bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased gene expression of water channel in cirrhotic rat kidneys
Authors: Asahina Yasuhiro , Izumi Namiki , Enomoto Nobuyuki , Sasaki Sei , Fushimi Kiyohide , Marumo Fumiaki , Sato Chifumi
Published: March 2007

In patients with liver cirrhosis, impaired water and sodium excretion has been incriminated in the pathogenesis of ascites formation. Increased reabsorption of water in the distal nephron has been shown to play an important role in water retention in cirrhotic rat kidneys. Recently, a complementary DNA (cDNA) for the vasopressin-regulated water channel (the aquaporin of the apical membrane of the kidney collecting duct [AQP-CD]) has been cloned. It is suggested that AQP-CD plays an important role in renal water handling. Therefore, in the present study, to investigate the pathogenic role of the water channel in water retention in liver cirrhosis, gene expression of AQP-CD in the kidney was evaluated in cirrhotic rats. Liver cirrhosis was induced by an intraperitoneal administration of carbon tetrachloride twice a week for 12 weeks in 14 rats. Messenger RNA expression of AQP-CD in whole kidney homogenates determined by northern blot hybridization was significantly increased in cirrhotic rats (147%; P<.01) and dehydrated rats (206%; P<.0001) compared with control rats. Protein expression of AQP-CD in the homogenates of kidney medulla determined by Western blot analysis was significantly increased in cirrhotic rats (203%; P<.03) compared with control rats. Furthermore, mRNA expression of AQP-CD in the kidney showed a significant correlation with the volume of ascites in cirrhotic rats (r = 0.62, P<.02). No significant difference was observed in water intake, urinary volume, serum osmolality, serum sodium, and creatinine clearance between control and cirrhotic rats, suggesting that dehydration was unlikely in cirrhotic rats. From these results, it is concluded that renal mRNA expression of AQP-CD plays an important role in abnormal water retention followed by the development of ascites in liver cirrhosis. (Hepatology 1995;21:169-173).
Evaluation of purine nucleoside phosphorylase release as a measure of hepatic endothelial cell injury
Authors: Brass Clifford A. , Mody Milan G.
Published: March 2007

With emerging data that endothelial cell (EC) injury is the limiting factor in liver preservation and hepatic function, a simple and reliable biochemical technique for monitoring EC injury is needed. Measurement of purine nucleoside phosphorylase (PNP) release into the circulation from perfused liver has been proposed as such a method. However, our experiments with perfused rat liver did not display a clear or direct relationship between PNP release and endothelial cell injury. Therefore, we re-examined the suitability of using PNP as a measure of nonparenchymal injury by measuring its distribution in purified populations of hepatocytes, ECs, and Kupffer cells (KCs) and correlating cell injury and enzyme release in short-term cultures at 37±C of each cell type. Purified cells were incubated (4 × 106 cells/mL) in oxygen or nitrogen saturated Wisconsin solution or Krebs buffer for 6 hours, with cell viability and PNP release assayed every 2 hours. ECs had the lowest specific activity (27 ± 9 U/mg protein; mean ± standard error of the mean [SEM]) compared with both hepatocytes (115 ± 15) and KCs (66 ± 18). Despite a decrement in EC and KC viability over time in each incubation solution, there was poor correlation between time of incubation and PNP release (r = 0.01 to 0.22), and between cell viability and PNP release (r = 0.01 to 0.16). In contrast, PNP release from incubated hepatocytes correlated with the length of incubation (r = 0.57 to 0.78) as well as cell injury (r = 0.63 to 0.77) in all four test solutions. This data suggest that PNP release is unlikely to specifically reflect EC injury in the intact liver. (Hepatology 1995;21:174-179).
Structure and dynamics of the fenestrae-associated cytoskeleton of rat liver sinusoidal endothelial cells
Authors: Braet Filip , De Zanger Ronald , Baekeland Marijke , Crabbé Evelyne , Van Der Smissen Patrick , Wisse Eddie
Published: March 2007

This article describes the cytoskeleton associated with fenestrae and sieve plates of rat liver sinusoidal endothelial cells. Fenestrae control the exchange between the blood and parenchymal cells. We present evidence indicating that several agents that change the fenestrae and sieve plates also cause changes in the cytoskeleton. Cultured liver endothelial cells (LECs) were slightly fixed and treated with cytoskeleton extraction buffer. Detergent-extracted whole mounts of cultured cells were prepared for either scanning electron microscopy (SEM) or transmission electron microscopy (TEM). Extracted cells show an integral intricate cytoskeleton; sieve plates and fenestrae are delineated by cytoskeleton elements. Fenestrae are surrounded by a filamentous, fenestrae-associated cytoskeleton with a mean filament thickness of 16 nm. Sieve plates are surrounded and delineated by microtubuli, which form a network together with additional branching cytoskeletal elements. The addition of ethanol to cultured cells enlarged the diameter for these fenestrae-associated cytoskeleton rings by 5%, whereas serotonin treatment reduced the diameter by 20%. These observations indicate that the fenestrae-associated cytoskeleton probably changes the size of fenestrae after different treatments. After treatment with cytochalasin B the number of fenestrae increased. However, cytochalasin B did not change the structure of the fenestrae-associated cytoskeleton ring, but disperses the microtubuli. In conclusion, LECs have a cytoskeleton that defines and supports sieve plates and fenestrae. Fenestrae-associated cytoskeleton is a dynamic structure and plays a role in maintaining and regulating the size of fenestrae after different treatments. Therefore, the fenestrae-associated cytoskeleton controls the important hepatic function of endothelial filtration. (Hepatology 1995;21:180-189).
Concanavalin A—induced T-cell—mediated hepatic injury in mice: The role of tumor necrosis factor
Authors: Gantner Florian , Leist Marcel , Lohse Ansgar Wilhelm , Germann Paul Georg , Tiegs Gisa
Published: March 2007

