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1 IN THIS ISSUE OF HEPATOLOGY Volume 68 Number 4 October 2018 Hepatology Highlights 1213 Zaid H. Tafesh, Robert S. Brown, Jr., Joseph F. Pisa, Robert E. Schwartz, Russell Rosenblatt, Nicholas Russo, Nicole T. Shen, Shawn Shah, Amit Mehta, and Vikas Gupta Editorials 1217 Does Cirrhosis Associated with Well Controlled Viral Hepatitis Confer a Risk for Extrahepatic Cancer? Ju Dong Yang and Gregory J. Gores (See Article on Page 1245) 1220 Diabetes, Liver Cancer, and Cirrhosis: What Next? Hannele Yki-Järvinen and Panu K. Luukkonen *Human Study (See Article on Page 1308) Cover Figure: Gao and colleagues investigated the role of Lipocalin-2 (LCN2) and neutrophil extracellular traps (NETs) in the suppression of bacterial infection in liver disease. Here, bone marrow neutrophils were isolated from C57BL/6 mice and stimulated with 100 nm of the calcium ionophore A23187 (a known stimulator of NET formation in neutrophils) for 4 hours. Representative immunofluorescent staining photographs of cit-histone, LCN2, and 4,6-diamidino-2- phenylindole are shown by confocal microscopy. See article on page Diagnostic and Therapeutic Implications of Novel Peptides in Hepatocellular Carcinoma Jordan M Cloyd and Timothy M Pawlik (See Article on Page 1391) 1226 A Three-Pronged Epigenetic Approach to the Treatment of Hepatocellular Carcinoma Ryan A. Hlady and Keith D. Robertson (See Article on Page 1412) 1229 Bile Acids, Microbiota, and Metabolism Sarah A. Taylor and Richard M. Green (See Article on Page 1574) Rapid Communication 1232 *Restaging Patients With Hepatocellular Carcinoma Before Additional Treatment Decisions: A Multicenter Cohort Study Alessandro Vitale, Fabio Farinati, Giulia Noaro, Patrizia Burra, Timothy M. Pawlik, Laura Bucci, Edoardo G. Giannini, Chiara Faggiano, Francesca Ciccarese, Gian Lodovico Rapaccini, Maria Di Marco, Eugenio Caturelli, Marco Zoli, Franco Borzio, Rodolfo Sacco, Giuseppe Cabibbo, Roberto Virdone, Fabio Marra, Martina Felder, Filomena Morisco, Luisa Benvegnú, Antonio Gasbarrini, Gianluca Svegliati-Baroni, Francesco Giuseppe Foschi, Andrea Olivani, Alberto Masotto, Gerardo Nardone, Antonio Colecchia, Fabio Fornari, Massimo Marignani, Susanna Vicari, Emanuela Bortolini, Raffaele Cozzolongo, Alessandro Grasso, Camillo Aliberti, Mauro Bernardi, Anna Chiara Frigo, Mauro Borzio, Franco Trevisani, and Umberto Cillo; on behalf of the Italian Liver Cancer (ITA.LI.CA) group

2 Original Articles VIRAL HEPATITIS 1245 *Extrahepatic Cancers Are the Leading Cause of Death in Patients Achieving Hepatitis B Virus Control or Hepatitis C Virus Eradication Manon Allaire, Pierre Nahon, Richard Layese, Valérie Bourcier, Carole Cagnot, Patrick Marcellin, Dominique Guyader, Stanislas Pol, Dominique Larrey, Victor De Lédinghen, Denis Ouzan, Fabien Zoulim, Dominique Roulot, Albert Tran, Jean-Pierre Bronowicki, Jean-Pierre Zarski, Ghassan Riachi, Paul Calés, Jean-Marie Péron, Laurent Alric, Marc Bourliére, Philippe Mathurin, Jean-Frédéric Blanc, Armand Abergel, Lawrence Serfaty, Ariane Mallat, Jean-Didier Grangé, Pierre Attali, Yannick Bacq, Claire Wartelle, Thông