bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultrastructural aspects of liver injury with special reference to small bile ducts in patients with ulcerative colitis
Authors: Mattila Jorma , Pitkänen Reino , Halonen Pekka , Matikainen Martti
Published: August 2010

Abstract: Liver tissue specimens taken at colectomy from 29 patients with chronic ulcerative colitis were studied by electron microscope. The fine‐structural alterations were correlated with light microscopy and with biochemical liver function tests. The purpose was to identify ultrastructural features which could explain the pathogenesis of sclerosing cholangitis. Severely injured bile‐duct epithelial cells were seen in three out of the eight light‐microscopically diagnosed cholangitis cases, in the two cases of non‐specific reactive hepatitis, and in the two fatty livers. Four cholangitis cases had, in heavily thickened bile‐duct basement membranes, translucent areas containing bile‐like material. Bile‐duct microvilli were often blunted, and reduced in number. Intracanalicular bile thrombi and bile inclusions in hepatocytes were seldom seen, mostly but not exclusively in cholangitis. The fine‐structural alterations apparently represent various stages of liver injury. These findings do not appear to be specific, but their prominence seems to correlate with the progression of the disease, at least in the case of histological parameters, but also in serum enzyme activities indicative of cholestasis. The bile‐like electron‐dense material found in proliferating basement membranes, very possibly regurgitated into the injured bile‐duct wall after epithelial injury, could enhance the development of periductal fibrosis, leading to progression of sclerosing cholangitis.
HPV strain‐specific probes
Authors: Tenti P. , Zappatore R. , Carnevall L. , Silini E. , Romagnoli S. , Glanetti A.
Published: August 2010

Sixty different types of human papillomavirus (HPVs) have been isolated and characterized by molecular cloning in becteria (1). Animal models and pathological studies suggest an estiological role of HPV infection in the development and etiological role of HPV infection in the development of intraepithelial neoplasia and squamous cell carcinoma, particularly in the anogential tract, in the larynx and in edidermodysplasia verruciformis(2,3,4).
Detection of hepatitis C virus RNA by in situ hybridizaiton
Authors: Bilght Kerill , Trowbridge Rachel , Rewland Robert , Gowans Eric
Published: August 2010

Abstract: Persisient infection with hepatitis C Virus (HCV is associated with chronic hepatitis and cirrhosis which may eventually develop into primary hepatocellular carcinoma. The mechanism of pathogenesis is illdefined and nothing is known of the distribution, frequency or type of infected cell in the liver of HCV‐infected individuals. In this study we have examined liver tissue taken at autopsy from 2 anti‐HCV‐positive patients by in situ hybridization for the presence of HCV RNA. Viral RNA was detected by autoradiography after hybridizaiton with 125I‐labelled riboprobes. reprsenting approximately 35% of the HCV genome. Only a few positive cells were indentified in the HCV‐infected liver samples. but not a normal liver sample. Hybridizaiton with an unrelated probe was negative in all samples. The HCV RNA‐positive cells were detected with anti‐sense but not sense RNA probes, suggesting that they contained a high ratio of genomic:antigenomic RNA. The appearance and distribution of the HCV RNA‐positive cells suggested that they were not hepatocytes and were more likely to be lymphocytes or macrophages.
Modulation of the expression of galactose‐specific receptors on Kupffer cells after partial hepatectomy and zymosan stimulation
Authors: Dini L. , Lentini A. , Massimi M. , Mattioli P. , Conti‐Devirglliis L.
Published: August 2010

ABSTRACT— Partial hepatectomy (PH) and a single intravenous injection of zymosan were used to provoke expansion of the Kupffer cell population in rat liver. The number of Kupffer cells per unit of area of liver increased after both stimulations. During these growth phases the number of binding sites for galactose‐exposing ligands was studied on Kupffer cell plasma membranes. Both partial hepatectomy and zymosan stimulation affected the binding of lactosylated bovine serum albumin conjugated to gold particles (LacBSA‐Au5). The reduction observed depended on the time after the PH or zymosan injection studied. Low levels of binding sites were found at 24 h from PH and 5 days after zymosan stimulation and represented only 1/4 or 1/10 of the binding sites expressed on the cell surface of Kupffer cells from normal adult rats. In addition, in both experimental situations we observed that the clustered distribution of gold particles typical of adult Kupffer cell was changed.
Histological outcome of chronic hepatitis C treated with a 12‐month course of lymphoblastoid alfa interferon
Authors: De Alava Enrique , Camps Joan , Pardo‐Mindán Javier , García‐Granero Marta , Muñoz Miguel , Sola Jesús , Civeira María P. , Contreras Félix , Vázquez Jesús J. , Castilla Alberto , Prieto Jesús
Published: August 2010

ABSTRACT— To assess the effect of long‐term alfa interferon therapy (12 months) on liver histology of chronic hepatitis C, we studied 61 treated patients, and compared their outcome with 28 untreated cases followed as controls. A liver biopsy was taken from all patients, before (month 0) and after the completion of the treatment or the control period (month 12). A third liver specimen taken at month 24 was available in 29 treated cases. Liver biopsies were blindly graded following Knodell's method. In 33 out of the 61 treated patients (54.1%), aminotransferase levels became normal shortly after starting therapy and remained within normal values until the end of treatment (sustained response). Nine (27%) sustained responders relapsed after interferon discontinuation, while the remaining 24 (73%) continued with normal aminotransferase values during follow‐up (16.8 ± 9.9 months). All histological parameters, except fibrosis, improved significantly after 12 months of therapy (periportal necrosis, month 0: 2.7 ± 1.0, month 12: 1.6 ± 1.1, p<0.0001; lobular damage, month 0: 2.5 ± 1.1, month 12: 1.4 ± 0.9, p < 0.0001; portal inflammation, month 0: 3.6 ± 0.5, month 12: 3.0 ± 0.9, p<0.0001). Histological improvement was especially marked in patients who did not relapse, although those who relapsed and partial responders also improved. Overall histological diagnoses improved in most patients. A sustained response to inteferon was predicted by high periportal and lobular scores, and by a low fibrosis score on the pretreatment liver biopsy. At 24 months, histological improvement persisted in patients without posttreatment relapse, while liver inflammation had returned to pretreatment levels in the remaining cases.
Distribution of asialoglycoprotein receptor in human hepatocellular carcinoma
Authors: Hyodo Ichinosuke , Mizuno Motowo , Yamada Gotaro , Tsuji Takao
Published: August 2010

