bluuebunny/crossref_metadata_2025 huggingface dataset:
Alcohol and liver injury: dose‐related or permissive effect?
Authors: Sørensen Thorkild I. A.
Published: August 2010

ABSTRACT— Studies addressing the risk of development of cirrhosis of the liver in relation to alcohol consumption have been based on comparisons at the aggregate population level and, at the individual level, on case‐control studies and cohort studies, and on retrospective and prospective assessment of alcohol consumption. The ideal, but unfeasible, study design for estimation of the risk function is a prospective monitoring of alcohol consumption and recording of the rate of development of cirrhosis per unit of time. Two recent studies, approaching this design, suggested that above a rather low, but not precisely determined, level of alcohol consumption the risk of development of cirrhosis is not further influenced by the amount of alcohol consumed. A critical analysis of previous studies suggests that this risk function is actually compatible with their findings. The contention that alcohol abuse has a permissive rather than a dose‐dependent role in the development of alcoholic liver injury encourages research into the additional factors that must act before the liver injury occurs.
Human chorionic gonadotropin and alpha‐fetoprotein in cholangiocarcinoma in relation to the expression of ras p21: an immunohistochemical study
Authors: Nonomura Akitaka , Mizukami Yuji , Matsubara Fujitsugu , Izumi Ryohei , Nakanuma Yasuni , Hayashi Morimoto , Watanabe Kishichiro , Takayanagi Nobutatsu
Published: August 2010

ABSTRACT— The immunohistochemical localization of human chorionic gonadotropin (HCG) and alpha‐fetoprotein (AFP) was studied in 44 cases with cholangiocarcinoma (CC) to determine the correlation to the expression of ras oncogene product p21 on tumor cells. HCG‐immunoreactivity was found in 10 of 44 cases (23%) and AFP in only one (2.3%), whereas the expression of ras p21 was demonstrated in 39 (88.6%). The incidence of HCG‐positive cells within the tumor was less than 1% in 8 of 10. The incidence of AFP‐positive cells was less than 0.01%. All were histologically classified as adenocarcinoma and none of them had histologic features of trophoblastic tumors, yolk sac tumor or hepatocellular carcinoma. Nine of 10 HCG‐positive and one AFP‐positive CC expressed ras p21 on their tumor cells. However, one HCG‐positive CC was negative for ras p21, though the incidence of HCG‐positive cells within the tumor was 25%. HCG‐ and AFP‐immunoreactivity were more frequently observed in poorly or undifferentiated tumor cells than in moderately or well‐differentiated areas, whereas the expression of ras p21 was more diffuse in well‐differentiated tumor and stronger in moderately differentiated areas, but rarely found in poorly and undifferentiated tumor. These results suggest that HCG production by CC of the usual adenocarcinoma variety is not rare, when compared to AFP production, and is preferentially localized in a small number of poorly differentiated and undifferentiated carcinoma cells, and there is no correlation between the production of HCG or AFP and the expression of ras p21 in CCs.
Prolonged IgM antibodies and histopathological evidence of chronicity in hepatitis A
Authors: McdOnald G. S. A. , Courtney M. G. , Shattock A. G. , Weir D. G.
Published: August 2010

ABSTRACT— The case of a young man with hepatitis A and a chronic course is presented. The patient received a short course of steroid therapy for recurrence of symptoms following acute hepatitis A. Thereafter, liver enzymes have remained marginally elevated for 4 years and annual liver biopsies have shown evidence of chronicity. HAV IgM Ab persisted for 1034 days with subsequent development of HAV IgG Ab. The possibility of other viruses in the aetiology and the role of steroids in the development of chronicity are discussed.
Natural course after the development of cirrhosis in patients with chronic type B hepatitis: a prospective study
Authors: Liaw Yun‐Fan , Lin Deng‐Yn , Chen Tong‐Jong , Chu Chia‐Ming
Published: August 2010

ABSTRACT— To examine the early stage of the natural course of liver cirrhosis, a prospective follow‐up study was conducted in a series of 76 patients with recent development of cirrhosis during the course of chronic type B hepatitis. During a mean follow‐up period of 34.4 months, 45 episodes of acute exacerbation were recorded; the majority of the episodes occurred within 2 years after entry. The calculated annual incidence of acute exacerbation was significantly higher in patients seropositive for hepatitis B e antigen (HBeAg) and/or hepatitis B virus (HBV)‐DNA (25.9%) than in those without these markers (11.9%). Three‐fourths of the acute exacerbations were attributable to the reactivation of HBV. Spontaneous HBeAg seroconversion to anti‐HBe also occurred in the early phase, but less than 30% of the events were preceded by acute exacerbation. Late hepatitis B surface antigen clearance occurred in two patients. Hepatic decompensation, esophageal variceal bleeding and hepatocellular carcinoma developed relatively late in the course of the disease with a calculated annual incidence of 2.3%, 2.3% and 2.8%, respectively. Seven patients (9.2%) died of hepatic failure or variceal bleeding, usually more than 3 years after entry. The estimated 5‐year survival rate was 80%. The results suggest that the natural events of chronic HBV infection, including exacerbation, seroconversion and its sequelae could occur after the development of cirrhosis. In addition, these events might be responsible for the clinicopathological changes and the outcomes of these cirrhotic patients.
Diffuse nodular regenerative hyperplasia of the liver (DNRH). A clinicopathologic study of 24 cases
Authors: Colina F. , Alberti N. , Solis J. A. , Martinez‐Tello F. J.
Published: August 2010

