Lipotoxicity induces hepatic protein inclusions through TANK binding kinase 1–mediated p62/sequestosome 1 phosphorylation

Chun‐Seok Cho, Hwan‐Woo Park, Allison Ho, Ian A. Semple, Boyoung Kim, Insook Jang, Haeli Park, Shannon Reilly, Alan R. Saltiel, Jun Hee Lee – 18 December 2017 – Obesity commonly leads to hepatic steatosis, which often provokes lipotoxic injuries to hepatocytes that cause nonalcoholic steatohepatitis (NASH). NASH, in turn, is associated with the accumulation of insoluble protein aggregates that are composed of ubiquitinated proteins and ubiquitin adaptor p62/sequestosome 1 (SQSTM1).

Chitinase 3‐like‐1 promotes intrahepatic activation of coagulation through induction of tissue factor in mice

Zhao Shan, Xiaodong Liu, Yuan Chen, Meng Wang, Yue Rachel Gao, Liangguo Xu, Wasim A. Dar, Chun Geun Lee, Jack Angel Elias, Pavel Davizon Castillo, Jorge Di Paola, Cynthia Ju – 18 December 2017 – Coagulation is a critical component in the progression of liver disease. Identification of key molecules involved in the intrahepatic activation of coagulation (IAOC) will be instrumental in the development of effective therapies against liver disease.

11Beta‐hydroxysteroid dehydrogenase‐1 deficiency or inhibition enhances hepatic myofibroblast activation in murine liver fibrosis

Xiantong Zou, Prakash Ramachandran, Timothy J. Kendall, Antonella Pellicoro, Elena Dora, Rebecca L. Aucott, Kajal Manwani, Tak Yung Man, Karen E. Chapman, Neil C. Henderson, Stuart J. Forbes, Scott P. Webster, John P. Iredale, Brian R. Walker, Zoi Michailidou – 18 December 2017 – A hallmark of chronic liver injury is fibrosis, with accumulation of extracellular matrix orchestrated by activated hepatic stellate cells (HSCs). Glucocorticoids limit HSC activation in vitro, and tissue glucocorticoid levels are amplified by 11beta‐hydroxysteroid dehydrogenase‐1 (11βHSD1).

Nucleic acid polymer REP 2139 and nucleos(T)ide analogues act synergistically against chronic hepadnaviral infection in vivo in Pekin ducks

Jonathan Quinet, Catherine Jamard, Madeleine Burtin, Matthieu Lemasson, Sylviane Guerret, Camille Sureau, Andrew Vaillant, Lucyna Cova – 18 December 2017 – Nucleic acid polymer (NAP) REP 2139 treatment was shown to block the release of viral surface antigen in duck HBV (DHBV)‐infected ducks and in patients with chronic HBV or HBV/hepatitis D virus infection. In this preclinical study, a combination therapy consisting of REP 2139 with tenofovir disoproxil fumarate (TDF) and entecavir (ETV) was evaluated in vivo in the chronic DHBV infection model.

Capicua suppresses hepatocellular carcinoma progression by controlling the ETV4–MMP1 axis

Eunjeong Kim, Donghyo Kim, Jeon‐Soo Lee, Jeehyun Yoe, Jongmin Park, Chang‐Jin Kim, Dongjun Jeong, Sanguk Kim, Yoontae Lee – 18 December 2017 – Hepatocellular carcinoma (HCC) is developed by multiple steps accompanying progressive alterations of gene expression, which leads to increased cell proliferation and malignancy. Although environmental factors and intracellular signaling pathways that are critical for HCC progression have been identified, gene expression changes and the related genetic factors contributing to HCC pathogenesis are still insufficiently understood.

Overexpression of periostin and distinct mesothelin forms predict malignant progression in a rat cholangiocarcinoma model

Miguel Á. Manzanares, Deanna J.W. Campbell, Gabrielle T. Maldonado, Alphonse E. Sirica – 18 December 2017 – Periostin and mesothelin have each been suggested to be predictors of poor survival for patients with intrahepatic cholangiocarcinoma, although the clinical prognostic value of both of these biomarkers remains uncertain. The aim of the current study was to investigate these biomarkers for their potential to act as tumor progression factors when assessed in orthotopic tumor and three‐dimensional culture models of rat cholangiocarcinoma progression.

Surveillance for hepatobiliary cancers in patients with primary sclerosing cholangitis

Ahmad Hassan Ali, James H. Tabibian, Navine Nasser‐Ghodsi, Ryan J. Lennon, Thomas DeLeon, Mitesh J. Borad, Moira Hilscher, Marina G. Silveira, Elizabeth J. Carey, Keith D. Lindor – 15 December 2017 – Primary sclerosing cholangitis (PSC) is a risk factor for cholangiocarcinoma (CCA) and gallbladder carcinoma (GBCa). Surveillance for GBCa is recommended, but the clinical utility of surveillance for other hepatobiliary cancers (HBCa) in PSC, namely CCA and hepatocellular carcinoma (HCC), remains unclear.

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