ABSTRACT— Altered expression of asialoglycoprotein (ASGP) receptors on hepatocytes has been reported during hepatic neoplasia mostly in animal models. In this study, we examined immunohistochemically the distribution of the ASGP receptor in humans with various liver diseases, including ten cases of hepatocellular carcinoma (HCC). In livers of acute hepatitis, chronic hepatitis, cirrhosis and the non‐cancerous tissues (mostly cirrhosis) adjacent to HCC, the receptor was present in its normal distribution, i.e. mostly along the sinusoidal margin and partly on the lateral surface of hepatocytes. In four of six well‐differentiated HCCs, the receptor was also normally distributed on the plasma membrane; by immunoelectron microscopy, it was seen in the endoplasmic reticulum and in pits in the plasma membrane but not on bile canaliculus‐like structures, suggesting that it was synthesized, transported, and integrated into the plasma membrane in a polar manner. In contrast, there was no surface expression of the ASGP receptor in the remaining six HCCs (two well‐differentiated and four poorly differentiated). In two of the poorly differentiated HCCs, the receptor, although absent from the cell surface, was prominent in the endoplasmic reticulum, suggesting disturbed transport of the ASGP receptor to the cell surface. When we examined proliferative activity of HCCs by immunohistochemical labeling of DNA polymerase a, HCCs with high percentages (above 30%) of DNA polymerase α‐positive cells had lost the cell‐surface expression of the receptor. Thus, the expression of the ASGP receptor in human HCC appears to be closely related to differentiation and proliferative activity of the tumor cells.
Submassive hepatic necrosis induced by dichloropropanol
Authors: Haratake Joji , Furuta Akiko , Iwasa Toshio , Wakasugi Choei , Imazu Kazuhiko
Published: August 2010

ABSTRACT— A hitherto undescribed industrial liver injury of fulminant form induced by dichloropropanol is reported. Two middle‐aged men developed severe hepatic injury just after cleaning a dichloropropanol tank at a plant producing dichloropropanol. They died from hepatic failure 4 and 11 days respectively, after carrying out the work. Liver specimens taken at autopsy from one of the cases showed submassive hepatic necrosis. This accident prompted us to undertake an experimental study in rats of intraperitoneal one‐shot injection of two isomeric substances of dichloropropanol, that is, 2,3‐dichloro‐l‐propanol (DCIP) and 1,3‐dichloro‐2‐propanol (DC2P). Saline was injected into the control rats. One, two, four, six, 24, 48, 72 h, and 1 week after the injection, rats in each group were sacrificed. Neither control nor DC IP‐injected rats showed significant biochemical or histopathological abnormalities. DC2P‐injected rats revealed elevations of transaminase from 6 h after the injections, and submassive necrosis of the liver was observed in many rats. It was concluded that the severe liver injuries in both the human cases and rats in our study were caused by DC2P.
Inhibition of calcium hydroxyapatite formation by polyamines
Authors: Crowther Roger C. , Pritchard C. Matthew , Qiu Sul‐Min , Soloway Roger D.
Published: August 2010

ABSTRACT— The lithogenic potential of bile depends not only on supersaturation of solutes but also on the presence of pro‐ and anti‐nucleating factors. For example, glycine‐conjugated dihydroxy bile salt dimers are potent inhibitors of calcium hydroxyapatite precipitation that function by “poisoning” the nascent crystal. Although most inhibitors of apatite formation are anions, theoretically polycations should also be effective, and because significant concentrations of polyamines are present in bile, we have investigated the ability of these molecules to inhibit apatite formation. In vitro, each polyamine (2–10 mmol/l) was able to inhibit apatite formation, and the inhibiting power was correlated with ionic charge. Thus putrescine (2+) was the weakest inhibitor and spermine (4+) was the strongest. Mixtures of polyamines were less effective than were the individual polyamines, except at higher concentrations. Although polyamines were effective over short periods of time (270 min), over longer times (3 days) spermine was unable to prevent apatite formation. Using infrared spectroscopy, we found no evidence for interaction between phosphate ions and spermine in solution. Taken together, these results suggest that polyamines are modest inhibitors of apatite formation that likely function by retarding the dissolution of the intermediate amorphous calcium phosphate phase.
The expression of p53 antigen in primary malignant epithelial tumors of the liver: an immunohistochemical study
Authors: Choi Sang Wook , Hytiroglou Prodromos , Geller Stephen A. , Kim Sun Moo , Chung Kyu Won , Park Doo Ho , Theise Neil D. , Thung Swan N.
Published: August 2010

ABSTRACT— We examined the expression of mutant p53 gene products in primary malignant epithelial tumors of the liver. Fourteen of 68 hepatocellular carcinomas, one of seven hepatoblastomas and one of nine intrahepatic cholangiocarcinomas showed nuclear staining for p53 proteins. None of the surrounding non‐tumorous tissues expressed nuclear staining. The detection of p53 proteins in tumor cells was significantly higher in hepatocellular carcinomas of Oriental patients (31.6%) compared to non‐Orientals (6.7%, p<0.015). No significant differences were seen in p53 antigen expression between hepatitis B and non‐hepatitis B associated hepatocellular carcinomas in Oriental patients. These results suggest a role for other environmental factors, such as aflatoxin, in the etiology of p53 mutation in hepatocellular carcinoma in Oriental patients.
Remission of active diabetic hepatitis after correction of hyperglycemia
Authors: Tak Paul P. , Ten Kate Flbo J. W.
Published: August 2010

2Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands

ABSTRACT— A 60‐year‐old obese woman with type II diabetes mellitus and hepatomegaly exhibited progression of steatosis to hepatitis and cirrhosis. The patient was treated with large amounts of insulin combined with sulfonylurea, resulting in correction of the hyperglycemia. In the subsequent 9 months, weight loss did not occur, whereas insulin therapy could be discontinued. The liver decreased in size, and liver tests normalized. We suggest that intensive treatment of hyperglycemia may result in reversal of insulin resistance in patients with diabetic liver disease, while correction of hyperglycemia can lead to resolution of the hepatic abnormalities associated with diabetes mellitus.
Detection of hepatitis C virus RNA in the liver by in situ hybridization
Authors: Tanaka Yujiro , Enomoto Nobuyuki , Kojima Shigeru , Tang Liang , Goto Mieko , Marumo Fumiaki , Sato Chlfumi
Published: August 2010

ABSTRACT— To examine HCV infection histologically, we attempted nonradioactive in situ hybridization of HCV‐RNA in the liver. We amplified cDNA probe (360 base pairs) by PCR using the primers deduced from the core region of the HCV genome. The probe was labelled with digoxigenin by PCR and used for in situ hybridization on paraformaldehyde‐fixed frozen liver sections. The hybrids were visualized immunohistochemically with alkaline‐phosphatase‐conjugated anti‐digoxigenin and alkaline‐phosphatase substrates. HCV‐RNA‐cDNA hybrids were detected in 21 of 24 patients with positive serum HCV markers, whereas there were no positive signals in the liver of 12 cases without HCV infection. The signal intensity of HCV‐RNA‐cDNA hybrids was abolished after RNase treatment. Various other specificity experiments also verified specific hybridization of HCV‐RNA‐cDNA. HCV‐RNA was visualized in liver cells and most of them were regarded as hepatocytes from their characteristic features. The infected hepatocytes were frequently associated with mononuclear cell infiltration. Hepatocytes positive for HCV‐RNA were sometimes binuclear and distributed in various patterns among cases tested. The present in situ hybridization of HCV RNA is highly sensitive and specific and the results suggest the host immune response to HCV‐infected cells.
Clinical significance of the antibody to the putative core protein of hepatitis C virus in patients with chronic liver disease
Authors: Manzini Paola , Calvo Pier Luigi , Brunetto Maurizia Rossana , Baldi Maurizio , Abate Maria Lorena , Oliveri Filippo , Negro Francesco , Balzola Federico , Saracco Giorgio , Verme Giorgio , China Joe , Miyamura Tatsuo , Bonino Ferruccio
Published: August 2010

ABSTRACT— We evaluated the clinical significance of the antibody to hepatitis C core protein (anti‐p22) analysing 147 sera from 99 patients; 45 of them had post‐transfusion non A non B (NANB) hepatitis, 28 cryptogenic non A non B hepatitis, 12 chronic hepatitis B, 7 chronic hepatitis D, 6 other forms of liver disease (4 primary biliary cirrhosis, 2 autoimmune hepatitis) and 1 rheumatoid arthritis. All sera were tested by commercial 1st and 2nd‐generation ELISAs and anti‐p22 single antibody ELISA. We found a highly significant correspondence between anti‐p22 and commercial assays (p = 0.0001). HCV‐RNA was detected by reverse transcriptase polymerase chain reaction (RT‐PCR) in sera showing positive or negative concordant results and in all sera (24) that showed discordant results by anti‐p22 and comercial ELISAs. HCV‐RNA was found in 14 of 17 (82%) anti‐p22 positive sera that were negative by commercial ELISAs, in 1 of 7 (14.3%) anti‐p22 negative sera that were positive by commercial ELISAs (p = 0.001) and in all control sera from patients with positive concordant results. It was undetectable in 7 sera from patients with autoimmune diseases (negative by all ELISAs). We studied followup sera from 16 patients treated with interferon: 8 long‐term responders (with persistently normal ALT levels for at least 24 months after discontinuation of therapy and histological remission) and 8 non‐responders. Sera were also tested by a 4‐antigen recombinant immunoblotting assay (RIBA II). A relation was observed between the optical density of anti‐p22 ELISA and anti‐C22 as detected by RIBA and between the persistence of high levels of anti‐p22 and HCV‐RNA (p = 0.001). These results suggest that anti‐p22 ELISA is comparable for specificity and sensibility with commercially available assays. It appears to be a convenient and easy to perform test for diagnosis and monitoring of HCV infection.
Human hepatic infarction: histopathological and postmortem angiological studies
Authors: Saegusa Makoto , Takano Yasuo , Okudaira Masahiko
Published: August 2010

