Human leukocyte antigen class II molecules confer both susceptibility and progression in Japanese patients with primary biliary cirrhosis

Takeji Umemura, Satoru Joshita, Tetsuya Ichijo, Kaname Yoshizawa, Yoshihiko Katsuyama, Eiji Tanaka, Masao Ota, The Shinshu PBC Study Group – 27 September 2011 – Along with twin and family studies, recent genome‐wide association studies suggest that genetic factors contribute to the susceptibility and severity of primary biliary cirrhosis (PBC).

Regulation of hepatic lipin‐1 by ethanol: Role of AMP‐activated protein kinase/sterol regulatory element‐binding protein 1 signaling in mice

Ming Hu, Fengming Wang, Xin Li, Christopher Q. Rogers, Xiaomei Liang, Brian N. Finck, Mayurranjan S. Mitra, Ray Zhang, Dave A. Mitchell, Min You – 27 September 2011 – Lipin‐1 is a protein that exhibits dual functions as a phosphatidic acid phosphohydrolase enzyme in the triglyceride synthesis pathways and a transcriptional coregulator. Our previous studies have shown that ethanol causes fatty liver by activation of sterol regulatory element‐binding protein 1 (SREBP‐1) and inhibition of hepatic AMP‐activated protein kinase (AMPK) in mice.

miR‐25 targets TNF‐related apoptosis inducing ligand (TRAIL) death receptor‐4 and promotes apoptosis resistance in cholangiocarcinoma

Nataliya Razumilava, Steve F. Bronk, Rory L. Smoot, Christian D. Fingas, Nathan W. Werneburg, Lewis R. Roberts, Justin L. Mott – 27 September 2011 – It has been established that microRNA expression and function contribute to phenotypic features of malignant cells, including resistance to apoptosis. Although targets and functional roles for a number of microRNAs have been described in cholangiocarcinoma, many additional microRNAs dysregulated in this tumor have not been assigned functional roles.

Osteopontin, an oxidant stress sensitive cytokine, up‐regulates collagen‐I via integrin αVβ3 engagement and PI3K/pAkt/NFκB signaling

Raquel Urtasun, Aritz Lopategi, Joseph George, Tung‐Ming Leung, Yongke Lu, Xiaodong Wang, Xiaodong Ge, Maria Isabel Fiel, Natalia Nieto – 27 September 2011 – A key feature in the pathogenesis of liver fibrosis is fibrillar Collagen‐I deposition; yet, mediators that could be key therapeutic targets remain elusive. We hypothesized that osteopontin (OPN), an extracellular matrix (ECM) cytokine expressed in hepatic stellate cells (HSCs), could drive fibrogenesis by modulating the HSC pro‐fibrogenic phenotype and Collagen‐I expression.

Identification of osteopontin as a novel marker for early hepatocellular carcinoma

Sufen Shang, Amelie Plymoth, Shaokui Ge, Ziding Feng, Hugo R. Rosen, Suleeporn Sangrajrang, Pierre Hainaut, Jorge A. Marrero, Laura Beretta – 27 September 2011 – The aim of this study was to identify a biomarker that could improve alpha‐fetoprotein (AFP) performance in hepatocellular carcinoma (HCC) surveillance among patients with cirrhosis. We performed proteomic profiling of plasma from patients with cirrhosis or HCC and validated selected candidate HCC biomarkers in two geographically distinct cohorts to include HCC of different etiologies.

Patients with minimal hepatic encephalopathy show impaired mismatch negativity correlating with reduced performance in attention tests

Vicente Felipo, Juan F. Ordoño, Amparo Urios, Nisrin El Mlili, Carla Giménez‐Garzó, Carolina Aguado, Olga González‐Lopez, Remedios Giner‐Duran, Miguel A. Serra, Abdallah Wassel, Jose M. Rodrigo, José Salazar, Carmina Montoliu – 27 September 2011 – Attention deficit is an early event in the cognitive impairment of patients with minimal hepatic encephalopathy (MHE). The underlying mechanisms remain unclear. Mismatch negativity (MMN) is an auditory event‐related potential that reflects an attentional trigger.

Hepatocyte polarization is essential for the productive entry of the hepatitis B virus

Andreas Schulze, Kerry Mills, Thomas S. Weiss, Stephan Urban – 27 September 2011 – Human hepatitis B virus (HBV) is characterized by a high species specificity and a distinct liver tropism. Within the liver, HBV replication occurs in differentiated and polarized hepatocytes. Accordingly, the in vitro HBV infection of primary human hepatocytes (PHHs) and the human hepatoma cell line, HepaRG, is restricted to differentiated, hepatocyte‐like cells.

The transcription factor c‐Jun protects against sustained hepatic endoplasmic reticulum stress thereby promoting hepatocyte survival

Matthias Fuest, Karolina Willim, Sabine MacNelly, Nicole Fellner, Guenter P. Resch, Hubert E. Blum, Peter Hasselblatt – 27 September 2011 – Endoplasmic reticulum (ER) stress due to accumulation of hepatoviral or misfolded proteins is increasingly recognized as an important step in the pathogenesis of inflammatory, toxic, and metabolic liver diseases. ER stress results in the activation of several intracellular signaling pathways including Jun N‐terminal kinase (JNK).

Translationally controlled tumor protein induces mitotic defects and chromosome missegregation in hepatocellular carcinoma development

Tim Hon Man Chan, Leilei Chen, Ming Liu, Liang Hu, Bo‐jian Zheng, Vincent Kwok‐Man Poon, Pinzhu Huang, Yun‐Fei Yuan, Jian‐dong Huang, Jie Yang, George Sai‐wah Tsao, Xin‐Yuan Guan – 27 September 2011 – Emerging evidence implicates the chromodomain helicase/ATPase DNA binding protein 1–like gene (CHD1L) as a specific oncogene in human hepatocellular carcinoma (HCC).

A mouse model of accelerated liver aging caused by a defect in DNA repair

Siobhán Q. Gregg, Verónica Gutiérrez, Andria Rasile Robinson, Tyler Woodell, Atsunori Nakao, Mark A. Ross, George K. Michalopoulos, Lora Rigatti, Carrie E. Rothermel, Irene Kamileri, George A. Garinis, Donna Beer Stolz, Laura J. Niedernhofer – 27 September 2011 – The liver changes with age, leading to an impaired ability to respond to hepatic insults and increased incidence of liver disease in the elderly. Therefore, there is critical need for rapid model systems to study aging‐related liver changes.

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