bluuebunny/crossref_metadata_2025 huggingface dataset:
Different aetiology of chronic active hepatitis in U.K. and Iraq
Authors: Holdstock G. , Rassam Suha , Millward‐Sadler G. H. , Wright Ralph
Published: August 2010

ABSTRACT— We have compared the clinical, biochemical and immunological features of patients with biopsy‐proven chronic active hepatitis from Iraq and from the United Kingdom. Clear‐cut differences emerge, which can mostly be attributed to the HBV status, as 91% of patients from Iraq were HBsAg‐positive compared to only 6% from the U.K. Most patients from Iraq presented insidiously with established cirrhosis, while those from the U.K. presented more acutely and systemic symptoms were more common. Autoantibodies and associated autoimmune conditions were common in U.K. patients but extremely rare in Iraqis.
Lymphocyte cytotoxicity to autologous hepatocytes in alcoholic liver disease
Authors: Actis Giovanni , Mieli‐Vergani Giorgina , Portmann Bernard , Eddleston Adrian LWF , Davis Michael , Williams Roger
Published: August 2010

ABSTRACT— Cytotoxicity of peripheral blood lymphocytes for autologous hepatocytes has been studied in 18 patients with different histological types of alcoholic liver disease. Cytotoxicity was significantly increased in five of ten patients with cirrhosis and/or alcoholic hepatitis but in only one of eight with fatty infiltration or minor histological changes. The cytotoxic effect of T‐ and non‐T‐effector cells was separately evaluated in 11 cases. Of six patients with alcoholic hepatitis, non‐T lymphocyte cytotoxicity was increased in five and T‐cell in only one. These preliminary results are consistent with the concept that autoimmune reactions may play a role in the development and progression of alcoholic hepatitis and cirrhosis, although it is likely that direct hepatotoxic effects of ethanol or its metabolites are also important in determining the pattern of liver injury and perhaps in initiating the immune reactions observed in this study.
Hepatocellular carcinoma in a patient with sarcoidosis‐associated chronic active hepatitis and the MZ alpha‐1‐antitrypsin phenotype
Authors: Kronborg I. J. , Bhathal P. S. , Mackay I. R. , Storey E. , Long T. M.
Published: August 2010

ABSTRACT— A case of primary hepatocellular carcinoma is described in a patient with long‐standing sarcoidosis of the liver associated with chronic active hepatitis, and the MZ alpha‐1‐antitrypsin phenotype. This association appears to be unique. The respective roles of alpha‐1‐antitrypsin deficiency, sarcoidosis and chronic active hepatitis in the development of hepatocellular carcinoma in this case are uncertain.
The value of clinical, biochemical, ultrasound and liver biopsy data in assessing patients with liver disease
Authors: Theodossi A. , Spiegelhalter D. , Portmann B. , Eddleston A. L. W. F. , Williams Roger
Published: August 2010

ABSTRACT— To determine the value of clinical, biochemical, ultrasound and liver biopsy data in the management of patients with liver disease, eight doctors each assessed 75 case histories. With clinical and biochemical data alone, the predictive accuracy was significantly higher when identifying patients as ‘medical’ rather than ‘surgical’ (97 compared with 79%, p<0.001). However, when making a specific diagnosis as opposed to classifying into medical and surgical categories, clinical and biochemical information resulted in a much lower predictive accuracy for both medical (67%) and surgical (56%) patients. With ultrasound data the predictive accuracy increased to 91% when identifying patients as ‘surgical’; with liver biopsy it increased to 99% when identifying patients as ‘medical’.

The value of the different data assessed involves more than an evaluation of diagnostic accuracy, and in this study the relative worth of each test was therefore assessed on a five point scale based on the effect of the information on the doctors. This included a willingness to give specific treatment and make a specific diagnosis, as well as classifying patients into medical and surgical categories and the confidence they felt in their diagnoses. After clinical, biochemical and ultrasound information the doctors were only prepared to give specific treatment to 11.9% of the medical and 9.3% of the surgical patients. After liver biopsy data, however, they were willing to give specific treatment to an additional 66.6% of the medical patients and 25% of the surgical patients. Further evidence of the value of liver biopsy information came from an analysis of the changes in the doctors' confidence in a diagnosis. Thus, 96 patients were assigned a correct specific diagnosis with clinical and biochemical data alone but none were considered as ‘definitive’ by the doctors; when liver biopsy information was provided 59 (61%) were placed in this category.
Comparison of the diagnosis of oesophageal varices by oesophagoscopy and transhepatic portography
Authors: Sørensen T.I.A. , Burcharth Flemming , Aagaard J. , Jensen L. I. , Christensen U.
Published: August 2010

ABSTRACT— We compared the diagnosis of oesophageal varices obtained by oesophagoscopy and percutaneous transhepatic portography in 78 patients with hepatic cirrhosis who were suspected of having oesophageal varices because of ascites and/or preceding upper gastrointestinal haemorrhage. Portograms were evaluated independently of the clinical and endoscopical findings. Endoscopy showed varices in 59 patients and portography in 54 patients. The two methods agreed on the presence of varices only in 46 patients (59%), on the absence of varices in 11 patients (14%), and disagreed in 21 patients (27%). Among the patients showing varices by endoscopy, portography agreed on the diagnosis in 78%, and among patients without endoscopical varices, portography agreed in 58%. The corresponding rates of agreement expected by chance alone are 69% and 31%, respectively. The free portal pressure was lowest in patients with no varices according to both techniques, highest in patients with varices by both techniques and intermediate in patients in whom there was disagreement on the diagnosis. Modification of the criteria for endoscopical and portographical diagnosis of varices and distinction between patients with and without ascites and preceding haemorrhage had no appreciable effect on the agreement. We conclude that endoscopy and portography show only moderate agreement in the diagnosis of oesophageal varices.
Relationship between liver histopathological changes and HBs Ag in 111 patients treated by long‐term hemodialysis
Authors: Degott Claude , Degos Françoise , Jungers Paul , Naret Catherine , Courouce Anne‐Marie , Potet François , Crosnier Jean
Published: August 2010