ABSTRACT— Twenty hepatic infarction cases selected from 5420 consecutive autopsy cases were investigated to clarify the pathogenetic aspects of this disease. Additional postmortem angiological studies of 24 normal human livers obtained at autopsy were also further performed to analyse the effects of blocking vascular structures on lesion development. Seventeen of the 20 cases (85%) were clinically associated with systemic circulatory insufficiency, especially hepato‐ and/or renal failure. Histopathologically, there was a significantly closer relationship between the location of infarcted regions and portal vein thrombosis than with either hepatic vein thrombosis or hepatic arterial damage. The borders between infarcted regions and surviving hepatic parenchyma were located around central veins, corresponding with the microcirculatory periphery of the portal venous system. Postmortem angiographic studies revealed that hepatic lobuli mainly consist of portal vein branches. Moreover, postmortem embolization studies of six normal livers using glass beads and bariumgelatin injection showed that physical occlusion of portal vein branches produced defects in broad areas of the hepatic parenchyma. Therefore, it is suggested that the development of hepatic infarction principally depends on disturbances of the portal venous system. In addition, systemic circulatory insufficiency, which reduces the intrahepatic blood flow, probably contributes greatly to the development of hepatic infarction.
Changes of serum 2‘,5’‐oligoadenylate synthetase activity during interferon treatment of chronic hepatitis C
Authors: Solinas Antonio , Cossu Pierangela , Poddighe Paola , Tocco Andreina , Deplano Angelo , Garrucciu Giovanni , Diana Maria Silvana Antonolla
Published: August 2010

ABSTRACT— It was our aim to evaluate whether the baseline activity of 2–5 oligoadenylate synthetase (2–5 OAS) in serum and changes induced by the treatment with interferon are relevant factors in remission of chronic hepatitis C. Seventeen out of 30 adult patients with chronic hepatitis C were randomized to receive recombinant alpha‐2b interferon at the dosage of 3 MU three times weekly. By the end of the third month, nine patients had normalized transaminase levels and continued to receive 3 MU of interferon for an additional 3 months, whereas in eight non‐responders the dosage was increased to 6 MU for the same period of time. A single patient responded to the increased dosage. Baseline 2–5 OAS serum activity was significantly higher in patients with chronic hepatitis when compared with normal controls. Follow‐up on the 13 untreated cases showed that 2–5 OAS elevation was stable and unrelated to concomitant infections. Comparison of responders and non‐responders showed that the latter had higher baseline 2–5 OAS activity, tended to have an earlier and higher peak in the enzyme during the first 4 weeks of treatment, and maintained higher levels during the first 3 months of therapy. The increased dosage of interferon in this group led to an additional, although temporary, increase in 2–5 OAS. Our data suggest that HCV infection by itself induces elevated 2–5 OAS levels. The paradoxical increase in non‐responders indicates that monitoring of the enzyme in serum does not predict the response to interferon. The role of the 2–5 OAS pathway in inducing the antiviral state in HCV infection should be further evaluated at tissue level.
Low frequency of allelic loss in the cyclin A gene in human hepatocellular carcinomas: a study based on PCR
Authors: Di Mitri Maria Stella , Pisi Emilio , Bréchot Christian , Patarlini Patrizia
Published: August 2010

ABSTRACT— The cyclin A gene was first identified at a site of hepatitis B virus DNA integration in a primary liver cancer (PLC). It has now been mapped to 4q27, in the proximity of a chromosomal locus (4q32) which is frequently rearranged and deleted in PLC. We took advantage of the TaqI polymorphism recently described in the cyclin A gene to search for allelic loss in this gene by means of PCR. Tumorous and non‐tumorous tissue from 50 patients with PLC was analyzed: 27 samples (54%) were homozygous for the A1 type allele (i.e. the allele bearing the TaqI restriction site), three (6%) were homozygous for the A2 type allele (without the TaqI site) and 20 (40%) were heterozygous. Comparison of tumorous and non‐tumorous patterns showed that only one (5%) tumorous tissue out of 20 heterozygous patients was homozygous, indicating the loss of an allele at this locus. We conclude that allelic loss in the cyclin A gene is a rare event in patients with PLC, and that PCR is rapid and reliable for the detection of allelic loss in the cyclin A gene when only small amounts of DNA are available.
Evidence of direct interaction between Kupffer cells and colon cancer cells: an ultrastructural study of the co‐culture
Authors: Yonel Yoshikazu , Kurose Iwao , Fukumura Dai , Saito Hidetsugu , Miura Soichiro , Tsukada Nobuhiro , Oda Masaya , Tsuchiya Masaharu
Published: August 2010

Abstract: A co‐culture study of purified rat Kupffer cells and human colon cancer cells was performed, and the process of the tumor cell injury was observed under an inverted type fluorescence microscope loaded with propidium iodide, and also under an electron microscope. Ultrastructurally there was direct membrane‐to‐membrane interaction between Kupffer cells and colon cancer cells in time. The interaction occurred 1 h after start of the co‐culture, and injured tumor cells were observed closely attached to pseudopodia of Kupffer cells at 6 h. The number of propidium iodide‐positive tumor cells with damage increased in time. Pretreatment with NG‐monomethyl‐L‐arginine reduced the number of injured tumor cells without preventing morphological interactions, but superoxide dismutase did not prevent the tumoricidal effect. Pretreatment with trypsin completely inhibited cell interaction and damage to tumor cells. In conclusion, the morphological interaction of Kupffer cells as a first step and the involvement of nitric oxide‐derived free radicals as a second step seem to play a significant role in the host‐defense mechanism.
The arterial blood ketone body ratio as a possible marker of multi‐organ failure in patients with alcoholic hepatitis
Authors: Saibara Toshiji , Maeda Takashi , Onishi Saburo , Yamamoto Yasutake
Published: August 2010

