Mitochondrial protection by the JNK inhibitor leflunomide rescues mice from acetaminophen‐induced liver injury

Calivarathan Latchoumycandane, Catherine W. Goh, Michie M.K. Ong, Urs A. Boelsterli – 5 January 2007 – Acetaminophen (APAP) is a widely used analgesic and antipyretic drug that is safe at therapeutic doses but which can precipitate liver injury at high doses. We have previously found that the antirheumatic drug leflunomide is a potent inhibitor of APAP toxicity in cultured human hepatocytes, protecting them from mitochondria‐mediated cell death by inhibiting the mitochondrial permeability transition.

Bile duct proliferation in liver‐specific Jag1 conditional knockout mice: Effects of gene dosage

Kathleen M. Loomes, Pierre Russo, Matthew Ryan, Anthony Nelson, Lara Underkoffler, Curtis Glover, Hong Fu, Thomas Gridley, Klaus H. Kaestner, Rebecca J. Oakey – 5 January 2007 – The Notch signaling pathway is involved in determination of cell fate and control of cell proliferation in multiple organ systems. Jag1 encodes a ligand in the Notch pathway and has been identified as the disease‐causing gene for the developmental disorder Alagille syndrome. Evidence from the study of human disease and mouse models has implicated Jag1 as having an important role in the development of bile ducts.

Cost‐effectiveness of screening for hepatopulmonary syndrome in liver transplant candidates

D. Neil Roberts, Miguel R. Arguedas, Michael B. Fallon – 4 January 2007 – The hepatopulmonary syndrome (HPS) is present in 15–20% of patients with cirrhosis undergoing orthotopic liver transplantation (OLT) evaluation. Both preoperative and post‐OLT mortality is increased in HPS patients particularly when hypoxemia is severe. Screening for HPS could enhance detection of OLT candidates with sufficient hypoxemia to merit higher priority for transplant and thereby decrease mortality. However, the cost‐effectiveness of such an approach has not been assessed.

Trends and experiences in liver retransplantation over 15 years

Robert Pfitzmann, Birgit Benscheidt, Jan Michael Langrehr, Guido Schumacher, Ruth Neuhaus, Peter Neuhaus – 4 January 2007 – Compared to primary liver transplantation (LT), the inferior results in the outcome of liver retransplantation (re‐LT) continue to be a major challenge. The purpose of this study was to analyze changes in and outcomes of re‐LT over a period of 15 years at the Charité Virchow Clinic. Between 1989 and 2003, we performed 1,619 LTs and 157 re‐LTs (9.7%) in 1,462 patients.

Early histologic changes in fibrosing cholestatic hepatitis C

Lisa R. Dixon, James M. Crawford – 4 January 2007 – Recurrent hepatitis C (RHCV) after liver transplantation is almost universal, and occasional patients will have an aggressive course characterized histologically by pericellular/sinusoidal fibrosis and cholestasis, known as fibrosing cholestatic hepatitis (FCH). The early stages and evolution of this disease have not been well characterized. A total of 77 liver biopsies performed for indication (nonprotocol) were evaluated for necroinflammation, rejection, cholestasis, and fibrosis.

Long‐term survival and predictors of relapse after orthotopic liver transplantation for alcoholic liver disease

Robert Pfitzmann, Jeannette Schwenzer, Nada Rayes, Daniel Seehofer, Ruth Neuhaus, Natascha C. Nüssler – 4 January 2007 – The relevance of sobriety for outcome after orthotopic liver transplantation (OLT) for alcoholic liver disease (ALD) is still discussed controversially. We conducted a retrospective analysis of 300 patients transplanted for ALD with regard to recurrent alcohol consumption, risk factors for drinking after OLT, and long‐term survival. The 300 patients underwent OLT for ALD between 1989 and 2002. Median follow‐up was 89 months.

Risk factors for new‐onset diabetes mellitus following liver transplantation and impact of hepatitis c infection : An observational multicenter study

Faouzi Saliba, Mohamed Lakehal, Georges‐Philippe Pageaux, Bruno Roche, Claire Vanlemmens, Christophe Duvoux, Jérôme Dumortier, Ephrem Salamé, Yvon Calmus, Didier Maugendre, Diapason Study Group – 27 December 2006 – New‐onset diabetes mellitus (NODM) remains a common complication of liver transplantation (LT). We studied incidence and risk factors in 211 French patients who had undergone a primary LT between 6 and 24 months previously. This is a cross‐sectional and retrospective multicenter study. Data were collected on consecutive patients at a single routine post‐LT consultation.

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