Delayed liver regeneration in peroxisome proliferator‐activated receptor‐α‐null mice

Steven P. Anderson, Lawrence Yoon, Erika B. Richard, Corrie S. Dunn, Russell C. Cattley, J. Christopher Corton – 30 December 2003 – Peroxisome proliferator chemicals, acting via the peroxisome proliferator‐activated receptor‐α (Pparα), are potent hepatic mitogens and carcinogens in mice and rats. To test whether Pparα is required for hepatic growth in response to other stimuli, we studied liver regeneration and hepatic gene expression following partial hepatectomy (PH) of wild‐type and Pparα‐null mice.

A randomized 4‐arm multicenter study of interferon alfa‐2b plus ribavirin in the treatment of patients with chronic hepatitis C relapsing after interferon monotherapy

Giorgio Saracco, Alda Olivero, Alessia Ciancio, Silvia Carenzi, Antonina Smedile, Giuseppe Cariti, Massimo Andreoni, Pier Giulio Orsi, Alberto Biglino, Marco Tabone, Luigi Roffi, Guido Croce, Aldo Manca, Gianfranco Tappero, Giovannino Ciccone, Mario Rizzetto – 30 December 2003 – To determine whether a higher dosage of interferon (IFN) and/or a prolonged time of administration may improve the efficacy of combination therapy, we conducted a 4‐arm randomized trial on patients with chronic hepatitis C relapsing after 1 or more previous treatment courses with IFN monotherapy.

Predictive value of ALT levels for histologic findings in chronic hepatitis C: A European collaborative study

Pierre Pradat, Alfredo Alberti, Thierry Poynard, Juan‐Ignacio Esteban, Ola Weiland, Patrick Marcellin, Salvatore Badalamenti, Christian Trépo – 30 December 2003 – The aim of this retrospective study was to determine the predictive value of alanine aminotransferase (ALT) levels for histologic findings in patients with chronic hepatitis C virus (HCV) infection. Data on 864 HCV RNA–positive patients were collected. ALT values were obtained at the time of biopsy (before treatment), and normal ALT values were defined as normal values obtained at serial evaluations during a 6‐month period.

Imbalanced intrahepatic expression of interleukin 12, interferon gamma, and interleukin 10 in fulminant hepatitis B

Ludger Leifeld, Silvia Cheng, Jan Ramakers, Franz‐Ludwig Dumoulin, Christian Trautwein, Tilman Sauerbruch, Ulrich Spengler – 30 December 2003 – In murine models, overexpression of interleukin (IL)‐12 and interferon (IFN)‐γ can induce severe liver damage, whereas IL‐10 has anti‐inflammatory and hepatoprotective properties.

Inducible differentiation and morphogenesis of bipotential liver cell lines from wild‐type mouse embryos

Hélène Strick‐Marchand, Mary C. Weiss – 30 December 2003 – This work shows that hepatic cell lines reproducibly can be derived from E14 embryos of many mouse inbred strains. These bipotential mouse embryonic liver (BMEL) cell lines present a mixed morphology, containing both epithelial and palmate‐like cells, and an uncoupled phenotype, expressing hepatocyte transcription factors (HNF1α, HNF4α, GATA4) but not functions (apolipoproteins, albumin). BMEL cells are bipotential: under inducing conditions they express hepatocyte and bile duct functions.

Region selective alterations of soluble guanylate cyclase content and modulation in brain of cirrhotic patients

Regina Corbalán, Nicolas Chatauret, Sönke Behrends, Roger F. Butterworth, Vicente Felipo – 30 December 2003 – Modulation of soluble guanylate cyclase (sGC) by nitric oxide (NO) is altered in brain from experimental animals with hyperammonemia with or without liver failure. The aim of this work was to assess the content and modulation of sGC in brain in chronic liver failure in humans. Expression of the α‐1, α‐2, and β‐1 subunits of sGC was measured by immunoblotting in autopsied frontal cortex and cerebellum from cirrhotic patients and controls.

Recombinant alfa‐interferon plus ribavirin therapy in children and adolescents with chronic hepatitis C

Stefan Wirth, Thomas Lang, Stephan Gehring, Patrick Gerner – 30 December 2003 – Treatment with alfa‐interferon alone yielded poor results in children with chronic hepatitis C and was not generally recommended. Owing to limited experience with combination therapy in children, the aim of the study was to evaluate the efficacy and tolerability of alfa‐interferon 2b in combination with ribavirin in these patients with different routes of viral transmission.

Risk factors for hepatocellular carcinoma: Synergism of alcohol with viral hepatitis and diabetes mellitus

Manal M. Hassan, Lu‐Yu Hwang, Chiq J. Hatten, Mark Swaim, Donghui Li, James L. Abbruzzese, Palmer Beasley, Yehuda Z. Patt – 30 December 2003 – Risk factors associated with hepatocellular carcinoma (HCC) are well documented, but the synergisms between these risk factors are not well examined. We conducted a hospital‐based, case‐control study among 115 HCC patients and 230 non–liver cancer controls. Cases and controls were pathologically diagnosed at The University of Texas M. D. Anderson Cancer Center and were matched by 5‐year age groups, sex, and year of diagnosis.

Future therapy of hepatitis C

John G. McHutchison, Keyur Patel – 30 December 2003 – Currently available therapies for the treatment of chronic hepatitis C are effective in half of patients, but are expensive, often poorly tolerated, and unsuitable for certain patient populations. The ideal therapy would be highly effective, orally bioavailable, have minimal side effects, be cost effective, and suitable for the majority of patients with hepatitis C.

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