bluuebunny/crossref_metadata_2025 huggingface dataset:
Giant mitochondria in the alcoholic liver diseases – their identification, frequency and pathologic significance
Authors: Uchida Toshikaza , Kronborg Ian , Peters Robert L.
Published: August 2010

ABSTRACT— Three types of giant mitochondria have been described in hepatocytes, and we have investigated their ultrastructural features and occurrence in alcoholic liver disease. Type I mitochondria are spherical, with a paucity of cristae. Type II are elongated and have long crystalline insertions. Type III are relatively smaller and often bizarre in shape, containing multiple crystalline insertions. We defined megamitochondria as spheroidal giant mitochondria with a diameter roughly more than one third of the hepatocyte nucleus and visible under light microscopy. Type I was the most common form of megamitochondria in livers with ALD. Megamitochondria were present in livers of 58 (27.8%) of 209 consecutive patients with alcoholic liver disease, compared with 1 (0.7%) of a series of 145 patients with non‐alcoholic liver disease. The frequency and occurrence of megamitochondria varied in different types and/or stages of alcoholic liver disease. In particular, livers with alcoholic foamy degeneration had significantly increased frequency and numbers of megamitochondria compared to other patterns of alcoholic liver disease. The ultrastructural studies showed that hepatocytes containing Type I mitochondria frequently had other damaged organelles and extensive focal cytoplasmic degradation. Enzyme histochemistry showed the foamy hepatocytes containing Type I had markedly decreased staining for glucose‐6‐phosphatase and slightly decreased staining for succinic dehydrogenase activities, while the hepatocytes with Type II or III had normal staining. In general, Type I giant mitochondria seem more characteristic to alcoholic liver disease, or conditions that produce similar hepatic morphology. It is particularly seen in alcoholic foamy degeneration and may be part of decompensation of the hepatocytes, while Types II and III occurred in hepatocytes of both alcoholic and non‐alcoholic patients and had preserved function.
Production and preliminary characterization of monoclonal antibodies to human liver‐specific lipoprotein (LSP)
Authors: Lambert K. J. , Major G. N. , Welsh C. J. R. , Ryall J. E. , McFarlane I. G. , Williams Roger
Published: August 2010

ABSTRACT— Monoclonal antibodies (mc/anti‐LSP) have been prepared by polyethylene glycol fusion of P3/NSI/Ag4–1 myeloma cells with spleen cells from Balb/c mice hyperimmunized with human liver‐specific membrane lipoprotein (LSP). Ten hybridomas, cloned by limiting dilution, produced mc/anti‐LSP reacting (by ELISA) with human LSP but not with normal human plasma proteins nor with a variety of other proteins likely to co‐purify with LSP. Three of these (A15/7, A9/63 and B20), producing high‐titre IgG1 mc/anti‐LSP, were biosynthetically radiolabelled and used as index antibodies. By competitive inhibition of binding of the index antibodies to LSP in an immunoradiometric assay, the ten hybridoma products were classified into four distinct groups according to their specificities for different epitopes in LSP. None of the index antibodies reacted, on ELISA, with glutaraldehyde‐fixed PLC/PRF/5, Chang, Daudi or HSB‐2 cell lines nor with human peripheral blood leucocytes. However, A15/27 (but not A9/63 or B20) reacted with saponin‐permeabilized PLC/PRF/5 and Chang cells and also with rabbit LSP. The results emphasize the polyantigenic nature of LSP and indicate that at least one of the mc/anti‐LSP (A15/27) recognises a species crossreactive antigen that is present in liver‐derived cell lines.
Decrease in suppressor/cytotoxic T‐cells with histamine receptors in patients with chronic active hepatitis
Authors: Colombo Massimo , Rumi Maria Grazia , Roffi Luigi , Del Ninno Ersilio
Published: August 2010

ABSTRACT— A fluorescence assay was employed to measure the levels of circulating suppressor/cytotoxic T cells with membrane receptors for histamine (H + T cells) in 33 patients with chronic active hepatitis, in seven patients with metabolic and vascular liver disorders and in 25 healthy individuals. The H + T cells were decreased in patients with CAH (4.6 ± 2.2 cells/mm3 vs 16 ± 3.9 cells/mm3; p<0.001), but were normal in patients with metabolic or vascular liver diseases (17.6 ± 6 cells/mm3 vs 16 ± 3.9 cells/mm3; NS). Patients with HBsAg‐negative CAH had fewer circulating H + T cells than those with HBsAg‐positive CAH (p < 0.05). The same was true for patients with cirrhosis as compared to those without. The lymphocyte alterations were independent of the nature and course of CAH, but correlated inversely with the serum levels of gammaglobulins and with the histological features of hepatic inflammation (p<0.05). Like other sets of lymphocytes, the H + T cells in CAH may have locally either immunomodulatory or cytotoxic effects. In analogy with other immune disorders (histiocytosis X, atopic dermatitis), one might speculate that the alterations in H + T cells in CAH represent derangement of the immunoregulatory cell network. The absence of systemic features of autoimmunity in viral CAH correlates with the demonstration that H + T cells exert their immunoregulatory effects at the sites of inflammation where histamine is being released.
Value of serum immunoglobulins in the diagnosis of liver disease
Authors: Martin David M. , Vroon David H. , Nasrallah Salah M.
Published: August 2010