Dao, Dominique Thabut, Christophe Pilette, Christine Silvain, Christos Christidis, Eric Nguyen-Khac, Brigitte Bernard-Chabert, David Zucman, Vincent DI Martino, Angela Sutton, Eric Letouzé, Etienne Audureau, and Françoise Roudot-Thoraval; for the ANRS CO12 CirVir Group (See Editorial on Page 1217) 1260 *SIRT3 Restricts Hepatitis B Virus Transcription and Replication Through Epigenetic Regulation of Covalently Closed Circular DNA Involving Suppressor of Variegation 3-9 Homolog 1 and SET Domain Containing 1A Histone Methyltransferases Ji-Hua Ren, Jie-Li Hu, Sheng-Tao Cheng, Hai-Bo Yu, Vincent Kam Wai Wong, Betty Yuen Kwan Law, Yong-Feng Yang, Ying Huang, Yi Liu, Wei-Xian Chen, Xue-Fei Cai, Hua Tang, Yuan Hu, Wen-Lu Zhang, Xiang Liu, Quan-Xin Long, Li Zhou, Na-Na Tao, Hong-Zhong Zhou, Qiu-Xia Yang, Fang Ren, Lin He, Rui Gong, Ai-Long Huang, and Juan Chen 1277 *12 Weeks of a Ribavirin- Free Sofosbuvir and Nonstructural Protein 5 A Inhibitor Regimen Is Enough to Treat Recurrence of Hepatitis C After Liver Transplantation Pauline Houssel-Debry, Audrey Coilly, Claire Fougerou-Leurent, Caroline Jezequel, Christophe Duvoux, Victor De Ledinghen, Sylvie Radenne, Nassim Kamar, Vincent Leroy, Vincent Di Martino, Louis D'Alteroche, Valérie Canva, Filomena Conti, Jerome Dumortier, Héléne Montialoux, Pascal Lebray, Danielle Botta-Fridlund, Albert Tran, Christophe Moreno, Christine Silvain, Camille Besch, Philippe Perre, Claire Francoz, Armando Abergel, François Habersetzer, Maryline Debette-Gratien, Carole Cagnot, Alpha Diallo, Stéphane Chevaliez, Emilie Rossignol, Aurélie Veislinger, Jean-Charles Duclos-Vallee, Georges-Philippe Pageaux, and the ANRS CO23 CUPILT study group 1288 *De Novo Hepatocellular Carcinoma Among Liver Transplant Registrants in the Direct Acting Antiviral Era Allison J. Kwong, W. Ray Kim, and Jennifer A. Flemming 1298 *Glecaprevir/Pibrentasvir Treatment in Liver or Kidney Transplant Patients With Hepatitis C Virus Infection Nancy Reau, Paul Y. Kwo, Susan Rhee, Robert S. Brown Jr, Kosh Agarwal, Peter Angus, Edward Gane, Jia-Horng Kao, Parvez S. Mantry, David Mutimer, K. Rajender Reddy, Tram T. Tran, Yiran B. Hu, Abhishek Gulati, Preethi Krishnan, Emily O. Dumas, Ariel Porcalla, Nancy S. Shulman, Wei Liu, Suvajit Samanta, Roger Trinh, and Xavier Forns STEATOHEPATITIS/METABOLIC LIVER DISEASE 1308 *Diabetes, Plasma Glucose, and Incidence of Fatty Liver, Cirrhosis, and Liver Cancer: A Prospective Study of 0.5 Million People Yuanjie Pang, Christiana Kartsonaki, Iain Turnbull, Yu Guo, Robert Clarke, Yiping Chen, Fiona Bragg, Ling Yang, Zheng Bian, Iona Y. Millwood, Juanzhi Hao, Xianyong Han, Yajing Zang, Junshi Chen, Liming Li, Michael V. Holmes, and Zhengming Chen (See Editorial on Page 1220) 1319 *New Pediatric Percentiles of Liver Enzyme Serum Levels (Alanine Aminotransferase, Aspartate Aminotransferase, γ- Glutamyltransferase): Effects of Age, Sex, Body Mass Index, and Pubertal Stage Sarah Bussler, Mandy Vogel, Diana Pietzner, Kristian Harms, Theresa Buzek, Melanie Penke, Norman Händel, Antje Körner, Ulrich Baumann, Wieland Kiess, and Gunter Flemming