Concanavalin A activates T lymphocytes in vitro and causes T-cell-dependent hepatic injury in mice. T lymphocytes were previously identified as effector cells of concanavalin A-induced liver injury. Here we report that hepatic injury is characterized by apoptotic cell death. On concanavalin A challenge, the cytokines tumor necrosis factor-α (TNF α), interleukin-2, granulocyte macrophage-colony stimulating factor, and interferon-γ were detectable in the circulation of the mice. Pretreatment of mice with anti-mouse TNF-α antiserum protected them from concanavalin A-induced liver injury. Nude mice failed to release TNF-α or interleukin-2 after concanavalin A challenge and were protected from liver injury. Lymph node cell transfer from responder mice to resistant nude mice resulted in susceptibility of the latter towards concanavalin A, i.e., to induction of cytokine release and hepatotoxicity. These experiments suggest that immunocompetent T cells play a pivotal role in concanavalin A-stimulated TNF-α release in vivo. After intravenous administration of fluorescein isothiocyanate-labeled concanavalin A to mice, the most fluorescence was found within the liver. In vitro, concanavalin A stimulation of separate cultures of mouse lymph node cells or nonparenchymal liver cells induced the release of minute amounts of TNF, whereas stimulation of cocultures of these cells resulted in production of substantial amounts of TNF-α. These findings may explain the hepatotropic effect of concanavalin A. In conclusion, T-cell-dependent concanavalin A-induced apoptotic liver injury in mice is related to immunological and cytokinemediated disorders and possibly to autoreactive hepatic processes. (Hepatology 1995;21:190-198).
Effect of deoxycholate on immunoglobulin G concentration in bile: Studies in humans and pigs
Authors: Sanabria Juan R. , Upadhya Aravinda , Mullen Brendan , Harvey Robert P. C. , Strasberg Steven M.
Published: March 2007

Because an increase in biliary deoxycholate levels seems to be a risk factor for cholesterol gallstone formation, we determined the relationship between deoxycholate levels and levels of the pronucleating protein, immunoglobulin G (Ig) in human gallbladder bile. Patients with cholesterol gallstones had a higher concentration of biliary IgG compared with a pigmented stone group and control patients. This was associated with the simultaneous presence of two conditions in the cholesterol stone group, supersaturated bile and a high deoxycholate/cholate ratio. The other patient groups met only one of the two conditions. Next, animal studies were performed to determine if model biles mimicking the two conditions could affect IgG secretion by the gallbladder. Gallbladders were exposed in vivo and then in an Ussing chamber to model biles. The voltage clamp technique was used to monitor functional integrity of the preparation. Three different model biles were tested: (1) taurodeoxycholate (TDC), 80%; taurocholate (TC), 20%; and cholesterol saturation index (CSI), 1.2; (2) TDC, 20%; TC, 80%; and CSI, 1.2; and (3) TDC, 80%; TC, 20%; and CSI, 0.6. IgG concentrations became significantly higher in group 1 than in the other two groups. The concentration of mucous glycoprotein was also significantly greater in group 1 when compared with group 2. Plasma cells were increased in number in mucosal and submucosal layers in group 1. We conclude that cholesterol supersaturated model bile with high content of TDC induces gallbladder epithelial alterations, which increase the luminal concentration of IgG and mucous glycoprotein. (Hepatology 1995;21:215-222).
Uw-preservation of cultured human gallbladder epithelial cells: Phenotypic alterations and differential mucin gene expression in the presence of bile
Authors: Campion Jean-Pierre , Porchet Nicole , Aubert Jéan-Pierre , L'Helgoualch Annie , Clément Bruno
Published: March 2007

In orthotopic liver transplantation, extended cold ischemia of the graft may induce cell damage, particularly in biliary epithelium. We have investigated the effects of a cold University of Wisconsin (UW) solution on cultured human gallbladder biliary epithelial cells (GBEC) exposed or not exposed to stagnant bile. In UW solution, morphological alterations of cultured GBEC were not prominent under light microscopy after 16 hours at 4°C, being more striking after 24 to 48 hours. Ultrastructural examination of GBEC showed a condensation of chromatin at the periphery of the nuclei after 16 hours in cold UW solution. Both protein and DNA syntheses were strikingly reduced in these cells. After rewarming in standard Williams' medium at 37°C for 24 hours, cultured GBEC exhibited both normal morphology and function. As in both freshly isolated and routinely cultured GBEC, rewarmed cells expressed various mucin genes, namely MUC1, MUC3, MUC4, MUC5AC, and MUC5B genes, whereas MUC2 mRNAs were barely detectable. A dramatic decline in the steady-state mRNA levels of both MUC3 and MUC5B was found in cultured GBEC versus freshly isolated cells. Addition of bile into UW solution at 4°C had no significant effect on GBEC morphology and DNA and protein syntheses. When bile was added during the rewarming period, both protein and DNA syntheses were strongly reduced. Addition of bile during either storage in UW solution or rewarming period induced increased steady-state MUC2, MUC3 and MUC5AC mRNA levels. These results show that UW is a reliable cold storage solution for GBEC and the presence of stagnant bile within the culture medium during the rewarming period leads to deleterious phenotypic alterations of these cells. This suggests changes in the management of liver graft during orthotopic liver transplantation. (Hepatology 1995;21:223-231).
Non-ABCDE hepatitis: IS there another enterically transmitted hepatitis virus?
Authors: Mast Eric E. , Purdy Michael A.
Published: March 2007

