Induction of heme oxygenase 1 prevents progression of liver fibrosis in Mdr2 knockout mice

Roja Barikbin, Daniel Neureiter, Jan Wirth, Annette Erhardt, Dorothee Schwinge, Johannes Kluwe, Christoph Schramm, Gisa Tiegs, Gabriele Sass – 27 September 2011 – Induction or overexpression of the heme‐degrading enzyme, heme oxygenase 1 (HO‐1), has been shown to protect mice from liver damage induced by acute inflammation. We have investigated the effects of HO‐1 induction in a mouse model of chronic liver inflammation and fibrogenesis with progression to hepatocellular carcinoma (HCC) (Mdr2ko; FVB.129P2‐Abcb4tm1Bor).

Mature hepatocytes exhibit unexpected plasticity by direct dedifferentiation into liver progenitor cells in culture

Yixin Chen, Philip P. Wong, Lucas Sjeklocha, Clifford J. Steer, M. Behnan Sahin – 27 September 2011 – Although there have been numerous reports describing the isolation of liver progenitor cells from the adult liver, their exact origin has not been clearly defined; and the role played by mature hepatocytes as direct contributors to the hepatic progenitor cell pool has remained largely unknown. Here, we report strong evidence that mature hepatocytes in culture have the capacity to dedifferentiate into a population of adult liver progenitors without genetic or epigenetic manipulations.

Myeloid suppressor cells induced by hepatitis C virus suppress T‐cell responses through the production of reactive oxygen species

Robert S. Tacke, Hai‐Chon Lee, Celeste Goh, Jeremy Courtney, Stephen J. Polyak, Hugo R. Rosen, Young S. Hahn – 27 September 2011 – Impaired T‐cell responses in chronic hepatitis C virus (HCV) patients have been reported to be associated with the establishment of HCV persistent infection. However, the mechanism for HCV‐mediated T‐cell dysfunction is yet to be defined. Myeloid‐derived suppressor cells (MDSCs) play a pivotal role in suppressing T‐cell responses. In this study we examined the accumulation of MDSCs in human peripheral blood mononuclear cells (PBMCs) following HCV infection.

The human gallbladder secretes fibroblast growth factor 19 into bile: Towards defining the role of fibroblast growth factor 19 in the enterobiliary tract

Serge J.L.B. Zweers, Klaske A.C. Booij, Mina Komuta, Tania Roskams, Dirk J. Gouma, Peter L.M. Jansen, Frank G. Schaap – 27 September 2011 – Fibroblast growth factor 19 (FGF19) plays a crucial role in the negative feedback regulation of bile salt synthesis. In the postprandial state, activation of ileal farnesoid X receptor (FXR) by bile salts results in transcriptional induction of FGF19 and elevation of circulating FGF19 levels. An intestinal‐liver axis of FGF19 signaling results in down‐regulation of bile salt synthesis.

Hepatocellular Carcinoma Confirmation, Treatment, and Survival in Surveillance, Epidemiology, and End Results Registries, 1992‐2008

Sean F. Altekruse, Katherine A. McGlynn, Lois A. Dickie, David E. Kleiner – 27 September 2011 – Approaches to the diagnosis and management of hepatocellular carcinoma (HCC) are improving survival. In the Surveillance, Epidemiology, and End Results‐13 registries, HCC stage, histological confirmation, and first‐course surgery were examined. Among 21,390 HCC cases diagnosed with follow‐up of vital status during 1998‐2008, there were 4,727 (22%) with reported first‐course invasive liver surgery, local tumor destruction, or both.

Patient decision making about organ quality in liver transplantation

Michael L. Volk, Rachel S. Tocco, Shawn J. Pelletier, Brian J. Zikmund‐Fisher, Anna S. F. Lok – 19 September 2011 – It is challenging to discuss the use of high‐risk organs with patients, in part because of the lack of information about how patients view this topic. This study was designed to determine how patients think about organ quality and to test formats for risk communication. Semistructured interviews of 10 patients on the waiting list revealed limited understanding about the spectrum of organ quality and a reluctance to consider anything but the best organs.

CD59 incorporation protects hepatitis C virus against complement‐mediated destruction

Tohti Amet, Marwan Ghabril, Naga Chalasani, Daniel Byrd, Ningjie Hu, Ayslinn Grantham, Ziqing Liu, Xuebin Qin, Johnny J. He, Qigui Yu – 19 September 2011 – Several enveloped viruses including human immunodeficiency virus type 1 (HIV‐1), cytomegalovirus (CMV), herpes simplex virus 1 (HSV‐1), Ebola virus, vaccinia virus, and influenza virus have been found to incorporate host regulators of complement activation (RCA) into their viral envelopes and, as a result, escape antibody‐dependent complement‐mediated lysis (ADCML).

Excellent posttransplant survival for patients with nonalcoholic steatohepatitis in the United States

Anita Afzali, Kristin Berry, George N. Ioannou – 19 September 2011 – Because of the ongoing epidemics of obesity and diabetes, nonalcoholic steatohepatitis (NASH) may become a leading indication for liver transplantation. There are concerns about the posttransplant survival of patients with NASH because of associated cardiovascular and metabolic risk factors. We aimed to determine recent trends in the proportion of patients undergoing transplantation for NASH‐related cirrhosis in the United States and to estimate their posttransplant survival.

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