ABSTRACT— We studied liver biopsies performed between January 1972 and June 1980 in 111 patients receiving regular dialysis treatment. Biopsies were performed either because of suspected liver disease (61 patients) or routinely during abdominal surgery or kidney transplantation (50 patients). Repeat biopsies were done in 14 cases. Hepatitis B virus markers, assayed every 3 months during the observation period, were detected at some time in 71 patients (64%); 51 remained persistently positive. Histological examination showed normal liver in 39 cases, lobular hepatitis in 15, chronic persistent hepatitis in 36 and chronic active hepatitis in 21. All patients with chronic active hepatitis were chronic HBsAg carriers, and repeated biopsies showed aggravation only in these patients. The course was remarkably asymptomatic, with lesions leading to fibrosis despite the lack of histopathological patterns of severe necrosis and/or inflammation, which were conspicuously absent in this series.
Immunohistochemical study of delta antigen in an American metropolitan population
Authors: Thung Swan N. , Gerber Michael A.
Published: August 2010

ABSTRACT— Delta antigen, a transmissible agent associated with hepatitis B virus, has been detected primarily in Italian patients. The preservation of δ‐antigen in formalin‐fixed, paraffin‐embedded liver tissue enabled us to study the prevalence of this agent in our material. Using the peroxidase‐antiperoxidase method, δ‐antigen was found in 2 of 65 consecutive biopsy specimens of patients with HBsAg‐positive liver disease. In addition, δ‐antigen was demonstrated in 2 of 14 autopsy specimens from HBsAg‐positive patients. Of the δ‐antigen‐positive patients, one was Italian, one was a polytransfused American‐born Italian and two were American homosexuals. All four δ‐Ag‐positive patients had chronic active hepatitis. In one patient, the agent persisted for 5 years while chronic active hepatitis reverted to chronic persistent hepatitis during prednisone therapy. These findings suggest that transmission of δ‐antigen follows that of hepatitis B virus infection, although it is relatively uncommon in New York City.
Analysis with OKT monoclonal antibodies of T‐lymphocyte subsets present in blood and liver of patients with chronic active hepatitis
Authors: Mariani Erminia , Facchini A. , Miglio F. , Stefanini G. F. , Mazzetti Maura , Leupers Tine , Gasbarrini G. , Labo G. , Astaldi A.
Published: August 2010

ABSTRACT— The relative distribution of T lymphocyte subsets, as defined by the monoclonal antibodies OKT, was determined by cytofluorimetric analysis in peripheral blood and in cells isolated from liver biopsies of 31 patients with chronic active hepatitis (CAH). The percentage of peripheral blood lymphocytes binding OKT8 (directed against cytotoxic/suppressor T cells) was found to be elevated in patients with HBsAg and HBeAg positive chronic active hepatitis. Patients with CAH who had seroconverted to anti‐HBe, had an increased number of OKT3‐positive cells in their blood, which was directed against a common T cell surface antigen, associated with a decreased number of OKT8 positive cells. Lymphocytes isolated from liver biopsies of patients with CAH presented a general increase of OKT8‐positive cells associated with a decreased number of OKT4‐positive (helper/inducer) T cells. It is likely that OKT8‐positive cells found in liver biopsies represent cytotoxic T cells directed against either viral or liver cell determinants.
Cellular cytotoxicity against autologous hepatocytes in alcoholic liver disease
Authors: Poralla T. , Hütteroth T. H. , zum Büschenfelde K.‐H. Meyer
Published: August 2010

ABSTRACT— We tested lymphocyte cytotoxicity against autologous hepatocytes in patients with alcoholic liver disease (ALD). The following cytotoxicity values were found (mean ± SEM): alcohol‐induced steatosis with or without fibrosis 16.5±2% (n = 29), alcoholic cirrhosis 28±4% (n = 13), controls with normal liver histology or minimal changes 6±2% (n = 11). The differences were statistically significant (both forms of ALD versus controls p<0.005). T‐cell as well as non‐T‐cell‐enriched lymphocyte fractions showed increased cytotoxicity in ALD. We did not observe a correlation between cellular cytotoxicity and the degree of biochemical or histological alterations within the groups tested. Thus, our study demonstrating enhanced cellular cytotoxicity against autologous hepatocytes in ALD further supports the hypothesis that cellular immune reactions are involved in the pathogenesis of ALD, especially of alcoholic cirrhosis.
Effect of griseofulvin treatment and neoplastic transformation on transglutaminase activity in mouse liver
Authors: Denk Helmut , Bernklau Gertraud , Krepler Reinhard
Published: August 2010

ABSTRACT— The present study was undertaken in order to elucidate the effect of liver injury exerted by the antimicrotubular drug griseofulvin on hepatic transglutaminase activity in mice. Griseofulvin treatment of mice leads to a significant increase of transglutaminase activity associated with the 105 000 x g supernatant of liver homogenate, which is readily reversible after replacement of the griseofulvin‐containing diet by a normal diet. Neoplastic nodules originally induced by prolonged griseofulvin feeding also show increased transglutaminase activity in contrast to reports in the literature. The increase in hepatic transglutaminase activity in griseofulvin‐fed mice could be due either to mitotic inhibition exerted by the drug or to disturbance of intracellular Ca++ homeostasis following membrane injury. The second possibility could also account for the increased enzyme activity in neoplastic nodules. Similar events have been described as occurring in aging erythrocytes and terminally differentiating keratinocytes. The pathologic consequences and the substrates of increased hepatic transglutaminase activity have still to be elucidated.
Hepatitis D (delta agent) in primary hepatocellular carcinoma and liver disease in Senegal
Authors: Cronberg Stig , Hansson Bengt‐Göran , Thermos Mohammed , Moestrup Torkil , Sow Amadou Moustapha
Published: August 2010

