Blocking H1/H2 histamine receptors inhibits damage/fibrosis in Mdr2–/– mice and human cholangiocarcinoma tumorigenesis

Lindsey Kennedy, Laura Hargrove, Jennifer Demieville, Walker Karstens, Hannah Jones, Sharon DeMorrow, Fanyin Meng, Pietro Invernizzi, Francesca Bernuzzi, Gianfranco Alpini, Steven Smith, Austin Akers, Vik Meadows, Heather Francis – 30 March 2018 – Primary sclerosing cholangitis (PSC) patients are at risk of developing cholangiocarcinoma (CCA). We have shown that (1) histamine increases biliary hyperplasia through H1/H2 histamine receptors (HRs) and (2) histamine levels increase and mast cells (MCs) infiltrate during PSC and CCA.

Landscape of immune microenvironment in hepatocellular carcinoma and its additional impact on histological and molecular classification

Yutaka Kurebayashi, Hidenori Ojima, Hanako Tsujikawa, Naoto Kubota, Junki Maehara, Yuta Abe, Minoru Kitago, Masahiro Shinoda, Yuko Kitagawa, Michiie Sakamoto – 30 March 2018 – Immune cells constitute an important element of tumor tissue. Accumulating evidence indicates their clinicopathological significance in predicting prognosis and therapeutic efficacy. Nonetheless, the combinations of immune cells forming the immune microenvironment and their association with histological findings remain largely unknown.

Outcomes of surgical management of familial intrahepatic cholestasis 1 and bile salt export protein deficiencies

Laura N. Bull, Ludmila Pawlikowska, Sandra Strautnieks, Irena Jankowska, Piotr Czubkowski, Jennifer L. Dodge, Karan Emerick, Catherine Wanty, Sami Wali, Samra Blanchard, Florence Lacaille, Jane A. Byrne, Albertien M. van Eerde, Kaija‐Leena Kolho, Roderick Houwen, Steven Lobritto, Vera Hupertz, Patricia McClean, Giorgina Mieli‐Vergani, Etienne Sokal, Philip Rosenthal, Peter F. Whitington, Joanna Pawlowska, Richard J.

Indeterminate pediatric acute liver failure is uniquely characterized by a CD103+CD8+ T‐cell infiltrate

Catherine A. Chapin, Thomas Burn, Tomas Meijome, Kathleen M. Loomes, Hector Melin‐Aldana, Portia A Kreiger, Peter F. Whitington, Edward M. Behrens, Estella M. Alonso – 30 March 2018 – The cause of pediatric acute liver failure (PALF) is unknown in up to 40% of cases. Evidence suggests that aberrant immune system activation may play a role. We hypothesized that indeterminate PALF cases would exhibit a unique pattern of hepatic inflammation. This was a retrospective and prospective study of PALF cases due to indeterminate (iPALF), autoimmune hepatitis, or known diagnosis (dPALF) etiology.

Loss of PDK4 switches the hepatic NF‐κB/TNF pathway from pro‐survival to pro‐apoptosis

Jianguo Wu, Yulan Zhao, Young‐Ki Park, Ji‐Young Lee, Ling Gao, Jiajun Zhao, Li Wang – 30 March 2018 – It has been established that nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) members promote survival by upregulating antiapoptotic genes and that genetic and pharmacological inhibition of NF‐κB is required for tumor necrosis factor (TNF)‐induced hepatocyte apoptosis. In this study, we demonstrate that this pro‐survival pathway is switched to pro‐apoptosis under pyruvate dehydrogenase kinase 4 (PDK4)‐deficient conditions.

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