bluuebunny/crossref_metadata_2025 huggingface dataset:
Focal tuberculosis of the liver with local hemorrhage in a patient with acquired immunodeficiency syndrome
Authors: Brmbolić Branko J. , Boriĉić Ivan , Salemović Dubravka R. , Jevtović Djordje Li. , Ranin Jovan T. , Begić‐Janeva Ana
Published: August 2010

Abstract: Tuberculosis of the liver is common in patients with acquired immunodeficiency syndrome (AIDS). Tuberculous liver granulomas in such patients are usually atypical. The liver granulomas may be even totally absent, but liver tissue usually reveals numerous acid‐fast bacilli. Focal tuberculosis of the liver is a less common form of liver tuberculous infection. We present a 33‐year old white homosexual man infected with the human immunodeficiency virus. He had three tumour‐like lesions in the left liver lobe, which were subsequently diagnosed as focal hepatic tuberculosis with local hemorrhage. This unusual presentation of liver tuberculosis indicates the necessity of an aggressive diagnostic approach for the evaluation of focal liver lesions in patients with AIDS.
Variation between centers in technique and guidelines for liver biopsy
Authors: Sue Michael , Caldwell Stephen H. , Dickson Rolland C. , Macalindong Chona , Rourk R. Michael , Charles Clarence , Doobay Ramsundar , Cambridge Sean L. , Barritt A. Sidney , McCallum Richard W.
Published: August 2010

Abstract: Hospitals have few published guidelines to follow when performing a liver biopsy. In 1992, we began revising our protocol in an effort to institute new guidelines for our teaching hospitals. To assess the current practice of liver biopsy, we sent 500 multilingual questionnaires to international academic centers, and 85 U.S. centers were surveyed by telephone. The survey assessed: 1) patient preparation, 2) technical aspects of the biopsy, and 3) post‐procedural care. One hundred and eighty international centers and 85 U.S. centers responded (total=265). We found a wide variation in the practice of this surgical procedure at both national and international centers. Many Asian centers (73%) performed a bleeding time prior to liver biopsy. This practice was seen in only 36% of the U.S. centers. Most centers preferred platelet counts of 50,000/mm3 and above. The aspiration needle was more widely used in the U.S. (74%) and in many international centers, but Asian centers (61%) preferred a cutting needle. Thirty percent of Japanese centers performed more than 50% of their liver biopsies laparoscopically. Few laparoscopics were done at other centers. While about a quarter of the reported U.S., European, Asian, and South American centers observed patients for 4–6 hours after a biopsy, the majority of centers observed patients 10 hours or more. In addition to the wide variation seen, this survey provided us with an academic view of the contemporary practice of liver biopsy and an insight into how to redefine our present guidelines.
Post‐infantile giant cell hepatitis in patients with primary sclerosing cholangitis and autoimmune hepatitis
Authors: Protzer U. , Dienes H. P. , Bianchi L. , Lohse A. W. , Helmreich‐Becker I. , Gerken G. , zum Büschenfelde K. H. Meyer
Published: August 2010

Abstract: In post‐infancy, multinucleated giant cell hepatitis is rare. Various conditions and diseases associated with post‐infantile giant cell hepatitis have been described, but the pathogenesis remains unknown. In this paper we review the case reports of four patients (3 male, 1 female; aged 22 to 32 years) with primary sclerosing cholangitis and autoimmune hepatitis. The follow‐up ranges from five to seven years. All patients showed cholestasis and repeated elevation of hepatic transaminases. Patients with viral infections, metabolic disorders and toxic influences were excluded. Histopathology of liver tissue in all four patients revealed giant cell formation with up to 20 nuclei in 20–70% of all hepatocytes. Post‐infantile giant cell hepatitis was defined histopathologically. The clinical course of all four patients markedly improved after immunosuppressive treatment. Further improvement was observed with the addition of ursodeoxycholic acid. Follow‐up liver biopsies during treatment showed reduced inflammation and a decreased number of giant cells. One patient, who initially was admitted to the hospital with liver cirrhosis died five years later due to a sepsis. The clinical course of the other three patients remained stable during the observation period, and no progression of liver fibrosis was recorded as long as immunosuppressive treatment was continued. Cholestasis and autoimmunity seem to be two important mechanisms triggering hepatic giant cell formation in post‐infancy. In the reported cases long‐lasting cholestasis in primary sclerosing cholangitis together with features of autoimmune hepatitis seem to have triggered the formation of syncytial hepatic giant cells.
Telomere length in human liver diseases
Authors: Urabe Yoshiaki , Nouso Kazuhiro , Higashi Toshihiro , Nakatsukasa Harushige , Hino Naoki , Ashida Kouzou , Kinugasa Nobuyuki , Yoshida Keigo , Uematsu Shuji , Tsuji Takao
Published: August 2010

Abstract: To determine the role of telomere‐mediated gene stability in hepatocarcinogenesis, we examined the telomere length of human liver with or without chronic liver diseases and hepatocellular carcinomas (HCC). The mean telomere restriction fragment (TRF) length of normal liver (n=13), chronic hepatitis (n=11), liver cirrhosis (n=24) and HCC (n=24) was 7.8±0.2, 7.1±0.3, 6.4±0.2 and 5.2±0.2 kb, respectively (mean±standard error). TRF length decreased with a progression of chronic liver diseases and that in HCC was significantly shorter than that in other chronic liver diseases (p<0.05). The ratios of TRF length of HCC to that of corresponding surrounding liver of well differentiated (n=7), moderately differentiated (n=10) and poorly differentiated (n=4) HCCs were 0.83±0.06, 0.75±0.05 and 0.98±0.09, respectively. The ratio of poorly differentiated HCC was significantly higher than that of moderately differentiated HCC (p<0.05). A comparison between the size and telomere length ratio of moderately differentiated HCCs revealed a decrease of the ratio with size until it reached 50 mm in diameter. In contrast, the ratio increased as the size enlarged over 50 mm. These findings suggest that the gene stability of the liver cells mediated by the telomere is reduced as chronic liver disease progresses and that telomerase is activated in poorly differentiated HCC and moderately differentiated HCC over 50 mm in diameter.
Hepatocellular carcinoma in long‐term oral contraceptive use
Authors: Fiel M. Isabel , Min Albert , Gerber Michael A. , Faire Bridget , Schwartz Myron , Thung Swan N.
Published: August 2010