ABSTRACT— The authors report 24 cases of diffuse nodular regenerative hyperplasia of the liver (DNRH) seen in a General Hospital during the last 9 years (prevalence: 3'1/100 000, incidence: 0'34/100 000). DNRH was diagnosed in 0.52% of the liver biopsies and 0.72 of the autopsies. These results suggest that DNHR is probably more frequent than suspected, and 1 DNRH was seen for each 39 biopsied cases of liver cirrhosis. Fourteen patients did not have hepatic symptoms. Portal hypertension was present in 9 cases. The biochemical disturbance most frequently found was a moderate elevation of GGT and APh, associated with slight elevation of SGOT, SGPT and bilirubin levels. Normal liver function tests could be seen (3 cases). Previous exposure to potentially hepatotoxic drugs or chemicals was discovered in 15 cases (62.5%). Diseases associated were circulatory disturbances (6 cases), autoimmune disease (5 cases), hemopathies (5 cases), and visceral carcinomas (4 cases). Two patients were recipients of renal transplant. Nodules distributed through the whole liver tissue were found in 16 cases, while 8 patients showed areas of normal parenchyma in their livers. Impairment of small hepatic vessels was detected in 16 cases. Some uneven cytologic findings were discovered: clusters of small basophilic cells (4 cases), large clear cells (8 cases), and dysplastic hepatocytes (10 cases), which suggests that DNRH could be a preneoplastic condition.
HEPAR: an expert system for the diagnosis of disorders of the liver and biliary tract
Authors: Lucas P. J. F. , Segaar R. W. , Janssens A. R.
Published: August 2010

ABSTRACT— The HEPAR system is a medical expert system intended as a supportive tool for the diagnosis of disorders of the liver and biliary tract. In the system, the role of information from the medical interview, physical examination, and simple non‐invasive diagnostic methods, such as ultrasonography, is emphasized in order to reduce the number of diagnostic procedures to be applied. Medical diagnosis is modelled in the system using the formalism of if‐then rules. Based on patient data available, the system determines whether the data indicate a hepatocellular or a biliary obstructive disorder, and whether or not benign or malignant features are present. Moreover, the system produces a subset of possible diagnoses out of a set of more than 70 diagnostic categories. The system is still under development. In a preliminary study, the HEPAR system has been evaluated using data from 94 jaundiced patients. Conclusions with respect to the hepatocellular or biliary obstructive nature of the disorder, the benign or malignant nature of the disorder, and the final diagnosis, were reached in 95%, 65%, and 80% of the cases, respectively. These conclusions were correct in 85%, 92%, and 80% of the classified cases, respectively. The system was shown not to be sensitive to incompleteness of information.
Histological changes of the liver in experimental graft‐versus‐host disease across minor histocompatibility barriers. IV A study of lymphocyte‐endothelial interaction
Authors: Nonomura Akitaka , Kono Naoko , Yoshida Kazuharu , Mizukami Yuji , Matsubara Fujitsugu , Nakanuma Yasuni
Published: August 2010

ABSTRACT— It has been reported in human hepatic graft‐versus‐host disease (GVHD) that an attachment of lymphocytes to vascular wall, the feature called “endothelialitis”, is the most important predictive histologic sign of GVHD. However, its precise nature and significance in GVHD are still unknown. We developed experimental mouse GVHD across minor histocompatibility barriers and examined the lesion during a 14‐month period after transplantation. The lesion was transiently found, appearing first at 4 days after transplantation, reaching a maximal level at 2 weeks and disappearing 5 weeks after transplantation. Electron microscopically, an intimate interaction between lymphocyte and endothelial cell was demonstrated. Lymphocytes showed irregular cytoplasmic processes and pseudopods and were in close contact with endothelial cells. Lymphocytes frequently penetrated in between and under the endothehal cells, and migrated into the perivascular spaces. Immunohistochemical analysis revealed that the vast majority of lymphocytes attached to the endothelial cells are helper/inducer T cells, indicating the cardinal role of helper/inducer T cell in lymphocyte‐endothelial cell interactions. These results, together with previous evidence of the presence of Ia antigens and an antigen‐presenting ability of vascular endothelial cells, suggest that the attachment of lymphocytes to the vascular endothelial cells in the early course of GVHD may represent an in situ morphologic representation of antigen presentation by endothelial cells to helper T cells.
Kupffer cell function in chronic ethanol‐fed rats
Authors: Shiratori Yasushi , Teraoka Hitoshi , Matano Sunao , Matsumoto Kazunori , Kamii Kazuo , Tanaka Mitsugu
Published: August 2010

ABSTRACT— In an attempt to clarify the Kupffer cell function in alcoholism, chronic ethanol‐fed rats were investigated. The clearance of latex particles in the rat was analysed to estimate the function of the reticuloendothelial system in the liver, and the phagocytic function of Kupffer cells was measured by counting particles in the cell after isolation of non‐parenchymal cells by collagenase digestion of the liver following an injection of latex particles and subsequently by staining of endogenous peroxidase activities. In addition, the number of Kupffer cells and their phagocytic function were examined histologically in fresh frozen sections of liver after an injection of particles. Serum ethanol concentration in the ethanol‐fed rats was 10–60 μmol/1. The clearance of latex particles was markedly reduced in the ethanol‐fed rats as compared with the paired controls (P < 0.01). Markedly decreased‐phagocytic function was found in 20% of Kupffer cells in the chronic ethanol‐fed rats. The number of Kupffer cells in the ethanol‐fed rats was increased as compared with the paired control rats. Chemotaxis analysis revealed that hepatocytes when incubated with ethanol, produced chemotactic factor for Kupffer cells and polymorphonuclear cells. These abnormal Kupffer cell functions may contribute to the pathogenesis of alcoholic liver disease.
Sanded nuclei in delta patients
Authors: Moreno A. , Cajal S. Ramón Y , Marazuela M. , Carreño V. , Milicua J. M. , Cerezo E. , Cuesta C. , Oliva H.
Published: August 2010