Many epidemics of water-borne hepatitis have occurred throughout India. These were thought to be epidemics of hepatitis A until 1980, when evidence for an enterically transmitted non-A, non-B hepatitis was first reported. Subsequently, hepatitis E virus was discovered and most recent epidemics of enterically transmitted non-A, non-B hepatitis have been attributed to hepatitis E virus infection. However, only a limited number of cases have been confirmed by immuno electron microscopy, polymerase chain reaction, or seroconversion. In the present study we have performed a retrospective seroepidemiologic study of 17 epidemics of water-borne hepatitis in India. We have confirmed that 16 of the 17 epidemics were caused at least in part by serologically closely related hepatitis E viruses. However, one epidemic, in the Andaman Islands, and possibly a significant minority of cases in other epidemics, appears to have been caused by a previously unrecognized hepatitis agent.
Bone marrow augmentation in solid organ transplantation-any conclusions?
Authors: Fung John J.
Published: March 2007

Donor-specific bone marrow infusion after organ grafting can induce tolerance in animals. In this randomized, controlled study we show it has no benefit in patients undergoing liver transplantation. Of 25 patients, 9 received bone marrow 5 days after a 10 day course of antithymocyte globulin. Immunosuppression was maintained with cyclosporin only. An average of 3·0 rejection episodes per patient was seen in the bone marrow group compared to 3·1 in the controls. Chimerism was not found in peripheral blood or bone marrow of recipients using erythrocyte antigen markers, PCR for donor class II DNA or γ-probe in-situ hybridisation in one female recipient of male liver and bone marrow.
A unique insertion in the S gene of surface antigen-negative hepatitis B virus Chinese carriers
Authors: Hou Jinlin , Karayiannis Peter , Waters Jenny , Luo Kangxian , Liang Chishen , Thomas Howard C.
Published: March 2007

The presence of unique hepatitis B virus (HBV) variants has been investigated in two Chinese patients with chronic liver disease, whose sera were positive for HBV-DNA by dot blot hybridization or polymerase chain reaction (PCR) but hepatitis B surface antigen (HBsAg)-negative by conventional polyclonal antibody based immunoassays. PCR amplification of HBV-DNA followed by direct sequencing showed an insertion of six nucleotides, which introduced two additional amino acids between codons 122 and 123 in one patient (Isolate 1), whereas a nine nucleotide insertion in the other patient (Isolate 2) gave rise to three amino-acids between codons 123 and 124 immediately upstream from the ‘a’ determinant in the S gene. These insertions have not been described previously in any published sequences of the known subtypes and were absent from sequences of 30 HBsAg-positive Chinese patients from the same region. In the cases under study, the insertion is associated with four consecutive adenine molecules from nucleotides 516 to 519. It seems likely that this area is a hot spot for insertions in HBV. We found none of the previously described amino-acid deletions or substitutions in the pre-S1, pre-S2 and S genes, which are involved in unusual antigenic profiles. This finding suggests that genetic mutations in the S gene outside the ‘a’ determinant may be responsible for failure to detect HBsAg in some Chinese patients with chronic hepatitis caused by HBV infection. (Hepatology 1995;21:273-278.)
Prophyria cutanea tarda and hepatitis C and B viruses infection: A retrospective study
Authors: Navas Sonia , Bosch Orencio , Castillo Inmaculada , Marriott Eduardo , Carreño Vicente
Published: March 2007

Based on the knowledge that patients with porphyria cutanea tarda (PCT) usually have chronic liver disease, several authors studied a possible relationship to hepatotropic virus infections. However, the prevalence of hepatitis B virus (HBV)-DNA by polymerase chain reaction (PCR) in serum of these patients, as well as the presence of hepatitis C virus (HCV)-RNA in paired liver, peripheral blood mononuclear cells (PBMCs), and serum samples in these patients has not been reported. We have studied 34 patients with sporadic PCT. Antibodies against HBV were detected in 91% of the patients, but in only 41% of the patients against HBV (P < .01). Viral genomes of HCV and HBV were detected in 65% and 40% of our patients, respectively (P < .05). Genomic and antigenomic HCV strands were found in liver biopsy specimens (100% and 54%), mononuclear cells (100% and 54%), and serum (45% and 0%) from 11 patients. Twelve patients were retrospectively studied, and no correlation was observed between the appearance or disappearance of viral genomes and the simultaneous presence of both genomes with the course of porphyria. In our patients with PCT, detection of viral genomes did not correlate with phlebotomy or length of time since PCT was diagnosed. Our findings demonstrate that HCV infection may be underestimated when detection is performed only in serum of PCT patients, and that HBV infection might also be increased in PCT. (Hepatology 1995;21:279-284.)
Ability of prolonged interferon treatment to suppress relapse after cessation of therapy in patients with chronic hepatitis C: A multicenter randomized controlled trial
Authors: Kasahara Akinori , Hayashi Norio , Hiramatsu Naoki , Oshita Masahide , Hagiwara Hideki , Katayama Kazuhiro , Kato Michio , Masuzawa Manabu , Yoshihara Harumasa , Kishida Yutaka , Shimizu Yoji , Inoue Atsuo , Fusamoto Hideyuki , Kamada Takenobu
Published: March 2007