The arterial blood ketone body ratio (AKBR: acetoacetate/3‐hydroxybutyrate) within 48 h of admission is reported to be an excellent prognostic indicator for acute hepatic failure. In this study, we assessed the AKBR in 63 patients receiving supportive medical therapy for alcoholic hepatitis, in order to investigate its efficacy for predicting complications and the prognosis. Twelve patients (19%) died and 51 patients (81%) survived. Hepatic encephalopathy, severe coagulopathy, and renal failure were the critical complications (P<0.01), and the AKBR at 72 h of hospitalization was closely correlated with these complications (P<0.01), although they could not be predicted in any other way during the early admission period. The AKBR of normal individuals ranged from 1.0 to 2.1 (1.54 ± 0.26, mean ± SD), so an AKBR > 1.0 (mean‐2SD) was defined as normal. The AKBR value at 48 and 72 h of hospitalization showed a significant difference between survivors and non‐survivors (P<0.01). All survivors showed an increase of the AKBR to above 0.7 at 72 h, with subsequent maintenance of the ratio over 1.0, while eight of the 12 non‐survivors had sustained suppression of the AKBR below 0.7 at 72 h. Seven of these eight patients subsequently developed multiple organ failure. These findings suggest that the AKBR could be a possible marker of potentially fatal complications and a poor prognosis in patients with alcoholic hepatitis.
Reduced ubiquinone plasma levels in patients with liver cirrhosis and in chronic alcoholics
Authors: Bianchi G. P. , Fiorella P. L. , Bargossi A. M. , Grossi G. , Marchesini G.
Published: August 2010

Ubiquinone (CoQ10 coenzyme) is part of the respiratory chain in mitochondria, and acts as a scavenger in oxidative stress in cell membranes. Ubiquinone is mainly synthesized in the liver and partly derived from the diet; its plasma levels significantly correlate with tissue levels in experimental animals and in pathological states in man. By means of an original high‐performance liquid chromatography technique, we measured ubiquinone plasma levels in 10 healthy subjects, in 27 patients with cirrhosis and in 22 chronic alcoholics with normal liver function. Ubiquinone levels were markedly reduced in cirrhosis (0.25 [SD 0.21] μg/ml vs. 0.92 [0.38] in controls; P<0.001), without any difference between alcohol‐ and non‐alcohol‐related disease. Also, in chronic alcoholics ubiquinone levels were nearly halved (0.49 [0.24]). In cirrhosis, ubiquinone plasma levels significantly correlated with cholesterol (P<0.05), and with total bilirubin levels (P<0.01). Our study highlights a remarkable deficiency in ubiquinone levels in patients with cirrhosis and in chronic alcoholics, to which both reduced hepatic synthesis and nutritional defects may contribute.
Ribavirin treatment for chronic hepatitis D: a pilot study
Authors: Garripoli A. , DI Marco V. , Cozzolongo R. , Costa C. , Smedile A. , Fabiano A. , Bonino F. , Rizzetto M. , Verme G. , Craxi A. , Rosina F.
Published: August 2010

To assess whether therapy with Ribavirin may affect the course of chronic delta hepatitis, nine Italian patients with this disease received the drug orally at a dosage of 15 mg/kg daily for 16 weeks. At the end of the therapy period, all patients were followed for 12 additional months. Seven patients completed the trial. Two patients were withdrawn: one developed hemolytic anemia, and the other intractable itching. At the end of treatment HD viremia was reduced in one patient, had cleared in another, and was unchanged in the remaining five patients. None of the patients decreased their alanine transferase (ALT) levels by more than 50%. At the doses given in this study. Ribarivin did not show significant antiviral effects in chronic hepatitis D, and was not effective in reducing the biochemical markers of liver inflammation and necrosis.
Liver transplantation for severe Lepiota helveola poisoning
Authors: Meunier B. , Messner M. , Bardaxoglou E. , Spiliopoulos G. , Terblanche J. , Launois B.
Published: August 2010

Orthotopic liver transplantation in patients with fulminant hepatic failure secondary to Lepiota helveola poisoning has not, to our knowledge, been reported. Our recent experience with liver transplantation in a 27‐year‐old woman with acute hepatic failure secondary to this poisoning is described. The indications for orthotopic liver transplantation are discussed.
An electron microscopic study of apoptosis induced by cycloheximide in rat liver
Authors: Faa G. , Ledda‐Columbano G M. , Amhu R. , Congiu T. , Coni P. , Riva A. , Columbano A.
Published: August 2010

A histological and ultrastructural study, coupled with transmission and scanning electron microscopy of the early changes in the liver following a single administration of cycloheximide (CHX), was carried out in male Wistar rats. At the histological level, apoptosis was already present in the liver 2 h after treatment. By scanning electron microscopy, the following sequential changes were observed: brightness and progressive detachment of hepatocytes from neighbouring cells, formation of surface infolds with multiple blebs and, finally, release of several membrane‐bounded apoptotic bodies (ABs) in the extracellular space and into the sinusoidal lumen. Three hours after CHX administration, the apoptotic cycle was completed, as shown by the presence of phagocytosed ABs inside the cytoplasm of intact liver cells. Light microscopic examination of the liver 6 h after CHX administration showed ABs mainly located in the cytoplasm of intact hepatocytes and inside activated Kupffer cells. By transmission electron microscopy, it was possible to demonstrate that cells undergoing apoptosis were hepatocytes. At 24 h, the livers of treated animals appeared normal, with no evidence of apoptosis.
Biliary cystadenoma of the liver with elevated CA 19‐9
Authors: Schoonbroodt D. , Horsmans Y. , Gigot J. F. , Rahier J. , Geubel A. P.
Published: August 2010

ABSTRACT: A case of intrahepatic biliary cystadenoma with mesenchymal stroma is reported. The tumor was associated with strikingly elevated serum and intracystic levels of the tumor‐associated antigen CA19‐9. Two months after surgical enucleation, serum CA 19‐9 levels returned to normal.
Liver lesions in cryoglobulinemia associated with gastric non‐Hodgkin lymphoma: a case report
Authors: Muretto Pietro
Published: August 2010