ABSTRACT— Sanded nuclei are nuclei with eosinophilic inclusions identified by light microscopy in cases of chronic hepatitis B virus infection. In hematoxylin and eosinstained sections, these inclusions have an almost homogeneous, finely granular texture giving a sandy appearance. They have been related to excess hepatitis B core antigen formation. We have studied liver biopsies from two HBsAg positive immunosuppressed patients with numerous sanded nuclei, morphologically identical to those previously described in hepatitis B. Immunohistochemically, sanded nuclei showed a strong nuclear positivity for delta antigen, but were negative for hepatitis B core antigen. Hepatitis B core particles were not demonstrable by electron microscopy. To our knowledge, this is the first time that sanded nuclei have been related to hepatitis delta virus (HDV) infection.
Reactivation of viral replication in anti‐HBe positive chronic HBsAg carriers
Authors: Krogsgaard Kim , Aldershvile Jan , Kryger Peter , Pedersen Court , Andersson Poul , Dalbøge Henrik , Nielsen Jens Ole , Hansson Bengt Göran
Published: August 2010

ABSTRACT— Reactivation of hepatitis B virus replication was investigated in an unselected group of 44 HBV DNA negative, anti‐HBe positive chronic HBsAg carriers. Twenty‐five patients (54%) were intravenous drug addicts and 7 (16%) were male homosexuals. Sixteen patients had evidence of delta infection and five of the seven male homosexuals had human immunodeficiency virus infection. The patients were followed for 1 to 180 months (median, 24 months) while HBV DNA negative, anti‐HBe positive. Reactivation, defined as reappearance of HBV DNA or HBeAg, or both, was detected in six patients corresponding to an annual reactivation rate of 5%. Reactivation in four patients was detected by reversion to HBV DNA positivity only, whereas HBeAg/anti‐HBe status remained unchanged. Two patients became both HBV DNA and HBeAg positive. None of the patients developed hepatitis‐like symptoms and transaminase elevation was only observed in two patients. Reactivation in two patients was ascribed to human immunodeficiency virus infection and in one patient to chronic lymphatic leukaemia. It is concluded that HBV DNA seems to be superior to HBeAg in the detection of reactivation of HBV replication and that reactivation associated with clinical symptoms leading to progression in chronic liver disease is a rare event in the population studied.
Expression of cytokeratin 19 during human liver organogenesis
Authors: Stosiek P. , Kasper M. , Karsten U.
Published: August 2010

ABSTRACT— Immunohistochemistry with monoclonal anti‐cytokeratin antibodies has revealed the presence of cytokeratin 19 in embryonic and early fetal hepatocytes. With the differentiation of bile ducts at about the 10th week, cytokeratin 19 disappears from liver cells but remains in bile duct cells. This marks an important step in the organogenesis of the liver.
The synthesis of glycosaminoglycans in isolated hepatocytes during experimental liver fibrogenesis
Authors: Meyer D. , Zimmmermann T. , Müller D. , Franke H. , Dargel R. , Gressner A. M.
Published: August 2010

ABSTRACT— During human and experimental liver fibrogenesis, the pattern of glycosaminoglycans in fibrotic liver matrix is greatly changed by severalfold increases of hyaluronic acid, chondroitin sulfate, and dermatan sulfate, respectively. The present study aimed to determine whether hepatocytes take part during fibrogenesis in the alteration of the glycosaminoglycan profile in liver matrix. Rats received thioacetamide orally for 2 and 10 weeks, respectively. After 10 weeks a typical micronodular cirrhosis had developed. Hepatocytes isolated at these time points were characterized by light and electron microscopy and incubated for up to 4 h in suspension cultures in [35S]‐sulfate and [3H]‐glucosamine containing medium to study the synthesis and intra‐/extracellular distribution of total and specific types of glycosaminoglycans. A biphasic change of glycosaminoglycan synthesis in hepatocytes was found. After 2 weeks of TAA‐treatment parenchymal cells synthesized about 25% more labeled glycosaminoglycans than control liver cells, but at 10 weeks the synthesis was reduced by more than 40%. Thus, between 2 and 10 weeks of TAA‐treatment hepatocellular glycosaminoglycan synthesis decreased by more than 50%. The major portion of newly synthesized glycosaminoglycans was nitrous acid labile and, hence, identified as heparan sulfate. Its fractional synthesis decreased from 0.90 in control cells to 0.84 (2 weeks TAA) and 0.76 (10 weeks TAA), respectively. Thus, the absolute synthesis of heparan sulfate was reduced by 50% in hepatocytes from cirrhosis liver. Eighty to 90% of labeled glycosaminoglycans remained cell‐associated. Hyaluronic acid was detected neither in normal hepatocytes nor in hepatocytes from injured liver. We conclude from these data that parenchymal liver cells will not contribute actively to the accumulation of galactosaminoglycans (chondroitin sulfate, dermatan sulfate) and hyaluronic acid in the extracellular matrix during fibrogenesis. The diminished rate of synthesis of heparan sulfate in hepatocytes from cirrhotic liver might explain its fractional decrease in cirrhotic liver matrix.
Origin and involution of hyperplastic bile ductules following total biliary obstruction
Authors: Gall John A. M. , Bhathal Prithi S.
Published: August 2010