ABSTRACT— Serum immunoglobulins were determined in 145 consecutive patients with biopsy‐proven steatosis, alcoholic hepatitis, alcoholic hepatitis with fibrosis, alcoholic hepatitis with cirrhosis, inactive cirrhosis, chronic active alcoholic hepatitis, chronic active hepatitis, primary biliary cirrhosis and nonspecific hepatitis. IgM was both a sensitive (90.5%) and specific (86.2%) marker for primary biliary cirrhosis, and mean IgM levels were higher in primary biliary cirrhosis than in other diagnostic categories (p < 0.05). IgA levels were most commonly elevated in alcoholic liver disease (p < 0.005). IgA detected 95% of alcoholic disease, but was poorly specific (41.1%). A trend of rising IgA with increasing severity of alcoholic injury was observed, but the differences were not significant. IgG was most commonly elevated in chronic active hepatitis and alcoholic hepatitis with cirrhosis, but the IgG values did not differ significantly from those found in other diagnostic categories. Our results substantiate assertions of a diagnostic sensitivity for elevated IgA in alcoholic liver disease and IgM in primary biliary cirrhosis. With the exception of IgM in primary biliary cirrhosis, however, serum immunoglobulins are not specific markers of liver histology.
Influence of long‐term anticonvulsant treatment on liver ultrastructure in man
Authors: Pamperl H. , Gradner W. , Fridrich L. , Pointner H. , Denk H.
Published: August 2010

ABSTRACT—In 35 patients on long‐term anticonvulsant treatment (7–35 years, x̄ = 19.6 years), various liver enzymes were measured. In 32 cases (91.4%), elevated levels of serum‐gamma‐glutamyl‐transpeptidase (GGT) were found. Liver biopsy was performed in five of 13 patients with GGT levels of >60 U/1 (75–257, x̄ = 123 U/1). Light microscopy showed a minimal steatosis and fine granular appearance of hepatocytes in two cases, and a slight portal fibrosis in one case. Two cases showed an unremarkable histology. Electron microscopy revealed signs of enzyme induction as overall swelling of the smooth endoplasmic reticulum and additionally a dilatation of the rough endoplasmic reticulum in all five specimens. No signs of liver damage or disturbance of liver function could be observed.
Binding activity of HBsAg particles from chronic HBsAg carriers to polystyrene beads coated with polymerized human serum albumin: diagnostic relevance of the assay
Authors: Hopf U. , Möller B. , Schermer M. , Lobeck H.
Published: August 2010

ABSTRACT—The binding activity of HBsAg particles to polystyrene beads coated with polymerized human serum albumin (pHSA) was studied by radioimmunoassay in 48 patients with chronic HBsAg carrier state. The pHSA assay was positive in all 16 HBeAg‐positive patients and in 22 HBeAg‐negative HBsAg carriers with chronic hepatitis. Asymptomatic, “healthy” HBsAg carriers did not react in the pHSA assay. Mean binding activity was significantly higher in the HBeAg‐positive group (P/N ratio 39.3) than in HBeAg‐negative carriers with chronic hepatitis in various stages (P/N ratio 19.2). Fractionation of five representative HBeAg‐positive sera by density gradient ultracentrifugation in cesium chloride yielded three peaks of HBsAg particles at 1.28, 1.22 and. 1.18 g/ml. The first HBsAg peak contained Dane particles and exhibited strong reactivity in pHSA assay. The second and third peaks, both consisting of 22 nm particles, reacted differently in pHSA assay. While about half of the HBsAg particles in the second peak were bound, reaction in the third HBsAg peak was predominantly negative. Intrahepatic HBsAg was detectable with the immunofluorescence technique in 19 of 22 HBsAg carriers. HBcAg was found in seven of 10 HBeAg‐positive cases and in three of 16 HBeAg‐negative patients with chronic hepatitis. The diagnostic value of pHSA assay might be seen in differentiation between HBeAg‐negative chronic HBsAg carriers with liver disease or “healthy” carrier state.
Kinetics of urea synthesis and alanine uptake by perfused rat livers
Authors: HANSEN JENS ANKER , VILSTRUP HENDRIK
Published: August 2010

ABSTRACT—Eight livers of 200 g rats were isolated and perfused in a single pass system with a semi‐synthetic medium to which alanine was added to concentrations from 0.5 to 15 mmol/l. In each liver, 4–5 sets of urea synthesis rate and alanine uptake rate at different alanine concentrations were measured. The urea synthesis rate in relation to the alanine concentration was compatible with substrate inhibition kinetics. The kinetic constants were (mean ± SD): Vmax= 10.34 ± 3.41 μmol urea‐N/(min 100 g b.w.), Km= 1.56 ± 0.67 mmol/1, and Ki= 5.35 ± 2.44 mmol/1. The alanine uptake rate followed Michaelis‐Menten kinetics with the constants (mean ± SD) Vmax = 7.51 ± 1.68 μmol/ (min 100 g b.w.) and Km= 2.14 ± 1.04 mmol/1. The constants were assessed by nonlinear iterative regression analysis. Urea synthesis exceeded alanine uptake at alanine concentrations below 2 mmol/1, and was smaller at higher concentrations. In two experiments, alanine metabolites were measured. The glucose production rate in relation to the alanine concentration suggested substrate inhibition. At high alanine concentrations, ammonia, lactate and pyruvate were released by the livers. The results indicate that whole liver urea synthesis and gluconeogenesis is inhibited by high blood alanine concentrations, in contrast to alanine uptake.
Prognostic value of hepatitis B core antigen (HBcAg) expression in the liver of children with chronic hepatitis type B
Authors: BORTOLOTTI F. , ALBERTI A. , CADROBBI P. , RUGGE M. , ARMIGLIATO M. , REALDI G.
Published: August 2010

