Reduction of hepatic steatosis in rats and mice after treatment with a liver‐targeted thyroid hormone receptor agonist

Edward E. Cable, Patricia D. Finn, Jeffrey W. Stebbins, Jinzhao Hou, Bruce R. Ito, Paul D. van Poelje, David L. Linemeyer, Mark D. Erion – 28 January 2009 – Non‐alcoholic fatty liver disease (NAFLD) is one of the most common forms of chronic liver disease, with a prevalence ranging from 10% to 30%. The use of thyroid hormone receptor (TR) agonists for the treatment of NAFLD has not been considered viable because thyroid hormones increase free fatty acid (FFA) flux from the periphery to the liver, induce hepatic lipogenesis, and therefore could potentially cause steatosis.

Missense mutations and single nucleotide polymorphisms in ABCB11 impair bile salt export pump processing and function or disrupt pre‐messenger RNA splicing

Jane A. Byrne, Sandra S. Strautnieks, Gudrun Ihrke, Franco Pagani, A.S. Knisely, Kenneth J. Linton, Giorgina Mieli‐Vergani, Richard J. Thompson – 28 January 2009 – The gene encoding the human bile salt export pump (BSEP), ABCB11, is mutated in several forms of intrahepatic cholestasis. Here we classified the majority (63) of known ABCB11 missense mutations and 21 single‐nucleotide polymorphisms (SNPs) to determine whether they caused abnormal ABCB11 pre‐messenger RNA splicing, abnormal processing of BSEP protein, or alterations in BSEP protein function.

Transcription factor 7–like 2 polymorphism modulates glucose and lipid homeostasis, adipokine profile, and hepatocyte apoptosis in NASH

Giovanni Musso, Roberto Gambino, Giovanni Pacini, Gianfranco Pagano, Marilena Durazzo, Maurizio Cassader – 28 January 2009 – Genetic factors underlying the association of NAFLD with diabetes and atherosclerosis are unknown. Recent human studies suggest transcription factor 7–like 2 (TCF7L2) polymorphism predisposes to diabetes through modulation of β‐cell function and modulates lipid levels in familial dyslipidemia. Emerging experimental evidence connects TCF7L2 to adipocyte metabolism and lipid homeostasis, as well.

Predicting in‐hospital mortality in patients with cirrhosis: Results differ across risk adjustment methods

Robert P. Myers, Hude Quan, James N. Hubbard, Abdel Aziz M. Shaheen, Gilaad G. Kaplan – 28 January 2009 – Risk‐adjusted health outcomes are often used to measure the quality of hospital care, yet the optimal approach in patients with liver disease is unclear. We sought to determine whether assessments of illness severity, defined as risk for in‐hospital mortality, vary across methods in patients with cirrhosis. We identified 258,731 patients with cirrhosis hospitalized in the Nationwide Inpatient Sample between 2002 and 2005.

Complex dynamics of hepatitis B virus resistance to adefovir

Coralie Pallier, Christophe Rodriguez, Rozenn Brillet, Patrice Nordmann, Christophe Hézode, Jean‐Michel Pawlotsky – 28 December 2008 – In patients with hepatitis B e antigen‐negative chronic hepatitis B, adefovir dipivoxil administration selects variants bearing reverse transcriptase rtN236T and/or rtA181V/T substitutions in 29% of cases after 5 years.

Ex vivo effects of high‐density lipoprotein exposure on the lipopolysaccharide‐induced inflammatory response in patients with severe cirrhosis

Arnaud Galbois, Dominique Thabut, Khalid A. Tazi, Marika Rudler, Morvarid Shir Mohammadi, Dominique Bonnefont‐Rousselot, Hind Bennani, Annie Bezeaud, Zera Tellier, Cécile Guichard, Nicolas Coant, Eric Ogier‐Denis, Richard Moreau, Didier Lebrec – 28 December 2008 – High‐density lipoproteins (HDL) are known to neutralize lipopolysaccharide (LPS). Because patients with cirrhosis have lower HDL levels, this may contribute to LPS‐induced ex vivo monocyte overproduction of proinflammatory cytokines.

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