ABSTRACT— The origin of biliary epithelial cells (BEC) lining hyperplastic bile ductules in the liver in biliary disease is uncertain. Depending on the underlying condition, the hyperplastic BEC may arise by multiplication of existing BEC, transdifferentiation of liver cells to BEC or by both mechanisms. Using histological, autoradiographic and immunohistochemical techniques, the development of these ductules was assessed in rats following total biliary obstruction (TBO) for periods of up to 50 days. Histologically, a biliary cirrhosis developed after 21 days. Apoptosis was observed in both liver cells and BEC at all stages following TBO, and focal involution of hyperplastic ductules by this mode of cell deletion was noted at 50 days. The 3H‐thymidine labelling index was approximately 25 times greater (p<0.0005) than control values in both liver cells and BEC at all stages following TBO, reaching peak values at 48 h of 6.07±0.82% for liver cells and 15.99±1.47% for BEC. In sections stained by the immunoperoxidase technique and using a prekeratin antiserum to identify BEC, an increase in the number of canals of Hering was observed at days 7 and 21. An intermediate‐type cell possessing the morphological appearance of a liver cell and expressing prekeratin antigens was seen in an occasional canal of Hering. On the basis of the high cell replication rate of liver cells and BEC and the very occasional intermediate‐type cell, it was concluded that hyperplastic BEC are derived essentially from existing BEC by cell division. The contribution to the BEC pool from an intermediate cell type within the canals of Hering was small.
Ascitic fluid concentrations of fibronectin and cholesterol: comparison of differential diagnostic value with the conventional protein determination
Authors: Gerbes Alexander L. , Xie Yining , Mezger Jörg , Jüngst Dieter
Published: August 2010

ABSTRACT— Ascitic fluid concentrations of fibronectin, cholesterol and protein were determined in 95 patients: 38 with cirrhosis of the liver, 10 with miscellaneous nonmalignant diseases, 43 with peritoneal carcinomatosis and 4 with liver metastases or hepatocellular carcinoma. Fibronectin, cholesterol and protein at discrimination values of 7.5 mg/100 ml, 45 mg/100 ml and 3.0 g/100 ml, respectively, separated patients with peritoneal carcinomatosis from patients with cirrhosis with an efficiency of 94%, 90% and 85%, respectively. Thus, ascitic fluid determinations of fibronectin and cholesterol offer good discrimination of cirrhotic ascites from ascites related to peritoneal carcinomatosis, superior to the conventional protein determination. However, the failure of all parameters to distinguish ascites caused by miscellaneous nonmalignant diseases from malignancy‐related ascites underscores the importance of highly specific methods to confirm a suspected diagnosis of malignancy‐related ascites.
Quantitative changes in acid phosphatase, alkaline phosphatase and 5‘‐nucleotidase activity in rat liver after experimentally induced cholestasis
Authors: Frederiks Wilma M. , van Noorden Cornelis J. F. , Aronson Daniël C. , Marx Frans , Bosch Klazina S. , Jonges Geertruida N. , Vogels Ilse M. C. , James Jan
Published: August 2010

ABSTRACT— Acid phosphatase, alkaline phosphatase and 5′‐nucleotidase activities were analyzed cytophotometrically in cryostat sections of rat liver up to 8 weeks after ligation and transsection of the common bile duct. Ligation resulted in cholestasis and induced alterations in both localization and activity of the enzyme investigated. The cellular distribution but not the activity of acid phosphatase changed in liver parenchyma. In control liver, the final reaction product was localized as discrete granules in the bile canalicular region of hepatocytes. The final reaction product was precipitated more diffusely within the cytoplasm after induction of cholestasis, most probably due to increased fragility of lysosomal membranes. In control liver, alkaline phosphatase activity was low and localized in the bile canalicular plasma membranes only. The total parenchymal activity increased threefold after the induction of cholestasis and is considered to be a compensatory mechanism in order to enhance the excretion of bile salts from hepatocytes. 5′‐Nucleotidase was present at the bile canalicular and sinusoidal surfaces of plasma membranes of hepatocytes in control liver; total activity in pericentral areas was significantly higher than in periportal areas. Induction of cholestasis resulted in higher total activity and redistribution of the activity over all three surfaces of the plasma membranes, whereas heterogeneity over the different zones of the acinus disappeared. The appearance of the enzyme at lateral plasma membranes is suggested to be related to the formation of new sites for bile salt transport out of the hepatocytes. With respect to all three enzymes studied, alterations of liver parenchymal cells due to a disturbed bile transport were already established during the first week of cholestasis.
Calcium‐associated cytoprotective effect of taurine on the calcium and oxygen paradoxes in isolated rat hepatocytes
Authors: Nakashima Toshiaki , Seto Yoshifumi , Nakajima Toshikazu , Shima Toshihide , Sakamoto Yoshikuni , Cho Ninko , Sano Atsushi , Iwai Masaki , Kagawa Keizo , Okanoue Takeshi , Kashima Kei
Published: August 2010

ABSTRACT— Our study was designed to determine the calcium and oxygen paradoxes in isolated rat hepatocytes, and to evaluate the cytoprotective effects of taurine on hepatocytes during oxygenation, hypoxia, and on these paradoxes. The calcium and oxygen paradoxes were clearly revealed in isolated rat hepatocytes. As the formation of the superoxide radical was accelerated by the hyperbaric conditions and the calcium ions, drugs such as superoxide dismutase and a calcium channel blocking agent (verapamil), prevented these paradoxes. Taurine decreased the oxygenation‐induced lipid peroxidation of hepatocytes, and prevented the hypoxia‐induced hepatocyte death in a calcium‐containing medium, but not in a calcium‐free medium. Taurine also protected the hepatocytes from injuries associated with the calcium and oxygen paradoxes due to the inhibition of sudden calcium influx into the hepatocytes.
Liver disease among Polish alcoholics. Contribution of chronic active hepatitis to liver pathology
Authors: Laskus T. , Slusarczyk J. , Lupa E. , Cianciara J.
Published: August 2010