ABSTRACT— During a prospective follow‐up study of 65 children with chronic hepatitis B, the HBcAg expression pattern in the liver was investigated, by immunofluorescence, in relation to biochemical and histological features and to the evolution of the disease. HBcAg was detected in 50 (77%) cases, with a diffuse pattern of distribution (more than 60% positive nuclei) in 20 cases, and with a focal pattern (less than 40% positive nuclei) in 30 cases. The diffuse pattern significantly prevailed in younger children, while the focal pattern was more frequent in children beyond 10 years of age. Transaminase levels were higher and histological features of activity were more frequent in patients with the focal pattern than in those with a diffuse pattern. Twenty‐five hepatitis B e antigen (HBeAg) positive children, all initially HBcAg positive, were followed prospectively for 24 months. Seroconversion to anti‐HBe, with subsequent normalization of transaminases, occurred in 72% of cases with a focal pattern, but only in 21% of those with a diffuse HBcAg pattern. In four patients transition from the diffuse to the focal pattern was observed during follow‐up. These results suggest that, in children with chronic hepatitis B, the diffuse HBcAg pattern in the liver might reflect an earlier phase of infection. In HBeAg positive cases the focal HBcAg pattern may represent a prognostic marker of short‐term favourable evolution of the disease.
Chronic human schistosomiasis mansoni ‐ schistosomal antigen, immunoglobulins and complement C3 detection in the liver
Authors: De Brito T. , Shimizu Sumie Hoshino , Yamashiro Edite , Da Silva L. C.
Published: August 2010

ABSTRACT— The distribution of schistosomal antigen, immunoglobulins and complement C3 was studied by IF stain in 26 biopsies of human liver from 21 cases of hepatosplenic and five of intestinal schistosomiasis mansoni. Schistosomal antigen and immunoglobulins, chiefly of the IgG class and in a lesser intensity complement C3, were seen focally as scanty deposits in cells of the sinusoidal wall. They probably correspond to antigen‐antibody insoluble large aggregates which are being removed by local cells of the mononuclear phagocyte system. Gamma globulin of the IgG class and antigens were also present in the granuloma around S. mansoni eggs and dead worms in the human liver. During the early phase of the granulomatous reaction the structure was not efficient enough to wall off completely the antigen, which is seen in cells at the center of the granuloma. As the granuloma matures, antigen demonstration becomes restricted to the miracidium, and immunoglobulins are observed mainly at the periphery. The kinetics of the granuloma formation with intralesional antibody presence promote a progressive antigen neutralization.
Liver disease and its effect on haemostasis during liver transplantation
Authors: Haagsma Elizabeth B. , Gips Chris H. , Wesenhagen Hans , Van Imhoff Gustaaf W. , Krom Ruud A. F. ,   Liver Transplantation Group, Groningen
Published: August 2010

ABSTRACT— In a prospective study involving 25 consecutive adult orthotopic liver transplantation (OLT) patients, of whom 23 had cirrhosis, we have related pretrans‐plantation recipient parameters to blood loss during transplantation. In phase I (explantation of diseased liver) blood loss was 0.1–7.2 1, in phase 3 (following restoration of the portal blood flow after implantation) 0.1–39.7 1, and total blood loss was 1.6–47.2, median 9.21. Five patients (20%) died from causes directly related to defective haemostasis during the operation. Pretransplantation cholinesterase, antithrombin III and albumin correlated most strongly with blood loss in phase 1; a history of ascites, antithrombin III and cholinesterase levels correlated with blood loss in phase 3, and a history of ascites, urinary sodium and antithrombin III with total blood loss. Cholestasis did not influence blood loss. Portal hypertension per se presumably played only a restricted role. A pretransplant 24‐h urinary sodium excretion of 10 mmol or less and a serum sodium of 132 mmol/1 or less were highly predictive of blood loss exceeding 10 1 during OLT. Urinary sodium determination under test conditions and serum sodium measurement should already be part of the assessment of potential OLT candidates by the referring hospital.
Estimation of the hepatic blood “flow” by galactose plasma clearance in patients with liver disease
Authors: Zaramella Maria Grazia , Vallini Roberto , Tiribelli Claudio
Published: August 2010

ABSTRACT— Following intravenous administration of 500 mg/kg b.wt. galactose, Galactose Elimination Capacity (GEC, mg/min/kg) was determined in 24 subjects with chronic non‐cirrhotic liver disease (CLD), 33 with liver cirrhosis and 11 controls. GEC was significantly (P<0.01) reduced in both CLD and cirrhosis. A statistically significant difference (P<0.01) was present between these two groups. Following the plasma disappearance curve at concentrations below 1.25 mmol/1, at which the extraction coefficient is assumed to be equal to one, the “Efficient Hepatic Blood Flow” (EHBF, ml/min) was determined in 11 consecutive cirrhosis patients, seven patients with CLD and 11 controls. EHBF was normal or slightly reduced in CLD as compared to controls (1046 ± 216 vs. 1471 ± 156 ml/min, mean ± SEM, n.s.) whereas it was markedly reduced in cirrhosis (846 ± 96 ml/min, mean ± SEM, p<0.001). Interestingly, a significant linear correlation (r = 0.757, p<0.001) was present between EHBF and the plasma clearance of sulfobromophthalein. No correlation was present, on the other hand, between the value of GEC and that of EHBF. These data indicate that after a single intravenous injection of galactose, the hepatic blood flow passing through the enzymatically active parts of the liver (i.e. excluding shunts) can be measured.
DNA content of hepatocytes in various stages of liver cirrhosis
Authors: Koike Yuriko , Kamijyo Kensuke , Suzuki Yoichi , Kiyosawa Kendo , Nagata Atsuo , Furuta Seiichi , Nagata Tetsuji
Published: August 2010