Abstract: Hepatocellular carcinoma (HCC) is one of the most common malignancies in certain parts of the world, particularly in Africa and Asia, but it is less commonly encountered in the United States. It is closely associated with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, and almost always develops in a cirrhotic liver. In non‐cirrhotic livers, HCC is found in about 20% of asymptomatic carriers of HBV and rarely in patients taking androgenic‐anabolic or oral contraceptive (OC) steroids. We report four patients, who developed HCC after prolonged use of OC steroids. Whether OC steroids act as mutagen or co‐carcinogen in hepatocarcinogenesis is not clear. To exclude latent HCV and HBV infections which may occur in the absence of their serological markers, we employed polymerase chain reaction for the detection of HBV and HCV sequences in the tumor and non‐tumorous liver tissue. Viral sequences of HBV and HCV were undetectable in all four cases. These findings suggest OC use as the only known risk factor in these cases and, therefore, strengthen its possible role in hepatocar‐cinogenesis.
Clonal accumulation of Vβ5.1‐positive cells in the liver of a patient with autoimmune cholangiopathy
Authors: Shimizu Yukihiro , Higuchi Kiyohiro , Kashii Yoshirou , Miyamoto Megumi , Tsukishiro Takashi , Watanabe Akiharu
Published: August 2010

Abstract: We describe a 43‐year‐old woman with clinical features compatible with autoimmune cholangiopathy recently reported by Ben Ari et al. She was negative for anti‐mitochondrial antibody, positive for high titer anti‐nuclear antibody with homogeneous pattern, high levels of serum immunoglobulin G and nearly normal levels of serum immunoglobulin M for more than five years. In the early stages of the disease, the elevations of serum transaminase, alkaline phosphatase and γ‐glutamyl transpeptidase were well controlled by the administration of ursodeoxycholic acid. After five years of follow‐up, she showed the second exacerbation of liver function tests, which then rapidly improved by prednisone administration. To analyze the antigen diversity recognized by T‐cells in the liver, T‐cell receptor repertoire was examined by immunohistochemistry. The liver biopsy obtained in the early stage showed clonal accumulation of Vβ5.1‐positive cells in portal areas, which was found in patients neither with primary biliary cirrhosis nor autoimmune hepatitis. In conclusion, these data suggest that T‐cell response in autoimmune cholangiopathy is different from those two autoimmune liver diseases, which may imply a distinct entity of the disease.
Hepatic regeneration in humans with various liver disease as assessed by Ki‐67 staining of formalin‐fixed paraffin‐embedded liver tissue
Authors: Kaita K. D. E. , Pettigrew N. , Minuk G. Y.
Published: August 2010

Abstract: The ability to document nuclear proliferation in the liver is essential to our understanding of hepatic regeneration and hepatocellular carcinoma. While numerous tests are available to provide such information in experimental animals, few can be applied to patients with liver disease. Ki‐67 is a proliferating nuclear antigen present in replicating cells. Recent data indicates that staining for Ki‐67 reflects nuclear proliferation in these tissues. To date, the technique has had only limited application to human liver tissues in formalin‐fixed paraffin embedded tissue. In the present study, we documented Ki‐67 staining in archival liver tissue from patients with mild chronic hepatitis, severe chronic hepatitis, inactive cirrhosis, hepatocellular carcinoma, and in normal livers. We found that Ki‐67 staining was increased in patients with mild chronic hepatitis (labelling index 29±25), severe chronic hepatitis (labelling index 41 ±40), and hepatocellular carcinoma (labelling index 71 ±61), when compared to patients with inactive cirrhosis, (labelling index 1.4±3.1), and normal livers (labelling index 2.5±3.2). In conclusion, Ki‐67 maybe a useful tool to assess hepatocyte proliferation in formalin‐fixed paraffin‐embedded human liver tissue.
Heterogeneity in androgen receptor levels and growth response to dihydrotestosterone in sublines derived from human hepatocellular carcinoma line (KYN‐1)
Authors: Yu Liqun , Kubota Hirofumi , Imai Katsuyuki , Yamaguchi Minekazu , Nagasue Naofumi
Published: August 2010

Abstract: Heterogeneity in the growth response to androgen and androgen receptor (AR) status in an AR‐positive human hepatocellular carcinoma (HCC) line, KYN‐1, was investigated in the present study. Seven sublines were obtained from KYN‐1 by the limited dilution method. Four of them had no detectable amounts of AR and did not show any growth response to dihydrotestosterone (DHT) at the concentration up to 1000 nM, while the other three had varying amounts of both cytosolic and nucleosolic AR that were 5‐ to 7‐fold higher than that of the parent cell. In the parent cell, the addition of DHT caused a modest but significant increase in the cell number (21%) in a 14‐day culture. Such effect was increased by 2‐ to 7‐fold in two AR‐positive sublines. In addition, the sensitivity of the response in these two sublines was increased by up to 24‐fold. The one remaining AR‐positive subline did not show any growth response to DHT, although the behavior of its AR in sucrose gradient ultracentrifugation and Western blotting was the same as that of the other two sublines. These data clearly show that sublines derived from an established human HCC line have a broad heterogeneity in the growth response of HCC to androgen as well as in AR status and could be classified into three groups on the basis of the growth responsiveness to androgen and the AR expression.
A combined hepatocellular/cholangiocellular carcinoma with sarcomatoid features
Authors: Papotti M. , Sambataro D. , Marchesa P. , Negro F.
Published: August 2010