ABSTRACT— A total of 308 individuals belonging to ten different ethnic groups in Senegal were investigated. They suffered from primary hepatocellular carcinoma (PHC), liver cirrhosis, chronic hepatitis and other liver diseases, or were healthy controls. Their sera were investigated for the presence of markers of infection with hepatitis B and D (delta agent) virus. Out of 130 clinically diagnosed patients with PHC, 88 had alpha‐fetoprotein levels above 100 μg/l, supporting the diagnosis. After clinical examination, 133 subjects were considered to be healthy or to have a liver disease other than PHC. Among these, 83 (31 clinically healthy and 52 with liver disease) had alpha‐foetoprotein less than 15 μg/l and were therefore considered not to have PHC. Out of the 88 patients with definite PHC, 74% were positive for HBsAg, whereas out of the 83 subjects without PHC, 50% of those with other liver disease and 26% of the healthy controls were positive. Anti‐delta was present in 21% of the patients with or without PHC. It was found in nine different ethnic groups in the country. The present data confirm that HBV is related to the etiology of PHC. The present investigation showed a high prevalence of delta antibodies in patients with PHC, but against the role of hepatitis D infection in the evolution of malignancy is the fact that it was equally common in chronic liver disease without evidence of carcinoma.
Changes induced in human liver by long‐term anticonvulsant therapy Functional and ultrastructural data
Authors: Jezequel A. M. , Librari M. L. , Mosca P. , Novelli G. , Lorenzini I. , Orlandi F.
Published: August 2010

ABSTRACT—The study reports functional and morphological findings in eight male subjects undergoing anticonvulsant therapy for periods from 20 days up to 15 years. All subjects showed an increased activity of the hepatic microsomal NADPH cytochrome c reductase and an increased amount of smooth membranes in hepatocytes. The enzymatic activity was higher in the first years of treatment. Quantitative ultrastructural analysis showed that a twofold increase of the smooth membranes of hepatocytes had already been reached after 20 days of therapy, with a modest additional increase occurring thereafter. Both enzymatic and structural changes appear to be related to therapy. In addition, abnormal lipofuscin‐related cytoplasmic formations were present in the hepatocytes of five subjects. Such formations are thought to represent an accumulation of abnormal degradation products, possibly related to an interaction of the drug(s) metabolites with cellular components.
Cholestatic features in focal nodular hyperplasia of the liver
Authors: Vila M. M. Butron , Haot J. , Desmet V. J.
Published: August 2010

ABSTRACT— Twenty specimens of focal nodular hyperplasia were studied with special attention to the histological features of chronic cholestasis (grouped under the headings of cholestasis, cholate‐stasis and signs of ductular reabsorption). In all specimens, evidence was found for one or more features of cholestasis and cholate‐stasis. Signs of ductular reabsorption were less constant, and apparently varied according to the developmental stage of the lesion. The cholestatic features emphasize the bile secretory capacity of the lesional parenchyma, and are apparently due to the lack of real bile ducts in the portal tract equivalents of the lesional tissue. Evidence is presented that the “ductular component” in FNH is not due to proliferation of pre‐existing ductules, but rather derives from ductular metaplasia of liver cell plates in zone 1 equivalents. This metaplastic development of a ductular network may serve the function of reabsorbing the biliary constituents produced by the lesional parenchyma, leading to periductular inflammation and progressive fibrosis, thus producing an equivalent of biliary fibrosis and biliary cirrhosis.
Hyperplastic foci in the atrophic liver of rats after portacaval anastomosis
Authors: DUBUISSON LILIANE , VONNAHME FRANZ‐JOSEF , STZARK FRANCOIS , BIOULAC‐SAGE PAULETTE , BALABAUD CHARLES
Published: August 2010

ABSTRACT— Hyperplastic focal areas were investigated in livers of male rats 1 and 9 months after portacaval anastomosis (PCA) by light and electron microscopy. These alterations, predominantly found in periportal areas, were characterized by light microscopy as clusters of enlarged hepatocytes along narrowed sinusoids, contrasting in the remaining liver acinus with smaller hepatocytes along widened sinusoids. No differences were observed between 1 and 9 months PCA except for glycogen content, which was homogeneously distributed in the liver at 1 month but completely lacking in foci at 9 months. The most striking ultrastructural alterations were the sinusoids delimited in these hyperplastic areas by a thickened barrier consisting of thick endothelial cells encircled by numerous subendothelial processes of the perisinusoidal fat‐storing cells. Deep and widened recesses of the sinusoidal lumen separated the two‐cell‐thick plates of the hyperplastic cells. Hepatocytes in foci, thought to represent regenerative areas, tend to increase their exchange surface. Their progressive loss in glycogen and their two‐cell‐thick plates architecture should be in favour of a potential malignancy. However, the spontaneous evolution of these foci which do not necessarily give rise to nodules, as well as the lack of other features of transformation, do not support this possibility.
Clinical and serological events accompanying changes in hepatitis B viral replication: case reports
Authors: Dusheiko G. M. , Bowyer S. M. , Paterson A. , Song E. , Dibisceglie A. , Kew M. C.
Published: August 2010