3 1331 Lipotoxicity Induces Hepatic Protein Inclusions Through TANK Binding Kinase 1 Mediated p62/sequestosome 1 Phosphorylation Chun-Seok Cho, Hwan-Woo Park, Allison Ho, Ian A. Semple, Boyoung Kim, Insook Jang, Haeli Park, Shannon Reilly, Alan R. Saltiel, and Jun Hee Lee 1347 *Neutrophil Extracellular Traps Promote Inflammation and Development of Hepatocellular Carcinoma in Nonalcoholic Steatohepatitis Dirk J. van der Windt, Vikas Sud, Hongji Zhang, Patrick R. Varley, Julie Goswami, Hamza O. Yazdani, Samer Tohme, Patricia Loughran, Robert M. O Doherty, Marta I. Minervini, Hai Huang, Richard L. Simmons, and Allan Tsung 1361 *Hepatic CREBZF Couples Insulin to Lipogenesis by Inhibiting Insig Activity and Contributes to Hepatic Steatosis in Diet-induced Insulin-resistant mice Feifei Zhang, Zhimin Hu, Gaopeng Li, Shaofeng Huo, Fengguang Ma, Aoyuan Cui, Yaqian Xue, Yamei Han, Qi Gong, Jing Gao, Hua Bian, Zhuoxian Meng, Haifu Wu, Gang Long, Yi Tan, Yan Zhang, Xu Lin, Xin Gao, Aimin Xu, and Yu Li 1376 *Metabolic Features of Nonalcoholic Fatty Liver (NAFL) in Obese Adolescents: Findings From a Multiethnic Cohort Domenico Tricò, Sonia Caprio, Giuseppina Rosaria Umano, Bridget Pierpont, Jessica Nouws, Alfonso Galderisi, Grace Kim, Mariana M. Mata, and Nicola Santoro HEPATOBILIARY MALIGNANCIES 1391 Fluorescent Peptide Highlights Micronodules in Murine Hepatocellular Carcinoma Models and Humans in vitro Renwei Jing, Xiaoli Zhou, Jingwen Zhao, Yushuang Wei, Bingfeng Zuo, Abin You, Quan Rao, Xianjun Gao, Rong Yang, Lu Chen, Zhen Lu, Qibing Zhou, Ning Zhang, and HaiFang Yin (See Editorial on Page 1223) 1412 Integrative Epigenetic Analysis Reveals Therapeutic Targets to the DNA Methyltransferase Inhibitor Guadecitabine (SGI-110) in Hepatocellular Carcinoma Minmin Liu, Lian Zhang, Hongtao Li, Toshinori Hinoue, Wanding Zhou, Hitoshi Ohtani, Anthony El-Khoueiry, John Daniels, Casey O'Connell, Tanya B. Dorff, Qianjin Lu, Daniel J. Weisenberger, and Gangning Liang (See Editorial on Page 1226) 1429 *Institutional Decision to Adopt Y90 as Primary Treatment for Hepatocellular Carcinoma Informed by a 1,000-Patient 15-Year Experience Riad Salem, Ahmed Gabr, Ahsun Riaz, Ronald Mora, Rehan Ali, Michael Abecassis, Ryan Hickey, Laura Kulik, Daniel Ganger, Steven Flamm, Rohi Atassi, Bassel Atassi, Kent Sato, Al B. Benson, Mary F. Mulcahy, Nadine Abouchaleh, Ali Al Asadi, Kush Desai, Bartley Thornburg, Michael Vouche, Ali Habib, Juan Caicedo, Frank H. Miller, Vahid Yaghmai, Joseph R. Kallini, Samdeep Mouli, and Robert J. Lewandowski 1441 *Fibrolamellar Carcinoma in the Carney Complex: PRKAR1A Loss Instead of the Classic DNAJB1- PRKACA Fusion Rondell P. Graham, Carolin Lackner, Luigi Terracciano, Yessica González-Cantú, Joseph J. Maleszewski, Patricia T. Greipp, Sanford M. Simon, and Michael S. Torbenson 1448 *Reframing the Approach to Patients With Hepatocellular Carcinoma: Longitudinal Assessment With Hazard Associated With Liver Transplantation for HCC (HALTHCC) Improves Ablate and Wait Strategy Daniel J. Firl, Shoko Kimura, John McVey, Koji Hashimoto, Heidi Yeh, Charles M. Miller, James F. Markmann, Kazunari Sasaki, and Federico N. Aucejo