ABSTRACT: Liver lesions in cryoglobulinaemia, associated with gastric non‐Hodgkin lymphoma, are described in a 67‐year‐old woman. Histological examination showed capillaropoiesis in some portal tracts with vessels containing amorphous, eosinophilic and PAS‐positive material, which immunohistochemically was shown to contain IgM and k light‐chains.
Beta‐carotene (provitamin A) decreases the severity of CCl4‐induced hepatic inflammation and fibrosis in rats
Authors: Seifert W. F. , Bosma A. , Hendriks H. F. J. , van Leeuwen R. E. W. , van Thiel‐de Ruiter G. C. F. , Seifert‐Bock I. , Knook D. L. , Brouwer A.
Published: August 2010

Earlier data from experiments in rats have shown that administration of retinyl esters (vitamin A) strongly influences the effects of CCl4 on the liver. The accumulation of collagen was inhibited, but an increase in CCl4‐toxicity with high mortality was observed. The present study was conducted to examine the effects of β‐carotene (provitamin A) on CCl4‐related general and hepatic toxicity in rats. Oral administration of β‐carotene during CCl4‐treatment resulted, biochemically, in a significantly lower increase in the hydroxyproline liver content and, histopathologically, in less severe liver fibrosis as compared with the liver of rats not treated with β‐carotene. The study also showed that β‐carotene administration could prevent the long‐term loss of retinoids from the CCl4‐injured liver. No significant toxic effects of β‐carotene, as previously found with retinyl esters (vitamin A), were observed. This experimental study suggests that β‐carotene has the therapeutic potential to decrease the severity of liver fibrosis without marked toxicity.
Hepatitis B virus precore mutations and HBeAg negative reactivation of chronic hepatitis B after interferon therapy
Authors: Talbodec N. , Loriot M. A. , Gigou M. , Guigonis V. , Boyer N. , Bezeaud A. , Erlinger S. , Benhamou J. P. , Marcellin P.
Published: August 2010

The objective of this study was to look for HBV precore mutations in three patients with chronic active hepatitis B who developed HBV‐DNA‐positive/HBeAg‐negative reactivation after HBe seroconversion induced by interferon therapy. Direct sequencing of polymerase chain reaction products was performed on serum collected before and after HBe seroconversion. In two patients precore sequence showed only wild‐type HBV before and after interferon therapy. In one patient, precore sequence showed only wild‐type HBV before interferon therapy and a mixed infection by wild‐type HBV and precore mutant viruses (1858 and 1896 nucleotide mutations) after treatment. The presence of HBeAg/anti‐HBe immune complexes was found after HBe seroconversion in all cases. Our results suggest that: 1) precore mutations are not always found in patients with chronic hepatitis B who develop HBV DNA‐positive/HBeAg‐negative reactivation; and 2) HBeAg negativity, despite the presence of wild‐type HBV, might be due to HBeAg/anti‐HBe immune complexes. We speculate that the production of these immune complexes may be favored by interferon therapy.
Endotoxin inactivating action of plasma in patients with liver cirrhosis
Authors: Fukui Hiroshi , Tsujita Shigenobu , Matsumoto Munesuke , Morimura Masafumi , Kitano Hiroyuki , Kinoshita Kunihiro , Kikuchi Eiryou , Okamoto Yasuyuki , Tsujii Tadasu
Published: August 2010

The endotoxin inactivating action of plasma was evaluated in 62 patients with cirrhosis and 10 healthy subjects. Endotoxin from E. coli 0111: B4 was added to each plasma sample to a final concentration of 250 pg/ml and the percentage loss of endotoxin activity by incubation (37°C for 1 h) was calculated as the endotoxin inactivating rate. The plasma endotoxin inactivating rate in cirrhotics was significantly greater than that in healthy subjects, although patients with Child C cirrhosis and marked hyperbilirubinemia had a significantly lower endotoxin inactivating rate than other cirrhotics. The plasma endotoxin inactivating rate was positively correlated to serum HDL‐cholesterol levels. In patients with Child A and Child B cirrhosis, the endotoxin inactivating rate was positively correlated to the endotoxin binding capacity of plasma albumin. The present results support the assumption that the plasma of cirrhotics has a high endotoxin inactivating capacity. Its decrease may augment endotoxicity in patients with advanced liver cirrhosis.
Humoral and cellular immune responses to dihydrolipoamide dehydrogenase (E3): lack of specificity for primary biliary cirrhosis
Authors: Tanaka Hajime , Maeda Takashi , Onishi Saburo , Yamamoto Yasutake
Published: August 2010

Abstract: Immune responses to dihydrolipoamide dehydrogenase, the E3 subunit which is a common component of 2‐oxoacid dehydrogenase complexes, have been suggested to be associated with the etiology of primary biliary cirrhosis (PBC). However, since an antibody to E3 could be detected in Caucasian patients with PBC, but was not specific for the disease, the proposal is not evident at the antibody level. We have identified the antibody also in Japanese patients with PBC by immunoblotting with sera at a 1: 100 dilution and have assessed cellular immune responses to E3 by proliferation assay of peripheral blood lymphocytes. Anti‐E3 antibody was detected more frequently in 25 of 43 PBC (58.1%) than in normal controls (p>0.01) and in chronic liver diseases (p>0.05), but the antibody was not specific for PBC as reported in Caucasian PBC. Anti‐E3 antibody‐positive sera of PBC patients or normal controls and their IgG fraction did not inhibit the enzyme activity of E3. Lymphocyte blastogenesis to E3 in PBC was significantly greater than normal controls (p>0.05), but was not significant as compared with chronic liver disease or non‐hepatic autoimmune diseases. Thus, these data do not support the hypothesis that the immune response to the E3 subunit is associated with etiology of PBC.
Hepatitis C virus infection and genotypes in Japanese hemophiliacs
Authors: Isobe Kazuo , Imoto Masami , Fukuda Yoshihide , Koyama Yasuo , Nakano Isao , Hayakawa Tetsuo , Takamatsu Junki
Published: August 2010

