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.

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).

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.

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.

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).

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.

Transjugular intrahepatic portosystemic shunt compared with endoscopic treatment for prevention of variceal rebleeding: A meta‐analysis

George V. Papatheodoridis, John Goulis, Gioacchino Leandro, David Patch, Andrew K. Burroughs – 30 December 2003 – Endoscopic treatment (ET) is frequently used to prevent variceal rebleeding but this still occurs in about 50% of patients. Recently, transjugular intrahepatic portosystemic shunt (TIPS) has been compared with ET in several trials. Using a meta‐analysis, we evaluated randomized trials comparing TIPS to ET assessing prevention of rebleeding, survival, and the effects on resource use and the quality of patients' lives.

Persistent activation of nuclear factor‐κB in cultured rat hepatic stellate cells involves the induction of potentially novel rel‐like factors and prolonged changes in the expression of IκB family proteins

Ahmed M. Elsharkawy, Matthew C. Wright, Ron T. Hay, Michael J. Arthur, Timothy Hughes, Matthias J. Bahr, Klaus Degitz, Derek A. Mann – 30 December 2003 – Rat hepatic stellate cells (HSC) cultured in serum‐containing medium underwent a rapid (3‐hour) classical induction of p50:p65 and p65:p65 nuclear factor‐κB (NF‐κB) dimers. Subsequent culturing was associated with prolonged expression of active p50:p65 and persistent induction of a high‐mobility NF‐κB DNA binding complex consisting of potentially novel Rel‐like protein(s).

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