ABSTRACT—We measured serum markers of hepatitis B virus replication in two HBsAg‐, HBeAg‐positive hepatitis B carriers with chronic active hepatitis and cirrhosis. The first of these patients was HBsAg‐, HBeAg‐, HBV DNA‐ and HBV DNA polymerase‐positive initially and spontaneously lost HBV DNA polymerase and HBV DNA. During the HBeAg‐positive, DNA polymerase‐negative “window phase”, an increase in viral replication, characterized by the reappearance of HBV DNA and HBV DNA polymerase occurred, together with an aggravation of the underlying chronic hepatitis. In the second HBsAg‐, HBeAg‐positive carrier, spontaneous fluctuations in HBV replication were associated with clinical deterioration. Delta agent and hepatitis A virus superinfection were excluded. These observations suggest that spontaneous low‐grade fluctuations of HBV replication accompanied by an increase in the biochemical activity of the underlying chronic hepatitis can be observed in certain HBV carriers.
Antipyrine metabolism during hepatic regeneration in the rat
Authors: POULSEN HENRIK E. , PILSGAARD HELLE
Published: August 2010

ABSTRACT—We investigated antipyrine clearance and urinary excretion of 4‐hydroxyantipyrine, 3‐hydroxymethylantipyrine and nor‐antipyrine in rats after 70% partial hepatectomy. Antipyrine clearance recovered more slowly than liver weight but after 240 h both liver weight and antipyrine clearance had reached control values. During hepatic regeneration conversion of antipyrine to the three major metabolites was reduced, conversion to 3‐hydroxymethylantipyrine being reduced more than conversion to the other metabolites. Antipyrine clearance was closely correlated to liver weight (r = 0.81), indicating a close relation between the functional hepatic mass and the liver weight during hepatic regeneration.
Early alcoholic liver injury: changes of the Disse space in acinar zone 3
Authors: HORN THOMAS , JUNGE JETTE , CHRIS‐TOFFERSEN PER
Published: August 2010

ABSTRACT— One hundred and twelve consecutive liver biopsies were studied by transmission electron microscopy. In 18 out of 23 biopsies from chronic alcoholics showing preserved architecture by light microscopy, basal laminas were found in acinar zone 3 applied to endothelial cells as well as to hepatocytes. Basal laminas occurred independently of Mallory bodies and lipogranulomas, and were observed even in cases where light microscopy showed no fibrosis in zone 3. In addition to basal laminas, deposition of collagen and defenestration of the endothelial cells were observed. Basal laminas were seen only rarely in biopsies from non‐alcoholics. We suggest that basal lamina formation in acinar zone 3 is initiated by changes in the perisinusoidal space and that it may contribute to impaired liver cell function and possibly initiate liver cell necrosis.
The role of delta superinfection in acute exacerbations of chronic type B hepatitis
Authors: Chu Chia‐Ming , Farci Patrizia , Liaw Yun‐Fan , Balestrieri Angelo , Thomas Howard C.
Published: August 2010

ABSTRACT— Serum specimens collected from patients with chronic type B hepatitis during their acute exacerbations were studied with radioimmunoassay for serological markers of delta (δ) agent infection. Serum δ antigen was negative in all 56 hepatitis B e antigen (HBeAg)‐positive and 25 anti‐HBe‐positive acute exacerbations. Two (3.6%) HBeAg‐positive and five (20%) anti‐HBe‐positive acute exacerbations were found to be positive for both IgG anti‐δ and IgM anti‐δ. The incidence in anti‐HBe‐positive patients was significantly higher than in HBeAg‐positive patients. These results indicated that some of the acute exacerbations, particularly in anti‐HBe‐positive phase, could be attributed to δ‐superinfection. However, acute exacerbations preceding HBeAg/anti‐HBe seroconversion were not associated with δ‐superinfection.
Characterization of effector cells in lymphocytotoxicity to autologous hepatocytes in HBsAg‐positive and autoimmune chronic active hepatitis (CAH)
Authors: Barnaba V. , Levrero M. , Franco A. , Ruberti G. , Musca A. , Bonavita M. S. , Balsano F.
Published: August 2010

ABSTRACT—Peripheral blood lymphocyte subsets involved in cytotoxicity to autologous hepatocytes have been characterized by isolation on antibody‐coated Petri dishes in autoimmune and HBsAg‐positive chronic active hepatitis (CAH). In autoimmune CAH and in HBsAg‐positive CAH without HBcAg in liver tissue, cytotoxicity is sustained by non‐T lymphocytes and is confined to M1‐positive cells bearing Fc receptors: M1 cytotoxicity inhibition by adding aggregated IgG suggests that these cells are responsible for an antibody‐dependent cell‐mediated mechanism (ADCC). Moreover, when T‐enriched fractions were separated in T4, T8 and 5/9 positive subsets, only the first one showed a significant cytotoxicity: T4 positive cells might act as cytotoxic T cells or might be involved in delayed type hypersensitivity (DTH) reactions. Cytotoxic T lymphocytes in HBsAg‐positive CAH with HBcAg in liver tissue are confined in T8 positive subset, while helper/inducer T cells (T4 positive or 5/9 positive) seem to play an important role only in the induction of cell‐mediated injury against hepatocytes. The inhibition of T cell‐cytotoxicity by preincubating liver cells with monoclonal antibody (Mab) anti‐HLA AB and not with Mab anti‐HLA DR or aggregated IgG supports the involvement of the class I major histocompatibility complex (MHC) expressed on the hepatocyte surface.
Pathologic features of the liver in acquired immune deficiency syndrome (AIDS)
Authors: NAKANUMA YASUNI , LIEW CHOONG T. , PETERS ROBERT L. , GOVINDARAJAN SUGANTHA
Published: August 2010

