Estimating progression to cirrhosis in chronic hepatitis C virus infection

Anthony J. Freeman, Gregory J. Dore, Matthew G. Law, Max Thorpe, Jan Von Overbeck, Andrew R. Lloyd, George Marinos, John M. Kaldor – 30 December 2003 – To gain a clearer understanding of the rate of progression to cirrhosis and its determinants in chronic hepatitis C virus (HCV) infection, a systematic review of published epidemiologic studies that incorporated assessment for cirrhosis has been undertaken. Inclusion criteria were more than 20 cases of chronic HCV infection, and information on either age of subjects or duration of infection.

Endothelial cell–mediated uptake of a hepatitis B virus: A new concept of liver targeting of hepatotropic microorganisms

Klaus M. Breiner, Heinz Schaller, Percy A. Knolle – 30 December 2003 – The liver is a target for many infectious agents, most notably hepatitis viruses. However, several receptor molecules identified so far for hepatitis viruses were found to be ubiquitously expressed and can thus not account for efficient liver targeting. Using a model hepatitis B virus, the duck hepatitis B virus (DHBV), we have obtained data indicating that scavenging liver sinusoidal endothelial cells (LSEC), rather than hepatocytes themselves, play the key role in the initial uptake of viral pathogens into the liver.

Sequential treatment with lamivudine and interferon monotherapies in patients with chronic hepatitis B not responding to interferon alone: Results of a pilot study

Lawrence Serfaty, Dominique Thabut, Fabien Zoulim, Tony Andreani, Olivier Chazouillères, Nicolas Carbonell, Alain Loria, Raoul Poupon – 30 December 2003 – Sustained viral suppression using monotherapy with interferon alfa (IFN‐α) or lamivudine can only be achieved in a small percentage of patients with chronic hepatitis B. The concomitant administration of lamivudine and IFN‐α does not enhance efficacy. We postulated that the optimal timing of therapy might be sequential treatment with lamivudine and IFN‐α.

Hepatitis C virus–like particles induce virus‐specific humoral and cellular immune responses in mice

Martin Lechmann, Kazumoto Murata, Jujin Satoi, John Vergalla, Thomas F. Baumert, T. Jake Liang – 30 December 2003 – We have recently described the production of hepatitis C virus–like particles (HCV‐LPs) in insect cells that resemble the putative virions. Here we evaluate the humoral and cellular immunogenicity of the virus‐like particles with or without viral p7 protein, a small viral polypeptide that resides between the structural and nonstructural regions of the HCV polyprotein and whose function has not been defined.

Involvement of intrasinusoidal hemostasis in the development of concanavalin a–induced hepatic injury in mice

Yuko Miyazawa, Hiroko Tsutsui, Hidekazu Mizuhara, Hiromi Fujiwara, Kenji Kaneda – 30 December 2003 – Concanavalin A (Con A) stimulation induces T‐cell activation–associated hepatic injury. This study is designed to show the involvement of microcirculatory disturbance in the pathogenesis.

Cerebral blood flow and metabolism in patients with chronic liver disease undergoing orthotopic liver transplantation

Barbara J. Philips, Ian R. Armstrong, Anthony Pollock, Alistair Lee – 30 December 2003 – Changes in cerebral hemodynamics and metabolism associated with anesthesia and liver transplantation may present particular hazards for patients with cirrhosis. Fifteen patients undergoing liver transplantation were studied, 7 of whom had encephalopathy. Cerebral blood flow (CBF) was measured at the start of surgery, during veno‐venous bypass and post reperfusion, using a method based on the Kety‐Schmidt method.

Hepatitis B virus with antigenically altered hepatitis B surface antigen is selected by high‐dose hepatitis B immune globulin after liver transplantation

Ulrike Protzer‐Knolle, Uta Naumann, Ralph Bartenschlager, Thomas Berg, Uwe Hopf, Karl‐Hermann Meyer zum Büschenfelde, Peter Neuhaus, Guido Gerken – 30 December 2003 – “Escape” variants of hepatitis B virus (HBV) can cause infection despite previous immunization. These viruses show alterations of the immunogenic major hydrophilic loop of the HBV small surface protein (s‐protein).

A two‐year prospective study of the effect of ursodeoxycholic acid on urinary bile acid excretion and liver morphology in cystic fibrosis–associated liver disease

Anders Lindblad, Hans Glaumann, Birgitta Strandvik – 30 December 2003 – The efficacy of 2 years of treatment with ursodeoxycholic acid (UDCA) in cystic fibrosis (CF)‐associated liver disease was evaluated by liver biopsies and liver function tests in 10 patients aged 8 to 28 years. The metabolism of UDCA was investigated by analysis of urinary bile acids with fast atom bombardment mass spectrometry (FABMS) and gas‐liquid chromatography–mass spectrometry. Eight patients responded with normalization of liver function tests (LFT) and all with decreased serum levels of immunoglobulin G (IgG).

Carrier‐mediated entry of 4‐methylumbelliferyl sulfate: Characterization by the multiple‐indicator dilution technique in perfused rat liver

Masato Chiba, Andreas J. Schwab, Carl A. Goresky, K. Sandy Pang – 30 December 2003 – The hepatocellular entry of 4‐methylumbelliferyl sulfate (4MUS) a highly ionized and highly bound anion capable of futile cycling, was examined in the single‐pass albumin‐free perfused rat liver preparation. Desulfation of 4MUS to 4‐methylumbelliferone (4MU) was verified in vitro to be a low‐affinity, high‐capacity process (Km= 731 μmol/L;Vmax= 414 nmol min−1g−1 liver).

Nitric oxide suppression reversibly attenuates mitochondrial dysfunction and cholestasis in endotoxemic rat liver

Masaya Shiomi, Yoshiyuki Wakabayashi, Tsuyoshi Sano, Yuichi Shinoda, Yuji Nimura, Yuzuru Ishimura, Makoto Suematsu – 30 December 2003 – This study aimed to examine whether nitric oxide (NO) plays a causal role in endotoxin‐induced dysfunction of biliary transport. Rats were treated with intraperitoneal injection of endotoxin (O111B4, 4 mg/kg). At 2 hours, the liver was excised and perfused ex vivowith taurocholate (TC)‐containing Krebs‐Ringer solution under monitoring bile output and NO2in the perfusate and tissue cyclic guanosine monophosphate (cGMP) levels as indices of NO production.

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