The aim of this study was to determine whether 12 months course of interferon alfa (IFN-α) therapy could improve the beneficial effect of IFN in chronic hepatitis C. Eighty-eight patients were treated with natural IFN-α for either 28 weeks (45 cases) or 52 weeks (43 cases). Sustained response was achieved in 15 (33.3%) of 45 cases treated for 28 weeks and in 23 (53.5%) of 43 cases treated for 52 weeks. Transient response with relapse of alanine transaminase (ALT) after completion of therapy was observed in 13 cases (28.9%) treated for 28 weeks and in 4 cases (9.3%) treated for 52 weeks. Thus, ALT relapse was suppressed by prolonged IFN treatment. No response was found in 17 cases (37.8%) treated for 28 weeks and in 16 cases (37.2%) treated for 52 weeks, indicating that approximately 38% of the patients with chronic hepatitis C were resistant to IFN therapy even with prolonged treatment. The rate of sustained response was significantly higher in patients with type 2a or 2b than in those with type 1b. Even in type 1b cases, it was higher in the 52-week treatment group than in the 28-week treatment group, and the rate of transient response was lower in the 52-week treatment group, indicating that relapse in type 1b cases was suppressed by prolonged IFN therapy. IFN therapy was not effective for patients with advanced liver fibrosis. In multivariate regression analysis viral genotype and pretreatment level of serum hepatitis C virus (HCV) RNA were correlated independently with sustained response. Periportal necrosis, intralobular inflammation, and hepatic fibrosis scores were significantly improved in the sustained response group by IFN therapy. In the transient response group, a significant decrease in scores for intralobular inflammation and portal inflammation was observed, whereas all four histological scores were not improved in the no response group. In conclusion, prolonged IFN therapy can suppress relapse of chronic hepatitis C, even in type 1b patients. However, approximately 38% of the patients are resistant to prolonged IFN therapy, suggesting the need to develop a new therapy. (Hepatology 1995;21:291-297.)
Localization of hepatitis C virus antigens in liver and skin tissues of chronic hepatitis C virus-infected patients with mixed cryoglobulinemia
Authors: Sansonno Domenico , Cornacchiulo Vito , Iacobelli Anna Rina , Di Stefano Rita , Lospalluti Mario , Dammacco Franco
Published: March 2007

Skin and/or liver biopsy specimens were obtained from the following patients: 15 anti-hepatitis C virus (HCV), HCV RNA-positive patients and 3 anti-HCV, HCV RNA-negative patients with type II mixed cryoglobulinemia (MC); 7 anti-HCV, HCV RNA-positive patients with chronic active liver disease (CALD); 5 anti-HCV, HCV RNA-negative patients with noncryoglobulinemic vasculitis; and 7 anti-HCV, HCV RNA-negative patients with lichen ruber planus. A pool of murine monoclonal antibodies (MAbs) developed against c22-3, c33c, and c100-3 proteins was used to detect HCV-related antigens (Ags) by indirect immunohistochemistry. Acid electroelution (AEE) of tissue sections was performed to enhance the sensitivity of the immunohistochemical method. In anti-HCV-positive MC patients, specific HCV-related Ags were detected in the small vessels of the skin and in the cytoplasm of hepatocytes. Prior AEE of biopsy sections allowed detection of HCV Age in 6 of 15 (40%) skin biopsy and in 9 of 14 (64.3%) liver biopsy specimens. HCV immunoreactive deposits in the skin displayed two immunohistochemical patterns: (1) coarse intraluminal material associated with dermal inflammatory infiltrates and intravascular deposition of eosinophilic hyaline material; and (2) reactivity confined to the vessel wall in the context of an apparently normal tissue. Immunoglobulin (Ig) G and IgM deposition in the skin showed immunohistochemical features comparable with those found for HCV Ag deposits. In addition, tissue complement reactivity was detected in 6 (40%) of them and was strictly associated with histological and clinical signs of active vasculities. Five of 7 (71.4%) liver biopsy specimens, but none of 7 skin biopsy specimens, from anti-HCV, HCV RNA-positive patients without circulating cryoglobulins displayed immune reactivity after AEE procedure. Consistently negative results were obtained with skin and liver sections from all anti-HCV, HCV RNA-negative patients. These findings indicate that, under the experimental conditions used, in 40% of anti-HCV, HCV RNA-positive patients with MC, skin tissue deposits consist of HCV-containing immune complexes. In addition, the occurrence of HCV reactivity in apparently normal blood vessels suggests that deposition of viral Ags precedes and possibly initiates tissue damage. Whether in the remaining patients HCV Ags cannot be detected because of the insufficient sensitivity of the method or the involvement of Ags other than those assayed, remains to be determined. (Hepatology 1995;21:305-312.)
Human immunodeficiency virus infection as risk factor for mother-to-child hepatitis C virus transmission; Persistence of anti-hepatitis C virus in children is associated with the mother's anti-hepatitis C virus immunoblotting pattern
Authors: Manzini Paola , Saracco Giorgio , Cerchier Antonella , Riva Caterina , Musso Alberto , Ricotti Emanuela , Palomba Elvia , Scolfaro Carlo , Verme Giorgio , Bonino Ferruccio , Tovo Pier Angelo
Published: March 2007