ABSTRACT— The livers of 26 adult males with acquired immune deficiency syndrome (AIDS) were reviewed. The occurrence of portal tracts with diminished lymphocytes, probably reflecting generalized exhaustion of the lymphoid system, was a characteristic morphologic change, and was found in all cases. Kupffer cell hyperplasia was also a frequent finding and probably reflected generalized infection(s). Punched‐out clusters of foamy histiocytes filled with acid‐fast bacilli, typical for infection with Mycobacterium avium intracellulare (MAC), were found in three patients. In addition, MAC was cultured from two livers without the foamy histiocytic changes. Chronic viral hepatitis (three cases) and deposition of polarizable materials (one case) in the liver might be related to unusual habits of patients with AIDS. In conclusion, livers from patients with AIDS disclosed several kinds of lesions reflecting underlying or associated conditions in AIDS, but these did not contribute to the cause of death in our patients.
Evaluation of liver volume and liver function following hepatic resection in man
Authors: Zoli M. , Marchesini G. , Melli A. , Viti G. , Marra A. , Marrano D. , Pisi E.
Published: August 2010

ABSTRACT— In a longitudinal study liver volume and liver function were measured in a series of 12 patients undergoing partial liver resection for focal hepatic lesions. Ultrasonography revealed that liver volume, reduced by about 50% by the resection, progressively increased, and 6 months after surgery it returned to nearly normal values. A variable reduction in routine liver function tests was observed, possibly reflecting the influence of the different reserve synthetic capacity of the liver and, in the early postoperative phase, plasma half‐life of liver products and blood loss or changes in plasma volume. The galactose elimination capacity was only marginally reduced in the early period (from a pre‐surgery value of 2.49 ± SE 0.21 mmol/min to 2.31 ± 0.14 after 7 days; p = ns) and reached a nadir at 14 days (1.97 ± 0.16; p<0.001). When expressed per unit of liver volume, the galactose elimination (22 ± 2 μmol/min per unit before resection) progressively decreased during the regeneration phase from 36 ± 4 at 14 days to 26 ± 3 at 6 months (P vs 14‐day: <0.01). At 6 months both galactose elimination and galactose elimination per unit of liver volume were no longer different from baseline values. Our data show that, following hepatic resection, both liver volume and liver function increase and progressively return to nearly normal values. In agreement with data obtained in animal studies, it appears that the metabolic activity of the remaining parenchyma is increased in the early postoperative phase, and it slows down in the course of regeneration.
The psycho‐social impact of a liver transplant programme
Authors: Tymstra Tj. , Bucking J. , Roorda J. , van den Heuvel W. J. A. , Gips C. H.
Published: August 2010

ABSTRACT— Through in‐depth interviews, an inventory has been made of the experiences of 18 liver patients who have been considered for or undergone a liver transplant. Interviews were also held with the patients' relatives. Chronic patients especially seem to regard a transplant as their last chance, and all their hopes become based on it. The strict selection procedure is distressing, and being turned down causes negative feelings. As far as the operation itself is concerned, patients are inclined to create high success rates for themselves in relation to their survival chances and the expectations of quality of life. For some patients a transplant means a marked improvement in the various aspects of their functioning. Others are not so fortunate, but do not give up hope of improvement. From the relatives of the patients who had died post‐operatively, no negative feelings were encountered over the ‘failure’ of the ‘technology’
Clinical, biochemical and histological features of primary haemochromatosis: a report of 67 cases
Authors: Conte Dario , Piperno Alberto , Mandelli Clara , Fargion Silvia , Cesana Marina , Brunelli Lucia , Ferrario Luciana , Velio Pietro , Zaramella Maria Grazia , Tiribelli Claudio , Fiorelli Gemino , Bianchi Paolo A.
Published: August 2010

ABSTRACT— In 67 patients (mean age 51 years, range 26–79), at diagnosis of primary haemochromatosis (PH), grade III or IV liver iron overload was present in all cases, cirrhosis in 85%, transferrin saturation > 80% in 75%, serum ferritin > 1000 μg/1 in 84%, and overt diabetes in 48%. Alcohol intake was > 150 g/day in 11 patients; six were chronic hepatitis B surface antigen (HBsAg) carriers. HLA‐A3 and B7 antigens were present in 64% and 23% versus respectively 22% (p<0.01) and 9% (p<0.025) in controls. Iron overload was found in the stomach, duodenum, skin and bone marrow in 57, 43, 45 and 59% of the patients studied. Sixty‐three patients were followed for 1–260 months (median 24); 43 received regular iron‐depleting treatment and 20 did not because of liver failure, cancer or refusal. Cumulative survival was 79%, 67% and 61% at 1, 4 and 10 years, respectively. Ten patients died from hepatocellular carcinoma and two from extrahepatic cancer. The early high mortality rate was due to some cases of advanced disease or cancer. Cumulative survival in the regularly treated group was 95% at 1 year and 91% at 4 and 10 years, which was higher than in the untreated group.
Ground squirrel hepatitis virus (GSHV) infection and hepatocellular carcinoma in the Canadian Richardson ground squirrel (Spermophilus richardsonii)
Authors: Minuk G. Y. , Shaffer E. A. , Hoar D. I. , Kelly J.
Published: August 2010

ABSTRACT— Sera and livers from 40 Richardson ground squirrels were examined for evidence of ground squirrel hepatitis virus (GSHV) infection and hepatocellular carcinoma. Twenty‐five sera were obtained from fully grown adult ground squirrels and 15 from young ground squirrels estimated to be between 6–8 weeks of age. All animals had been caught in the wild and had spent less than 1 month in captivity. Sixteen sera (40%) had at least one serologic marker of GSHV (2 with GSHV surface antigen, 3 GSHV core antigen, 5 GSHV antibody to core antigen and 11 GSHV antibody to surface antigen). Two cases of hepatocellular carcinoma were detected, both in adult ground squirrels. Tumour tissue and adjacent normal liver tissue were negative for GSHV surface and core antigen by direct immunofluorescence in both livers and negative for GSHV‐DNA by molecular hybridization in the one tumour examined. These results indicate that: A) GSHV is geographically more widespread than previously considered; B) viral transmission occurs early in life, probably via the vertical route; and C) hepatocellular carcinoma is a relatively common finding in these animals while still in their wild state. Any causal relationship between hepatocellular carcinoma and GSHV infection in these animals, however, has yet to be demonstrated.
Acute hepatic failure due to Plasmodium falciparum liver injury
Authors: Joshi Y. K. , Tandon B. N. , Acharya S. K. , Babu S. , Tandon M.
Published: August 2010