Abstract— A group of 70 chronic alcoholics – 65 men and 6 women – has been studied. HBsAg was found in 11 (16%), and at least one marker of HBV infection was present in sera from 31 (44%) persons, these results being significantly higher than in a matched control population. The commonest single histological patterns were: steatosis (18 cases), and alcoholic hepatitis (18 cases), followed by normal liver (14 cases) and chronic active hepatitis (12 cases). Cirrhosis was diagnosed in only 4 cases. Five cases of chronic active hepatitis could be attributed to infection with HBV or HDV; in the remaining 7 cases the etiology was unclear. Infection with HBV seems to play an important role as the cause of liver disease among alcoholics in Poland, and chronic active hepatitis of various etiology may be an important form of liver pathology among them.
Application of a numerical scoring system for assessment of histological outcome in patients with chronic posttransfusion non‐A, non‐B hepatitis with or without antibodies to hepatitis C
Authors: Mattsson Lars , Weiland Ola , Glaumann Hans
Published: August 2010

Abstract— A numerical scoring system was applied and compared to the conventional histological classification to assess the histological status of liver specimens from 37 patients with chronic posttransfusion non‐A, non‐B hepatitis followed for 7 to 105 months (mean 35 months). Four histological categories of alterations were assessed and scored: piecemeal necrosis (PMN), fibrosis and cirrhosis, lobular necrosis and portal inflammation. Sequential liver biopsies were obtained from 19 patients. PMN was generally mild but still predictive of progressing fibrosis. Thus, in none of the biopsies from four patients with initial PMN score 0 was there any increase in the fibrosis score in the follow‐up biopsy, while in 10/15 (67%) patients with an initial PMN score of ± 1 the fibrosis score increased with time (p = 0.033). Lobular necrosis and portal inflammation were not predictive of progressing fibrosis. Judging from the scoring method, 22% of all the 37 patients displayed cirrhosis and 27% bridging fibrosis in the latest liver biopsy performed. Patients with antibodies to hepatitis C did not differ in histological status or outcome from those without antibodies to hepatitis C. It is concluded that the scoring system can be used to monitor the histological long‐term follow‐up in patients with chronic posttransfusion non‐A, non‐13 hepatitis, and offers a means of predicting the histological outcome.
Clinicopathological characteristics of hepatocellular carcinoma bearing Mallory bodies: an autopsy study
Authors: Hoso Masahiro , Nakanuma Yasuni
Published: August 2010

Abstract— Mallory bodies are known to occur in hepatocellular carcinoma. The simple question whether or not there are any clinicopathological features characterizing Mallory body‐positive hepatocellular carcinoma remains unresolved to date. The present study of 200 consecutive autopsy cases of hepatocellular carcinoma showed several important differences between 49 cases bearing Mallory bodies and 151 cases bearing no Mallory bodies in carcinoma cells. The patients in the former group were older, showed a higher association rate of liver cirrhosis, and their liver weight was lighter. As to the gross pathology of hepatocellular carcinoma, the nodular type was relatively frequent in Mallory body‐positive hepatocellular carcinoma, while the massive and diffuse types were relatively frequent in Mallory body‐negative cases. The frequency of extrahepatic metastases in the Mallory body‐positive group was lower than that in the Mallory body‐negative cases. The reasons for these differences remain speculative.
Demonstration of nucleolar organizer regions in intrahepatic bile duct carcinoma by the silver‐staining technique
Authors: Nonomura Akitaka , Matsubara Fujitsugu , Mizukami Yuji , Izumi Ryohei , Nakanuma Yasuni , Kurumaya Hiroshi , Watanabe Kishichiro , Takayanagi Nobutatsu
Published: August 2010

Abstract— A silver colloid technique to identify argyrophilic nucleolar organizer region associated protein (AgNOR) was applied to 43 cases of intrahepatic bile duct carcinoma (cholangiocarcinoma, CC), 2 with bile duct adenoma (BDA), 5 with focal duct epithelial hyperplasia (FEH) associated with hepatolithiasis, 15 with posthepatitic ductular proliferation (PHDP) associated with massive or submassive hepatic necrosis and 20 of normal liver. In the present study, only discrete, easily counted black dots within nuclei and silver‐stained nucleolus were counted under a magnification of X 400 without oil‐immersion objectives. The mean AgNOR count of CC was significantly higher than those of BDA, FEH, PHDP and normal controls (P>0.05, P>0.001, P>0.01, and P>0.001, respectively). Among CCs the mean AgNOR numbers of papillary adenocarcinoma (pap), moderately (tub2) and poorly differentiated (por) adenocarcinoma, and adeno‐squamous carcinoma (as) were significantly higher than that of normal controls (P > 0.01, P > 0.001, P > 0.001 and P > 0.001, respectively), and those of tub2, por and as were also significantly higher than those of BDA, FEH and PHDP, whereas that of well differentiated tubular adenocarcinoma (tub 1) was not different from those of BDA, FEH, PHDP and normal controls, and that of pap was not different from those of BDA, FEH and PHDP. The mean numbers of AgNORs of BDA and FEH were not different from that of normal controls, whereas that of PHDP was significantly higher than that of normal controls (P > 0.01). Interestingly, the mean AgNOR counts of tubular adenocarcinoma were increased with histologic tumor grades. All cases with AgNOR counts of more than 2.24 had CC. Furthermore, not only quantitative but also striking qualitative abnormalities of AgNORs were seen in CCs. Large and/or irregularly shaped AgNORs without uniformity in size and density were characteristic for CCs, even in well differentiated adenocarcinoma, in contrast to the small, round, regular AgNORs seen in normal bile duct epithelium and rather large but regular AgNORs seen in benign bile duct lesions. These results indicate that the enumeration of AgNORs in various bile duct lesions is useful to identify moderate and high grade CCs and to evaluate tumor grade, but not useful to discriminate well differentiated adenocarcinoma from benign lesions. In case of normal or equivocal AgNOR counts, the presence of large and/or irregularly shaped AgNORs without uniformity in size and density would favor a diagnosis of carcinoma rather than benign counterparts.
Endoscopically inserted biliary endoprosthesis in malignant obstructive jaundice A survey of the literature
Authors: NAGGAR ESSAM , KRAG EINAR , MATZEN PETER
Published: August 2010