Abstract: A case of primary liver cancer showing combined hepatocellular and cholangiocellular features and an associated pseudosarcomatous (schwannomatous) component is presented. Histologically, compact microtrabecular and glandular patterns in a dense fibrous stroma were recognized. The latter showed transition towards spindle cell sarcomatous growth in several areas of both the primary and the lymph‐node metastasis. Glandular areas expressed acidic mucins and AE1‐reactive keratins; albumin mRNA was detected by in situ hybridization in both trabecular and glandular areas. Vimentin and S‐100 protein were mostly expressed in the pseudosarcomatous areas. Both the morphological patterns and the phenotypic features indicate that divergent differentiation along both epithelial and mesenchymal lineages took place in this rare primary liver tumor.
Cytoprotection by glycine against hypoxia‐induced injury in cultured hepatocytes
Authors: Nagatomi Atsuko , Sakaida Isao , Matsumura Yasuhiro , Okita Kiwamu
Published: August 2010

Abstract: The aim of this study was to investigate the mechanism of cytoprotection by glycine against hypoxia‐induced hepatocellular injury. Incubation under hypoxic conditions (95% N2 and 5% CO2) for 5 h induced about 50% cell death, but administration of glycine remarkably reduced hepatocellular death without preventing a loss in ATP content. Anaerobic glycolysis generated lactic acid, reducing extracellular pH, but glycine had no effect on changes in extracellular pH. Chloride‐channel inhibitors [anthracene‐9‐carboxylic acid (A9C), furosemide, and strychnine] also significantly reduced hepatocellular death induced by hypoxia. These results suggest that the mechanism of protection by glycine against hypoxic injury is not related to the prevention of ATP depletion or to changes in extracellular pH, but may be due to inhibition of chloride ion influx into the hepatocyte.
Comparison between sporadic cytomegalovirus hepatitis and Epstein‐Barr virus hepatitis in previously healthy adults
Authors: Watanabe Seishiro , Arima Keiji , Nishioka Mikio , Yoshino Sumi , Hasui Hiroki , Fujikawa Masanao
Published: August 2010

Abstract: In order to determine the factors responsible for the differentiation of cytomegalovirus (CMV) hepatitis and Epstein‐Barr virus (EBV) hepatitis, the clinical features and laboratory data of both types of hepatitis were retrospectively analyzed in 20 patients with CMV and 11 patients with EBV. While most signs and symptoms of CMV and EBV hepatitis showed no significant differences, we found that cervical lymphadenopathy was more common in EBV hepatitis than in CMV hepatitis (p < 0.01). Frequency of epigastralgia was more common in CMV hepatitis than EBV hepatitis (p<0.05). The percentage of peripheral blood monocytes in the white blood cell count in CMV hepatitis was greater than in EBV hepatitis (p<0.01). Low CD4 levels and high CD8 levels made CD4/CD8 low in peripheral lymphocytes of both groups of hepatitis. Ten EBV hepatitis patients received antibiotics in the early stage of the disease in which two (25%) developed severe erythematous rashes. Four CMV hepatitis patients received antibiotics and did not develop rashes. Identification of early clinical parameters capable of differentiating CMV hepatitis from EBV hepatitis is important.
Are alanine aminotransferase, hepatitis B virus DNA or IgM antibody to hepatitis B core antigen serum levels predictors of histological grading in chronic hepatitis B?
Authors: Zavaglia Claudio , Mondazzi Luca , Maggi Giovanni , Lamoni Gianmaria , Gelosa Franco , Bellati Giorgio , Colloredo Guido , Bottelli Riccardo , Ideo Gaetano
Published: August 2010

Abstract: Paired sera and liver biopsies from 105 patients with chronic hepatitis B virus infection (34 HBeAg positive and 71 anti‐HBe positive) were studied to investigate the relation between the degree of histological activity and alanine aminotransferase (ALT), hepatitis B virus DNA (HBV‐DNA) or IgM antibody to hepatitis B core antigen (IgM anti‐HBc) levels. ALT levels were significantly higher in patients with piecemeal necrosis (155±124 vs 75±42, p=0.0017), but there were no differences in the ALT values of patients with or without intralobular necrosis. ALT values were within normal range in 29% of 31 patients without versus 15% of 65 with piecemeal necrosis (p=0.19). Serum HBV‐DNA levels were not related to the grade of lobular or portal/periportal activity in HBeAg‐positive patients. Anti‐HBe‐positive subjects with piecemeal necrosis had higher HBV‐DNA levels (34±93 vs 4±6, p=0.01). IgM anti‐HBc indexes were significantly higher in patients with intralobular necrosis (0.635±0.600 vs 0.356±0.367, p=0.0005) or piecemeal necrosis (0.671 ±0.633 vs 0.321 ±0.219, p=0.0002). In summary, since serum IgM anti‐HBc‐IMx indexes can reflect the grade of histological activity, the quantitative assessement of this antibody could be useful for non‐invasive monitoring of hepatocellular damage in chronic hepatitis B.
Histological improvement in patients with chronic hepatitis B virus infection treated with lamivudine
Authors: Honkoop Pieter , de Man Robert A. , Zondervan Pieter E. , Schalm Solko W.
Published: August 2010