ABSTRACT— In order to search for some parameters that would make it possible to predict a potentially high risk of evolution from liver cirrhosis to hepatocellular carcinoma (HCC), the DNA content of hepatocytes in patients with liver cirrhosis with or without development to HCC was investigated by means of microspectrophotometry in Feulgen‐stained specimens. In patients without development of HCC in more than 5 years of follow‐up, 90% or more of tested hepatocytes were diploid, whereas in patients with liver cirrhosis who developed HCC within 3 years the frequency histogram of nuclear DNA content was widely spread from diploid to hyperpolyploid with a small peak of triploid. Furthermore, in the latter group of patients, many of the binucleate cells had different DNA contents in each paired nucleus. In noncancerous portions of HCC, the ploidy histogram of nuclear DNA content was widely spread from diploid to polyploid with different DNA contents of each paired nucleus in binucleate cells, without the small peak of triploid. These results suggest that the deranged cell kinetics of hepatocytes in cirrhosis may be considered to be a state of potentially high risk for the evolution of HCC, and that a patient with liver cirrhosis with such an abnormal hepatocyte DNA content should be followed up carefully for the early diagnosis of HCC.
Acute viral hepatitis superimposed on alcoholic liver cirrhosis: clinical and histopathologic features
Authors: FELLER AXEL , UCHIDA TOSHIKAZU , RAKELA JORGE
Published: August 2010

ABSTRACT— Of 20 patients with alcoholic liver cirrhosis and a superimposed episode of acute viral hepatitis, 12 developed hepatic encephalopathy or ascites or both. Four died of hepatic failure. Seventeen patients had received blood transfusions within 6 months before the acute hepatitic episode. Two patients were HBsAg‐positive; the other 18 were presumptively diagnosed as having non‐A, non‐B hepatitis. However, hepatitis A virus infection was excluded in only three of the 18 patients. Histologic examination performed in 13 cases disclosed necrotizing inflammatory activity, which is commonly observed in acute viral hepatitis. The distinctive histologic feature was a meager regenerating activity. We conclude that patients with alcoholic cirrhosis complicated by acute viral hepatitis frequently develop hepatic failure and have a high fatality rate (20% in our series).
Mortality of alcohol abusing men prospectively assessed in relation to history of abuse and degree of liver injury
Authors: ORHOLM MARIANNE , SØRENSEN THORKILD I. A. , BENTSEN KIRSTEN , HØYBYE GERDA , EGHØJE KNUD , CHRISTOFFERSEN PER
Published: August 2010

ABSTRACT— A prospective evaluation of mortality in relation to a broad range of alcoholic abuse and biopsy‐assessed stage of alcoholic liver injury was carried out by following 315 men admitted to hospital for various medical disorders. During 10–13 years, 184 patients (58%) died, which, according to national mortality statistics, corresponds to a mortality ratio of 3.07.43% of the excess mortality could be attributed to liver disease. Our results indicate that the alcohol abuse, irrespective of its magnitude and duration, is associated with a rather constant excess mortality and that the occurrence and severity of hepatic injury ranging from normal liver to active cirrhosis is directly associated with a subsequent liver‐disease‐related excess mortality.
Copper toxicosis and tolerance in the rat. II. Tolerance – a liver protective adaptation
Authors: HAYWOOD S. , LOUGHRAN M.
Published: August 2010

ABSTRACT— Copper tolerance was induced in rats to determine the effective dose, duration and subsequent response to copper challenge on liver copper and associated changes. Male weanling rats were fed powdered diets supplemented with copper as follows: a) 3000, 4000, 5000 and 6000 mg/kg Cu for 15 weeks, b) 3000 mg/kg Cu for 52 weeks, c) 6000 mg/kg Cu for 3 weeks to animals which had previously received either 3000 mg/kg Cu or the control diet (10–20 mg/kg Cu) for 15 weeks. Animals in Groups (a) and (b) were weighed and killed at regular intervals. All livers were examined histologically and by Atomic Absorption Spectroscopy for copper. Animals on the copper‐supplemented diets accumulated copper in the liver with associated damage. Subsequently, in rats receiving up to 5000 mg/kg copper, liver copper concentration declined, regeneration occurred, growth resumed and the animals became tolerant. This adaptation continued for 52 weeks in animals on 3000 mg/kg copper with an inverse correlation between body weight and liver copper concentration. Rats on 6000 mg/kg copper maintained their hepatic overload and did not recover. Copper primed animals were less susceptible to a test dose of Cu than previously unchallenged animals. Tolerance to high dietary copper can be invoked within a dose range determined by the level of previous exposure. The adaptation is liver‐sparing and involves the progressive readjustment of copper homeostasis.
Hepatitis B virus and delta infection in male homosexuals
Authors: Hess G. , Bienzle U. , Slusarczyk J. , Hansson B. G. , Büschenfelde K. H. Meyer Zum
Published: August 2010

ABSTRACT—Six hundred and sixty‐six homosexuals were analysed in respect of hepatitis B virus and delta infections. Evidence of ongoing or recent hepatitis B virus infection was found in 450/666 (67.6%) homosexuals; 44 were HBsAg positive. Anti‐delta was found in two HBsAg‐positive homosexuals. Both individuals had a non‐replicative form of HBV infection and biochemical evidence of liver disease. The study confirms that HBV infection is frequent in homosexuals and indicates that delta‐infection is rare in male homosexuals.
Characteristic histologic triad in liver adjacent to metastatic neoplasm
Authors: GERBER MICHAEL A. , THUNG SWAN N. , BODENHEIMER HENRY C. , KAPELMAN BARBARA , SCHAFFNER FENTON
Published: August 2010