To determine the rate of vertical transmission of hepatitis C virus (HCV), we prospectively studied 45 babies born to anti-HCV-positive women with or without con-comitant infection with the human immunodeficiency virus (HIV). We performed a second-generation recombinant immunoblotting assay, alanine transaminase (ALT) evaluation, and HCV-RNA testing on sera from 27 infants of HCV+, HIV- mothers and 18 babies of HCV+, HIV+ women, at birth and thereafter. After birth, HCV antibodies progressively disappeared within 12 months in all children but one, whose mother was HCV+, HIV+; this child was the only one who showed detectable levels of HCV-RNA and abnormal ALT values throughout the follow-up (range, 12 to 27 months). Viremia was persistently negative, and ALT levels were continuously normal in the remaining infants, showing that “seronegative” infection with HCV was absent in both groups. Clearance of passively acquired anti-HCV antibodies was found to be slower among babies born to HIV+ mothers (22.3% vs. 3.8% at 12 months, P = .03) and children whose mothers showed three of four anti-HCV reactivities by immunoblotting maintained anti-HCV for longer periods compared with babies born to mothers with one or two anti-HCV reactivities (P = .0001). Seventeen of 27 babies born to HCV+, HIV- mothers were breast-fed, and none of them was infected, confirming the apparent safety for HCV of breast milk. In summary, according to our study, vertical transmission of HCV is an infrequent event, and the presence of HIV in the mother is not an important co-factor for transmission of HCV infection. (Hepatology 1995;21:328-332.)
Long-term clinical and virological outcome after liver transplantation for cirrhosis caused by chronic delta hepatitis
Authors: Samuel Didier , Zignego Anna-Linda , Reynes Michel , Feray Cyrille , Arulnaden Jean Louis , David Marie-Françoise , Gigou Michèle , Bismuth Alain , Mathieu Danielle , Gentilini Paolo , Benhamou Jean-Pierre , Brechot Christian , Bismuth Henri
Published: March 2007

Liver transplantation for liver diseases related to hepatitis B virus (HBV) and hepatitis delta virus (HDV) remains problematic because of the risk of viral recurrence. We report here the long-term virological outcome of patients transplanted for HDV-related liver cirrhosis (HDV cirrhosis). From December 1984 to December 1990, 76 patients with HDV cirrhosis underwent liver transplantation. Before transplantation, all the patients were HBsAg-positive/anti-HDV positive, and all but one were HBV DNA-negative by dot blot hybridization. HDV RNA was detected by HDV RT-PCR and liver HDAg by fluorescent HDV Ab. After transplantation, all the patients except four received continuous long-term anti-HBs passive immunoprophylaxis. The actuarial 5-year survival was 88%. All patients who did not receive anti-HBs immunoprophylaxis remained HBsAg-positive and developed hepatitis. Among the 68 patients receiving anti-HBs immunoprophylaxis with a minimum follow-up of 2 months, HBsAg reappeared in 7 (10.3%) after a mean of 17 months. These seven patients developed hepatitis, with simultaneous HBV and HDV replication; and four cleared later HBsAg. Patients without HBV reinfection were studied for HDV reinfection: liver HD Ag or serum HDV RNA were present in 88% of the patients during the first year, without developing hepatitis; however, they were no longer detectable after 2 years in 95% of the patients. In conclusion, liver transplantation for HDV cirrhosis gives good results, with a 5-year actuarial survival of 88%. Reappearance of HBsAg occurred in 13.2% and was associated with HBV and HDV reactivation and hepatitis. Among patients who remained HBsAg negative, HDV markers were detectable during the first year, without the development of hepatitis, but disappeared in the long term in most cases. (Hepatology 1995;21:333-339.)
Spontaneous bacterial peritonitis in cirrhotic patients treated using paracentesis or diuretics: Results of a randomized study
Authors: Solà Ricard , Andreu Montserrat , Coll Susana , Vila Maria Carme , Oliver Maria Isabel , Arroyo Vicente
Published: March 2007

Diuretic treatment in cirrhotic patients with ascites increases ascitic fluid concentration of total protein and complement components, and opsonic activity. These changes are not observed in patients treated with paracentesis. Based on these data it has been suggested that therapeutic paracentesis may be associated with an increased risk of spontaneous bacterial peritonitis (SBP) development. To assess this possibility, 80 cirrhotic patients with tense ascites were randomly allocated in two therapeutic groups: group 1 (40 patients) was treated with total paracentesis associated with plasma volume expansion and group 2 was treated with diuretics. After mobilization of ascites, patients from both groups received diuretics to avoid reaccumulation of ascites; cases that developed tense ascites during follow-up (mean follow-up period, 60 ± 6 and 55 ± 4 weeks, respectively) were treated according to initial randomization. Patients from both groups had similar results regarding baseline clinical and standard laboratory data, ascitic fluid concentration of total protein, complement components, and opsonic activity. Sixteen patients (7 from group 1 and 9 from group 2) developed SBP during the study period. The 4-week and 1-year probability of SBP occurrence were 2.5% and 18.6%, respectively, in group 1 patients, and 11.9% and 24%, respectively, in group 2 patients. Therefore, our study indicates that therapeutic paracentesis does not increase the early- and long-term risk of SBP development in cirrhotic patients with tense ascites. (Hepatology 1995;21:340-344.)
Histopathological heterogeneity in fulminant hepatic failure
Authors: Hanau Cheryl , Munoz Santiago J. , Rubin Raphael
Published: March 2007

The clinicopathological features of 38 patients admitted consecutively for fulminant hepatic failure were studied. Histopathological material was reviewed in all patients. Both percutaneous and whole livers (either explanted or autopsy specimens) were available in 16 patients: whole livers only in 12 patients and biopsy specimens only in 10 patients. All patients were negative for antibodies to hepatitis C, whereas 24% had hepatitis B infection and 10% had adverse drug reactions. Livers from 75% of patients showed confluent hepatic necrosis. However, there was considerable variability in the extent of necrosis, and biopsy specimens from about 50% of the most severely affected livers showed only minimal bridging necrosis. In patients with massive hepatic necrosis, percutaneous liver biopsy specimens were frequently misleading because of regional inhomogeneities. Interestingly, five patients (13%) had established cirrhosis at the time of diagnosis. The best clinical predictors of survival were age and the maximal grade of encephalopathy. By contrast, neither the severeity of confluent hepatic necrosis nor the etiology predicted the decision to transplant or the outcome. There were no differences in the histopathology corresponding to different etiologies. In summary, the approach to the patient with fulminant hepatic failure should be guided principally on clinical grounds, and further classification should be based on pathological and etiologic considerations. However, histological classification and prognosis based on percutaneous biopsy specimens alone may be misleading. (Hepatology 1995;21:345-351.)
Whole-body and segmental bioelectrical parameters in chronic liver disease: Effect of gender and disease stages
Authors: Panella Carmine , Guglielmi Francesco William , Mastronuzzi Tecla , Francavilla Antonio
Published: March 2007