ABSTRACT— Eighty‐seven publications in English on endoscopic bile duct stenting for palliation of obstructive jaundice were electronically or manually retrieved. Only eight of these studies were found to represent series of more than 20 patients and to include only a single presentation of data from patients published more than once. These eight studies refer to data on 856 patients, of whom 702 are from four open series, whereas 154 are from four randomized trials comparing endoscopic insertion of endoprosthesis to percutaneous stents or surgical by‐pass. Endoscopic insertion was successful in about 90% of the patients. Stent diameters were 7–12 French. Patient survival was not affected as it is governed by the natural history of the underlying malignant disease. Endoscopic endoprosthesis was superior to percutaneous stenting and equal to surgical by‐pass, but probably less resource consuming. The most important unsolved problem is the tendency to cholangitis and clogging of endoprostheses. Some suggestions concerning questions to be addressed in a more uniform manner in future publications on this subject are presented.
Liver‐derived high density lymphocytes as a new member of resident cells in mouse liver
Authors: MATSUNAGA YOUICHI , SAIBARA TOSHIJI , ONISHI SABURO , YAMAMOTO YASUTAKE , ENZAN HIDEAKI
Published: August 2010

ABSTRACT— Pit cells, which are recovered in low density fraction of lymphocytes derived from the liver (L‐Fr. 1,2), are recognized as perisinusoidal cells. In the present study, the accumulation of liver‐derived low (L‐Fr. 1,2) and high (L‐Fr.3,4) density 51Cr‐labeled lymphocytes was assessed in the liver, spleen and peripheral blood of syngeneic BALB/c mice in comparison with those derived from the spleen (S‐Fr.1,2 and S‐Fr.3,4) and peripheral blood (P‐Fr.1,2 and P‐Fr.3,4). L‐Fr. 1,2, L‐Fr.3,4 and P‐Fr.1,2 accumulated selectively in the liver, whereas P‐Fr.3,4 did not accumulate in the liver. L‐Fr.3,4 was composed of two major subpopulations; Thy l+CD4+ and Thy1 + CD8 +. This suggested that L‐Fr.3,4 were distinctive from P‐Fr.3,4 or L‐Fr.1,2 and inhabited the liver. P‐Fr.1,2 and S‐Fr.1,2 tended to accumulate in the liver and 51Cr labeled P‐Fr.1,2 and S‐Fr.1,2 were recovered mainly in L‐Fr.1,2, L‐Fr.3,4, S‐Fr.1,2 and P‐Fr.3,4 48 h after the transfer of these cells, suggesting that a part of P‐Fr.1,2 and S‐Fr.1,2 might be in dynamic equilibrium with those of L‐Fr.1,2 and could be a part of the source of L‐Fr.3,4. Results also suggested that some of L‐Fr.1,2 of T cell lineage might change into L‐Fr.3,4 in the liver and might be released into the systemic circulation. Thereafter, L‐Fr.3,4 might behave as P‐Fr.3,4 and no longer show organ‐specific accumulation.
Iron load increases ferritin synthesis and secretion in adult human hepatocyte cultures
Authors: Lescoat G. , Hubert N. , Moirand R. , Jego P. , Pasdeloup N. , Brissot P.
Published: August 2010

ABSTRACT— In order to determine if iron load was able to stimulate specifically ferritin synthesis and secetion in adult human hepatocytes, primary cultures were submitted to increasing concentrations of ferric iron. The following results were obtained: 1. iron incorporation within the hepatocytes increased as a function of culture time and reached a high level after 48 h of treatment; 2. a dose‐dependent significant stimulation of ferritin synthesis and secretion was observed when the medium iron concentration increased from 1 to 40 μmol · l‐1; 3. transferrin and albumin secretions were unaffected. The present data demonstrate that, in adult human primary cultures, iron load increases ferritin synthesis and secretion in a specific manner.
Histological outcome in interferon alpha‐2b treated patients with chronic posttransfusion non‐A, non‐B hepatitis
Authors: Schvarcz Robert , Glaumann Hans , Weiland Ola , Norkrans Gunnar , Wejstål Rune , Frydén Aril
Published: August 2010

ABSTRACT— The histological outcome in liver biopsies following 9 months of interferon alpha‐2b treatment was assessed in detail in 19 patients with chronic posttransfusion non‐A, non‐B hepatitis (PTH‐NANB) and compared with 12 untreated PTH‐NANB patients. Fourteen (74%) treated and 7 (58%) control patients were reactive for antibodies against hepatitis C virus (anti‐HCV). Liver biopsies taken before and after the 9‐month period were scored numerically for portal inflammation, piecemeal necrosis (PMN) and fibrosis, without knowledge of whether the specimens came from control or treated patients. There were no score differences in the initial biopsies between the treated and control group. In the follow‐up biopsies the treated group showed significantly less portal inflammation, PMN and fibrosis than the control group (p < 0.05–0.01). When paired samples from the treated group were compared, significantly regressed portal inflammation, PMN and fibrosis were noted in the follow‐up biopsies (p < 0.05–0.001). The presence or not of anti‐HCV antibodies in serum had no impact on the histological response to interferon treatment. We conclude that a 9‐month course of interferon alpha‐2b treatment significantly diminishes not only inflammation but also fibrosis in the liver of patients with PTH‐NANB whether they are anti‐HCV reactive or not.
Reversible cholestasis with bile duct injury following azathioprine therapy. A case report
Authors: Horsmans Y. , Rahier J. , Geubel A. P.
Published: August 2010