Abstract: Lamivudine is an oral nucleoside analogue with strong antiviral activity against hepatitis B virus (HBV). In previous clinical studies, a course of lamivudine for 4–12 weeks induced a profound decrease in HBV viraemia with excellent tolerance, but data on histology have not yet been reported. We studied the liver histology of 13 patients with stable chronic HBV infection treated with 25 mg, 100 mg or 300 mg lamivudine daily for 6 months. All patients became HBV‐DNA negative during treatment. The paired biopsies taken at entry and during treatment were scored by two independent observers, using the components of the histology activity index (HAI) and fibrosis (modified Knodell). The items scored were piecemeal necrosis, focal necrosis, confluent necrosis, portal inflammation and fibrosis. Before treatment, the biopsies yielded a mean HAI of 4.4 (±0.8), which decreased to HAI 2.8 (±0.5) during treatment. An analysis of the individual components of the classification system showed a significant decrease in piecemeal necrosis from a pre‐treatment 1.4 (±0.3) to 0.8 (±0.1) during treatment (p=0.02). Although a trend was found for the other components, it was not statistically significant, probably due to the number of pairs examined. In conclusion these results suggest that prolonged suppression of viral replication by lamivudine can improve liver histology. In contrast to previously published reports on α‐interferon therapy, this study indicates that the improvement in liver histology with lamivudine is independent of HBe‐seroconversion.
Antimitochondrial antibody profiles in primary biliary cirrhosis distinguish at early stages between a benign and a progressive course: a prospective study on 200 patients followed for 10 years
Authors: Klein Reinhild , Pointner Herwig , Zilly Walter , Glässner‐Bittner Beate , Breuer Norbert , Garbe Wolfram , Fintelmann Volker , Kalk Johann F. , Müting Dieter , Fischer Rudolf , Tittor Wolfgang , Pausch Jürgen , Maier Klaus Peter , Berg Peter A.
Published: August 2010

Abstract:In recent retrospective studies, it was shown that subtypes of antimitochondrial antibodies (AMA) can help to discriminate between a benign [only anti‐M9 and/or anti‐M2 positive by enzyme‐linked immunosorbent assay (ELISA)] and a rather progressive course (anti‐M2, ‐M4 and/or ‐M8 positive). According to different constellations of these AMA subspecificities in ELISA and complement fixation test (CFT), four AMA profiles (A‐D) were defined. In 1984 we started a prospective study based on 200 PBC patients with known AMA profiles in order to correlate the antibody pattern with the clinical outcome. Progression was defined primarily as the necessity of liver transplantation and death due to hepatic failure or variceal bleeding. At entry, 18 (9%) of the 200 patients had AMA profile A (only anti‐M9), 57 (29%) profile B (only anti‐M2 with or without anti‐M9), 74 (37%) profile C (anti‐M2 in association with anti‐M4/‐M8 by ELISA), and 51 (26%) profile D (anti‐M2/‐M4/‐M8 by ELISA and CFT). At the beginning of the study, 177 patients had PBC stage I/II. During the observation period of ten years, ten patients died and in 18 orthotopic liver transplantation (OLT) was performed; all these patients belonged to profile C/D. Furthermore, 44% of the patients with profile C and 31% of the patients with profile D progressed to late stages, as defined by histology and clinical manifestations such as portal hypertension and increase of bilirubin, while only one of the patients with profile B and none of the profile A‐patients developed late stage PBC. A significant increase of bilirubin was observed only in C/D‐patients. AMA profiles did not change during the follow‐up. In conclusion, AMA profiles discriminate between a benign and a progressive course of PBC already at early stages.
Lamellar fibrosis in the fibrolamellar variant of hepatocellular carcinoma: a role for transforming growth factor beta
Authors: Orsatti Giulia , Hytiroglou Prodromos , Thung Swan N. , Ishak Kamal G. , Paronetto Fiorenzo
Published: August 2010

Abstract: Transforming growth factor‐beta (TGF‐β) is a pluripotent regulatory molecule, found in at least five different isoforms. It is produced in many different organs. In the liver, TGF‐β is expressed in non‐parenchymal cells, but not in hepatocytes. This growth factor is known to induce fibrosis in the course of a variety of pathologic processes. Recently, TGF‐β has also been identified in hepatocellular carcinoma (HCC) cells, and the suggestion has been made that this growth factor may play a role in hepatocarcinogenesis. In this study, we report the findings of immunohistochemical stains for TGF‐β, performed on paraffin sections of 14 human HCCs of the usual type and 11 examples of the fibrolamellar variant (FLC). TGF‐β was detected in tumor cells of 3 HCCs (21%) and 9 FLCs (82%). Compared with the HCCs, the FLCs displayed a more diffuse and intense staining pattern for TGF‐β. Our findings suggest that lamellar fibrosis, which is a histologic hallmark of FLC, may be due to the action of TGF‐β produced by tumor cells.
Expression of transforming growth factor alpha and epidermal growth factor receptor in human hepatocellular carcinoma
Authors: Kira Shinsuke , Nakanishi Toshio , Suemori Shoichi , Kitamoto Mikiya , Watanabe Yasuyuki , Kajiyama Goro
Published: August 2010

Abstract: Transforming growth factor alpha (TGF‐alpha) is thought to be involved in liver regeneration, cellular proliferation, and hepatocarcinog‐enesis. We have looked at the relationship between TGF‐alpha and it's receptor, and have attempted to relate the expression of TGF‐alpha and it's receptor to the differentiation of hepatocellular carcinoma (HCC) on serial sections of HCC. We examined immunohistochemically the expression of the TGF‐alpha and of epidermal growth factor receptor (EGFR) proteins in the same area of 53 nodules (<5 cm in diameter) of HCC obtained from patients. Immnnoreactive proteins were visualized by using a biotin‐streptoavidin system (LSAB Kit, Dako). TGF‐alpha was strongly expressed in 29 of 53 (54.7%) nodules. Specimens strongly positive for TGF‐alpha were found mainly in well‐differentiated HCC, while specimens positive for EGFR were found mainly in poorly differentiated HCC (p<0.05). In the tissues that stained weakly positive for TGF‐alpha, the expression of EGFR differed significantly, according to the degree of HCC histologic differentiation (p<0.05). These results led us to speculate that the expression of TGF‐alpha and EGFR might be related to the pattern of histologic differentiation of HCC.
Deleted form of hepatocyte growth factor (dHGF) increases the number of platelets in rats with liver cirrhosis
Authors: Masunaga Hiroaki , Fujise Nobuaki , Yamashita Yasushi , Shiota Akira , Yasuda Hiroshi , Higashio Kanji
Published: August 2010

