Multitarget Direct‐Acting Antiviral Therapy Is Associated With Superior Immunologic Recovery in Patients Coinfected With Human Immunodeficiency Virus and Hepatitis C Virus

Shikha Shrivastava, Manasa Bhatta, Haley Ward, Sara Romani, Rebecca Lee, Elana Rosenthal, Anu Osinusi, Anita Kohli, Henry Masur, Shyam Kottilil, Eleanor Wilson – 27 September 2018 – Patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) have higher levels of immune activation, impaired antigen‐specific responses, and accelerated fibrogenesis compared to patients monoinfected with HCV. Whether different direct‐acting antiviral (DAA) combinations have differential effects on immunophenotypes and functions following successful HCV therapy remain unknown.

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.

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.

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).

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.

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