ABSTRACT— A 67‐year‐old patient, with primary polymyositis and without previous evidence of liver disease, developed clinical and biochemical features of severe cholestasis 3 months after initiation of azathioprine therapy. Liver biopsy showed cholestasis with both cytological and architectural alterations of interlobular bile ducts. Azathioprine withdrawal resulted after 7 weeks in the resolution of clinical and biochemical abnormalities. It is believed that this is the first reported case of reversible azathioprine‐induced cholestasis associated with histological evidence of bile duct injury.
Detection of proliferating hepatocytes in patients with acute hepatic failure by mitotic figures and a monoclonal antibody against DNA polymerase alpha
Authors: Seki Shuichi , Sakaguchi Hiroki , Kawakita Nobuyoshi , Yanai Atsushi , Kuroki Tetsuo , Mizoguchi Yasuhiro , Kobayashi Kenzo , Monna Takeyuki
Published: August 2010

ABSTRACT— Information on the ultrastructure and phenotypes of proliferative hepatocytes is scarce, so we set out to detect proliferating hepatocytes immunohistochemically by use of a monoclonal antibody against DNA polymerase alpha (DNA‐PA). The findings from this method were compared with conventional features, such as mitotic figures, and hepatic regeneration after injury was considered in the light of these findings. The subjects of the basic study were 23 patients with acute hepatic failure. There were 6.8 ± 5.5 (mean ± SD) mitotic hepatocytes per 1000 hepatocytic nuclei, and 209 ± 158 hepatocytes stained for DNA‐PA per 1000 hepatocytic nuclei. By light and electron microscopy (n=4), hepatocytes stained for DNA‐PA showed various morphological features, including development of organelles, but some resembled hepatocytes in mitosis. Accordingly, this histochemical method may be useful in studies of hepatic regeneration. In acute confluent necrosis, when hepatocytic proliferation is urgently needed for survival, small hepatocytes next to necrotic areas (probably immature cells, to judge from the development of their organelles) were predominant in hepatic regeneration. These findings suggest that hepatocytes in different stages of development can easily enter the mitotic cell cycle repeatedly when rapid regeneration is needed.
Acute encephalopathy with hepatic steatosis induced by pantothenic acid antagonist, calcium hopantenate, in dogs
Authors: Noda Shousaku , Haratake Joji , Sasaki Ayato , Ishii Nobuyoshi , Umezaki Hirotoshi , Horie Akio
Published: August 2010

ABSTRACT— In Japan, acute encephalopathy with hepatic steatosis resembling Reye's syndrome has been reported to occur after treatment with the pantothenic acid antagonist, calcium hopantenate. We studied the causal relationship and the pathogenesis in dogs. The agent was administered to seven dogs at increasing doses over a period of 8 weeks. Anorexia, vomiting, and diarrhea were common clinical findings. In four dogs, coma suddenly developed after the appearance of gastrointestinal signs. Three animals died during periods when they were not under direct observation. The effects of the agent appear to be related to dose. Laboratory findings representing significant changes at the time of coma included hypoglycemia, leukocytosis, hyperammonemia, hyperlactatemia, and elevated levels of serum transaminases. Microvesicular hepatic steatosis and mitochondrial abnormalities were consistent pathological findings. The hepatic mitochondria were enlarged and characterized by an increased number of cristae and the presence of crystalloid inclusions. In a second group of four dogs, pantothenic acid was given in addition to and in the same amount as calcium hopantenate at increasing doses over a period of 8 weeks. All four dogs survived the 8 weeks and only one developed mild anorexia. No significant biochemical changes were found and neither hepatic steatosis nor mitochondrial abnormalities were observed. The addition of pantothenic acid prevented the development of the disorder in the four animals. These results show that calcium hopantenate produces acute encephalopathy with hepatic steatosis in dogs, by inducing a deficiency of pantothenic acid. The hepatic mitochondrial changes of this reaction differ from those of Reye's syndrome.
Immunological abnormalities in acute posttransfusion hepatitis non‐A non‐B
Authors: Salillas Pilar , Barcena Rafael , Nocito Mercedes , Erdozain José‐Carlos , Botella Ana , Brieva José A.
Published: August 2010

ABSTRACT— A variety of immunological parameters has been serially examined in the blood of 12 patients with acute post‐transfusion hepatitis non‐A non‐B (PTHNANB). Several alterations of these tests were transiently detected when comparing with healthy, extensively transfused subjects as well as with normal volunteers: 1. Low proportions of CD8+ T lymphocytes were observed at the disease onset, and these returned to normal after 1 month; 2. A diminution of the proliferative response of blood lymphocytes to mitogens was detected during the same period of time; 3. By the third month of disease, an enhanced spontaneous IgG secretion by cultured lymphocytes was found, and this observation was restricted to those patients who had not recovered. These alterations suggest that the immune system might be involved in the course of hepatitis C virus infection.
Expression of hepatitis B surface antigen subtypes in liver of patients with hepatocellular carcinoma; comparison of subtypes in serum and liver
Authors: Nakatsuji Yoshiyuki , Kiyosawa Kendo , Tanaka Eiji , Sodeyama Takeshi , Horigome Naoto , Kajikawa Shoji , Naito Shigeko , Akahane Yoshihiro
Published: August 2010