Abstract: The effect of the deleted form of hepatocyte growth factor (dHGF) on thrombopoiesis was studied in rats. When normal rats were injected with dHGF (0.5 mg/kg i.v. twice a day), the number of platelets increased to about 1.5‐fold the initial level. In addition, the treatment with dHGF (0.5 mg/kg i.v. twice daily) significantly increased the number of platelets in rats with liver cirrhosis induced by carbon tetrachloride and phenobarbital. When dHGF was given to rats at a dose of 0.05 or 0.5 mg/kg from the beginning of the induction of dimethylnitrosamine liver cirrhosis to day 28, dHGF dose‐dependently ameliorated thrombocytopenia and completely prevented it at a dose of 0.5 mg/kg. These results indicate that dHGF may be applicable to the treatment of thrombocytopenia associated with liver cirrhosis.
In vivo and in vitro hepatic 31P magnetic resonance spectroscopy and electron microscopy of the cirrhotic liver
Authors: Taylor‐Robinson Simon D. , Sargentoni Janet , Bell Jimmy D. , Saeed Nadeem , Changani K. Kumar , Davidson Brian R. , Rolles Keith , Burroughs Andrew K. , Hodgson Humphrey J. F. , Foster Christopher S. , Cox I. Jane
Published: August 2010

Abstract: In vivo 31P magnetic resonance spectroscopy (MRS) provides direct biochemical information on hepatic metabolic processes. To assess in vivo changes in hepatic 31P MRS in liver transplant candidates, we studied 31 patients with cirrhosis of varying aetiology; 14 with compensated cirrhosis (Pugh's score <7) and 17 with decompensated cirrhosis (Pugh's score <8). Underlying cellular abnormalities were characterised using in vitro 31P MRS and electron microscopy. In vitro spectra were obtained from liver extracts, freeze‐clamped at recipient hepatectomy, from all subjects. Electron microscopy of liver tissue was also performed in 17 cases. Relative to nucleotide triphosphates, elevations in phosphomonoesters and reductions in phosphodiesters were observed in vivo with worsening liver function. In vitro spectra showed elevated phosphoethanolamine and phosphocholine, and reduced glycerophosphorylethanolamine and glycerophosphorylcholine, mirroring the in vivo changes, but no distinction was noted between compensated and decompensated cirrhosis. With electron microscopy, functional decompensation was associated with reduced endoplasmic reticulum in parenchymal liver disease, but elevated levels in biliary cirrhosis. We conclude that in vivo spectral abnormalities in cirrhosis are consistent with alterations in phospholipid metabolism and quantity of endoplasmic reticulum. However, in individual patients the biopsy results do not always mirror in vivo findings.
Unusual spontaneous hepatic vein to paraumbilical vein shunt in a patient with Budd‐Chiari syndrome and cirrhosis: a case report
Authors: Bloom Allan I. , Cohen Shmuel E. , Lebensart Pinchas D. , Pappo Orit , Eid Ahmed
Published: August 2010

Abstract: A very unusual portosystemic shunt was identified using color flow Doppler sonography in an adult male with Budd‐Chiari syndrome and cirrhosis secondary to a hypercoagulability state. Hepatofugal blood flow was demonstrated between the middle hepatic vein and a recanalized paraumbilical vein, resulting clinically in prominent periumbilical veins. The clinical and radiological features are described.
Transjugular liver biopsy: a comparison of aspiration and trucut techniques
Authors: Sada Prio N. , Ramakrishna Banumathi , Thomas C. P. , Govil Shalini , Koshi Thomas , Chandy George
Published: August 2010

Abstract: The results of 67 transjugular liver biopsies are described. Two failures were encountered due to inability to pass the needle into acutely angulated hepatic veins. Thirty‐four patients underwent a liver aspiration biopsy using a Colapinto needle, while the remainder were biopsied using a trucut needle. The success rate with the Colapinto needle was 68% and with the trucut model, 97%. Capsular perforation occurred in three cases, but without significant morbidity or mortality. It is concluded that the trucut needle biopsy is more reliable than aspiration biopsy, when the transjugular approach is mandated, in obtaining optimal liver tissue for histopathological diagnosis.
Signal transduction in hepatic stellate cells
Authors: Pinzani Massimo , Marra Fabio , Carloni Vinicio
Published: August 2010

ABSTRACT— Hepatic stellate cells (HSC) are presently regarded as one of the key cell types involved in the progression of liver fibrosis and in the related pathophysiological and clinical complications. Following acute or chronic liver tissue damage, HSC undergo a process of activation towards a phenotype characterised by increased proliferation, motility, contractility and synthesis of extracellular matrix (ECM) components. Several factors have been shown to play a key role in the promotion of the full‐blown picture of activated HSC. These include extensive changes in the composition and organisation of the ECM, the secretion of several growth factors, cytokines, chemokines, products of oxidative stress and other soluble factors. It is evident that each cellular response to extracellular stimuli must be framed in a scenario where different forces modulate one another and result in a prevalent biological effect. Along these lines, the identification and characterisation of intracellular signalling pathways activated by different stimuli in HSC represent a mandatory step. In this review article we have made an attempt to summarise recent acquisitions to our knowledge of the involvement of different intracellular signalling pathways in key aspects of HSC biology.
Hepatitis C associated with Guillain‐Barré syndrome
Authors: Lacaille Florence , Zylberberg Hervé , Hagège Hervé , Roualdès Brigitte , Meyrignac Christian , Chousterman Michel , Girot Robert
Published: August 2010