ABSTRACT— More than 25% of undirected percutaneous liver needle biopsies that are performed in search of metastatic neoplasms yield false negative specimens. Often, however, histologic changes are observed in the liver adjacent to space‐occupying lesions due to focal obstruction of bile and blood flow. These alterations were defined by semi‐quantitative evaluation of 20 liver biopsy specimens with metastatic neoplasms, and revealed a characteristic histologic triad consisting of proliferated and abnormal bile ductules, polymorphonuclear leukocytes in edematous portal tracts and focal sinusoidal dilatation. When 15 patients with this combination of histologic alterations, but without malignant cells in liver biopsy specimens, were investigated prospectively, 13 patients (87%) were found to have hepatic metastases. Therefore, the observation of the histologic triad described here should lead to a continued search for space‐occupying lesions in the liver.
The sinusoidal lining cells in “normal” human liver. A scanning electron microscopic investigation
Authors: HORN THOMAS , HENRIKSEN JENS H. , CHRISTOFFERSEN PER
Published: August 2010

ABSTRACT— The scanning electron microscope was used to study the fenestrations of human liver sinusoids. Thirteen biopsies, where light microscopy and transmission electron microscopy revealed normal sinusoidal architecture, were investigated. The number of fenestrae was calculated in acinar zone 3 and acinar zone 1 areas. The porosity, i.e. fenestrated area relative to total area of the sinusoidal lining wall, was estimated on micrographs by using a Texture Analysing System (TAS). A zonal gradient was found with median 23.5 fenestrae per μm2 in zone 3, as compared to 19.2 fenestrae per μm2 in the zone 1 area (p<0.005). Increasing porosity towards the terminal hepatic vein was found (9.1% in zone 3 vs. 7.6% in zone 1 (p<0.05)). This was due to an increased number of fenestrae measuring 100 nm or less in diameter in zone 3 areas. The number of fenestrae measuring more than 100 nm but less than 300 nm was unchanged along the sinusoids. Fenestrae larger than 300 nm were rare and randomly distributed. The results suggest a different permeability along the sinusoidal lining, which may influence the transport between blood and hepatocytes and thus be of importance to hepatocellular function.
Liver morphology in marmosets infected with epidemic non‐A, non‐B hepatitis in India
Authors: INOUE OSAMI , NAGATAKI SHIGENOBU , ITAK‐URA HIDEYO , IIDA FUSAE , SHIMIZU YOHKO , YANO MICHITAMI , SHIKATA TOSHIO , TANDON B. N.
Published: August 2010

ABSTRACT— In this study the morphological changes in the livers of marmosets inoculated with stool extracts from epidemic non‐A, non‐B hepatitis patients in India were examined. The histologic changes of epidemic non‐A, non‐B hepatitis in marmosets consisted mainly of round cell infiltration in the portal tracts, spotty liver cell necrosis, sinusoidal lymphocyte infiltration, and Kupffer cell mobilization. By electron microscopy, liver cells from infected marmosets showed cisternal dilation of the endoplasmic reticulum, irregularly‐shaped nucleus, and disorganization of the mitochondrial cristae. In some areas interaction of lymphocytes with hepatocytes was observed. Similar observations have been made in type B hepatitis infection, presumably due to liver cell damage mediated by immune mechanisms. The result of our study is also compatible with the interpretation that the liver cell damage in this experimental model may be mediated by immune mechanisms.
Cerebral metabolism during cross‐circulation in experimental hepatic failure in the pig
Authors: Tønnesen Klaus
Published: August 2010

ABSTRACT— The effect of hepatic assistance on cerebral metabolism was evaluated in a series using cross‐circulation, anticipating increased efficiency of hepatic support. The experimental model for liver failure was pigs with totally devascularized liver. Cross‐circulation with a normal sibling pig, cross‐circulation with inflow in the donor directly into the portal vein and cross‐perfusion with isolated perfused liver starting 20 h after elimination of liver function in the recipient and lasting for 3 h did not increase survival. Before cross‐circulation in these three groups, the cerebral flow and oxygen uptake were decreased; during the cross‐circulation a significant but temporary increase was found. In experiments with early and prolonged perfusion with isolated perfused liver no changes in cerebral flow, oxygen or glucose uptake were found, and these variables were still normal 6 h after termination of the perfusion. The survival time was significantly increased. In the control group a significant rise in blood and CSF ammonia was found with a mean CSF/blood ratio of 0.92. After cross‐circulation, the CSF/blood ratio was 0.52 and 0.62, respectively, indicating a proportionally greater elimination of ammonia from the cerebrospinal fluid than from the blood. Cross‐circulation did not significantly change the α‐ketoglutarate, glutamate or glutamine CSF concentrations. After prolonged cross‐perfusion, the ammonia blood/CSF ratio was 0.24. It is concluded that by extended extracorporeal hepatic assistance it is possible to increase survival and to prevent changes in cerebral metabolism and ammonia accumulating in the cerebrospinal fluid.
Immunohistochemical study on bile ductular proliferation in various hepatobiliary diseases
Authors: Nakanuma Yasuni , Ohta Goroku
Published: August 2010

ABSTRACT‐ Proliferation of the two types of bile ductules, typical and atypical, in the portal and periportal areas was examined in various liver diseases other than cirrhosis to determine any difference in their immunohistochemical properties and presumed histogenesis. While the typical ductules with a well‐formed lumen were frequently seen in a large spectrum of diseases, atypical ductules with a poorly defined lumen were encountered much more frequently in prolonged biliary diseases, including primary biliary cirrhosis and primary sclerosing cholangitis, than in nonbiliary hepatic diseases. Immunocytochemically, cytoplasmic keratin was intensively positive in typical ductules, and the degree of its intensity and extent was variable in atypical ductules. Simultaneously, some of the periportal hepatocytes revealed weak staining for keratin. Luminal borders of typical ductules usually revealed an expression of both carcinoembryonic antigen and epithelial membrane antigen, while atypical ductules and periportal hepatocytes lacked epithelial membrane antigen. The atypical ductules, together with the adjoining hepatocytes, appeared on occasion to form anastomosing cords in prolonged biliary diseases. Thus, atypical ductules seem likely to originate from ductular transformation of the periportal hepatocytes and the typical ductules might result from the proliferation of preexisting interlobular bile ducts and ductules.
Ketoconazole‐induced hepatitis: a case with a definite cause‐effect relationship
Authors: van Parys G. , Evenepoel C. , van Damme B. , Desmet V. J.
Published: August 2010

