L S Friedman – 1 October 1996

C Merkel, G Marchesini, A Fabbri, S Bianco, G Bianchi, E Enzo, D Sacerdoti, M Zoli, A Gatta – 1 October 1996 – There is increasing interest for the use of surrogate end points in the evaluation of treatments in patients with liver disease, but adequate validation is seldom available. This study aimed to describe the different course of galactose elimination capacity in patients with alcoholic cirrhosis who continued to drink or abstained from alcohol consumption during follow‐up, and to validate changes in galactose elimination as a surrogate end point for death from liver‐related causes.

L D DeLeve – 1 October 1996 – Hepatic venoocclusive disease (HVOD) is caused by the disruption of the microcirculation by an as‐yet unknown mechanism. Previous in vitro studies with azathioprine, monocrotaline, and dacarbazine suggested that toxins that cause HVOD initially causing HVOD target sinusoidal endothelial cells (SEC) perhaps via profound glutathione (GSH) depletion. The current study examines cyclophosphamide toxicity in SEC and hepatocytes, as well as the interplay between the two cell types.

P A Knolle, G Gerken, E Löser, H P Dienes, F Gantner, G Tiegs, K Meyer zum Büschenfelde, A W Lohse – 1 October 1996 – CD4+ T lymphocytes have been identified as being responsible for organ damage in the murine model of experimental liver injury induced by intravenous injection of concanavalin A (Con A). Liver sinusoidal endothelial cells (SEC) and Kupffer's cells (KC) are among the first cells that come into contact with lymphocytes in the liver sinusoid.

A Michalak, C Rose, J Butterworth, R F Butterworth – 1 October 1996 – It has been proposed that alterations of excitatory and inhibitory amino acids play a role in the pathogenesis of hepatic encephalopathy in acute liver failure. To evaluate this possibility, in vivo cerebral microdialysis was used to sample extracellular concentrations of amino acids in the frontal cortex of unanesthetized rats at various times during the progression of encephalopathy resulting from acute liver failure.

J Córdoba, J Gottstein, A T Blei – 1 October 1996 – Brain myo‐inositol, an organic osmolyte, is decreased in cirrhotic patients with hepatic encephalopathy but appears unchanged in fulminant hepatic failure. An osmoregulatory response to the increase in brain glutamine may explain the decrease in brain myo‐inositol; if this is the case, organic osmolytes may account for differences in the development of brain edema seen in acute or chronic liver failure.

R H Moseley – 1 October 1996

P J Meier‐Abt – 1 October 1996

C Luscombe, J Pedersen, E Uren, S Locarnini – 1 October 1996 – Long‐term antiviral chemotherapy using the nucleoside analogue ganciclovir was undertaken with the aim of eliminating hepadnaviral covalently closed circular (CCC) DNA from the livers of ducks that were congenitally infected with the duck hepatitis B virus (DHBV). Twenty‐ four weeks of ganciclovir therapy caused a substantial reduction in viremia, intrahepatic viral DNA replicative intermediates, and viral core proteins.

M F Fromm, D Busse, H K Kroemer, M Eichelbaum – 1 October 1996 – Cytochrome P450 (CYP) enzymes, which metabolize numerous drugs, are expressed both in liver and in extrahepatic tissues. CYP3A4 for example is present and inducible by rifampin in epithelial cells of the gastrointestinal tract. It has been shown that such prehepatic metabolism contributes substantially to total clearance of CYP3A4 substrates (e.g., cyclosporine) before and even more pronounced during enzyme induction.