TY  - JOUR
A1  - Raselli, Tina
A1  - Hearn, Tom
A1  - Wyss, Annika
A1  - Atrott, Kirstin
A1  - Peter, Alain
A1  - Frey-Wagner, Isabelle
A1  - Spalinger, Marianne R.
A1  - Maggio, Ewerton M.
A1  - Sailer, Andreas W.
A1  - Schmitt, Johannes
A1  - Schreiner, Philipp
A1  - Moncsek, Anja
A1  - Mertens, Joachim
A1  - Scharl, Michael
A1  - Griffiths, William J.
A1  - Bueter, Marco
A1  - Geier, Andreas
A1  - Rogler, Gerhard
A1  - Wang, Yuqin
A1  - Misselwitz, Benjamin
T1  - Elevated oxysterol levels in human and mouse livers reflect nonalcoholic steatohepatitis
JF  - Journal of Lipid Research
N2  - Nonalcoholic steatohepatitis (NASH), a primary cause of liver disease, leads to complications such as fibrosis, cirrhosis, and carcinoma, but the pathophysiology of NASH is incompletely understood. Epstein-Barr virus-induced G protein-coupled receptor 2 (EBI2) and its oxysterol ligand 7 alpha,25-dihydroxycholesterol (7 alpha,25-diHC) are recently discovered immune regulators. Several lines of evidence suggest a role of oxysterols in NASH pathogenesis, but rigorous testing has not been performed. We measured oxysterol levels in the livers of NASH patients by LC-MS and tested the role of the EBI2-7 alpha,25-diHC system in a murine feeding model of NASH. Free oxysterol profiling in livers from NASH patients revealed a pronounced increase in 24- and 7-hydroxylated oxysterols in NASH compared with controls. Levels of 24- and 7-hydroxylated oxysterols correlated with histological NASH activity. Histological analysis of murine liver samples demonstrated ballooning and liver inflammation. No significant genotype-related differences were observed in Ebi2(-/-) mice and mice with defects in the 7 alpha,25-diHC synthesizing enzymes CH25H and CYP7B1 compared with wild-type littermate controls, arguing against an essential role of these genes in NASH pathogenesis. Elevated 24- and 7-hydroxylated oxysterol levels were confirmed in murine NASH liver samples. Our results suggest increased bile acid synthesis in NASH samples, as judged by the enhanced level of 7 alpha-hydroxycholest-4-en-3-one and impaired 24S-hydroxycholesterol metabolism as characteristic biochemical changes in livers affected by NASH.
KW  - nonalcoholic fatty liver disease
KW  - Epstein-Barr virus-induced gene 2
KW  - cholesterol 25 hydroxylase
KW  - 25-hydroxycholesterol 7 alpha-hydroxylase
KW  - mouse feeding model
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225004
VL  - 60
IS  - 7
ER  - 
TY  - JOUR
A1  - Banales, Jesus M.
A1  - Cardinale, Vincenzo
A1  - Carpino, Guido
A1  - Marzioni, Marco
A1  - Andersen, Jesper B.
A1  - Invernizzi, Pietro
A1  - Lind, Guro E.
A1  - Folseraas, Trine
A1  - Forbes, Stuart J.
A1  - Fouassier, Laura
A1  - Geier, Andreas
A1  - Calvisi, Diego F.
A1  - Mertens, Joachim C.
A1  - Trauner, Michael
A1  - Benedetti, Antonio
A1  - Maroni, Luca
A1  - Vaquero, Javier
A1  - Macias, Rocio I. R.
A1  - Raggi, Chiara
A1  - Perugorria, Maria J.
A1  - Gaudio, Eugenio
A1  - Boberg, Kirsten M.
A1  - Marin, Jose J. G.
A1  - Alvaro, Domenico
T1  - Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA)
JF  - Nature Reviews Gastroenterology & Hepatology
N2  - Cholangiocarcinoma (CCA) is a heterogeneous group of malignancies with features of biliary tract differentiation. CCA is the second most common primary liver tumour and the incidence is increasing worldwide. CCA has high mortality owing to its aggressiveness, late diagnosis and refractory nature. In May 2015, the "European Network for the Study of Cholangiocarcinoma" (ENS-CCA: www.enscca.org or www.cholangiocarcinoma.eu) was created to promote and boost international research collaboration on the study of CCA at basic, translational and clinical level. In this Consensus Statement, we aim to provide valuable information on classifications, pathological features, risk factors, cells of origin, genetic and epigenetic modifications and current therapies available for this cancer. Moreover, future directions on basic and clinical investigations and plans for the ENS-CCA are highlighted.
KW  - primary sclerosing cholangitis
KW  - growth-factor-receptor
KW  - biliary-tract cancer
KW  - epithelial-mesenchymal transition
KW  - fine-needle-aspiration
KW  - human intrahepatic cholangiocarcinoma
KW  - induce cyclooxygenase-2 expression
KW  - human cholangiocellular carcinoma
KW  - nucleoside transporter
KW  - hepatic stellate cells
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-189077
VL  - 13
IS  - 5
ER  -