4 1459 *Hepatoma Cell-Secreted Exosomal MicroRNA-103 Increases Vascular Permeability and Promotes Metastasis by Targeting Junction Proteins Jian-Hong Fang, Zi-Jun Zhang, Li-Ru Shang, Yu-Wei Luo, Yi-Fang Lin, Yunfei Yuan, and Shi-Mei Zhuang 1476 Cost-Effectiveness of Antiviral Treatment After Resection in Hepatitis B Virus related Hepatocellular Carcinoma Patients With Compensated Cirrhosis Li Xie, Juan Yin, Ruyi Xia, and Guihua Zhuang AUTOIMMUNE, CHOLESTATIC AND BILIARY DISEASE 1487 *The Impact of Autoimmune Hepatitis and Its Treatment on Health Utility Lin Lee Wong, Holly F Fisher, Deborah D Stocken, Stephen Rice, Amardeep Khanna, Michael A Heneghan, Ye Htun Oo, George Mells, Stuart Kendrick, Jessica Katharine Dyson, and David E. J. Jones LIVER FAILURE/CIRRHOSIS/PORTAL HYPERTENSION 1498 *A Risk Score to Predict the Development of Hepatic Encephalopathy In a Population- Based Cohort of Patients With Cirrhosis Elliot B. Tapper, Neehar D. Parikh, Neil Sengupta, Jessica Mellinger, David Ratz, Anna S.-F. Lok, and Grace L. Su 1508 *Hepatocyte Microvesicle Levels Improve Prediction of Mortality in Patients With Cirrhosis Audrey Payancé, Gilberto Silva-Junior, Julien Bissonnette, Marion Tanguy, Blandine Pasquet, Cristina Levi, Olivier Roux, Ouardia Nekachtali, Anna Baiges, Virginia Hernández-Gea, Cédric Laouénan, Didier Lebrec, Miguel Albuquerque, Valérie Paradis, Richard Moreau, Dominique Valla, François Durand, Chantal M. Boulanger, Juan-Carlos Garcia-Pagan, and Pierre-Emmanuel Rautou 1519 Disruption of Renal Arginine Metabolism Promotes Kidney Injury in Hepatorenal Syndrome in Mice Zoltan V. Varga, Katalin Erdelyi, Janos Paloczi, Resat Cinar, Zsuzsanna K. Zsengeller, Tony Jourdan, Csaba Matyas, Balazs Tamas Nemeth, Adrien Guillot, Xiaogang Xiang, Adam Mehal, György Hasko, Isaac E. Stillman, Seymour Rosen, Bin Gao, George Kunos, and Pal Pacher 1534 *Influence of Progenitor-Derived Regeneration Markers on Hepatitis C Virus -Related Cirrhosis Outcome (ANRS CO12 CirVir cohort) Dominique Wendum, Richard Layese, Nathalie Ganne-Carrié, Valérie Bourcier, Fatiha Merabtene, Carole Cagnot, Emmanuel Sauce, Pierre Bedossa, Benoit Terris, Janick Selves, Paulette Bioulac-Sage, Nathalie Sturm, Christophe Sattonnet, Pierre Nahon, Françoise Roudot-Thoraval, and Marianne Ziol; for the ANRS CO12 CirVir Group 1549 *Antibiotic-Associated Disruption of Microbiota Composition and Function in Cirrhosis is Restored by Fecal Transplant Jasmohan S. Bajaj, Genta Kakiyama, Tor Savidge, Hajime Takei, Zain A. Kassam, Andrew Fagan, Edith A. Gavis, William M. Pandak, Hiroshi Nittono, Phillip B. Hylemon, Prapaporn Boonma, Anthony Haag, Douglas M. Heuman, Michael Fuchs, Binu John, Masoumeh Sikaroodi, and Patrick M. Gillevet LIVER INJURY/REGENERATION 1559 *Outcomes After Multiple Courses of Granulocyte Colony-Stimulating Factor and Growth Hormone in Decompensated Cirrhosis: A Randomized Trial Nipun Verma, Amritjyot Kaur, Ratiram Sharma, Ashish Bhalla, Navneet Sharma, Arka De, and Virendra Singh

