Prioritization of Therapeutic Targets and Trial Design in Cirrhotic Portal Hypertension

Juan G. Abraldes, Jonel Trebicka, Naga Chalasani, Gennaro D’Amico, Don C. Rockey, Vijay H. Shah, Jaime Bosch, Guadalupe Garcia‐Tsao – 15 October 2018 – Portal hypertension (PH) is the main driver of cirrhosis decompensation, the main determinant of death in patients with cirrhosis. PH results initially from increased intrahepatic vascular resistance. Subsequently, increased inflow from splanchnic vasodilation and increased cardiac output lead to a further increase in portal pressure (PP). Reducing PP in cirrhosis results in better outcomes. Removing the cause of cirrhosis might improve PP.

New Systemic Treatments in Advanced Hepatocellular Carcinoma

Marco Sanduzzi‐Zamparelli, Álvaro Díaz‐Gonzalez, María Reig – 13 October 2018 – The principal advancements in the treatment of hepatocellular carcinoma (HCC) are the use of new systemic treatments, such as lenvatinib in first‐line treatment and regorafenib, cabozantinib, and ramucirumab in second‐line treatment, because of their benefits in terms of overall survival. In addition, nivolumab as a second‐line agent was approved by the US Food and Drug Administration in 2017 based on improved radiological response data.

Optimizing the Use of Geriatric Livers for Transplantation in the Eurotransplant Region

Jacob D. de Boer, Joris J. Blok, Hein Putter, Jacob J. E. Koopman, Bart van Hoek, Undine Samuel, Marieke van Rosmalen, Herold J. Metselaar, Ian P. J. Alwayn, Markus Guba, Andries E. Braat, for the Eurotransplant Liver and Intestine Advisory Committee – 13 October 2018 – Acceptance criteria for liver allografts are ever more expanding because of a persisting wait‐list mortality. Older livers are therefore offered and used more frequently for transplantation. This study aims to analyze the use and longterm outcome of these transplantations.

Auxiliary Partial Orthotopic Liver Transplantation for Selected Noncirrhotic Metabolic Liver Disease

Ashwin Rammohan, Mettu S. Reddy, Gomathy Narasimhan, Rajesh Rajalingam, Ilankumaran Kaliamoorthy, Naresh Shanmugam, Mohamed Rela – 13 October 2018 – Auxiliary partial orthotopic liver transplantation (APOLT) in selected noncirrhotic metabolic liver diseases (NCMLDs) is a viable alternative to orthotopic liver transplantation (OLT) as it supplements the function of the native liver with the missing functional protein. APOLT for NCMLD is not universally accepted due to concerns of increased technical complications and longterm graft atrophy.

An Intravenous Fish Oil–Based Lipid Emulsion Successfully Treats Intractable Pruritus and Cholestasis in a Patient with Microvillous Inclusion Disease

Lorenzo Anez‐Bustillos, Duy T. Dao, Alexis K. Potemkin, Antonio R. Perez‐Atayde, Bram P. Raphael, Alexandra N. Carey, Daniel S. Kamin, Jay R. Thiagarajah, McGreggor Crowley, Kathleen M. Gura, Mark Puder – 12 October 2018

An Intravenous Fish Oil–Based Lipid Emulsion Successfully Treats Intractable Pruritus and Cholestasis in a Patient with Microvillous Inclusion Disease

Lorenzo Anez‐Bustillos, Duy T. Dao, Alexis K. Potemkin, Antonio R. Perez‐Atayde, Bram P. Raphael, Alexandra N. Carey, Daniel S. Kamin, Jay R. Thiagarajah, McGreggor Crowley, Kathleen M. Gura, Mark Puder – 12 October 2018

Diet‐Induced Dysbiosis and Genetic Background Synergize With Cystic Fibrosis Transmembrane Conductance Regulator Deficiency to Promote Cholangiopathy in Mice

Dominique Debray, Haquima El Mourabit, Fatiha Merabtene, Loïc Brot, Damien Ulveling, Yves Chrétien, Dominique Rainteau, Ivan Moszer, Dominique Wendum, Harry Sokol, Chantal Housset – 10 October 2018 – The most typical expression of cystic fibrosis (CF)–related liver disease is a cholangiopathy that can progress to cirrhosis. We aimed to determine the potential impact of environmental and genetic factors on the development of CF‐related cholangiopathy in mice.

PI3Kδ Is a Therapeutic Target in Hepatocellular Carcinoma

Eunkyong Ko, Hyun‐Wook Seo, Eun Sun Jung, Soomi Ju, Baek‐hui Kim, Hyeki Cho, Yoon Jun Kim, Young Min Park, Jong‐Seo Kim, Guhung Jung – 9 October 2018 – Class I phosphoinositide 3‐kinase (PI3K) signaling is a major pathway in human cancer development and progression. Among the four PI3K isoforms, PI3Kα and PI3Kβ are ubiquitously expressed, whereas PI3Kγ and PI3Kδ are found primarily in leukocytes. Until now, PI3K targeting in solid tumors has focused on inhibiting PI3Kα‐mediated and PI3Kβ‐mediated cancer cell–intrinsic PI3K activity. The role of PI3Kδ in solid tumors is unknown.

Connexin and Pannexin (Hemi)Channels: Emerging Targets in the Treatment of Liver Disease

Axelle Cooreman, Raf Van Campenhout, Steven Ballet, Pieter Annaert, Bert Van Den Bossche, Isabelle Colle, Bruno Cogliati, Mathieu Vinken – 9 October 2018 – Connexin proteins are the building blocks of hemichannels, which dock further between adjacent cells to form gap junctions. Gap junctions control the intercellular exchange of critical homeostasis regulators. By doing so, gap junctions control virtually all aspects of the hepatic life cycle.

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