Abstract: Liver function and antibodies to hepatitis C virus and to human immunodeficiency virus‐1 were examined in 195 Japanese patients with hemophilia. One hundred and seventy‐three were positive for antibody to HCV and 61 for antibody to human immunodeficiency virus‐1. In 63 patients, we examined HCV genotypes according to the double polymerase chain reaction method. Forty cases (63%) were infected with hepatitis C virus with a single genotype, including type 1a in five, type 1b in 21, type 2a in seven and type 2b in seven; 16 (25%) were infected with double genotypes, including types 1a+1b in 14, types 1b+2a in one and types 1b+2b in one; and four (6%) were infected with triple genotypes, including types 1a+1b+2a in two and types 1a+1b+2b in two. Genotype could not be determined in three patients by this method. In the 191 non‐hemophiliac patients with chronic hepatitis C, HCV genotyping was as follows: type 1a in 0, type 1b in 121, type 2a in 40 and type 2b in 10 of 171 cases (89.5%) with single infection and types 1b+2a in five and types 2a+2b in one of six (5.5%) with double infection. In the remaining 14 patients, genotype could not be determined. Frequent transfusion of domestic and/or imported coagulation factor concentrates probably caused the high incidence of HCV infection with rare or mixed genotypes in Japanese hemophiliacs.
Defective copper binding to apo‐ceruloplasmin in a rat model and patients with Wilson's disease
Authors: Kojimahara Noriko , Nakabayashi Hiroki , Shikata Toshio , Esumi Mariko
Published: August 2010

Abstract: To examine the mechanism of decrease in serum ceruloplasmin (Cp) in Long‐Evans Cinnamon (LEC) rats, a proposed model of Wilson's disease, we analyzed Cp products at the stages of transcription and translation. Northern blot analysis and immunoblot analysis showed that the level and the molecular size of Cp mRNA and protein in LEC rats were similar to those in control Long‐Evans‐Agouti (LEA) rats. However, the ferroxidase activity of Cp was significantly decreased in LEC rats. We separated serum Cp into two forms by native polyacrylamide gel electrophoresis with pH modification: one was a holo‐Cp with copper and ferroxidase activity, and the other was an inactive apo‐Cp without copper. Holo‐Cp was the predominant form in LEA rats and normal humans, whereas apo‐Cp was the major form in LEC rats and patients with Wilson's disease. The cosegregation of apo‐Cp predominance with the disease in LEC rats was analyzed using backcross rats. Apo‐Cp was dominant in 8 of 11 offspring with disease but in none of 19 normal offspring. These results indicate that a genetic disturbance of copper binding to apo‐Cp may be closely associated with the pathogenesis in LEC rats, and probably in Wilson's disease.
Dual‐centre, double‐blind, randomised trial of lymphoblastoid interferon alpha with or without steroid pretreatment in children with chronic hepatitis B
Authors: Giacchino R. , Main J. , Timitilli A. , Giambartolomei G. , Facco F. , Cirillo C. , Jacyna M. R. , Brook M. G. , Callea F. , Kariayannis P. , Terragna A. , Thomas H. C.
Published: August 2010

Abstract: Thirty‐five children with chronic HBV infection, HBV‐DNA and eAg serum positivity, and HBcAg in liver tissue were treated with lymphoblastoid human interferon alpha with (16 cases) or without (19 cases) prednisolone pretreatment. The patients were double‐blind randomized to receive steroid or placebo for 4 weeks, followed after 2 weeks by 5 or 10 MU/m2 interferon for 12 weeks. The e anti‐e seroconversion rate reached 48%, which is much higher than the spontaneous seroconversion rate. The influence of “prednisolone priming” was not statistically significant. HBeAg clearance was similar in both groups (44% after prednisolone/interferon and 53% after interferon alone). The response to either treatment did not correlate with the pretreatment serum transaminase, HBV‐DNA or degree of histological activity. Interferon was well tolerated, the side effects being less severe than in adults, and never led to suspension of the treatment.
Effect of UV‐B (302 nm) irradiation on isolated rat hepatocytes
Authors: Lahiri Subhra , Habibullah C. M. , Ayesha Qamer , Khan A. A. , Srinivas V. K. , Naithani Rajeev
Published: August 2010

Abstract: The present study aimed to evaluate the effect of UV‐B irradiation on the functional integrity, and the metabolic and detoxifying capacity of isolated rat hepatocytes. Isolated rat hepatocytes were irradiated in various doses (400 Jm‐2, 600 Jm‐2, 800 Jm‐2 and 1000 Jm‐2). The cells were assayed for total lactate dehydrogenase, Na+‐K+‐ATPase, ornithine carbamyltransferase activity (OCT) and urea production capacity. Lactate dehydrogenase and Na+‐K+‐ATPase activity were significantly decreased in all four irradiated groups (P>0.001), whereas viability, OCT and urea production capacity showed no alterations.
β‐hexosaminidase in bile and plasma from patients with cholestasis
Authors: Hultberg B. , Pålsson B. , Isaksson A. , Masson P.
Published: August 2010

