Prohibitin 1 Acts As a Negative Regulator of Wingless/Integrated‐Beta‐Catenin Signaling in Murine Liver and Human Liver Cancer Cells

Nirmala Mavila, Yuanyuan Tang, Joshua Berlind, Komal Ramani, Jiaohong Wang, José M. Mato, Shelly C. Lu – 27 September 2018 – Prohibitin1 (PHB1) is a mitochondrial chaperone with diverse functions that include cell proliferation, apoptosis, and mitochondrial homoeostasis. Liver‐specific Phb1 knockout (KO) mice develop spontaneous injury and hepatocellular carcinoma (HCC). Our previous work demonstrated that PHB1 negatively regulates the H19‐insulin‐like growth factor 2 (IGF2)‐H19‐IGF2 axis signaling pathway and E‐box activity in hepatocytes and HCC cells.

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.

Hepatic Nuclear Receptor Expression Associates with Features of Histology in Pediatric Nonalcoholic Fatty Liver Disease

Erin E. Elbel, Joel E. Lavine, Michael Downes, Mark Van Natta, Ruth Yu, Jeffrey B. Schwimmer, Cynthia Behling, Elizabeth M. Brunt, James Tonascia, Ronald Evans – 27 September 2018 – Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children and adults. This study examined the relationship between hepatic nuclear receptor (NR) expression and histologic features of NAFLD. Drugs targeting a variety of NRs for nonalcoholic steatohepatitis (NASH) are in clinical trials.

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.

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.

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