ABSTRACT— We present the case of a female patient in whom acute hepatitis developed after 180 days of ketoconazole administration (200 mg/day). A prompt renewed hepatic injury after an unintentional rechallenge 6 months later provided definitive evidence for a causative relationship between ketoconazole and acute liver disease. The clinical and biochemical parameters of the case are reported. Histological examination revealed the picture of acute hepatitis with possible transition to chronicity. A prominent accumulation of perisinusoidal lipocytes (Ito cells) was observed.
Hepatic sinusoidal dilatation in Hodgkin's disease
Authors: Bruguera M. , Caballero T. , Carreras E. , Aymerich M. , Rodés J. , Rozman C.
Published: August 2010

ABSTRACT— Examination of needle liver biopsy specimens from 46 patients with Hodgkin's disease revealed sinusoidal dilatation with a predominantly centrolobular and midlobular localisation in 23 cases (50%). It was present in 90% of patients with general symptoms and in only 20% of those without them (p < 0.001), and it was unrelated to the staging, the existence of hepatic infiltration by the disease and the lymph node histology. The pathogenesis of the sinusoidal ectasia is not known, but it might be a consequence of an alteration of the sinusoidal barrier, since no abnormality of the hepatocytes or of the hepatic venules was detected at light microscopy. Sinusoidal dilatation may be considered as a further systemic manifestation of Hodgkin's disease.
Histological changes of bile duct in experimental graft‐versus‐host disease across minor histocompatibility barriers II. Electron microscopic observations
Authors: Nonomura Akitaka , Kono Naoko , Yoshida Kazuharu , Nakanuma Yasuni , Ohta Goroku
Published: August 2010

ABSTRACT— Electron microscopic features of intrahepatic bile ducts of experimental mouse graft‐versus‐host disease (GVHD) across minor histocompatibility barriers were studied for 14 months after transplantation. In GVHD mice, the bile duct epithelial layer was consistently infiltrated by lymphoid cells and often accompanied by polymorphonuclear leukocytes, monocytes and rarely by plasma cells. The epithelial cells in close contact with and in the vicinity of these infiltrated cells showed a variety of degenerative changes, including darkness of the cytoplasm and the nucleus with shrunken, irregular contours, increase in the amount of endoplasmic reticulum and number of mitochondria, and formation of intracytoplasmic vesicles and diverticula, cytoplasmic blebs, and apoptopic bodies. Lymphocytes were in close contact with epithelial cells through a number of point‐contacts and located in the lateral intercellular spaces and/or between the basement membranes and the epithelial cells. The localization of infiltrating lymphocytes beneath the epithelial cells with conspicuous detachment from the basement membranes strongly suggested a link with subsequent epithelial cell injury and death. The lymphoid cells had irregular cytoplasmic projections which occasionally extended into spaces created by retractions of the epithelial cell membranes, reflecting an activation of the lymphocytes. These findings support the notion that the bile duct lesions in GVHD across minor histocompatibility barriers are mediated by specifically sensitized lymphocytes against epithelial cell membrane antigens. From our previous finding that a large majority of the infiltrating lymphocytes had a phenotype of helper/inducer T cells, a putative role of these lymphocytes in the induction of the bile duct lesions is discussed.
Epithelioid hemangioendothelioma of the liver: report of two cases
Authors: Terg Ruben , Bruguera Miquel , Campo Elias , Hojman Ruben , Levi Diana , Podestá Ana
Published: August 2010

ABSTRACT— This report describes two patients with hepatic epithelioid hemangioendothelioma: a 33‐year‐old woman and a 28‐year‐old man. The first case presented with a palpable abdominal mass and has survived without treatment for 6 years since diagnosis, with ascites but a good general condition. The other patient presented with abdominal pain and cholestasis. He had a rapid course and death occurred 6 months after the onset of symptoms. Histologically the tumors consisted of a proliferation of neoplastic cells with an angiogenic tendency embedded in a myxohyaline stroma. Positivity for the factor VIII‐related antigen, for UEA‐I and for vimentin and negativity for keratin of the neoplastic cells in the immunohistochemical investigation permitted identification of their endothelial origin. In both cases, the initial diagnosis was erroneous.
Profile of alcoholic liver disease in an Indian hospital. A prospective analysis
Authors: Sarin S. K. , Malhotra V. , Nayyar A. , Sundaram K. R. , Broor S. L.
Published: August 2010

ABSTRACT— To study the profile of alcoholic liver disease in India, 144 consecutive, histologically diagnosed patients were prospectively studied. The patients were divided into those having alcoholic fatty liver (AFL) (Gr. I, n = 32), alcoholic hepatitis (AH) (Gr. II, n = 42) and alcoholic cirrhosis (AC) (Gr. III, n = 70) on the basis of their histological findings. All the patients were males, those with fatty liver being younger than those with cirrhosis. The amount of alcohol consumed by patients with AFL, AH and AC was not significantly different. Similarly, the duration of alcohol consumption was not significantly different between the three groups of patients. The clinical features of the patients were quite similar to those reported from the West, except that AH was relatively milder in our patients. Intake of poor quality country liquor was quite common (60%), but its use was not found to be associated with more severe liver injury as compared with the use of good quality foreign varieties of liquor.
Bile canalicular contraction in the isolated hepatocyte doublet is related to an increase in cytosolic free calcium ion concentration
Authors: Watanabe Sumio , Tomono Masahiro , Takeuchi Makoto , Kitamura Tsuneo , Hirose Miyoko , Miyazaki Akihisa , Namihisa Toshihiko
Published: August 2010

