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JCTH Associate Editors Dr. Timothy Billiar Dr. Kittichai Promrat OWNED BY THE SECOND AFFILIATED HOSPITAL OF CHONGQING MEDICAL UNIVERSITY Presbyterian University Hospital Alpert Medical School of Brown University Pittsburgh, USA Providence, USA Dr. John Birk Prof. Cheng Qian University of Connecticut Third Military Medical University Southwest Farmington, USA Hospital Chongqing, China Editors-in-Chief Prof. Li-Min Chen Dr. Arielle Rosenberg University Paris Descartes Prof. Hong Ren Peking Union Medical College Chengdu, China Paris, France General Editor-in-Chief The Second Affiliated Hospital of Chongqing Prof. Cheng-Wei Chen Prof. Naoya Sakamoto Medical University, China Hokkaido University Nanjing Military Command Sapporo, Japan Dr. Harry Hua-Xiang Xia Shanghai, China Editor-in-Chief Dr. Michael Schilsky Novartis Pharmaceuticals Corporation, USA Prof. Aziz A. Chentoufi Medicine King Fahad Medical College Yale University New Haven, USA Prof. George Y. Wu Riyadh, Saudi Arabia Comprehensive Editor-in-Chief Prof. Xiao-Guang Dou Dr. Tawesak Tanwandee University of Connecticut Heath Center, USA Siriraj Hospital, Mahidol University Shengjing Hospital of China Medical University Bangkok, Thailand Managing Editors Shengyang, China Prof. Fu-Sheng Wang Dr. Jean-François Dufour 302 Miltitary Hospital of China Huai-Dong Hu University of Bern Beijing, China Chongqing, China Bern, Switzerland Zhi Peng Prof. Lai Wei Prof. Marko Duvnjak Peking University People’s Hospital Chongqing, China Clinical Hospital Centre “Sestre milosrdnice” Beijing, China Zagreb, Croatia Executive Editor Prof. Faripour Forouhar Dr. Xue-Feng Xia University of Connecticut The Methodist Hospital Research Institute Houston, USA Hua He Farmington, USA Houston, USA Dr. Johannes Haybaeck Dr. Ke-Cheng Xu Medical University Graz Fuda Cancer Hospital Technical Editor Graz, Austria Guangzhou, China Wan-Chen Hu Prof. Jin-Lin Hou Prof. Man-Fung Yuen Wuhan, China Nanfang Hospital of Southern Medical The University of Hong Kong Queen Mary University Hospital Guangzhou, China Hong Kong, China Prof. Ke-Qin Hu Prof. Da-Zhi Zhang University of California The Second Affiliated Hospital of Chongqing Orange, USA Medical University Chongqing, China Prof. Ji-Dong Jia Capital Medical University Dr. Lan-Jing Zhang Beijing, China University Medical Center of Princeton Contact information Plainsboro, USA Telephone +86 23 63727251 Dr. Joseph Lim Yale University Fax +86 23 63701383 New Haven, USA E-mail [email protected] Prof. Lun-Gen Lu Address 74 Linjiang Road, Shanghai Jiaotong University School of Yuzhong District, Medicine Shanghai, China Chongqing, P. R. China, 400010 Dr. John Luk Johnson & Johnson Medical Ltd. Shanghai, China Publisher Prof. Yen-Hsuan Ni National Taiwan University Xia & He Publishing Inc. Taipei, Taiwan 11415 Ashford Willow, Sugar Land, Texas, 77478, USA Prof. Jun-Qi Niu Jilin University Changchun, China JOURNAL OF CLINICAL AND TRANSLATIONAL HEPATOLOGY Call for papers JCTH is a new, comprehensive specialist journal focusing on the recent progress in clinical and basic research with direct applications to clinical management of liver diseases. The studies published in JCTH will represent the most current trends in the field of hepatology, highlighting the topically relevant subjects of nations worldwide. Publications in JCTH will be presented in formats that emphasize clarity of the study’s objectives and implications of its findings, using high quality visual aids to enhance the manuscript’s esthetic appeal as well as its impact. For our upcoming issue, we encourage you and your group to submit original articles that showcase your work in hepatology and topically relevant reviews to promote our readers’ understanding of the field. CONTENTS 2016 4(2):76–168 Original Articles Accessibility to Oral Antiviral Therapy for Patients with Chronic Hepatitis C in the United States Sammy Saab, Melissa Jimenez, Tiffany Fong, Crystal Wu, Sherona Bau, Zoha Jamal, Jonathan Grotts and David Elashoff . 76 Postoperative Risk of Hepatic Decompensation after Orthopedic Surgery in Patients with Cirrhosis Eric M. Nyberg, Michael Batech, T. Craig Cheetham, Jose R. Pio, Susan L. Caparosa, Mary Alice Chocas and Anshuman Singh . 83 Effects of Granulocyte Colony-Stimulating Factor on Patients with Liver Failure: a Meta-Analysis Qiao Yang, Ying Yang, Yu Shi, Fangfang Lv, Jiliang He and Zhi Chen . 90 Review Articles Interferon-Free Treatments for Chronic Hepatitis C Genotype 1 Infection Alireza FakhriRavari, Mazyar Malakouti and Rebecca Brady . 97 Current Management of Alcoholic Hepatitis and Future Therapies Behnam Saberi, Alia S. Dadabhai, Yoon-Young Jang, Ahmet Gurakar and Esteban Mezey . 