ABSTRACT— Hepatitis C is frequently associated with immune‐mediated diseases, such as cryoglobulinemia. Guillain‐Barré syndrome is an acute demyelinating neuropathy of probable immune pathogenesis. We describe two patients with Guillain‐Barré syndrome, and associated chronic hepatitis C, the second one previously treated with interferon. The link between both conditions may be hepatitis C being the trigger of this immune polyneuropathy. Guillain‐Barré syndrome should be added to the list of conditions associated with hepatitis C.
Hyperbaric oxygen pretreatment attenuates hepatic reperfusion injury
Authors: Chen Miin‐Fu , Chen Han‐Ming , Ueng Steve W. N. , Shyr Ming‐Hwang
Published: August 2010

ABSTRACT— Microcirculatory derangement, energy depletion and lipid peroxidation have been related to development of ischemia‐reperfusion injury in the liver. This study investigates the effects of hyperbaric oxygen (HBO) on hepatic ischemia‐reperfusion injury. Adult, male Sprague‐Dawley rats were used. Three groups were evaluated: 1) sham‐operated control (laparotomy only, no ischemia, no HBO), n=8; 2) ischemia control (1‐h ischemia, 2‐h reperfusion, no HBO), n=8; and 3) HBO pretreatment (100% oxygen, 2.5 atm absolute, 90 min) plus ischemia (1‐h ischemia, 2‐h reperfusion), n=8. An in vivo microscope was used to investigate hepatic microcirculation. Tissue malondialdehyde (MDA) and adenosine triphosphate (ATP) were determined. In comparison with the ischemia control group, HBO significantly improved harmful insults following ischemia‐reperfusion. HBO lessened adherent leukocyte count (6.00±1.31 cells/200 μm vs 11.38±2.88 cells/200 μm), and improved flow velocity (1.72±0.26 mm/s vs 0.83±0.19 mm/s) in post‐sinusoidal venules. HBO also reduced MDA (1.04±0.24 nmol/mg protein vs 2.24±0.49 μmol/g protein), and increased ATP (2.03±0.17 μmol/g wet wt vs 0.73±0.11 μmol/g wet wt) levels. This study demonstrates that HBO before ischemia may ameliorate the ischemia‐reperfusion injury of the liver in the rat model.
Hepatoblastoma: DNA nuclear content, proliferative indices, and pathology
Authors: Rugge Massimo , Sonego Fulvia , Pollice Lucio , Perilongo Giorgio , Guido Maria , Basso Giuseppe , Ninfo Vito , Pennelli Natale , Gambini Claudio , Guglielmi Maurizio , Fabiano Alfredo , Leandro Gioacchino , Keeling Jean W.
Published: August 2010

Abstract: Hepatoblastoma (HB) is the most frequent malignant liver tumor in infancy, and both its biological features and its prognostic behavior are still under investigation. DNA content and proliferative activity of the tumor have been considered as biological parameters related to the tumor's aggressiveness. The present study attempts to investigate the possible association between histologic subtype, DNA content, and proliferative indices in HB. DNA content and the proportion of cells in the S‐phase were assessed by flow cytometry in 34 cases of HB (14 prior to chemotherapy, 20 after chemotherapy), using formalin‐fixed, paraffin‐embedded archival samples. The proliferative cell nuclear antigen (PCNA) labeling index was also evaluated by immunohistochemistry, and both the flow cytometry (FC) and the immunohistochemical data were correlated with tumor pathology. A significant association was found between histological type, DNA content and the percentage of cells in the S‐phase, with aneuploidy and the highest proportions of S‐phase cells significantly associated with embryonal tumors. The PCNA labeling index was found to be significantly higher in embryonal than in fetal phenotype. The biological heterogeneity of HB is confirmed by the different nuclear content of the fetal (diploid) and embryonal (aneuploid) epithelial components of the tumor, also ruling out the likelihood of fetal (diploid) clones deriving from the embryonal (aneuploid) neoplastic cells. Since the highly proliferative neoplastic clones (i.e., embryonal) are thought to be more sensitive to antimitotic drugs, further studies are indicated to determine the relationship between ploidy, proliferative indices and chemoresponsiveness.
Inhibitory effect of glycyrrhizin on NF‐κB binding activity in CC14‐ plus ethanol‐induced liver cirrhosis in rats
Authors: Wang Ji‐Yao , Guo Jin‐Sheng , Li Hai , Liu Shu‐Ling , Zern Mark A.
Published: August 2010

ABSTRACT— Aims/Background: Potenlini is an injectable compound whose active component is glycyrrhizin, which is extracted from licorice. Previous studies showed that it could reduce liver injury, improve alanine aminotransferase (ALT) levels and act as an antifibrotic agent. However, the mechanism of its action remains unclear. The aim of this study was to determine the molecular mechanism of its action by investigating the effects of potenlini on nuclear factor‐κB(NF‐κB) binding activity in an animal model of liver cirrhosis. Methods: Rats were randomly allocated into a normal control group, a model control group, and a potenlini group. Rats in the latter two groups were treated with CCl4 and ethanol solution in order to induce chronic liver injury. Rats in the potenlini group were given potenlini treatment at the same time. Results: Serum ALT levels were significantly reduced in rats treated with potenlini compared with levels in rats of the model control group, which had dramatically increased ALT levels. Histologically, liver steatosis and fibrosis were severe in the rats of the model group, but were significantly improved in rats of the potenlini group. NF‐κB binding activity was markedly increased in the liver specimens taken from the rats of the model control group in comparison with the binding of normal livers, but the binding levels were nearly normal in the livers of the potenlini group. Conclusions: The results suggest that potenlini can inhibit the NF‐κB binding activity in CCl4 and ethanol‐induced chronic liver injury, and that effect may be a possible mechanism by which potenlini protects the liver from hepatotoxin‐induced liver injury and cirrhosis.
Expression of type I and type III collagens during the course of dimethylnitrosamine‐induced hepatic fibrosis in rats
Authors: Shiba Masako , Shimizu Ichiro , Yasuda Mitugi , Ii Kunio , Ito Susumu
Published: August 2010

