Combination of interferon induction therapy and ribavirin in chronic hepatitis C

Peter Ferenci, Harald Brunner, Karin Nachbaur, Christian Datz, Michael Gschwantler, Harald Hofer, Rudolf Stauber, Franz Hackl, Wolfgang Jessner, Martha Rosenbeiger, Petra Munda‐Steindl, Karin Hegenbarth, Alfred Gangl, Wolfgang Vogel – 30 December 2003 – The initial clearance of hepatitis C virus (HCV) during interferon‐alfa therapy is dose‐dependent. Therefore, higher initial interferon doses (induction therapy) may improve treatment results. This concept was tested in a prospective, randomized controlled trial.

The processing and utilization of hepatocyte growth factor/scatter factor following partial hepatectomy in the rat

Peter Pediaditakis, Juan Carlos Lopez‐Talavera, Bryon Petersen, Satdarshan P. S. Monga, George K. Michalopoulos – 30 December 2003 – Hepatocyte growth factor/scatter factor (HGF/SF) is a pluripotent growth factor capable of acting as a motogen, a morphogen, and a mitogen. Originally, HGF/SF was found as a blood‐borne mitogen for hepatocytes and has since been determined to be very important in liver repair. Previous studies have established that HGF/SF must be proteolytically cleaved to elicit its effects.

Targeting dexamethasone to Kupffer cells: Effects on liver inflammation and fibrosis in rats

Barbro N. Melgert, Peter Olinga, Judith M.S. Van Der Laan, Betty Weert, Jaejin Cho, Detlef Schuppan, Geny M. M. Groothuis, Dirk K.F. Meijer, Klaas Poelstra – 30 December 2003 – Kupffer cells (KC) play an important role in the pathogenesis of inflammatory liver diseases leading to fibrosis. Anti‐inflammatory drugs are only effective when administered at high doses that may cause side effects. Therefore, dexamethasone coupled to mannosylated albumin (Dexa5‐Man10‐HSA) was designed by us to selectively deliver this anti‐inflammatory drug to the KC.

Adult hepatitis B vaccination using a novel triple antigen recombinant vaccine

Michael D. Young, David L. Schneider, Arie J. Zuckerman, Wei Du, Brian Dickson, Willis C. Maddrey – 30 December 2003 – Present hepatitis B vaccines use multidose prolonged regimens, which even healthcare workers at risk do not always complete. Moreover, when vaccination is completed there remain some who fail to achieve adequate protection. The protection of adults at risk could be improved if there were a more potent vaccine and/or a shorter vaccination regimen available.

Differential effects of microsomal enzyme–inducing chemicals on the hepatic expression of rat organic anion transporters, OATP1 and OATP2

Lesley C. Rausch‐Derra, Dylan P. Hartley, Peter J. Meier, Curtis D. Klaassen – 30 December 2003 – The organic anion transporting polypeptides, Oatp1 (Slc21a1) and Oatp2 (Slc21a5), mediate hepatic uptake of cardiac glycosides. Previously, we demonstrated that chemicals that increase cytochrome P450s differentially affect hepatic uptake of cardiac glycosides. We postulated that increased uptake of cardiac glycosides observed after pretreatment of animals with phenobarbital (PB) and pregnenolone‐16α‐carbonitrile (PCN) occurs via increased hepatic expression of Oatp1 and/or Oatp2.

Increasing incidence and mortality of primary intrahepatic cholangiocarcinoma in the United States

Tushar Patel – 30 December 2003 – Clinical observations suggest a recent increase in intrahepatic biliary tract malignancies. Thus, our aim was to determine recent trends in the epidemiology of intrahepatic cholangiocarcinoma in the United States. Reported data from the Surveillance, Epidemiology, and End Results (SEER) program and the United States Vital Statistics databases were analyzed to determine the incidence, mortality, and survival rates of primary intrahepatic cholangiocarcinoma.

Steatosis accelerates the progression of liver damage of chronic hepatitis C patients and correlates with specific HCV genotype and visceral obesity

Luigi E. Adinolfi, Michele Gambardella, Augusto Andreana, Marie‐françoise Tripodi, Riccardo Utili, Giuseppe Ruggiero – 30 December 2003 – The role of steatosis in the progression of liver damage in chronic hepatitis C (CHC) was studied. Enrolled were 180 consecutive liver biopsy‐proven CHC patients and 41 additional subjects with a known duration of infection. We evaluated the histological activity index (HAI), grade of fibrosis and steatosis, body mass index (BMI; kg/m2), distribution of body fat, HCV genotype, and levels of HCV RNA.

The phenobarbital response enhancer module in the human bilirubin UDP‐glucuronosyltransferase UGT1A1 gene and regulation by the nuclear receptor CAR

Junko Sugatani, Hiroyuki Kojima, Akiko Ueda, Satoru Kakizaki, Kouichi Yoshinari, Qi‐Hui Gong, Ida S. Owens, Masahiko Negishi, Tatsuya Sueyoshi – 30 December 2003 – The UDP‐glucuronosyltransferase, UGT1A1, is the critical enzyme responsible for detoxification of the potentially neurotoxic bilirubin by conjugating it with glucuronic acid. For decades, phenobarbital (PB) treatment for hyperbilirubinemia has been known to increase expression of the UGT1A1 gene in liver. We have now delineated the PB response activity to a 290‐bp distal enhancer sequence (−3483/−3194) of the UGT1A1 gene.

Zinc mesoporphyrin represses induced hepatic 5‐aminolevulinic acid synthase and reduces heme oxygenase activity in a mouse model of acute hepatic porphyria

Macé M. Schuurmans, Francine Hoffmann, Raija L. Lindberg, Urs A. Meyer – 30 December 2003 – Zinc mesoporphyrin (ZnMP) is a potent inhibitor of heme oxygenase (HO) and represses 5‐aminolevulinic acid synthase (ALAS). These properties make it a potential candidate for treatment of inducible acute hepatic porphyrias, diseases characterized by neurovisceral symptoms, and massive ALAS induction.

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