Abstract: β‐Hexosaminidase (Hex) activity was determined in bile from 18 patients with cholestasis, six patients without cholestasis and in ten normal liver biopsies. The difference in the mean activities in bile from patients with and without cholestasis was not significant. Only about 0.5 promille of total liver Hex activity was lost per day via the bile flow. Gel chromatography showed that enzyme forms present in bile had higher molecular weights than the forms present in liver tissue, indicating that the biliary enzyme was not routed through the lysosomes before release into the bile. In 32 patients with cholestasis, plasma Hex was increased compared to controls, and correlated to bilirubin. The activity was significantly higher in patients with severe cholestasis than in patients with less severe forms of cholestasis, but no significant difference in Hex activity was observed between patients with benign or malignant biliary obstruction. No significant difference was noted between patients with cholestasis for less than 1 week compared to those whose illness had lasted more than 1.5 weeks. The impact of biliary obstruction on plasma Hex is further illustrated by the observation that decompression lowered plasma Hex as well as bilirubin and alkaline phosphatase.
The measure of life‐time alcohol consumption in patients with cirrhosis: reproducibility and clinical relevance
Authors: Arico Sarino , Galatola Giovanni , Tabone Marco , Corrao Giovanni , Torchio Pierfederico , Valenti Marco , De La Pierre Marco
Published: August 2010

Abstract: Our aims were to design a reproducible method of measuring life‐time alcohol consumption in patients with cirrhosis, and to assess the risk of liver decompensation associated with alcohol intake using a case‐control design and a multivariate analysis. We studied 439 patients (“cases”) with decompensated cirrhosis, and 233 with compensated cirrhosis (“controls”). Mean life‐time daily amount and duration of alcohol intake were measured by a standardized questionnaire, whose reproducibility, assessed by interviewing 75 relatives, was 70% for daily alcohol intake and 84% for duration of intake. Better reproducibility was found by re‐interviewing patients at discharge from hospital. Daily alcohol intake was significantly higher in males, younger patients and patients with liver decompensation. After stratification according to the average life‐time daily alcohol intake, we found a significant increase in the risk of liver decompensation from 125 g ethanol intake per day onwards. No association was found between duration of alcohol intake and risk of liver decompensation. We conclude that alcohol intake can be reliably and reproducibly measured: in patients with cirrhosis, increased alcohol intake is associated with increased risk of liver decompensation, with a significant dose‐effect above a daily intake of 125 g ethanol.
Hepatitis C virus infection in Italian intravenous drug users: epidemiological and clinical aspects
Authors: Galeazzi Bruno , Tufano Antonio , Barbierato Emanuele , Bortolotti Flavia
Published: August 2010

Abstract: The epidemological and clinical features of hepatitis C virus infection have been evaluated in a cohort of 227 intravenous drug users enrolled at a drug dependence treatment center in the Veneto area in 1992–1993 and followed periodically. Hepatitis C virus infection was detected using second‐generation anti‐HCV ELISA in 171 (75%) subjects at enrollment. Anti‐HCV seropositivity correlated with: a) the duration of drug abuse: 91% of intravenous drug users injecting for more than 8 years were seropositive as compared to 40% of those with a history of abuse lasting 4 years or less, p<0.001; b) sharing of injection equipment: 85% anti‐HCV positive intravenous drug users had shared at some time as compared to 64% seronegative subjects, p<0.001; c) seropositivity for immunodeficiency virus infection: 25% anti‐HCV positive intravenous drug users were coinfected as compared to 3.5% anti‐HCV negative, p<0.001; d) markers of ongoing (two cases) or previous hepatitis B virus infection were detected in 62% of anti‐HCV positive but in 21% of anti‐HCV negative cases, p<0.01. Two initially anti‐HCV negative intravenous drug users seroconverted during follow up giving an incidence rate of hepatitis C virus infection of 6.2 per 100 person‐years. During the survey abnormal alanine aminotransferase levels were detected in 75% anti‐HCV positive but in 24% anti‐HCV negative cases (p<0.001), with significantly higher levels in the former. These findings suggest that the circulation of hepatitis C virus among intravenous drug users has been decreasing in recent years, although new infections still occur. In agreement with the high rate of chronicization of parenterally transmitted hepatitis C, the majority of anti‐HCV positive subjects had biochemical features of associated liver disease.
The arterial ketone body ratio and serum α‐fetoprotein level in patients with acute hepatic failure
Authors: Yamasaki Hisao , Saibara Toshiji , Maeda Takashi , Onishi Saburo
Published: August 2010

Abstract: Hepatocyte regeneration is essential for recovery in acute hepatic failure, although it requires a large amount of energy. The ratio of acetoacetate to beta‐hydroxybutyrate in arterial blood has been reported to reflect the cellular energy charge of hepatocytes, and we proposed that the recovery of the ratio in the early days of acute hepatic failure is essential for survival. However, there is no report on any marker of regeneration to confirm this hypothesis. In this study, we have assessed this ratio and the serum α‐fetoprotein level sequentially in 26 patients with acute hepatic failure. Ten patients recovered and 16 died. The arterial blood ketone body ratio 3 days after the onset of hepatic encephalopathy of grade II or more was below 0.6 in 15 of the 16 nonsurvivors, whereas that in the 10 survivors was above 0.6. There was a positive correlation between the arterial blood ketone body ratio and the maximal concentration of α‐fetoprotein (r=0.465, p<0.02 by Student's t‐test). These data indicate that the arterial blood ketone body ratio is a marker for the capacity of the liver to regenerate and for the prognosis in patients with acute hepatic failure: effective hepatocyte regeneration may be impossible if these metabolic changes in acute hepatic failure impair the hepatocyte energy charge severely.
Benign myxoid hepatocellular tumor: a variant of liver cell adenoma
Authors: Galassi Andrea , Pasquinade Gianandrea , Guerini Antonello , Martinelli Giuseppe , Venza Enzo
Published: August 2010

Abstract: A case of myxoid hepatocellular adenoma in the non‐cirrhotic liver of a 26‐year‐old man is described. Grossly, the tumor was well circumscribed, rounded and measured 16 cm in diameter. Histologically, the tumor was characterized by nests and strands of polygonal cells embedded in a myxoid extracellular matrix. Electron microscopy confirmed the hepatocellular nature of the neoplastic cells. The patient is alive and well, without evidence of disease, 2 years after a local excision.