). We studied 186 Greek HBsAg carriers for IgM anti‐HBc and attempted to correlate it with other HBV and hepatitis delta virus (HDV) markers. Overall, IgM anti‐HBc was detected more frequently than HBV DNA in this population (50% vs 34, p<0.001); this was also true for the 149 of the 186 HBsAg carriers with antibody to hepatitis B e antigen (anti‐HBe) (48% vs 22%, p<0.001). The opposite was found in the carriers positive for hepatitis B e antigen (HBeAg): HBV DNA was observed in 93% and IgM anti‐HBc in 64% of the cases (p<0.05). The detection of these markers was independent of sex. Serum alanine aminotransferase (ALT) levels were significantly more elevated in patients with positive tests for IgM anti‐HBc and HBV DNA than in patients positive only for HBV DNA (p<0.001) irrespective of their HBeAg or anti‐HBe status. Moreover, the detection of elevated ALT was independent of the intensity of the HBV DNA hybridization signal. Antibodies to hepatitis delta antigen (HDAg) were only found in 4 (2.4%) of 167 patients tested.
Brain cholecystokinin and vasoactive intestinal polypeptide: immunoreactivity in rabbits with hepatic coma
Authors: Meryn S. , Bauman W. A. , Pappas S. C. , Ferenci P. , Jones E. A.
Published: August 2010

ABSTRACT— Recent studies have suggested that decreased excitatory neurotransmission in the brain may contribute to the overall neural inhibition which characterizes the syndrome of hepatic encephalopathy (HE), and that vasoactive intestinal polypeptide (VIP) and cholecystokinin (CCK) may promote neural excitation in the brain. To determine if brain levels of these neuropeptides are altered in HE, measurements were made of the concentrations of immunoreactive VIP (iVIP) and immunoreactive CCK (iCCK) in cerebral cortex, cerebellum and hypothalamus isolated from normal rabbits and rabbits with galactosamin‐induced hepatic coma. Hepatic coma was associated with reduced concentrations of iVIP, small molecular weight iCCK and large molecular weight iCCK in the cerebral cortex but not in the cerebellum or hypothalamus. These findings are compatible with decreased VIP‐ and CCK‐mediated neural excitation occurring in the syndrome of HE.
Long‐term follow‐up of 60 patients with chronic hepatitis B. II. Hepatitis B virus DNA in serum correlated to the hepatitis Be‐system and presence of delta superinfection
Authors: Hansson B. G. , Lindh G. , Weiland O. , Glaumann H. , von Sydow M. , Nordenfeldt E.
Published: August 2010

ABSTRACT— Forty‐six patients with liver biopsy‐documented chronic hepatitis B were followed for a mean period of 44 months. A total of 200 serum samples from these patients was analyzed for the presence of hepatitis B virus DNA (HBV‐DNA). The results were correlated to the HBeAg/anti‐HBe status and to the presence of anti‐delta as a marker for delta superinfection. In the initial serum samples HBV‐DNA was detected in the vast majority of the patients independent of the HBeAg/anti‐HBe results and whether the patients were superinfected by delta agent or not. During the complete follow‐up period, HBV‐DNA was detected in 88% of those patients who were positive for HBeAg, irrespective of the presence or absence of a simultaneous delta infection. When anti‐HBe positive, 79% of the patients with anti‐delta had detectable HBV‐DNA in their sera, while only 43% of those negative for anti‐delta were positive for HBV‐DNA. The results indicate a high prevalence of virus release into the blood of patients with chronic hepatitis B, especially among patients positive for HBeAg and among those anti‐HBe positive patients who have a delta superinfection.
Histological and ultrastructural examination of the intrahepatic biliary tree in primary sclerosing cholangitis
Authors: Nakanuma Yasuni , Hirai Nobuyuki , Kono Naoko , Ohta Goroku
Published: August 2010

ABSTRACT— Intrahepatic bile ducts were examined histologically and ultrastructurally in wedge‐biopsied liver specimens from three patients with primary sclerosing cholangitis. Bile ducts with periductal concentric fibrosis, which is a characteristic finding in primary sclerosing cholangitis, revealed ultrastructurally finger‐like projections or fine undulations of the basal free surfaces with markedly duplicated basal lamina. The lamina was collared by a layer of elongated fibroblasts and thickened bundles of collagen fibers outwards. These changes were consistently found in all sizes of ducts examined, and might be related to progressive periductal fibrosis. Serial section observations showed that some severely affected ducts actually disappeared when accompanying severe periductal fibrosis. It would therefore appear that progressive periductal fibrosis may interrupt fluid and nutrient exchange between the bile duct epithelia and peribiliary capillary plexus, followed by obliteration of the biliary lumina. Although the bile ducts showed segmentally periductal lymphocytic infiltration and, ultrastructurally, point contacts between infiltrating lymphocytes and biliary epithelial cells were observed occasionally, the exact role of infiltrating lymphocytes in the pathogenesis of primary sclerosing cholangitis remains unclear.
State of hepatitis B viral DNA in the liver of patients with hepatocellular carcinoma and chronic liver disease
Authors: Hada Hajime , Arima Terukatsu , Togawa Kazumi , Okada Yoshio , Morichika Shigeru , Nagashima Hideo
Published: August 2010

