Pretherapy alanine transaminase level as a determinant for hepatitis B e antigen seroconversion during lamivudine therapy in patients with chronic hepatitis B

Rong‐Nan Chien, Yun‐Fan Liaw, Mark Atkins – 30 December 2003 – In the reported Asian lamivudine trial, the rate of hepatitis B e antigen (HBeAg) seroconversion, defined as HBeAg/hepatitis B virus (HBV) DNA seroclearance and development of anti‐HBe, during 52 weeks of treatment was only 13% to 16%. To evaluate whether any factors influenced HBeAg seroconversion, data from 345 patients in that trial were reanalyzed to correlate HBeAg seroconversion with variables including treatment, age, gender, body build, histology, baseline HBV‐DNA levels, and alanine transaminase (ALT) levels.

Inhibition of system A amino acid transport and hepatocyte proliferation following partial hepatectomy in the rat

Thomas L. Freeman, Hao Q. Ngo, Mark E. Mailliard – 30 December 2003 – System A, the sodium‐dependent neutral amino acid transport activity, has a 3‐fold increase in its initial uptake velocity into hepatocytes following partial hepatectomy (PH) in the rat. The purpose of this study was to examine the effect of inhibition of System A–mediated amino acid transport on hepatocyte proliferation and liver regeneration. We describe thein vivocompetitive inhibition of System A activity following PH by the nonmetabolizable, System A–specific substrate, α‐(methylamino)isobutyric acid (MeAIB).

Dominant negative mutants of the duck hepatitis B virus core protein interfere with RNA pregenome packaging and viral DNA synthesis

Fritz von Weizsäcker, Josef Köck, Stefan Wieland, Wolf‐Bernhard Offensperger, Hubert E. Blum – 30 December 2003 – Dominant negative (DN) mutants of the hepadnaviral core protein are potent inhibitors of viral replication. We have previously shown that fusion of sequences derived from the duck hepatitis B virus (DHBV) polymerase (Pol), DHBV small surface protein (S), bacterial β‐galactosidase (lacZ), or green fluorescent protein (GFP) to the carboxy terminus of the DHBV core protein yields DN mutants that inhibit viral replication at the posttranslational level.

Efficacy of interferon treatment for patients with chronic hepatitis C: Comparison of response in cirrhotics, fibrotics, or nonfibrotics

Gregory T. Everson, Donald M. Jensen, John R. Craig, Dirk J. van Leeuwen, Vincent G. Bain, Murray N. Ehrinpreis, Donald Albert, Tenshang Joh, Karsten Witt – 30 December 2003 – Chronic hepatitis C patients (472 patients) were treated with consensus interferon (CIFN) or interferon (IFN) alfa‐2b for 6 months in a large multicenter trial. Efficacy was assessed by clearance of hepatitis C virus (HCV) RNA using reverse transcription polymerase chain reaction (RT‐PCR) (<100 copies/mL), normalization of serum alanine aminotransferase (ALT), and histological improvement.

A case‐control study on a novel DNA virus (TT virus) infection and hepatocellular carcinoma

Alessandro Tagger, Francesco Donato, Maria Lisa Ribero, Giorgio Binelli, Umberto Gelatti, Giuseppe Portera, Alberto Albertini, Michele Fasola, Roberta Chiesa, Giuseppe Nardi – 30 December 2003 – We performed a case‐control study to evaluate the association of a new human DNA virus named TT virus (TTV) with hepatocellular carcinoma (HCC). We recruited 174 subjects hospitalized for HCC (84% males; mean age: 64 years) and 118 patients hospitalized for non‐liver diseases in Brescia, northern Italy, as controls (94% males; mean age: 66 years).

Interferon alfa for chronic hepatitis B infection: Increased efficacy of prolonged treatment

Harry L. Janssen, Guido Gerken, Vicente Carreño, Patrick Marcellin, Nikolai V. Naoumov, Antonio Craxi, Helmer Ring‐Larsen, George Kitis, Jan van Hattum, Richard A. de Vries, Peter P. Michielsen, Fiebo J. ten Kate, Wim C. Hop, Rudolf A. Heijtink, Pieter Honkoop, Solko W. Schalm – 30 December 2003 – Interferon alfa (IFN‐α) is the primary treatment for chronic hepatitis B. The standard duration of IFN‐α therapy is considered 16 weeks; however, the optimal treatment length is still poorly defined.

Zonal regulation of gene expression during liver regeneration of urokinase transgenic mice

Stephanie Locaputo, Terri L. Carrick, Jorge A. Bezerra – 30 December 2003 – Liver gene transcription plays a fundamental role in the hepatic reparative response to injury. However, little is known about the functional relationship of gene expression between diseased and regenerative compartments following a liver injury.

Infections caused by escherichia coli resistant to norfloxacin in hospitalized cirrhotic patients

Jordi Ortiz, Maria Carme Vila, Germán Soriano, Josep Miñana, Jordi Gana, Beatriz Mirelis, Maria Teresa Novella, Susana Coll, Miriam Sàbat, Montserrat Andreu, Guillem Prats, Ricard Solà, Carlos Guarner – 30 December 2003 – Selective intestinal decontamination with norfloxacin is useful to prevent bacterial infections in several groups of cirrhotic patients at high risk of infection. However, the emergence of infections caused by Escherichia coli resistant to quinolones has recently been observed in cirrhotic patients undergoing prophylactic norfloxacin.

Characterization of the human multidrug resistance protein isoform MRP3 localized to the basolateral hepatocyte membrane

Jörg König, Daniel Rost, Yunhai Cui, Dietrich Keppler – 30 December 2003 – Several members of the multidrug resistance protein (MRP) family are expressed in the liver. Adenosine triphosphate (ATP)–dependent transport of glutathione and glucuronoside conjugates across the hepatocyte canalicular membrane is mediated by the apical MRP isoform, MRP2 (APMRP), also known as canalicular multispecific organic anion transporter (cMOAT). We have cloned an additional MRP isoform, MRP3, from human liver and localized it to the basolateral membrane domain of hepatocytes.

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