ABSTRACT— To clarify the discrepancy in hepatitis B surface antigen (HBsAg) subtypes present in the serum and liver, as well as among hepatocytes, liver specimens which were resected from 37 HBsAg‐positive patients with hepatocellular carcinoma (HCC) were examined. We evaluated HBsAg and the subtypic determinants of HBsAg and hepatitis B core antigen (HBcAg) using the peroxidase‐antiperoxidase (PAP) staining method. Hepatitis B antigens were more frequently detected in small tumors (HBsAg in 67%, HBcAg in 40%) than in large ones (HBsAg in 36%, HBcAg in 14%). The prevalence of each subtypic determinant in the HBsAg positive non‐tumorous vs. tumorous areas was 100% vs. 67% in a, 100% vs. 57% in d, 100% vs. not tested in y, 100% vs. 53% in r and 25% vs. 0% in w (a, d, y, r and w represent subtypic determinants). There was virtually no difference in a set of subtypic determinants between the serum and liver. However, there were some variations in a set of subtypic determinants among the hepatocytes. On the other hand, liver tissue of compound subtype adyr in serum contained both cells with a,d,r and with a,y,r as well as a few cells with a,d,y,r. These findings suggest that HBV genomes in hepatocytes of type B chronic liver disease may differ genetically among cells even in the same liver tissue.
Myosin in hepatocytes is essential for bile canalicular contraction
Authors: Watanabe Sumio , Miyazaki Akihisa , Hirose Miyoko , Takeuchi Makoto , Ohide Hirosumi , Kitamura Tsuneo , Ueno Takasi , Kominami Eiki , Sato Nobuhiro
Published: August 2010

ABSTRACT— Active dynamic contraction of bile canaliculi has been observed in cultured doublet hepatocytes using time‐lapse cinephotomicrography. This contractile movement plays an important role in normal bile formation. The mechanism of bile canalicular contraction has been proved to involve the Ca2+‐calmodulin system and pericanalicular actin filaments. However, the role of myosin in this system is still unknown. In this study, using the newly synthesized myosin light‐chain kinase inhibitor ML‐9, we found that the treatment of cultured doublet hepatocytes with ML‐9 inhibited canalicular contraction. This inhibitory effect suggests that myosin is involved in this complex cellular function and that the integrity of the actin‐myosin system, as well as the Ca2a‐calmodulin system is essential for normal bile canalicular contraction.
Caliber of splenic and hepatic arteries and spleen size in cirrhosis of different etiology
Authors: Bolondi L. , Zironi G. , Gaiani S. , Bassi S. Li , Benzi G. , Barbara L.
Published: August 2010

ABSTRACT— The caliber of the splenic and hepatic arteries, the hepatic to splenic artery ratio and the spleen size (area of widest spleen section) were evaluated by real time ultrasonography (US) in 88 patients affected by liver cirrhosis of different etiology (26 alcoholic cirrhosis, 43 hepatitis B virus (HBV) related cirrhosis, 8 cryptogenic cirrhosis and 11 primary biliary cirrhosis) and in a control group of 21 normal subjects, in order to assess the possible influence of the etiology of the disease on these morphological parameters. The mean caliber of the hepatic artery was larger, and the mean caliber of the splenic artery smaller in alcoholic than in HBV‐related, cryptogenic and in primary biliary cirrhosis. This difference is emphasized when considering the hepatic to splenic artery ratio: this parameter was never greater than 0.9 in all cases of primary biliary cirrhosis, in 38 out of 43 patients with HBV‐related cirrhosis and in 6 out of 8 cryptogenic cirrhosis, while in the alcoholic group only in one out of 26 was it less than 0.9. The sensitivity, specificity and accuracy of this ratio in differentiating alcoholic from non‐alcoholic cirrhosis was 96%, 88% and 91%, respectively. Splenomegaly resulted more in primary biliary cirrhosis, in HBV‐related cirrhosis and in cryptogenic cirrhosis than in the alcoholic form. Finally, a significant correlation was found in all groups of cirrhotic patients between the diameter of the splenic artery and the spleen size. These results show that some ultrasonographic morphological features of liver cirrhosis differ according to its varied etiology, probably reflecting different pathophysiological mechanisms. Furthermore, we describe a new parameter – the hepatic to splenic artery ratio – that could be useful to differentiate alcoholic from non‐alcoholic cirrhosis.
Ultrastructural localization of type IV collagen and laminin in the Disse space of rat liver with carbon tetrachloride induced fibrosis
Authors: Nakayama Yoshihide , Takahara Terumi , Miyabayashi Chiharu , Itoh Hiroyuki , Watanabe Akiharu , Sasaki Hiroshi , Muragaki Yasuteru , Ooshima Akira , Inoue Kyoichi
Published: August 2010

ABSTRACT— Monospecific antibodies, directed against type IV collagen and laminin, were used to clarify the process of sinusoidal capillarization in rats after carbon tetrachloride (CCl4) intoxication by the direct immunoperoxidase method. After acute intoxication, both type IV collagen and laminin were increased in the area of hepatic necrosis, adjacent to the central veins; however, sinusoidal capillarization was not found. During chronic intoxication, deposition of laminin was co‐distributed with that of type IV collagen, but deposition proceeded more slowly than that of the type IV collagen. Deposition of laminin was increased in the Disse space. Sinusoidal capillarization was noted as thick deposition of both antigens by light microscopy. Immunoelectron microscopy showed that both components were continuously present in the Disse space. Intracellularly, both antigens were found in the rough endoplasmic reticulum (RER) of fat‐storing cells (FSC) and endothelial cells, and these cells showed morphological changes, becoming slender and flattened. In contrast, few immunoreactive products of the two components were observed in the hepatocytes. These findings suggest that type IV collagen and laminin are indispensable for the establishment of sinusoidal capillarization, and that FSC play an important role in the production of both components.