The aim of this study was to examine and compare whole-body and segmental impedance measurements in control subjects and patients with progression of liver disease and to investigate whole-body and segmental bioelectrical changes occurring during dehydration therapy or paracentesis. Males have lower resistance (R) and reactance (Xc) values than females in measurements both of the whole body and of the arm, leg, and trunk. This is not true in patients. In the three groups of patients, whole-body R and Xc were lower in each increased disease stage, suggesting that stage has a significant main effect on impedance measurements. The lower extremities were the segment most influenced by the progression of liver disease. The sum of the arm and leg R was only slightly lower than the value of wholebody resistance. The trunk has a meager influence on this parameter, as is clearly shown by the absence of variations before and immediately after paracentesis. In edematous cirrhotic patients without ascites treated with diuretics, our data also showed a significant correlation (r = .81; SEE = 1.2) between changes in body weight (BW) and in the bioelectrical evaluation of total body water (TBW). The association of a prevalent increment of Xc (≈40%) with a reduction of extracellular water is the most significant bioelectrical event during dehydration therapy. All these findings show that impedance measurements have a low sensitivity in detecting the volume of ascites in cirrhotic patients, whereas Xc has a clinical use in monitoring changes in extracellular water (EW). (Hepatology 1995;21:352-358.)
Detection and quantification of soluble asialoglycoprotein receptor in human serum
Authors: Yago Hirokazu , Kohgo Yutaka , Kato Junji , Watanabe Naoki , Sakamaki Sumio , Niitsu Yoshiro
Published: March 2007

We describe the first evidence that soluble asialoglycoprotein receptors (AGPR) are present in human serum and that they are quantifiable by an enzyme-linked immunosorbent assay (ELISA). An affinity chromatography gel immobilized with monoclonal antibodies (McAbs) against human liver AGPR was mixed with normal sera, and the bound fraction was analyzed both by sodium dodecyl sulfate polyacrylamide gel electrophoresis and by Western blot analysis. Immunoreactive bands corresponding to 35 to 40 kd were obtained, which were lower than those of liver AGPR (41 kd and 46 kd). Soluble AGPR in human serum was able to bind to D-galactose-immobilized beads, indicating that soluble AGPR remained ligand-binding activity. In order to quantify soluble AGPR, we established an ELISA using a monoclonal antibody (30220 McAb)-immobilized microplate and horseradish peroxidase-labeled F(ab′)2 of another monoclonal antibody (30201 McAb). Reproducibility of intra- and interassay of the ELISA were 4% to 14% and 7% to 14%, respectively. Analytical recoveries ranged from 93% to 99%. The detection limit was estimated to be 0.1 μg/L. By nonparametolic analysis, a median and a 90% tile of serum AGPR level obtained from 283 normal volunteers were 0.4 μg/L and 2.4 μg/L, respectively. (Hepatology 1995;21:383-388.)
Prognostic significance of nucleolar organizer regions in hepatocellular carcinoma
Authors: Shimizu Koichi , Izumi Ryohei , Ii Toru , Muraoka Keiichi , Inoue Tetsuya , Fukushima Wataru , Sakamoto Koya , Tani Takashi , Hashimoto Tetsuo , Yagi Masao , Miyazaki Itsuo , Nonomura Akitaka
Published: March 2007

It has been suggested that the number of argyrophilic nucleolar organizer regions (AgNORs) correlates with cellular activity and the aggressiveness of malignancy. The mean number of AgNORs per nucleus may, therefore, be a prognostic factor for hepatocellular carcinoma (HCC). The purpose of this study was to evaluate the prognostic significance of the number of AgNORs in HCC. The silver-staining technique was applied to surgically resected specimens to indicate AgNORs. Eightynine of the specimens were of HCC, 23 were of normal liver adjacent to HCC, and 32 were of cirrhotic liver adjacent to HCC. The number of AgNORs of HCC (mean ± SD, 3.26 ± 1.23) was significantly higher than those of normal liver (1.37 ± 0.13) and cirrhotic liver (1.49 ± 0.14). The number of AgNORs was significantly correlated with serum alpha-fetoprotein level, tumor size, portal vein invasion, and Edmondson-Steiner histological grade. In patients undergoing curative resection, the survival rate of those with a high number (>3.04) of AgNORs was significantly worse than that of those with a low number (≤3.04) of AgNORs. Multivariate analysis showed that the number of AgNORs was a significant prognostic indicator in patients without portal vein invasion, and portal vein invasion was the only significant variable when all patients undergoing curative resection were assessed together. The results of this study suggest that the number of AgNORs is useful as an indicator of the grade of malignancy and as a predictor of the prognosis of patients with HCC who do not have portal vein involvement. (Hepatology 1995;21:393-397.)
Effect of functional grade and etiology on in vivo hepatic phosphorus-31 magnetic resonance spectroscopy in cirrhosis: Biochemical basis of spectral appearances
Authors: Menon David K. , Sargentoni Janet , Taylor-Robinson Simon D. , Bell Jimmy D. , Cox Jane I. , Bryant David J. , Coults Glyn A. , Rolles Keith , Burroughs Andrew K. , Margan Marsha Y.
Published: March 2007