5 LIVER BIOLOGY/PATHOBIOLOGY 1574 Intestine Farnesoid X Receptor Agonist and The Gut Microbiota Activate G-Protein Bile Acid Receptor-1 Signaling To Improve Metabolism Preeti Pathak, Cen Xie, Robert G. Nichols, Jessica M. Ferrell, Shannon Boehme, Kristopher W. Krausz, Andrew D. Patterson, Frank J. Gonzalez, and John Y.L. Chiang (See Editorial on Page 1229) 1589 *The Wnt/β-Catenin Pathway Determines the Predisposition and Efficiency of Liver-to-pancreas Reprogramming Helit Cohen, Hila Barash, Irit Meivar-Levy, Kfir Molakandov, Marina Ben-Shimon, Michael Gurevich, Fatima Zoabi, Adi Har-Zahav, Rolf Gebhardt, Frank Gaunitz, Michael Gurevich, Eytan Mor, Philippe Ravassard, Shoshana Greenberger, and Sarah Ferber 1604 *Hepatocytes and Neutrophils Cooperatively Suppress Bacterial Infection by Differentially Regulating Lipocalin-2 and Neutrophil Extracellular Traps Hongjie Li, Dechun Feng, Yan Cai, Yudong Liu, Mingjiang Xu, Xiaogang Xiang, Zhou Zhou, Qiang Xia, Mariana J. Kaplan, Xiaoni Kong, and Bin Gao Concise Review 1621 Acute-on-Chronic Liver Failure: Getting Ready for Prime Time? Jasmohan S. Bajaj, Richard Moreau, Patrick S Kamath, Hugo E. Vargas, Vicente Arroyo, K. Rajender Reddy, Gyongyi Szabo, Puneeta Tandon, Jody Olson, Constantine Karvellas, Thierry Gustot, Jennifer C. Lai, and Florence Wong Review 1633 Assessment of Advanced Liver Fibrosis and the Risk for Hepatic Decompensation in Patients With Congestive Hepatopathy Alexander Lemmer, Lisa B. VanWagner, and Daniel Ganger Hepatology Elsewhere 1642 Changes in Arachidonic Acid Metabolism During Liver Ischemia Triggers Induction of Inflammatory Injury Takanori Konishi and Alex B. Lentsch 1644 What's Cold Got to Do With It? Cold-Induced Thermogenesis and Microbiome Modification may be Regulated by Bile Acid Physiology Nisreen Soufi and Rohit Kohli 1646 Nonalcoholic Fatty Liver Disease With Cirrhosis Increases Familial Risk for Advanced Fibrosis Cynthia A. Moylan and Manal F. Abdelmalek Clinical Observations in Hepatology 1649 *Low-Dose Interleukin-2 for Refractory Autoimmune Hepatitis Tiong Y. Lim, Marc Martinez-Llordella, Elisavet Kodela, Elisabeth Gray, Michael A. Heneghan, and Alberto Sanchez-Fueyo 1653 *Stereotactic Body Radiation Therapy Induced Abscopal Effect on Hepatocellular Carcinoma After Treatment for Lung Cancer: A Case Report Fumiko Chino, Kimberly Ellen Pollis, Steve Choi, Joseph K Salama, and Manisha Palta Correspondence 1656 Transplantation of Livers From Viremic Hepatitis C Virus Positive Donors Into Hepatitis C Virus Negative Recipients Paulo N. Martins 1657 Association of Nonalcoholic Fatty Liver Disease With Relative Skeletal Muscle Mass: A Public Health Perspective Saumya Pandey

6 1658 The Efficacy of Tenofivir to Prevent Perinatal Transmission in Chronic Hepatitis B Mothers. A Clinical Perspective Ghassan Mubarak and Richard Ferstenberg 1658 Reply Norah A. Terrault, Robert S. Brown, Jr., Anna S.F. Lok, John B. Wong, Natalie H. Bzowej, Kyong-Mi Chang, Jessica P. Hwang, Maureen M. Jonas, and Brian J McMahon 1660 Allogeneic Mesenchymal Stem Cells Therapy for the Treatment of Hepatitis B Virus Related Acute-on-Chronic Liver Failure Changhui Zhou, Weihua Wang, and Ying Mu 1661 Reply Jun-feng Chen and Bing-liang Lin 1662 A New Conception: Pre-HCC Disease Yao Yang, Yuemin Feng, Xinya Zhao, Le Wang, Xiaoyu Xie, Jie Li, Mindie H. Nguyen, and Qiang Zhu