ABSTRACT— Aims/Background: We wished to clarify the mechanisms that account for the increase in hepatic collagen accumulation during hepatic fibrosis. Methods: The gene expression of type I and type III procollagens and matrix metalloproteinase‐1 (MMP‐1) was measured by Northern blot analysis; immunolocalization of both types of collagen was estimated by indirect immunohistochemical assay; and the hepatic content of collagen and malondialdehyde (MDA), a product of lipid peroxidation, were assayed in hepatic fibrosis induced in rats with a single dose of dimethylnitrosamine (DMN). Results: During the experimental period, more type I procollagen mRNA was found than type III procollagen mRNA. The immunoreactive intensity of type I collagen was greater in necrotic areas near central veins 3 days after DMN treatment than it was on day 9, whereas the type III collagen immunodeposition for the latter period of the hepatic fibrosis was stronger than it was on day 3. As compared with controls, hepatic collagen content increased significantly after 3 days and continued, increasing gradually, as did type I and III procollagen mRNA levels. On day 14, fibrosis was greatest and both types of procollagen gene expression were at their highest, and type I and III procollagen mRNA levels and hepatic collagen content increased as the dosage of DMN was raised. MMP‐1 mRNA levels increased early in hepatic fibrogenesis, and increased on day 14 when DMN dosages were low. Hepatic MDA levels increased rapidly for 3 days after DMN treatment, remaining significantly higher than control values and showing a significant increase even in response to low DMN doses on day 14. Conclusions: Our results suggested that fibrotic liver collagen content may make its first notable increase due in part to the balance between type I collagen and MMP‐1 expression rates. Also, lipid peroxidation may be important in the mechanism of hepatofibrogenesis.
Hepatic hydrothorax in the absence of ascites
Authors: Kakizaki Satoru , Katakai Kenji , Yoshinaga Teruo , Higuchi Tsugio , Takayama Hisashi , Takagi Hitoshi , Nagamine Takeaki , Mori Masatomo
Published: August 2010

ABSTRACT— Pleural effusion due to hepatic cirrhosis and ascites is well known, but hepatic hydrothorax in the absence of ascites is a rare complication. We report a case of liver cirrhosis due to hepatitis C virus with a large and recurring pleural effusion that had an apparent abdominal source in the absence of ascites. We review the characteristics and treatment for hepatic hydrothorax in the absence of ascites.
Diagnosis of hepatopulmonary syndrome with contrast transthoracic echocardiography and histological confirmation
Authors: Aller R. , Moreira V. , Boixeda D. , Moya J. L. , de Luis D. A. , Enriquez J. L. , Fogué L.
Published: August 2010

ABSTRACT— We report a patient with cirrhosis and hepatopulmonary syndrome. This syndrome is an entity characterized by anomalies in the arterial oxygenation in patients with chronic hepatic disease and/or portal hypertension and demonstration of pulmonary vasodilatation (PV) in absence of primary cardiac or pulmonary disease. We show that the finding of PV with transthoracic contrast enhanced echocardiography (TCEE) in the diagnosis of PV is real and corresponds to direct measurement of capillary diameter by morphometry.
Changes in hepatic polyamine catabolism in elderly rats
Authors: Ferioli Maria Elena , Sessa Angela , Rabellotti Elisa , Tunici Patrizia , Pinotti Orietta , Perin Antonio
Published: August 2010

Abstract: Aims/Background: Given the important role of polyamines (putrescine, spermidine, spermine) in the modulation of macromolecular syntheses, gene expression and proteolysis, alterations in their metabolic pathways could be relevant during senescence. Since the few existing data address mainly polyamine biosynthesis, we studied the oxidative catabolism of polyamines in the liver of rats 3–36 months of age. Methods: Polyamine oxidase activity was fluorimetrically measured using N1‐acetyl‐spermine as substrate. Spermidine/spermine N1‐acetyltransferase and diamine oxidase were measured by radiochemical methods using labeled acetyl‐coenzyme A and putrescine, respectively, as substrate. Polyamines were separated by HPLC and fluorimetrically quantified after post‐column derivatization with o‐phthaldialdehyde. Results: Spermidine/spermine N1‐acetyltransferase activity increased in 36‐month‐old rats and polyamine oxidase activity in 24‐ and 36‐month‐old rats. A decline in spermine and increases in spermidine and putrescine in elderly rats suggested an activation of the interconversion pathway of higher into lower polyamines. The activity of diamine oxidase, which degrades putrescine, was enhanced starting from 12 months of age. Conclusion: In the liver of aged rats, an increase in the catabolic enzymes leads to a reconversion of the higher polyamines to putrescine. This increased catabolism may represent an important age‐related change and may contribute to impairment of the expression of growth‐related genes in senescence.
Stromal expression of urokinase‐type plasminogen activator receptor (uPAR) is associated with invasive growth in primary liver cancer
Authors: Akahane Takehiro , Ishii Motoyasu , Ohtani Haruo , Nagura Hiroshi , Toyota Takayoshi
Published: August 2010