Hepatic phosphorus-31 magnetic resonance spectroscopy (31P MRS) was undertaken in 85 patients with histoloically proven cirrhosis of varying etiologies and functional severity. Reference data were acquired from 16 healthy volunteers who had no history or evidence of liver disease or alcohol abuse. In vivo hepatic 31P MR spectra were acquired with pulse angle 45° and repetition times (TR) of 5 and 0.5 seconds. Peak area ratios of phosphomonoesters (PME), inorganic phosphate (Pi), and phosphodiesters (PDE) relative to βATP, and of PME relative to PDE were calculated from spectra acquired at TR 5 seconds. Estimates of saturation effects for individual resonances were obtained by dividing the peak height at TR 5 seconds by that at TR 0.5 seconds to yield a T1-related singnal height ratio (SHR). When compared with reference values, the patients with liver disease showed a significantly higher PME/ATP (P < .0001), PME/PDE (P < .0001), PME SHR (P < .001), and Pi SHR (P < .02) and a lower PDE/ATP (P < .001) and PDE SHR (P < .001). The magnitude of these changes increased significantly and progressively with increasing functional impairment. In patients with compensated cirrhosis spectral appearances varied with etiology; thus, patients with postviral cirrhosis showed a significantly higher Pi/ATP; those with alcoholic cirrhosis, a significantly lower PDE/ATP; and those with cirrhosis secondary to primary sclerosing cholangitis, a significantly lower Pi/ATP than the healthy volunteers or other etiological groups. However, spectral appearances did not vary with etiology in patients with decompensated disease. In vitro
31P MRS of perchloric extracts of samples of liver tissue obtained from 10 patients with cirrhosis at transplant hepatectomy showed increases in levels of the soluble PME metabolites, phosphorylcholine and phosphorylethanolamine, and reductions in the levels of the soluble PDE metabolites, glycerophosphorylcholine and glycerophosphorylethanlamine. These changes suggest regenerative activity in cirrhotic livers. The increases in soluble phosphomonoesters in the aqueous extracts accounted for the increased PME/ATP ratio seen in the in vivo spectra, and might account for the increase in PME SHR. The reduction in soluble phosphodiesters in the aqueous extracts did not entirely account for the reduction PDE/ATP ratio seen in vivo. This change in the PDE resonance in hepatic in vivo spectra may also be partly due to reduced contribution to this peak from hepatic endoplasmic reticulum, resulting from replacement of hepatocytes by fibrous tissue. Hepatic 31P MRS provides insights into the pathophysiology of liver injury and may contribute to the assessment of hepatic functional state. (Hepatology 1995;21:417-427.)
Interobserver and interquipment variability of echo-doppler examination of the portal vein: Effect of a cooperative training program
Authors: Sabbà Carlo , Merkel Carlo , Zoli Marco , Ferraioli Giovanna , Gaiani Stefano , Sacerdoti David , Bolondi Luigi
Published: March 2007

The aim of this study was to assess the interobserver, interequipment, and time-dependent variabilities of echo-Doppler measurements of portral blood flow velocity (PBV), portal vein diameters (PVDs) and their derived parameters, portal blood flow (PBF), and congestion index (CI) in cirrhotic patients. The influence of a cooperative training program of the opeators on the reproductibility of the results was also investigated. The echo-Doppler parameters were independently measured in 15 patients by four skilled operators, using four echo-Doppler machines (Acuson, ATL, Hitachi-Esaote, Toshiba. Eight of the 15 patients were restudied after 15 days by the same operators using only one machine. Significantly different values of PBV, PBF, and CI were obtained. PBV variance was equipment-related (32%) and operator-related in a smaller portion (5%). No systemiatic effect related to the time of investigation was found. After training to define a precise protocol, new measurements were performed by four operators on 8 different patients. No significant differences were found among the operators for any of the parameters and the 95% confidence limits (CL) and coefficients of variation (CV) of PBV showed a marked decrease (CL from ±26.4% to ±15.6%). These results indicate that (1) a significant systematic vaiability exists between Doppler measurements with different equipment; (2) there is no significant time-dependent systematic variability of Doppler measurements; and (3) a cooperative training program reduces the interobserver variability for direct measurements, such as PBV. (Hepatology 1995;21:428-433.)
Changes in hepatic lobe volume in biliary tract cancer patients after right portal vein embolization
Authors: Nagino Masato , Nimura Yuji , Kamiya Junichi , Kondo Satoshi , Uesaka Katsuhiko , Kin Yukoh , Hayakawa Naokazu , Yamamoto Hideo
Published: March 2007

Changes in lobar volume of the liver and in total hepatic function were studied in 19 patients with biliary tract cancer who underwent right portal vein embolization as preoperative management for extensive liver resection. Computed tomography (CT) was performed to estimate liver volume before and approximately 11 days after embolization. An indocyanine green (ICG) test was performed before and 11 to 13 days after embolization. The calculated volume of the right lobe decreased from 761 ± 181 cm3 to 625 ± 110 cm3 11 days after embolization (P < .0001), whereas the volume of the left lobe increased from 420 ± 94 cm3 to 555 ± 110 cm3 (P < .0001). Thus, portal embolization produced a gain in left lobe volume of 136 ± 62 cm3 and an almost equivalent loss in right lobe volume. The hypertrophy ratio of the left lobe, expressed as percentage of postembolization volume of the left lobe to preembolization size, of the 5 patients with diabetes mellitus (DM) was lower than that of the 14 patients without diabetes (116.7 ± 6.3% vs. 140.4 ± 18.4%; P < .005). The ICG disappearance rate in 16 patients improved from 0.163 ± 0.163 ± 0.034 to 0.177 ± 0.027 (P < .05). The improvement was especially evident in 9 of 14 postjaundice patients, although the rate decreased slightly in 2 patients without jaundice. We conclude that right portal vein embolization can produce a compensatory hypertrophy of the left lobe within 11 days without seriously affecting hepatic function. In diabetic patients, however, a longer interval between embolization and operation may be needed to achieve sufficient hypertrophy of the left lobe. (Hepatology 1995;21:434-439.)
Increased signals seen in globus pallidus in T1-weighted magnetic resonance imaging in cirrhotics are not suggestive of chronic hepatic encephalopathy
Authors: Thuluvath Paul J. , Edwin David , Yue Nancy Chang , Devilliers Cora , Hochman Sandra , Klein Andrew
Published: March 2007

