Intestinal bacterial translocation in rats with cirrhosis is related to compromised paneth cell antimicrobial host defense

Zora Teltschik, Reiner Wiest, Julia Beisner, Sabine Nuding, Claudia Hofmann, Juergen Schoelmerich, Charles L. Bevins, Eduard F. Stange, Jan Wehkamp – 16 November 2011 – Liver cirrhosis is associated with bacterial translocation (BT) and endotoxemia. Most translocating bacteria belong to the common intestinal microbiota, suggesting a breakdown of intestinal barrier function. We hypothesized that diminished mucosal antimicrobial host defense could predispose to BT.

Rosmarinic acid and baicalin epigenetically derepress peroxisomal proliferator‐activated receptor γ in hepatic stellate cells for their antifibrotic effect

Melissa D. Yang, Yi‐Ming Chiang, Reiichi Higashiyama, Kinji Asahina, Derek A. Mann, Jelena Mann, Clay C.C. Wang, Hidekazu Tsukamoto – 16 November 2011 – Hepatic stellate cells (HSCs) undergo myofibroblastic transdifferentiation (activation) to participate in liver fibrosis and identification of molecular targets for this cell fate regulation is essential for development of efficacious therapeutic modalities for the disease. Peroxisomal proliferator‐activated receptor γ (PPARγ) is required for differentiation of HSCs and its epigenetic repression underlies HSC activation.

Clinical relevance of detectable but not quantifiable hepatitis C virus RNA during boceprevir or telaprevir treatment

Patrick R. Harrington, Wen Zeng, Lisa K. Naeger – 16 November 2011 – Boceprevir‐ and telaprevir‐based treatments for chronic hepatitis C virus (HCV) infection use specific response‐guided therapy (RGT) guidelines. Eligibility for shortened treatment duration is based on achieving undetectable HCV RNA early during treatment. It is unclear whether a detected HCV RNA level that is below the assay lower limit of quantitation (detectable/BLOQ) is comparable to an undetectable HCV RNA level for RGT decision making.

Hepatocyte growth factor/c‐met signaling is required for stem‐cell–mediated liver regeneration in mice

Tsuyoshi Ishikawa, Valentina M. Factor, Jens U. Marquardt, Chiara Raggi, Daekwan Seo, Mitsuteru Kitade, Elizabeth A. Conner, Snorri S. Thorgeirsson – 16 November 2011 – Hepatocyte growth factor (HGF)/c‐Met supports a pleiotrophic signal transduction pathway that controls stem cell homeostasis. Here, we directly addressed the role of c‐Met in stem‐cell–mediated liver regeneration by utilizing mice harboring c‐met floxed alleles and Alb‐Cre or Mx1‐Cre transgenes.

Novel function of Niemann‐Pick C1‐like 1 as a negative regulator of Niemann‐Pick C2 protein

Yoshihide Yamanashi, Tappei Takada, Jun‐Ichi Shoda, Hiroshi Suzuki – 16 November 2011 – The hepatic expression of Niemann‐Pick C1‐like 1 (NPC1L1), which is a key molecule in intestinal cholesterol absorption, is high in humans. In addition to NPC1L1, Niemann‐Pick C2 (NPC2), a secretory cholesterol‐binding protein involved in intracellular cholesterol trafficking and the stimulation of biliary cholesterol secretion, is also expressed in the liver. In this study, we examined the molecular interaction and functional association between NPC1L1 and NPC2.

Albumin infusion in patients undergoing large‐volume paracentesis: A meta‐analysis of randomized trials

Mauro Bernardi, Paolo Caraceni, Roberta J. Navickis, Mahlon M. Wilkes – 16 November 2011 – Albumin infusion reduces the incidence of postparacentesis circulatory dysfunction among patients with cirrhosis and tense ascites, as compared with no treatment. Treatment alternatives to albumin, such as artificial colloids and vasoconstrictors, have been widely investigated. The aim of this meta‐analysis was to determine whether morbidity and mortality differ between patients receiving albumin versus alternative treatments.

Rapid generation of mature hepatocyte‐like cells from human induced pluripotent stem cells by an efficient three‐step protocol

Yu‐Fan Chen, Chien‐Yu Tseng, Hsei‐Wei Wang, Hung‐Chih Kuo, Vincent W. Yang, Oscar K. Lee – 16 November 2011 – Liver transplantation is the only definitive treatment for end‐stage cirrhosis and fulminant liver failure, but the lack of available donor livers is a major obstacle to liver transplantation. Recently, induced pluripotent stem cells (iPSCs) derived from the reprogramming of somatic fibroblasts, have been shown to resemble embryonic stem (ES) cells in that they have pluripotent properties and the potential to differentiate into all cell lineages in vitro, including hepatocytes.

Glucokinase links Krüppel‐like factor 6 to the regulation of hepatic insulin sensitivity in nonalcoholic fatty liver disease

Lars P. Bechmann, Amalia Gastaldelli, Diana Vetter, Gillian L. Patman, Laura Pascoe, Rebekka A. Hannivoort, Ursula E. Lee, Isabel Fiel, Ursula Muñoz, Demetrio Ciociaro, Young‐Min Lee, Emma Buzzigoli, Luca Miele, Kei Y. Hui, Elisabetta Bugianesi, Alastair D. Burt, Christopher P. Day, Andrea Mari, Loranne Agius, Mark Walker, Scott L. Friedman, Helen L.

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