ABSTRACT— Nine patients with acute liver failure due to Plasmodium falciparum liver injury admitted to the Rajgarhia Liver Unit of the All‐India Institute of Medical Sciences during 1982–84 are presented. The liver was palpable in all the patients, and eight had splenomegaly. Investigations revealed mild to moderate abnormality in liver function tests. All were negative for the markers of acute infection due to hepatitis A and B viruses. Blood film examination showed P. falciparum alone in seven and along with P. vivax in the remaining two patients. Liver histology, which was identical in all eight patients where liver biopsy was done, showed centrizonal necrosis and hyperplastic Kupffer cells loaded with malarial pigment. All the patients recovered with specific anti‐malarial and supportive treatment. Our observations suggest that malaria due to P. falciparum may present as jaundice and encephalopathy which stimulates acute hepatic failure due to fulminant hepatitis.
Sepsis and cholestasis: the in vitro effects of bacterial products on 14C‐taurocholate uptake by isolated rat hepatocytes
Authors: Minuk G. Y. , Rascanin N. , Sarjeant E. S. , Pai C. H.
Published: August 2010

ABSTRACT‐ Bacterial endotoxins are known to be an important cause of cholestasis, yet not all organisms that cause cholestasis produce endotoxins. In order to determine whether bacterial products other than endotoxins may be involved in the cholestatis process, 14C‐taurocholate (TC) uptake by isolated rat hepatocytes was measured in the presence of mid‐log, stationary and mid‐death phase bacterial broth supernatants from eight common bacterial pathogens. The results were then correlated with a quantitative assessment of endotoxin production by each organism. Supernatants from Haemophilus influenzae, Pseudomonas aeruginosa and Klebsiella pneumonia demonstrated a striking inhibitory effect on bile salt uptake (77.2 ± 6.7, 46.9 ± 6.5 and 32.9 ± 7.1% maximum inhibition of 14C‐TC uptake, respectively) when compared to sterile broth controls. Streptococcus faecalis (Enterococcus), Escherichia coli, Staphylococcus aureus and Bacteroides fragilis products, on the other hand, had relatively minor effects (12.3 ± 5.2, 12.0 ± 7.5, 8.4 ± 6.7 and < 5.0% inhibition respectively), while those from Proteus mirabilis had an intermediate effect (18.5 ± 8.3% inhibition). Bile salt efflux rates (16.0 ± 2.7 and 25.1 ± 4.2 nmol/min/106 hepatocytes, mean ± SEM) were similar in bacteria demonstrating marked uptake inhibition (Haemophilus influenzae, Pseudomonas aeruginosa) when compared to those with only minor inhibitory effects (Staphylococcus aureus, Bacteroides fragilis) (14.3 ± 1.1 and 18.4 ± 2.6 nmol/min/106 hepatocytes, respectively, p > 0.05). 14C‐TC uptake inhibition did not correlate with the amount of endotoxin produced by each organism (r = 0.251). The results of this study indicate that bacteria produce a factor other than endotoxin that significantly inhibits bile salt uptake by isolated rat hepatocytes. It is conceivable that this factor not only contributes to the cholestasis caused by endotoxin‐producing organisms but could also play an important role in the cholestasis caused by infection with non‐endotoxin producing bacteria.
Steroids in chronic B‐hepatitis. A randomized, double‐blind, multinational trial on the effect of low‐dose, long‐term treatment on survival
Authors:   A TRIAL GROUP OF THE EUROPEAN ASSOCIATION FOR THE STUDY OF THE LIVER
Published: August 2010

ABSTRACT‐The effect of long‐term, low‐dose prednisolone treatment on the survival of patients with chronic B‐hepatitis was studied in a randomized, double‐blind multicentre trial. Twenty‐two centres from 11 European countries included 99 patients in the trial. Survival analysis showed 2.9 (95% confidence limit 0.9‐9) times greater mortality in the prednisolone than in the placebo group (P = 0.07). In a Cox regression analysis, correcting for the influence of other prognostic factors, the detrimental effect of prednisolone treatment was unchanged. Mortality increased significantly with age, and patients without piece‐meal necrosis had 7 times higher mortality than those with this change on entry to the trial. It is concluded that long‐term, low‐dose prednisolone treatment is very unlikely to be beneficial, and should be considered harmful in chronic B‐hepatitis, particularly in the most severe and advanced cases.
Portal tract lipogranulomas in liver biopsies
Authors: Delladetsima J. K. , Horn T. , Poulsen H.
Published: August 2010

ABSTRACT— Portal lipogranulomas in liver biopsy specimens were investigated. The incidence of biopsies containing portal lipogranulomas was 2.4%. Out of 20 biopsies with lipogranulomas 10 biopsies contained only one lipogranuloma. Portal lipogranulomas show a distinctive morphology with fat vacuoles surrounded by macrophages. They are consistently found together with parenchymal steatosis and probably originate from parenchymal fat being transported to portal tracts. Portal lipogranulomas are of importance in the differential diagnosis from other granulomas.
Selection criteria and decisions in 375 patients with liver disease, considered for liver transplantation during 1977–1985
Authors: van der Putten A. B. M. M. , Bijleveld C. M. A. , Slooff M. J. H. , Wesenhagen H. , Gips C. H.
Published: August 2010