ABSTRACT‐ In order to clarify the relationship between the integration of hepatitis B virus (HBV) DNA and human hepatocellular carcinoma (HCC), the states of HBV DNA in liver tissues were examined by the Southern blot hybridization procedure. Integration of HBV DNA was found in 12 of 25 HCC cases and 5 of 12 cirrhotic cases. Of these 17 cases, 11 were positive for serum hepatitis B virus surface antigen (HBsAg) and the remaining six were positive for more than one of the serum HBV‐related antibodies. In all three cases of chronic hepatitis and 18 controls, integration of HBV DNA could not be detected. Free viral DNA was found in 12 of 15 cases with serum HBsAg. One patient without serum HBsAg also had free viral DNA in the liver. Integration of HBV DNA could be observed in HCC cases positive for serum HBsAg at the highest frequency. However, there was one HCC case from an HBsAg carrier in whom integration of HBV DNA might not have a causal effect on malignant transformation, because integrated HBV DNA could be detected only in a non‐tumor region. Since integrated HBV DNA could not be detected in 13 of 25 HCC cases, Other etiologic factors than the integration of HBV DNA must also be taken into consideration for HCC.
Portal hypertension: a permissive factor only in the development of ascites and variceal bleeding
Authors: Rector William G.
Published: August 2010

ABSTRACT‐ It is controversial whether the occurrence of ascites and gastrointestinal bleeding in cirrhosis is related to the severity of portal hypertension. Portal pressure was examined in 124 unselected patients with portal hypertension due to chronic liver disease to evaluate this issue. Portal pressure was less in patients without complications of chronic liver disease (11.7 ± 3.0 mmHg, n = 16) as compared to patients who had bled from varices or erosive gastritis (16.6 ± 3.4 mmHg, p < 0.001, n = 49), who had ascites (16.2 ± 3.0 mmHg, p < 0.001, n = 78) or both (16.5 ± 3.0 mmHg, p < 0.001, n = 19). Portal pressure was similar in patients bleeding from varices and erosive gastritis (16.7 ± 3.4 mmHg, n = 43; vs 16.2 ± 4.0 mmHg, n = 6, respectively) and in patients with refractory and nonrefractory ascites (16.2 ± 3.5, n = 21; vs 16.2 ± 3.5 mmHg, n = 57). The lowest portal pressure recorded in a patient with variceal bleeding was 9.0 mmHg. The lowest portal pressure recorded in a patient with ascites was 8.0 mmHg. Esophageal varices (graded 0–4 at endoscopy) were larger in patients with a history of bleeding from esophageal varices as compared to patients without such a history (3.2 ± 0.7 vs 2.0 ± 0.9, p < 0.001). Serum albumin concentration was greater in patients without ascites as compared to patients with ascites (33 ± 5 vs 26 ± 5 g/1 p < 0.001) but was similar in patients with refractory and nonrefractory ascites (25 ± 7 vs 26 ± 5 g/1, respectively). These data suggest that portal hypertension is a permissive factor only in the development of ascites and gastrointestinal bleeding in patients with chronic liver disease.
Biliary lipid composition in patients with non‐cirrhotic portal fibrosis – a comparison with compensated cirrhosis of the liver
Authors: Sarin S. K. , Lal K. , Sachdeva G. , Nanda R. , Tandon R. K.
Published: August 2010

ABSTRACT— Patients with non‐cirrhotic portal fibrosis (NCPF) are known to have mild hepatic functional abnormalities. To study the biliary lipid composition in these patients, duodenal bile was collected from 18 patients with NCPF, 15 patients with non‐alcoholic compensated cirrhosis of the liver and 18 matched, non‐obese, healthy control subjects. There were no significant differences in the mean (± SD) concentrations of cholesterol, phospholipids and bile acids in patients with NCPF and healthy controls. On the other hand, patients with cirrhosis had significantly lower concentrations of all the three biliary lipids as compared with the NCPF patients and controls (p<0.05). The cholesterol solubilizing capacity of the bile was the same in NCPF patients, cirrhotics and controls. It is concluded that the relative proportions of the three biliary lipids remain unchanged in patients with NCPF despite mild hepatic derangement.
Differential diagnosis of jaundice: applicability of the Copenhagen Pocket Chart proved in Stockholm patients
Authors: Lindberg Greger , Thomsen Carsten , Malchow‐Møller Axel , Matzen Peter , Hilden Jorgen
Published: August 2010

ABSTRACT— This paper shows that an algorithm for differential diagnosis of jaundice developed in Denmark has been successfully transferred for use in a Swedish hospital. The algorithm, which is based on data from nearly 1000 patients, utilises 21 items of information from the medical history, physical examination and blood chemistry. The algorithm recognises four diagnostic groups: benign obstructive jaundice, malignant obstructive jaundice, acute non‐obstructive jaundice, and chronic non‐obstructive jaundice. To each item of information, a score is attached reflecting its weight of evidence. Summing the scores for the symptoms and signs that are present leads to a probabilistic statement about the diagnosis. Because of missing data in the Swedish patient material, three of the items were excluded from the original algorithm. Corrections were made for differences in the distribution of diseases. In reclassification of 985 Danish patients the modified algorithm's “best bid”, i.e. the diagnosis given the highest probability, was correct in 78% of cases. More important, 93% of the cases given a “confident” diagnosis (probability >0.80) were correct. The corresponding figures when the algorithm was applied to Swedish patients were 76% and 93%. respectively. In both series the predicted probabilities were matched by a corresponding proportion of actual diagnostic hits. It is concluded that the algorithm leads to reliable estimates of diagnostic probabilities in jaundice and that the algorithm seems to work well in Sweden also.