The ascending pathophysiology of cholestatic liver disease

Peter L.M. Jansen, Ahmed Ghallab, Nachiket Vartak, Raymond Reif, Frank G. Schaap, Jochen Hampe, Jan G. Hengstler – 16 December 2016 – In this review we develop the argument that cholestatic liver diseases, particularly primary biliary cholangitis and primary sclerosing cholangitis (PSC), evolve over time with anatomically an ascending course of the disease process. The first and early lesions are in “downstream” bile ducts. This eventually leads to cholestasis, and this causes bile salt (BS)–mediated toxic injury of the “upstream” liver parenchyma. BS are toxic in high concentration.

Anti‐TNF‐α for necrotizing sarcoid granulomatosis of the liver

Marcial Sebode, Sören Weidemann, Malte Wehmeyer, Ansgar W. Lohse, Christoph Schramm – 16 December 2016 – We present a case of hepatosplenic necrotizing sarcoid granulomatosis, a variant form of “classical” sarcoidosis, that became clinically apparent in the form of multiple hepatic and splenic masses mimicking malignancy. Flow cytometry of intrahepatic T cells isolated from liver biopsy led to the targeted treatment with anti‐tumor necrosis factor‐alpha, which was highly effective in inducing remission. (Hepatology 2017;65:1410‐1412)

Hepatocyte autotaxin expression promotes liver fibrosis and cancer

Eleanna Kaffe, Aggeliki Katsifa, Nikos Xylourgidis, Ioanna Ninou, Markella Zannikou, Vaggelis Harokopos, Pelagia Foka, Alexios Dimitriadis, Kostas Evangelou, Anargyros N. Moulas, Urania Georgopoulou, Vassilis G. Gorgoulis, George N. Dalekos, Vassilis Aidinis – 16 December 2016 – Autotaxin (ATX) is a secreted lysophospholipase D that catalyzes the production of lysophosphatidic acid (LPA), a pleiotropic growth‐factor–like lysophospholipid.

Clinical presentations and outcomes of bile duct loss caused by drugs and herbal and dietary supplements

Herbert L. Bonkovsky, David E. Kleiner, Jiezhun Gu, Joseph A. Odin, Mark W. Russo, Victor M. Navarro, Robert J. Fontana, Marwan S. Ghabril, Huiman Barnhart, Jay H. Hoofnagle, for the U.S. Drug Induced Liver Injury Network Investigators – 16 December 2016 – Bile duct loss during the course of drug‐induced liver injury is uncommon, but can be an indication of vanishing bile duct syndrome (VBDS). In this work, we assess the frequency, causes, clinical features, and outcomes of cases of drug‐induced liver injury with histologically proven bile duct loss.

Targeting β‐catenin in hepatocellular cancers induced by coexpression of mutant β‐catenin and K‐Ras in mice

Junyan Tao, Rong Zhang, Sucha Singh, Minakshi Poddar, Emily Xu, Michael Oertel, Xin Chen, Shanthi Ganesh, Marc Abrams, Satdarshan P. Monga – 16 December 2016 – Recently, we have shown that coexpression of hMet and mutant‐β‐catenin using sleeping beauty transposon/transposase leads to hepatocellular carcinoma (HCC) in mice that corresponds to around 10% of human HCC. In the current study, we investigate whether Ras activation, which can occur downstream of Met signaling, is sufficient to cause HCC in association with mutant‐β‐catenin.

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