ABSTRACT— We performed a prospective study on 375 patients with liver disease, 60% female, for whom orthotopic liver transplantation (OLT) was considered during 1977–1985. Fifty‐four per cent had cirrhosis, 8.5% congenital/hereditary disorders, 25% malignant tumour, 6% benign tumour, 2% Budd‐Chiari syndrome, 1.5% acute hepatic failure, 3% other diagnoses, and 10% were under 15 years of age. As of July Ist, 1985, 99 patients (47 chronic active/inactive cirrhosis (CAC/CIC), 28 primary biliary cirrhosis (PBC), five hepatocellular carcinoma (HCC), 19 other diagnoses) were accepted for OLT (median age 40 years, 10% under age 15). By that date, 45 patients (median age 42), had had an OLT (20 CAC/CIC, 15 PBC, three biliary atresia, two HCC, five other diagnoses). Fifty‐four per cent (201 patients) were rejected for transplantation. The primary reasons for rejection were: no indication (11%), age (5%), other surgical procedures possible (3%), severe liver failure (14%), extrahepatic spread of liver tumour (11%), cardiovascular or pulmonary problems (2%), severe hepatic bone disease (1%), and miscellaneous (7%). Thirty per cent of the patients with CAC/CIC, 38% with PBC, 88% with HCC and 71% with biliary atresia were rejected. In the CAC/CIC, PBC and biliary atresia patients severe liver failure was the most frequent reason for rejection (62%, 50% and 60%, respectively). In HCC, extrahepatic tumour spread was the most frequent reason (72%) for rejection. In this category only two patients (7%) ultimately underwent liver transplantation.
Evaluation of an oral bile acid loading test for assessment of liver function in chronic hepatitis A comparison with fasting serum bile acids and i.v. galactose elimination test
Authors: Foberg U. , Broström C. , Fryden A. , Glaumann H. , Kågedal B. , Mårtensson J. , Tobiasson P. , Weiland O.
Published: August 2010

ABSTRACT—In 40 patients with histologically verified chronic hepatitis, (chronic persistent hepatitis, n = 13; chronic active hepatitis without, n = 14; or with cirrhosis, n = 13), of viral and autoimmune origin, serum bile acids (SBA) were measured before and during 3 h after oral ingestion of I g chenodeoxycholic acid (CDA). Fasting SBA were elevated in 22 (55%) patients, whereas the CDA loading test was abnormal in 15 (38%) patients and the galactose elimination was prolonged in 16 (40%) patients. In patients with chronic active hepatitis, 20/27 had elevated SBA either in the fasting state (18/27) or after the CDA loading test (13/27). Normal SBA values were found in 9/13 (70%) patients with chronic persistent hepatitis. Thus, fasting SBA is not sensitive enough to detect mild chronic inflammatory liver disease as chronic persistent hepatitis, but seems to be as sensitive as the galactose elimination or CDA loading tests in detecting potential severe liver disease. Fasting SBA may thus be used as a complement of conventional liver tests in the follow‐up of chronic hepatitis as assessment of liver function. An oral CDA loading and an i.v. galactose elimination test add no further information to that given by fasting serum bile acids.
Immunohistochemical localization of ras p21 and carcinoembryonic antigens (CEA) in cholangiocarcinoma
Authors: Nonomura Akitaka , Ohta Goroku , Hayashi Morimoto , Izumi Ryohei , Watanabe Kishichiro , Takayanagi Nobutatsu , Matsubara Fujitsugu
Published: August 2010

ABSTRACT— An expression of ras p21 proteins on cholangiocarcinoma (CC) (intrahepatic bile duct carcinoma) cells was examined by an immunoperoxidase method using an appropriate dilution of mouse monoclonal antibody RAP‐5, with which no positive staining was obtained in livers with normal histology. Of 44 CCs examined 39 were positive for the antigens; well‐differentiated adenocarcinoma usually showed a diffuse weak, cytoplasmic staining in nearly all tumor cells with the same staining intensity, while in moderately and poorly differentiated adenocarcinoma the expression of p21 varied markedly in intensity from cell to cell in the same cell nest. The number of positive cells decreased with the grade of tumor, and no or little staining was observed in undifferentiated areas. These findings indicate that the expression of ras p21 antigens was lost with increasing dedifferentiation of tumor cells. Carcinoembryonic antigens (CEA) were positive in 42 of 44 CCS. Well‐differentiated adenocarcinoma expressed CEA along the apical surfaces of the tumor glands. With the dedifferentiation of tumor cells, the expression of CEA became prominent not only at the apical surfaces but also on the basolateral surfaces and in the cytoplasms, and further in the surrounding stromal tissue. There was no clear‐cut correlation between the expression of p21 antigens and the production of CEA in CCs.
Identification of different degrees of hepatitis B virus (HBV) replication by serological (HBV‐DNAp, HBcAg and HBV‐DNA) and histological (HBcAg) methods
Authors: Quiroga Juan Antonio , Bartolomé Javier , Porres Juan Carlos , Mora Ignacio , Gutiez Julia , Guio Carlos Hernández , Carreño Vicente
Published: August 2010

