Global DNA 5‐Hydroxymethylcytosine and 5‐Formylcytosine Contents Are Decreased in the Early Stage of Hepatocellular Carcinoma

Jiao Liu, Jinhua Jiang, Jiezhen Mo, Dan Liu, Dan Cao, Hailin Wang, Yufei He, Hongyang Wang – 2 August 2018 – Methylation of the fifth position of cytosine (5mC) is an important epigenetic modification of DNA. It has been shown that the oxidized derivatives of 5mC, namely 5‐hydroxymethylcytosine (5hmC), 5‐formylcytosine (5fC), and 5‐carboxylcytosine (5caC), are in dynamic existence and have distinct regulatory functions.

Androgen Receptor Enhances Hepatic Telomerase Reverse Transcriptase Gene Transcription After Hepatitis B Virus Integration or Point Mutation in Promoter Region

Chiao‐Ling Li, Chen‐Yu Li, You‐Yu Lin, Ming‐Chih Ho, Ding‐Shinn Chen, Pei‐Jer Chen, Shiou‐Hwei Yeh – 2 August 2018 – The gender disparity of hepatocellular carcinoma (HCC) is most striking in hepatitis B virus (HBV)‐related cases. The majority of such HCC cases contain integrated HBV, and some hotspot integrations, such as those in the telomerase reverse transcriptase gene (TERT) promoter, activate gene expression to drive carcinogenesis.

HSP90 Inhibition Drives Degradation of FGFR2 Fusion Proteins: Implications for Treatment of Cholangiocarcinoma

Dante Lamberti, Giulia Cristinziano, Manuela Porru, Carlo Leonetti, Jan B. Egan, Chang‐Xin Shi, Simonetta Buglioni, Carla A. Amoreo, Loriana Castellani, Mitesh J. Borad, Stefano Alemà, Sergio Anastasi, Oreste Segatto – 1 August 2018 – About 15% of intrahepatic cholangiocarcinomas (ICCs) express constitutively active fibroblast growth factor receptor 2 (FGFR2) fusion proteins (FFs) generated by chromosomal translocations.

Increasing Liver Transplantation Wait‐List Dropout for Hepatocellular Carcinoma With Widening Geographical Disparities: Implications for Organ Allocation

Neil Mehta, Jennifer L. Dodge, Ryutaro Hirose, John P. Roberts, Francis Y. Yao – 1 August 2018 – Given the increasing incidence of hepatocellular carcinoma (HCC) and regional variation in liver transplantation (LT) rates for HCC, we investigated temporal and geographic disparities in LT and wait‐list dropout. LT candidates receiving Model for End‐Stage Liver Disease (MELD) exception from 2005 to 2014 were identified from the United Network for Organ Sharing database (n = 14,320). Temporal differences were compared across 2 eras (2005‐2009 and 2010‐2014).

Plasma From Patients Undergoing Liver Transplantation Is Resistant to Anticoagulant Activity of Soluble Thrombomodulin

Laura C. Burlage, Sarah Bos, Jelle Adelmeijer, Takumi Sakai, Robert J. Porte, Ton Lisman – 1 August 2018 – Recombinant human soluble thrombomodulin (ART‐123) is an anticoagulant and anti‐inflammatory agent clinically used for treatment of disseminated intravascular coagulation. Preclinical studies have shown that ART‐123 reduces hepatic ischemia/reperfusion. Although ART‐123 may therefore have clinical benefit in orthotopic liver transplantation, the substantial alterations in the hemostatic system may complicate its use in this setting.

Treatment Barriers in Portopulmonary Hypertension

Batool AbuHalimeh, Michael J. Krowka, Adriano R. Tonelli – 31 July 2018 – Portopulmonary hypertension (PoPH) is a form of pulmonary arterial hypertension (PAH) that can develop as a complication of portal hypertension. Treatment of PoPH includes PAH‐specific therapies, and in certain cases, such therapies are necessary to facilitate a successful liver transplantation. A significant number of barriers may limit the adequate treatment of patients with PoPH and explain the poorer survival of these patients when compared to patients with other types of PAH.

Idiopathic Portal Hypertension

Virginia Hernández‐Gea, Anna Baiges, Fanny Turon, Juan Carlos Garcia‐Pagán – 31 July 2018 – Idiopathic portal hypertension (IPH) is a rare disorder characterized by clinical portal hypertension in the absence of a recognizable cause such as cirrhosis. Laboratory tests often reveal a preserved liver function with anemia, leukopenia, and thrombocytopenia due to splenomegaly. Imaging studies reveal signs of portal hypertension, whereas liver stiffness and portal pressure values are usually normal or slightly elevated.

Emricasan (IDN‐6556) Lowers Portal Pressure in Patients With Compensated Cirrhosis and Severe Portal Hypertension

Guadalupe Garcia‐Tsao, Michael Fuchs, Mitchell Shiffman, Brian B. Borg, Nikolaos Pyrsopoulos, Kirti Shetty, Juan F. Gallegos‐Orozco, K. Rajender Reddy, Eyob Feyssa, Jean L. Chan, Mason Yamashita, James M. Robinson, Alfred P. Spada, David T. Hagerty, Jaime Bosch – 31 July 2018 – Caspases play a central role in apoptosis, inflammation, and fibrosis. They produce hemodynamically active, proinflammatory microparticles that cause intrahepatic inflammation, vasoconstriction, and extrahepatic splanchnic vasodilation.

DDX24 Mutations Associated With Malformations of Major Vessels to the Viscera

Pengfei Pang, Xiaojun Hu, Bin Zhou, Junjie Mao, Yu Liang, Zaibo Jiang, Mingsheng Huang, Ruihong Liu, Youyong Zhang, Jiesheng Qian, Jinsong Liu, Jinxin Xu, Yaqin Zhang, Maoheng Zu, Yiming Wang, Huanhuan He, Hong Shan – 31 July 2018 – Vascular malformations present diagnostic and treatment challenges. In particular, malformations of vessels to the viscera are often diagnosed late or incorrectly due to the insidious onset and deep location of the disease. Therefore, a better knowledge of the genetic mutations underlying such diseases is needed.

Hepatopulmonary Syndrome in Children: A 20‐Year Review of Presenting Symptoms, Clinical Progression, and Transplant Outcome

Suz Warner, Patrick J. McKiernan, Jane Hartley, Evelyn Ong, Indra D. Mourik, Girish Gupte, Mona Abdel‐Hady, Paolo Muiesan, Thamera Perera, Darius Mirza, Khalid Sharif, Deirdre A. Kelly, Susan V. Beath – 31 July 2018 – Hepatopulmonary syndrome (HPS) in stable patients with cirrhosis can easily be overlooked. We report on the presenting symptoms, disease progression, and outcomes after liver transplantation (LT) in children with HPS. Twenty patients were diagnosed with HPS between 1996 and 2016.

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