ABSTRACT—Dynamic contractions of bile canaliculi have been observed in cultured doublet hepatocytes by means of time‐lapse cinephotomicrography, and this contractile movement plays an important role in bile secretion. Although details of the mechanism are still unknown, the Ca2+‐calmodulin system is believed to play a main role in this mechanism. In this study we measured the intracellular Ca2+concentration of individual doublet hepatocytes using the Ca2+indicator “fura 2” and microscopic fluorometry. We also observed the effects of A23187, norepinephrine and epinephrine on bile canalicular contraction and intracellular Ca2+concentration. After loading 1 μmol/1 fura 2 in doublet cells, we added A23187, epinephrine or norepinephrine and then measured the Ca2+concentration in a given small area in the cytoplasm of individual doublet cell. A23187, norepinephrine and epinephrine caused a prompt increase of the intracellular Ca2+concentration and also caused bile canalicular contraction. The present study indicates that the sudden increase of intracellular Ca2+concentration causes bile canalicular contraction through the Ca2+‐calmodulin system.
Changes of serum HBV‐DNA in relation to serum transaminase level during acute exacerbation in patients with chronic type B hepatitis
Authors: Liaw Yun‐Fan , Pao Chia‐Chu , Chu Chia‐Ming
Published: August 2010

ABSTRACT— To examine the relationship between changes of serum hepatitis B virus‐dexoyribonucleic acid (HBV‐DNA) and transaminase levels during acute exacerbation of chronic type B hepatitis, serial serum specimens from 74 patients were assayed for HBV‐DNA by slot blot hybridization with 32P‐labeled cloned HBV‐DNA as probe. Of these patients, serial serum specimens were obtained with an interval of 2–7 days in 22 patients (Group I), 8–14 days in 30 patients (Group II) and 15–30 days in 22 patients (Group III). The peak of serum HBV‐DNA was reached shortly before or simultaneously with the maximum elevation of serum alanine transaminase (ALT) in most (>90%) of the acute exacerbations. In contrast, the peak of serum ALT was reached before maximum elevation of serum HBV‐DNA in only 13.6% of Group I, 3.3% of Group II and 13.6% of Group III (9.5% of whole series). The results suggest that the increase of serum HBV‐DNA is an event preceding, rather than the result of, hepatocytolysis in most of the acute exacerbations occurring in patients with chronic type B hepatitis.
Hypoceruloplasminemia and ultrastructural changes resembling Wilson's disease in non‐alcoholic liver steatosis
Authors: Geubel A. P. , Gregoire V. , Rahier J. , Lissens W. , Dive C.
Published: August 2010

ABSTRACT— We report five cases of asymptomatic patients with persistently abnormal liver function tests in whom copper metabolism abnormalities resulted in a misleading suspicion of Wilson's disease. Ceruloplasmin levels assessed by nephelometric immunoassay, single radial immunodiffusion and the enzymatic method averaged 53.8, 61 and 52.8% of the mean value obtained in age‐ and sex‐matched controls (p<0.001). Twenty‐four‐hour urinary copper excretion was higher than the normal range in three instances. Four patients exhibited hypertriglyceridemia. Liver histology showed fatty change with or without sinusoidal fibrosis. Electron microscopic examination unexpectedly disclosed mitochondrial and lysosomal changes identical to those described in Wilson's disease. The present observations indicate that biochemical and ultrastructural changes suggestive for Wilson's disease may be observed in the absence of increased liver copper content. Whether such cases represent isolated cases of heterozygosity for the Wilson's disease gene remains to be elucidated.
Latent hepatitis B virus infection with full‐length viral genome in a patient serologically immune to hepatitis B virus infection
Authors: Blum Hubert E. , Offensperger Wolf‐Bernhard , Walter Eike , Offensperger Silke , Gerok Wolfgang
Published: August 2010

ABSTRACT— The presence, state, physical structure and cellular localization of hepatitis B virus (HBV) DNA were investigated in a patient with hepatitis B surface antigen (HBsAg)‐negative chronic liver disease. HBV serology was positive for antibodies to hepatitis B core antigen (anti‐HBc), to hepatitis B e antigen (anti‐HBe) and to HBsAg (anti‐HBs); no HBV DNA was detectable in serum. Southern blot analyses of DNA extracted from the liver demonstrated free monomeric HBV DNA as two distinct species: a predominant species of fully double‐stranded relaxed circular molecules and a minor species of linear molecules of 3.2 kilobase pairs (kbp) length. Restriction enzyme analyses identified the HBV genome as HBsAg subtype adw2. Cell fractionation studies further revealed that the free viral DNA species were localized exclusively in liver cell nuclei. These findings in a patient serologically immune to HBV infection demonstrate that in hepatocytes HBV can establish a latent infection, characterized by the extrachromosomal presence of a full‐length viral genome without production of infectious virus or synthesis of viral antigens.
Cellular mechanisms of toxicity and tolerance in the copper‐loaded rat. I. Ultrastructural changes in the liver
Authors: Fuentealba I. , Haywood S.
Published: August 2010