ABSTRACT— The incidence of HBV‐DNA polymerase, HBV‐DNA and serum and liver HBcAg in 104 chronic HBsAg carriers was studied. HBV‐DNA was the most frequently detected marker, followed by HBcAg and HBV‐DNAp. According to their individual or combined presence, four different serological patterns of viral replication were discerned: 53 patients had all these markers, 30 had HBV‐DNA but lacked HBV‐DNAp (15 with and 15 without HBcAg) and 21 had no such markers detectable. The simultaneous positivity for all of those markers was observed only in HBeAg‐positive patients. HBV‐DNA alone or along with HBcAg was found in a similar incidence irrespective of the HBe system. Liver HBcAg was found in all but four patients with and in four without HBV‐DNA. Viral DNA concentration was significantly (p < 0.001) higher when HBV‐DNAp tested positive. Indeed, HBeAg rather than anti‐HBe patients had higher (p < 0.005) levels of HBV‐DNA. In HBeAg‐positive patients, the nuclear HBcAg staining was significantly (p < 0.05) higher when HBV‐DNAp tested positive. In DNA polymerase‐negative patients, but positive for HBV‐DNA, those with or without HBcAg had a similar percentage of core antigen staining. The same distribution was seen in anti‐HBe, HBV‐DNA‐positive patients. However, the mean percentage of hepatocytes displaying cytoplasmic HBcAg did not differ significantly among patients with HBV‐DNA, irrespective of the HBe system and the HBV‐DNAp status. Such patients had significantly (p < 0.001) higher ALT levels than those without viral DNA. Active viral replication can be assessed differentially through any of these serum markers and is associated with liver cell necrosis.
HBV‐DNA sequences are rarely detected in the liver of patients with HBsAg‐negative chronic active liver disease and with hepatocellular carcinoma in Italy
Authors: Pontisso P. , Stenico D. , Diodati G. , Marin G. , Caldironi M. V. , Glacchino R. , Realdi G. , Alberti A.
Published: August 2010

ABSTRACT— Hepatitis B virus sequences were studied by molecular hybridization in liver biopsies from patients with HBsAg‐negative chronic liver disease or hepatocellular carcinoma, collected in Italy. Among the 42 patients with chronic liver disease who had no history of drug addiction, alcohol abuse nor evidence of metabolic and autoimmune disorders, only two (5%) had HBV‐DNA sequences in the liver, although 23 of them (57%) were positive for antibodies to HBV in serum. HBV‐DNA was also demonstrated in integrated form in the tumorous tissue of one out of eight cases with HBsAg‐negative hepatocellular carcinoma. These incidences of HBV‐DNA positivity in the liver are lower than those reported from other Mediterranean areas and similar to those of North Europe, United States and Japan, suggesting that etiologic factors other than HBV are responsible for the majority of HBsAg‐negative chronic liver diseases in our region.
Serological assessment of HBcAg and HBV DNA: its prognostic relevance in acute hepatitis B
Authors: Möller B. , Hopf U. , Pöschke S. , Alexander M. , Friedrich‐Jähnicke B. , Mostertz P. , L'age M.
Published: August 2010

ABSTRACT— Treatment of serum precipitates with sodium thiocyanate in patients with hepatitis B virus (HBV) replication results in liberation of circulating hepatitis core antigen (HBcAg) which can be demonstrated radioimmunologically. Follow‐up investigations were performed in 80 patients with acute hepatitis B. Sera were examined for HBcAg, HBV DNA and conventional HBV markers. At the time of admission to hospital 34 of 80 (42%) patients were HBeAg positive. Twenty‐six (76%) of the 34 HBeAg positive patients were HBV DNA positive, and circulating HBcAg was detectable in 25 of 34 (73%) HBeAg positive cases. In patients with uncomplicated courses of acute hepatitis B the serological HBcAg assay and HBV DNA became negative 1 to 8 weeks before elimination of HBeAg and up to 12 weeks earlier than the sera became negative for HBsAg. Five patients (6%) showed transition to chronic hepatitis B with persistence of HBsAg, HBeAg, HBV DNA and HBcAg in serum. One patient with acute hepatitis B and development of chronic hepatitis suffered from acquired immunodeficiency syndrome and showed delayed formation of anti‐HBc. In this case uncomplexed HBcAg was demonstrable during the acute phase of hepatitis B. With the appearance of anti‐HBc HBcAg circulated in a complexed form. The data indicate that serological determinations of HBcAg and HBV DNA can serve as prognostic markers in the early phase of acute hepatitis B. The demonstration of uncomplexed HBcAg in serum of a patient with inadequate formation of anti‐HBc supports the hypothesis that circulating HBcAg is usually complexed by specific antibodies.
Follow‐up study of 582 liver cirrhosis patients for 26 years in Japan
Authors: Tanaka Ryoji , Itoshima Tatsuya , Nagashima Hideo
Published: August 2010

ABSTRACT—A long‐term follow‐up study of liver cirrhosis (LC) was performed in 582 patients diagnosed by peritoneoscopy and liver biopsy in the 26 years from 1958 to 1984. The etiology of LC consisted of hepatitis B virus (HBV) in 21%, alcoholic in 39% and cryptogenic in 39%. Fifty‐nine percent of patients had died. Causes of death were hepatocellular carcinoma (HCC 44%), liver failure (30%), rupture of esophageal varices (14%), gastrointestinal bleeding (4%) and non‐liver‐related causes (8%). HCC accounted for increasing percentages (68%) since 1980. In all groups classified by the etiology, the causes of death had the same order in incidence. The age of onset of LC increased by 10 years from 42 to 52 years old and the age of death by 15 years from 43 to 58 in the 26‐year period. The cumulative survival rate improved over the period. The 50% survival year was 7.9 in total patients, and 7.0, 8.5 and 10.0 in the three periods 1958–64, 1965–74 and 1975–84, respectively. It was 9.5, 6.3 and 9.8 in HBV, alcoholic and cryptogenic, respectively. LC patients survived 40–44% of the life expectancy of the general population in Japan in all age groups. Cox's multiregression life‐table method selected three important prognostic factors from 7 parameters: a poor prognosis with a history of heavy alcohol consumption and old age at onset, and a better prognosis with recent onset.