113 Nonalcoholic Lipid Accumulation and Hepatocyte Malignant Transformation Juanjuan Gu, Min Yao, Dengbing Yao, Li Wang, Xuli Yang and Dengfu Yao . 123 Acetaminophen-Induced Hepatotoxicity: a Comprehensive Update Eric Yoon, Arooj Babar, Moaz Choudhary, Matthew Kutner and Nikolaos Pyrsopoulos . 131 Hepatitis B Reactivation with Novel Agents in Non-Hodgkin’s Lymphoma and Prevention Strategies Oluwatobi O. Ozoya, Lubomir Sokol and Samir Dalia . 143 Immune Activation in the Liver by Nucleic Acids Qian Sun, Qingde Wang, Melanie J. Scott and Timothy R. Billiar . 151 The Evolving Nature of Hepatic Abscess: A Review Marianna G. Mavilia, Marco Molina and George Y. Wu . 158 Original Article Accessibility to Oral Antiviral Therapy for Patients with Chronic Hepatitis C in the United States Sammy Saab*1,2, Melissa Jimenez2, Tiffany Fong2, Crystal Wu2, Sherona Bau2, Zoha Jamal2, Jonathan Grotts3 and David Elashoff3 1Department of Medicine, University of California, Los Angeles, CA, USA; 2Department of Surgery, University of California, Los Angeles, CA, USA; 3Department of Biostatistics, University of California, Los Angeles, CA, USA Abstract © 2016 The Second Affiliated Hospital of Chongqing Medical University. Published by XIA & HE Publishing Inc. All rights re- Background: Hepatitis C (HCV) direct acting antiviral agents served. (DAAs) are safe, effective, and tolerable. Most contraindica- tions to interferon-based treatment are no long applicable. The aims of this study were to understand the predictors of approval to drug accessibility. Methods: We studied Introduction all consecutive patients with HCV prescribed DAAs between – October 2014 and July 2015. Data on demographic, socio- Up to 5 7 million Americans are believed to be infected with economic status, comorbidities, baseline laboratory values, chronic hepatitis C (HCV) Most of these individuals are unaware of their disease and are in the baby-boomer age and assessment of liver disease severity, insurance, and spe- 1 cialty pharmacy type were collected. Multivariate analyses group. Chronic hepatitis C infection is an important medical were performed to identify predictors of prescription approval. concern that has both hepatic and extrahepatic manifesta- tion.2 The viral infection can lead to cirrhosis, hepatocellular Results: In total, 410 patients were prescribed DAAs between 2–4 October 2014 and July 2015. Of those, 332 (81%) patients carcinoma (HCC), and liver failure. Indeed, HCV is the most common indication for liver transplantation in the were insurance approved for therapy. Of the 332 patients 5 accepted, 251 were accepted after the first prescription United States. Extrahepatic manifestations, such as cryoglo- bulinemia and kidney disease, are also important causes of attempt, and 38 were accepted after the second and third 6,7 attempts. The number of attempts for the other 43 approved morbidity and mortality. patients was unknown. Older age (p =0.001),employment Achieving a sustained viral response (SVR) is associated (p = 0.001), lack of comorbidities (p = 0.02), liver transplan- with a number of improved clinical outcomes, including liver- related outcomes and overall survival.8,9 Interferon has been tation (p = 0.018), and advanced liver disease (p =0.001) 10 were more likely associated with obtaining approval. House- the cornerstone of antiviral therapy for almost 2 decades. hold income was not associated with insurance approval. However, its utility is limited by a number of contraindications, such as uncontrolled depression and autoimmune In the multivariate analysis, Medicare insurance (odds ratio 11,12 – disorders. The introduction of all-oral direct-acting [OR]) 2.67, 95% confidence interval [CI] 0.96 7.20), lack 13,14 of nonliver comorbidities (OR 2.72, 95% CI 1.35–5.43), and agents (DAAs) has revolutionized the treatment of HCV. the presence of advanced liver disease (OR 1.82, 95% CI Compared to interferon, DAAs have been shown to increase 1.04–3.24) independently predicted drug approval. Conclu- SVR and improve tolerability compared to interferon. Few serious adverse effects are seen with DAAs, and rarely do sion: Despite the availability of DAAs for HCV, barriers 15 from insurance carriers continue to impair widespread use. patients discontinue use of DAAs due to adverse effects. Patients with advanced liver disease, Medicare, and without Antiviral therapy with DAAs has been not only been demon- strated to be safer, more effective, and better tolerated than comorbidities are most likely to be insurance approved 16–20 for DAAs. interferon-based therapy but also more cost effective. Nevertheless, DAAs are expensive and access to these drugs is not guaranteed. Thus, we examined the accessibility of these drugs to patients with HCV. We hypothesized that there Keywords: Hepatitis C; Healthcare access; Antiviral therapy. Abbreviations: 3D,