ABSTRACT— Ultrastructural changes have been studied in the copper‐loaded livers of rats in order to clarify the pathogenesis of damage induced by the metal and the subsequent recovery. Male rats fed a high copper diet (1500 ppm) for 16 weeks were killed at intervals. Their livers were removed and portions fixed in 4% paraformaldehyde and 2% glutaraldehyde for transmission electron microscopy and analysed for copper by AA spectrophotometry. Increasing copper concentrations were associated with an increase in the numbers and diversity of lysosomes, swelling of smooth endoplasmic reticulum, mitochondria and canalicular microvilli and fragmentation of rough endoplasmic reticulum. Nuclear degeneration occurred early, culminating in lysis. Subsequent changes included a decline in liver copper, extrusion of apoptotic bodies and the recovery of remaining hepatocytes with retention of inert remants (Mallory body‐like structures). Excess copper is associated primarily with irreversible nuclear damage and does not appear to cause disruption of lysosomes. The mechanism of cellular adaptation remains unclear.
Hepatitis B virus replication in hepatitis B and D coinfection
Authors: Morante A. Lopez , De La Cruz F. , De Lope C. Rodriguez , Echevarria S. , Rodriguez G. M. , Pons‐Romero F.
Published: August 2010

The clinical course, changes in liver function tests and the behaviour of viral markers over the course of time have been examined in 45 patients with acute hepatitis B and 14 patients with acute hepatitis caused by B and D viruses coinfection. There were no significant differences either in the clinical course or in the liver function tests, in the two groups. The changes in serum viral markers were as follows: HBV‐DNA was the first marker to disappear; this was closely followed by HBeAg, and HBsAg was the last marker to become negative, during convalescence. This pattern was not altered by Delta coinfection. When we quantified serum HBV‐DNA in both groups of patients, we found that Delta virus infection led to partial inhibition of HBV replication, so that serum HBV‐DNA levels were significantly lower in those patients with acute hepatitis B who were simultaneously infected with Delta virus.
Alcoholic foamy degeneration in Spain. Prevalence and clinico‐pathological features
Authors: Montull Santiago , Parés Albert , Bruguera Miquel , Caballería Joan , Uchida Toshikazu , Rodés Joan
Published: August 2010

Among 389 consecutive chronic alcoholics in whom a liver biopsy was performed for diagnostic purposes, nine patients (2.3%) had histological changes of “alcoholic foamy degeneration” (AFD), characterized by numerous small fat droplets in the swollen hepatocytes of the centrilobular area. In five cases, there were nonspecific clinical features, while the other four cases presented acute hepatic decompensation with jaundice and a reduced prothrombin activity. Seven patients had high serum lipid concentrations including hypertriglyceridemia and hypercholesterolemia, which improved after withdrawal of alcohol intake. In conclusion, AFD has a broad clinicopathological spectrum including asymptomatic patients and other cases with severe liver decompensation manifested by jaundice and reduced prothrombin activity. AFD is usually associated with hyperlipemia.
In situ localization of melanotransferrin (melanoma‐associated antigen P97) in human liver. A light‐ and electronmicroscopic immunohistochemical study
Authors: Sciot R. , De Vos R. , van Eyken P. , van der Steen K. , Moerman P. , Desmet V. J.
Published: August 2010

Using an indirect immunoperoxidase technique on frozen sections with the monoclonal antibody 96.5, we investigated the in situ distribution of melanotransferrin, a transferrin (Tf) and transferrin receptor (TfR) related glycoprotein, in human liver. Specimens included normal liver, liver in iron overload, hepatocellular carcinoma, angioma and foetal liver. On light microscopy, immunoreactivity was almost exclusively present on sinusoidal lining cells, apparently endothelial cells; the pattern was similar in normal and in iron‐loaded liver. A gradient of more enhanced staining in acinar zone II and III was observed. The endothelial localization of the staining was supported by the positivity of the central vein endothelium and of the angiomas. Immunoelectron microscopy on three liver specimens showed positivity on sinusoidal endothelial cells but not on Ito and Kupffer cells. In addition, positivity on rough endoplasmic reticulum vesicles of some hepatocytes was also present. Four hepatocellular carcinomas showed an intense staining in tumour cells, 3 were weakly positive and 3 were negative. In the foetal livers, the central vein endothelium was positive from 21 weeks of gestation onward and additional positivity of zone III sinusoidal endothelial cells was present from 27 weeks on. The present results show that in the liver melanotransferrin has a localization different from Tf and the TfR. These latter molecules are predominantly localized in parenchymal cells. In addition, there does not appear to be a coordinate regulation secondary to iron storage, between melanotransferrin, Tf and the TfR. The observed gradient in the staining pattern in foetal and adult liver specimens further supports the heterogeneity of the endothelial cell population in the liver and suggests a developmental relationship between endothelial cells of sinusoids and central vein.
Chronic non‐A, non‐B hepatitis developed after transfusions, illicit self‐injections or sporadically. Outcome during long‐term follow‐up – a comparison
Authors: Mattsson Lars , Weiland Ola , Glaumann Hans
Published: August 2010

Ninety‐two patients with biopsy‐proven chronic non‐A, non‐B hepatitis after blood transfusions, illicit self‐injections or sporadically were followed clinically for an average of nearly 5 years. In the posttransfusion hepatitis group, which comprised 37 patients with a mean age of 54 years (range 18–83 years), 59% developed chronic active hepatitis (CAH) and 46% also showed signs of early cirrhosis (eCi) or manifest cirrhosis (Ci). In the illicit self‐injection group, comprising 33 patients with a mean age of 26 years (range 17–63 years), 39% manifested CAH and 18% eCi or Ci. In the sporadic group, which consisted of 22 patients with a mean age of 32 years (range 16–62 years), 41% showed CAH and 23% eCi. Thus, in all, 44/92 (48%) of the patients with chronic non‐A, non‐B hepatitis developed CAH and 28/92 (30%) signs of early or manifest cirrhosis. Patients ≥30 years of age displayed CAH and signs of cirrhosis more often than patients <30 years of age (p<0.01). Chronic non‐A, non‐B hepatitis is a slowly progressive disease with a high incidence of cirrhosis, especially in patients ≥30 years of age and when caused by blood transfusion.