Increased, symmetrical signals of varying intensity in the globus pallidi on T1-weighted (T1W) images, without corresponding signals on T2-weighted (T2W) images, have been reported previously in chronic hepatic failure, It has been suggested that these signals are characteristic of chronic hepatic encephalopathy. To test this hypothesis, we evaluated the relationship of magnetic resonance imaging (MRI) abnormalities with ammonia, albumin, bilirubin, prothrombin time, ascites, clinical encephalopathy, and neuropsychological tests in 46 patients (16 with alcohol-induced cirrhosis and 30 with non-alcohol-induced cirrhosis). T1W signal and cortical atrophy were graded by a neuroradiologist in a blinded fashion. Eleven patients had no T1W signal, 18 had minimal T1W signal, and 17 had high T1W signal. Twenty-five patients had no cortical atrophy, 14 had mild atrophy, and 7 had moderate atrophy. Cortical atrophy was noted more commonly in patients with alcohol-induced liver disease. The neuropsychological tests correlated significantly with albumin, prothrombin time, Child-Pugh's score, clinical encephalopathy, and ammonia. T1W signal and cortical atrophy did not correlate with the neuropsychological tests, clinical encephalopathy, ascites, albumin, prothrombin time, ammonia, or Child-Pugh's score. Patients with high T1W signal showed significant correlation with bilirubin (P < .005). This study suggests that globus pallidus signal in T1W images observed in liver disease are not indicators of chronic hepatic encephalopathy as previously assumed. (Hepatology 1995;21:440-442.)
31P magnetic resonance spectroscopy of the liver: Correlation with standardized serum, clinical, and histological changes in diffuse liver disease
Authors: van Wassenaer-Van Hall Hester N. , van der Grond Jeroen , van Hattum Jan , Kooijman Carole , Hoogenraad Tjaard U. , Mali Willem P. Th. M.
Published: March 2007

The goal of this study was to analyze the possibilities of 31P MR spectroscopy to detect abnormal hepatic histological changes in patients with diffuse liver disease. 31P MR spectroscopy was performed, on a 1.5 T whole-body spectrometer using an image guided localization technique (ISIS), on 38 patients with various diffuse liver diseases, who all underwent histological and serum analysis, and 22 healthy volunteers. Phosphomonoester expressed as a fraction of total phosphorus (PME/P) showed a correlation with abnormal serum aspartate transaminase (AST), histological intralobular degeneration/focal necrosis, portal inflammation, and piecemeal necrosis. We found a lower correlation for PME/P with fibrosis. It was not possible to differentiate between fibrosis and cirrhosis. In summary, 31P MR spectroscopy is a technique to detect intralobular degeneration, inflammation and necrosis and to a less extent fibrosis. No diagnostic value was found with respect to steatosis and cholangitis. Furthermore, 31P MR spectroscopy is a poor method for classifying patients into diagnostic categories. (Hepatology 1995;21:443-449.)
Effect of Brefeldin A on transcytotic vesicular pathway and bile secretion: A study on the isolated perfused rat liver and isolated rat hepatocyte couplets
Authors: Alvaro Domenico , Benedetti Antonio , Gigliozzi Alessandro , Bini Adriano , Furfaro Sonia , Bassotti Cristina , La Rosa Tiziana , Jezequel Anne Marie , Capocaccia Livio
Published: March 2007

This study investigated the effect of Brefeldin A (BFA) on the transcytotic vesicular pathway labeled with horseradish peroxidase (HRP) in both isolated rat hepatocyte couplets (IRHC) and the isolated perfused rat liver (IPRL). To evaluate the role of the transcytotic vesicular pathway on bile secretion, the efffect of BFA on bile secretion in the IPRL was then investigated. In the basolateral area of IRHC, BFA showed no effect on the density and percentage of area of HRP-labeled vesicles. However, HRP-labeled vesicles tended to accumulate in the juxtanuclear area of BFA-treated hepatocytes (P < .001 vs. controls). In the pericanalicular area, on the other hand, HRP-labeled vesicles were depleted compared with controls (P < .001). In keeping with these findings, although the early peak remained unchanged, BFA inhibited as much as 50% of the late peak of HRP excretion in bile, after a pulse load of HRP in the IPRL. Bile flow and the biliary secretion of bile salts (BS) and phospholipids were not modified by BFA in isolated livers perfused without BS in the perfusate or with 1 μmol/min taurocholate (TCA). In BFA-treated livers, peak bile flow and BS output decreased by 20% (P < .05 vs. controls) only when a 5 μmol TCA bolus was administered. In conclusion, this study demonstrates that BFA inhibits the transcytotic vesicular pathway in the liver. However, BFA has no significant effect on bile secretion either in basal conditions or during perfusion with physiological amounts of BS. BFA slightly decreases bile flow and BS output only after an overload of BS, providing evidence against the physiological relevance of the transcytotic vesicular pathway in the process of bile formation. (Hepatology 1995;21:450-459.)