Abstract: Aims/Background: Expression of urokinase‐type plasminogen activator receptor (uPAR) was studied in 25 hepatocellular carcinomas (HCCs) and seven cholangiocellular carcinomas (CCCs) by immunohistochemistry. Methods and Results: uPAR was expressed mostly by host cells distributed along the tumour‐host interface in all cases of HCC and CCC, and its expression was higher in CCC. These uPAR‐positive cells were identified as macrophages by observation of serial sections stained for CD68, a marker for macrophages. Cancer cells were positive for uPAR in only one case of poorly differentiated HCC with sarcomatous changes and in three cases of CCC. Hepatocellular carcinomas were classified into two types: those with a fibrous capsule (expansive type) and those without a fibrous capsule (invasive type). Invasive‐type HCCs showed more prominent expression of uPAR by macrophages than expansive HCCs (p<0.001), to approximately the same degree as that of CCC. Extrahepatic metastasis was observed in two of 16 expansive HCCs, five of nine invasive HCCs and six of seven CCCs. Conclusions: Our findings suggest that uPAR expression mainly by macrophages is associated with invasive growth of cancer cells into the surrounding tissue in primary carcinoma of the liver.
Noninvasive assessment of spontaneous baroreflex sensitivity in patients with liver cirrhosis
Authors: Veglio Franco , Melchio Remo , Calva Sally , Rabbia Franco , Gallo Vittorio , Molino Paola , Mengozzi Giulio , Mulatero Paolo , Martini Gianpiero , Riva Piero , Chiandussi Livio
Published: August 2010

Abstract: Aims/Background: An impairment of baroreceptor sensitivity has been found in liver cirrhosis. Noninvasive and spontaneous estimates of baroreflex sensitivity are obtained from beat‐to‐beat blood pressure and heart rate recordings by means of cross‐spectrum analysis and calculation of alpha‐index (as a measure of baroreflex gain). The aim of the present study was to investigate the function of the spontaneous baroreflex sensitivity related to clinical Child score in liver cirrhosis. Methods: The alpha‐index was evaluated in 40 cirrhotic patients (18 with and 22 without ascites) and 17 healthy subjects by analysing finger arterial pressure recorded noninvasively with the Portapres device. Results: Baroreflex sensitivity was significantly lower in cirrhotic patients with and without ascites compared with healthy subjects (p<0.01). Furthermore, in patients with ascites the baroreflex gain was significantly related to plasma sodium (p<0.01). A significant inverse relationship was present between baroreflex gain and grade of Child score and the severity of ascites (p<0.01). There were no significant relationships between hormonal parameters (catecholamines, renin, aldosterone, arginine‐vasopressin, atrial natriuretic peptide and nitric oxide) and baroreflex gain. No significant differences were found between healthy subjects and cirrhotic patients with respect to systolic and diastolic blood pressure total variability in a supine position, whilst it was lower in cirrhotic patients with ascites in a tilted position (p<0.05). Conclusion: Our findings showed that baroreflex sensitivity was significantly impaired in cirrhotic patients when compared with healthy subjects. In addition, there was a significant trend toward lower baroreflex sensitivity values with the grade score of Child class (p<0.01). Spectral analysis of the alpha‐index provides viable alternatives to the pharmacological approach for estimation of baroreflex sensitivity and may represent a prognostic tool to identify cirrhotic patients at increased risk of adverse events.
EFFECT OF ANTI‐ANGIOTENSIN II ON BLOOD PRESSURE AND SENSITIVITY TO ANGIOTENSIN AND RENIN
Authors: Bing Jens , Poulsen Knud
Published: August 2010

1. Intravenous injection of anti‐angiotensin II causes a transient fall in the mean blood pressure of anaesthetized normal rats, showing that the angiotensin content in the blood plays a role for the normal blood pressure level. The subsequent return of the blood pressure to its initial level is probably caused by the cardio‐accelerator and pressor reflexes. The function of the baroreceptors is also thought to be the cause why a depressor effect of anti‐angiotensin is lacking in conscious normal rats. Lack of effect on anaesthetized nephrectomized rats conforms to the lack of angiotensin in their blood. The somewhat increased depressor response to anti‐angiotensin in rats with acute severe constriction of the renal arteries and the still more pronounced response in many (but not all) renal hypertensive rats conforms to increased plasma angiotensin in these rats. The somewhat decreased depressor response of ureterligated rats corresponds to their decreased sensitivity to angiotensin and renin. 2. Anti‐angiotensin causes a decreased response to injected angiotensin both in conscious normal and anaesthetized normal, nephrectomized, ureterligated and renal hypertensive rats, the sensitivity in several cases being reduced to less than 1 per cent. If angiotensin is continuously infused in doses of 9 ng/min, anti‐angiotensin will cause a fall of the blood pressure which in one half of the cases reaches the initial level, in the other half stops at a level above the initial, even when a second dose of anti‐angiotensin is injected. When anti‐angiotensin is given between two periods of continuous infusion of angiotensin, the second rise in blood pressure will be smaller, being up to 50 per cent of the first. 3. Anti‐angiotensin causes a decreased response to renin, but the above‐mentioned groups of rats do not react in the same way. In anaesthetized normal rats the sensitivity is reduced to about 5 to 10 per cent. Nephrectomized and ureterligated rats are still able to react with a pressor response to doses of renin which are without effect on the blood pressure of anti‐angiotensin pretreated normal rats. The maximum response of rats belonging in these two groups is, however, only up to 50 per cent of that found in non pretreated nephrectomized or ureterligated rats. If given shortly after renin, anti‐angiotensin injection will cause a rapid fall in the blood pressure to the initial level in normal and ureterligated rats, while there is only a partial return to a level markedly above the initial in nephrectomized rats.