rAAV‐mediated stable expression of heme oxygenase‐1 in stellate cells: A new approach to attenuate liver fibrosis in rats

Tung‐Yu Tsui, Chi‐Keung Lau, Jian Ma, Xiaobing Wu, Yan‐Qing Wang, Stefan Farkas, Ruian Xu, Hans J. Schlitt, Sheung‐Tat Fan – 15 July 2005 – Liver fibrosis is the consequence of activation of hepatic stellate cells mediated by persistent or recurrent liver injury, where oxidative stress or inflammatory response resulting from immune cells and cytokines are involved. Targeting of hepatic stellate cells could be an important strategy for the therapy of liver fibrosis.

Primary biliary cirrhosis is characterized by IgG3 antibodies cross‐reactive with the major mitochondrial autoepitope and its Lactobacillus mimic

Dimitrios‐Petrou Bogdanos, Harold Baum, Manabu Okamoto, Paolo Montalto, Umesh C. Sharma, Eirini I. Rigopoulou, John Vlachogiannakos, Yun Ma, Andrew K. Burroughs, Diego Vergani – 15 July 2005 – The serological hallmark of primary biliary cirrhosis (PBC) is the presence of pyruvate dehydrogenase complex E2 subunit (PDC‐E2) antimitochondrial antibodies (AMAs). Anti–PDC‐E2 antibodies cross‐react specifically with mycobacterial hsp65, and we have demonstrated that the motif SxGDL[ILV]AE shared by PDC‐E2212‐226 and hsp's is a cross‐reactive target.

Successful gene therapy of the Gunn rat by in vivo neonatal hepatic gene transfer using murine oncoretroviral vectors

Marta Bellodi‐Privato, Dominique Aubert, Virginie Pichard, Anne Myara, François Trivin, Nicolas Ferry – 15 July 2005 – Crigler‐Najjar type 1 disease (CN1) is a rare inherited metabolic disease characterized by complete absence of hepatic UDP‐glucuronosyl transferase (UGT1), resulting in high levels of unconjugated bilirubin. CN1 is an attractive candidate disease for gene therapy. Here we show that in vivo neonatal hepatocyte transduction using recombinant oncoretroviral vectors results in long‐term and complete phenotype correction in Gunn rats, a model for CN1.

Outcome and prognostic markers in severe drug‐induced liver disease

Einar Björnsson, Rolf Olsson – 15 July 2005 – The combination of high aminotransferases (hepatocellular injury) and jaundice has been reported to lead to a mortality rate of 10% to 50% for different drugs, a phenomenon known as “Hy's rule.” However, Hy's rule has never been validated, and limited data exist on predictors for outcome in hepatocellular and other forms of drug‐induced liver disease. All reports of suspected hepatic adverse drug reactions received by the Swedish Adverse Drug Reactions Advisory Committee (1970‐2004) were reviewed.

Treatment of advanced hepatitis C with a low accelerating dosage regimen of antiviral therapy

Gregory T. Everson, James Trotter, Lisa Forman, Marcelo Kugelmas, Arthur Halprin, Barbara Fey, Catherine Ray – 15 July 2005 – Patients with advanced hepatitis C virus (HCV) are at risk of death and are candidates for liver transplantation. After transplantation, HCV recurs and may rapidly progress to cirrhosis and graft loss. Treatment is needed to prevent progression of disease and minimize recurrence after liver transplantation.

Early response of α2(I) collagen to acetaldehyde in human hepatic stellate cells is TGF‐β independent

Gianluca Svegliati‐Baroni, Yutaka Inagaki, Ana‐Rosa Rincon‐Sanchez, Cindy Else, Stefania Saccomanno, Antonio Benedetti, Francesco Ramirez, Marcos Rojkind – 15 July 2005 – Acetaldehyde is fibrogenic and induces the expression of type I collagen genes in hepatic stellate cells. Some of these acetaldehyde‐dependent events are mediated by H2O2 and thus establish a direct connection between oxidative stress and collagen upregulation.

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