Toll‐like receptor 4 and myeloid differentiation factor 88 provide mechanistic insights into the cause and effects of interleukin‐6 activation in mouse liver regeneration

Javier Vaquero, Jean S. Campbell, Jamil Haque, Ryan S. McMahan, Kimberly J. Riehle, Renay L. Bauer, Nelson Fausto – 13 May 2011 – Partial hepatectomy (PH) consistently results in an early increase of circulating interleukin‐6 (IL‐6), which is thought to play a major role in liver regeneration. Activation of this cytokine after PH requires the adaptor protein, MyD88, but the specific MyD88‐related receptors involved remain unidentified. It is also unknown whether the magnitude of IL‐6 elevation determines the extent of subsequent hepatocyte proliferation.

Liver transplantation in patients with alcoholic liver disease

Michael R. Lucey – 12 May 2011 – Although alcoholic liver disease (ALD) is one of the most common indications for liver transplantation (LT), there are still unresolved controversies about the goals of treatment, the referral, evaluation, and selection of patients with ALD for LT, and their care after LT. It is uncertain whether there is a large unmet need for LT among patients with ALD because of the unmeasured effects of recent drinking, relapse, and recovery with abstinence in this population.

Successful heterozygous living donor liver transplantation for an oxysterol 7α‐hydroxylase deficiency in a Japanese patient

Tatsuki Mizuochi, Akihiko Kimura, Mitsuyoshi Suzuki, Isao Ueki, Hajime Takei, Hiroshi Nittono, Toshihiko Kakiuchi, Takanobu Shigeta, Seisuke Sakamoto, Akinari Fukuda, Atsuko Nakazawa, Toshiaki Shimizu, Takao Kurosawa, Mureo Kasahara – 12 May 2011 – Only 2 patients with an oxysterol 7α‐hydroxylase deficiency caused by mutations of the cytochrome P450 7B1 (CYP7B1) gene have been reported; for both, the outcome was fatal. We describe the clinical and laboratory features, the hepatic and renal histological findings, and the results of bile acid and CYP7B1 gene analyses for a third patient.

Inhibition of glycogen synthase kinase 3 beta ameliorates liver ischemia reperfusion injury by way of an interleukin‐10‐mediated immune regulatory mechanism

Feng Ren, Zhongping Duan, Qiao Cheng, Xiuda Shen, Feng Gao, Li Bai, Jun Liu, Ronald W. Busuttil, Jerzy W. Kupiec‐Weglinski, Yuan Zhai – 12 May 2011 – The ubiquitous serine/threonine kinase glycogen synthase kinase 3 beta (Gsk3β) differentially regulates macrophage Toll‐like receptor (TLR)‐triggered pro‐ and anti‐inflammatory cytokine programs. This study was designed to determine the in vivo role and therapeutic potential of Gsk3β modulation in tissue inflammation and injury in a murine model of liver partial warm ischemia/reperfusion injury (IRI).

Complementary vascular and matrix regulatory pathways underlie the beneficial mechanism of action of sorafenib in liver fibrosis

Dominique Thabut, Chittaranjan Routray, Gwen Lomberk, Uday Shergill, Kevin Glaser, Robert Huebert, Leena Patel, Tetyana Masyuk, Boris Blechacz, Andrew Vercnocke, Erik Ritman, Richard Ehman, Raul Urrutia, Vijay Shah – 12 May 2011 – Paracrine signaling between hepatic stellate cells (HSCs) and liver endothelial cells (LECs) modulates fibrogenesis, angiogenesis, and portal hypertension. However, mechanisms regulating these processes are not fully defined.

A key role for Pre–B cell colony–enhancing factor in experimental hepatitis

Alexander R. Moschen, Romana Gerner, Andrea Schroll, Teresa Fritz, Arthur Kaser, Herbert Tilg – 12 May 2011 – Pre–B cell colony–enhancing factor (PBEF), also known as nicotinamide phosphoribosyltransferase or visfatin, plays an important role in metabolic, inflammatory, and malignant diseases. Recent evidence suggests that blocking its enzymatic activity using a specific small‐molecule inhibitor (FK866) might be beneficial in acute experimental inflammation. We investigated the role of PBEF in human liver disease and experimental hepatitis.

Obesity is an independent risk factor for clinical decompensation in patients with cirrhosis

Annalisa Berzigotti, Guadalupe Garcia‐Tsao, Jaime Bosch, Norman D. Grace, Andrew K. Burroughs, Rosa Morillas, Angels Escorsell, Juan Carlos Garcia‐Pagan, David Patch, Daniel S. Matloff, Roberto J. Groszmann, the Portal Hypertension Collaborative Group – 12 May 2011 – Obesity is associated with an aggressive course in chronic viral hepatitis; however, its impact in the development of clinical decompensation (CD) in patients with established cirrhosis is uncertain.

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