Randomized, Double‐Blind, Placebo‐Controlled, Single Ascending Dose Trial of Synthetic Preimplantation Factor in Autoimmune Hepatitis

Christopher B. O’Brien, Eytan R. Barnea, Paul Martin, Cynthia Levy, Eden Sharabi, Kalyan R. Bhamidimarri, Eric Martin, Leopold Arosemena, Eugene R. Schiff – 26 September 2018 – Preimplantation factor (PIF) is an evolutionary conserved peptide secreted by viable embryos which promotes maternal tolerance without immune suppression. Synthetic PIF (sPIF) replicates native peptide activity. The aim of this study was to conduct the first‐in‐human trial of the safety, tolerability, and pharmacokinetics of sPIF in patients with autoimmune hepatitis (AIH).

Differing Impact of Sarcopenia and Frailty in Nonalcoholic Steatohepatitis and Alcoholic Liver Disease

Rahima A. Bhanji, Praveena Narayanan, Michael R. Moynagh, Naoki Takahashi, Mounika Angirekula, Cassie C. Kennedy, Kristin C. Mara, Ross A. Dierkhising, Kymberly D. Watt – 26 September 2018 – Sarcopenia and frailty are commonly encountered in patients with end‐stage liver disease and are associated with adverse clinical outcomes, including decompensation and wait‐list mortality. The impact of these entities in patients with differing disease etiologies has not been elucidated.

Inhibition of Plasminogen Activator Inhibitor 1 Attenuates Hepatic Steatosis but Does Not Prevent Progressive Nonalcoholic Steatohepatitis in Mice

Anne S. Henkel, Sadiya S. Khan, Shantel Olivares, Toshio Miyata, Douglas E. Vaughan – 26 September 2018 – Plasminogen activator inhibitor 1 (PAI‐1), an essential regulator of fibrinolysis, is increasingly implicated in the pathogenesis of metabolic disorders, such as obesity and nonalcoholic fatty liver disease (NAFLD). Pharmacologic inhibition of PAI‐1 is emerging as a highly promising therapeutic strategy for obesity and its sequelae.

Angiopoietin‐2 Promotes Pathological Angiogenesis and Is a Therapeutic Target in Murine Nonalcoholic Fatty Liver Disease

Sander Lefere, Frederique Van de Velde, Anne Hoorens, Sarah Raevens, Sanne Van Campenhout, Astrid Vandierendonck, Sara Neyt, Bert Vandeghinste, Christian Vanhove, Charlotte Debbaut, Xavier Verhelst, Jo Van Dorpe, Christophe Van Steenkiste, Christophe Casteleyn, Bruno Lapauw, Hans Van Vlierberghe, Anja Geerts, Lindsey Devisscher – 26 September 2018 – Angiogenesis contributes to the development of nonalcoholic steatohepatitis (NASH) and promotes inflammation, fibrosis, and progression to hepatocellular carcinoma (HCC). Angiopoietin‐2 (Ang‐2) is a key regulator of angiogenesis.

Intrahepatic Cholangiocarcinoma: Continuing Challenges and Translational Advances

Alphonse E. Sirica, Gregory J. Gores, John D. Groopman, Florin M. Selaru, Mario Strazzabosco, Xin Wei Wang, Andrew X. Zhu – 25 September 2018 – Intrahepatic cholangiocarcinoma (iCCA) has over the last 10‐20 years become the focus of increasing concern, largely due to its rising incidence and high mortality rates worldwide.

Gamma Glutamyltransferase Reduction Is Associated With Favorable Outcomes in Pediatric Primary Sclerosing Cholangitis

Mark R. Deneau, Cara Mack, Reham Abdou, Mansi Amin, Achiya Amir, Marcus Auth, Fateh Bazerbachi, Anne Marie Broderick, Albert Chan, Matthew DiGuglielmo, Wael El‐Matary, Mounif El‐Youssef, Federica Ferrari, Katryn N. Furuya, Frederic Gottrand, Nitika Gupta, Matjaž Homan, M.K. Jensen, Binita M. Kamath, Kyung Mo Kim, Kaija‐Leena Kolho, Anastasia Konidari, Bart Koot, Raffaele Iorio, Mercedes Martinez, Parvathi Mohan, Sirish Palle, Alexandra Papadopoulou, Amanda Ricciuto, Lawrence Saubermann, Pushpa Sathya, Eyal Shteyer, Vratislav Smolka, Atsushi Tanaka, Pamela L.

Niacin‐Induced Anicteric Microvesicular Steatotic Acute Liver Failure

Kenneth Leung, Michael Quezada, Zhengshan Chen, Gary Kanel, Neil Kaplowitz – 25 September 2018 – Niacin (vitamin B3) is available as a prescription medication and over‐the‐counter supplement. Although it is well known for its vasodilatory effect, it has also been associated with mild hepatotoxicity and, rarely, acute liver failure. We present the case of a 74‐year‐old Hispanic woman who developed acute liver failure (anicteric encephalopathy and coagulopathy) after her home dose of immediate‐release niacin was replaced with an extended‐release formulation during an inpatient hospital stay.

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