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HBV Cccdna: the Stumbling Block for Treatment of HBV Infection Shousheng Liu and Yongning Xin

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HBV Cccdna: the Stumbling Block for Treatment of HBV Infection Shousheng Liu and Yongning Xin JCTH Associate Editors Dr. Masahiro Arai Prof. Junqi Niu OWNED BY THE SECOND AFFILIATED HOSPITAL Toshiba General Hospital Jilin University OF CHONGQING MEDICAL UNIVERSITY Tokyo, Japan Changchun, China Dr. Roopjeet Bath Dr. Kittichai Promrat University of Connecticut Alpert Medical School of Brown University Farmington, USA Providence, USA Dr. Timothy Billiar Dr. Farzin Roohvand Editors-in-Chief Presbyterian University Hospital Pasteur Institute of Iran Prof. Hong Ren Pittsburgh, USA Tehran, Iran General Editor-in-Chief Dr. John Birk Dr. Arielle Rosenberg The Second Affiliated Hospital of Chongqing University of Connecticut University Paris Descartes Medical University, China Farmington, USA Paris, France Dr. Harry Hua-Xiang Xia Dr. Wendy Cao Dr. Michael Schilsky Editor-in-Chief New York University School of Medicine Yale University Novartis Pharmaceuticals Corporation, USA New York, USA New Haven, USA Prof. George Y. Wu Prof. Limin Chen Dr. Ashwani Singal Comprehensive Editor-in-Chief Peking Union Medical College University of Alabama at Birmingham University of Connecticut Heath Center, USA Chengdu, China Birmingham, USA Prof. Aziz A. Chentoufi Dr. Tawesak Tanwandee Medicine King Fahad Medical College Siriraj Hospital, Mahidol University Managing Editors Riyadh, Saudi Arabia Bangkok, Thailand Huaidong Hu Prof. Mohamed A Daw Dr. Fusheng Wang Chongqing, China University of Tripoli 302 Miltitary Hospital of China Beijing, China Sandeep Kumar Karn Tripoli, Libya Chongqing, China Prof. Xiaoguang Dou Prof. Lai Wei Shengjing Hospital of China Medical Peking University People’s Hospital University Beijing, China Executive Editor Shenyang, China Prof. Catherine Wu Hua He Prof. Marko Duvnjak University of Connecticut Houston, USA Clinical Hospital Centre “Sestre milosrdnice” Farmington, USA Zagreb, Croatia Dr. Xuefeng Xia Prof. Jinlin Hou The Methodist Hospital Research Institute Technical Editor Nanfang Hospital of Southern Medical Houston, USA Wanchen Hu University Guangzhou, China Prof. Manfung Yuen Wuhan, China Prof. Keqin Hu The University of Hong Kong Queen Mary University of California Hospital Orange, USA Hong Kong, China Prof. Jidong Jia Prof. Dazhi Zhang Capital Medical University The Second Affiliated Hospital of Chongqing Beijing, China Medical University Chongqing, China Prof. Douglas LaBrecque University of Iowa Prof. Lanjing Zhang Contact information Lowa, USA University Medical Center of Princeton Plainsboro, USA Telephone +86 23 63727251 Dr. Joseph Lim Yale University Fax +86 23 63701383 New Haven, USA E-mail [email protected] Prof. Lungen Lu Shanghai Jiaotong University School of Address 74 Linjiang Road, Medicine Yuzhong District, Shanghai, China Chongqing, P. R. China, Prof. Yen-Hsuan Ni 400010 National Taiwan University Taipei, Taiwan Publisher Xia & He Publishing Inc. 14090 Southwest Freeway, Suite 300, Sugar Land, Texas 77478, USA JOURNAL OF CLINICAL AND TRANSLATIONAL HEPATOLOGY Beginning with 2018, JCTH has been indexed and abstracted in Emerging Sources Citation Index (ESCI). CONTENTS 2019 7(3):195–283 Editorial HBV cccDNA: The Stumbling Block for Treatment of HBV Infection Shousheng Liu and Yongning Xin . 195 Original Articles Comparing the Efficacy and Safety of Treating Chronic Hepatitis B Infection during Pregnancy with Lamivudine, Telbivudine, and Tenofovir: A Meta-analysis Shahnaz Sali, Mohammad Darvishi, Mojtaba GhasemiAdl, Meisam Akhlaghdoust, Azin Mirzazadeh, Somayeh Elikaei Behjati, Hossein Sheikh-Zeinolabedini, Shervin Shokouhi and Soheil Tavakolpour. 197 Efficacy and Safety of All-oral, 12-week Ravidasvir Plus Ritonavir-boosted Danoprevir and Ribavirin in Treatment-na€ıve Noncirrhotic HCV Genotype 1 Patients: Results from a Phase 2/3 Clinical Trial in China Xiaoyuan Xu, Bo Feng, Yujuan Guan, Sujun Zheng, Jifang Sheng, Xingxiang Yang, Yuanji Ma, Yan Huang, Yi Kang, Xiaofeng Wen, Jun Li, Youwen Tan, Qing He, Qing Xie, Maorong Wang, Ping An, Guozhong Gong, Huimin Liu, Qin Ning, Rui Hua, Bo Ning, Wen Xie, Jiming Zhang, Wenxiang Huang, Yongfeng Yang, Minghua Lin, Yingren Zhao, Yanhong Yu, Jidong Jia, Dongliang Yang, Liang Chen, Yinong Ye, Yuemin Nan, Zuojiong Gong, Quan Zhang, Peng Hu, Fusheng Wang, Yongguo Li, Dongliang Li, Zhansheng Jia, Jinlin Hou, Chengwei Chen, Jinzi J. Wu and Lai Wei . 213 Efficacy and Safety of 12-week Interferon-based Danoprevir Regimen in Patients with Genotype 1 Chronic Hepatitis C Lai Wei, Jia Shang, Yuanji Ma, Xiaoyuan Xu, Yan Huang, Yujuan Guan, Zhongping Duan, Wenhong Zhang, Zhiliang Gao, Mingxiang Zhang, Jun Li, Jidong Jia, Yongfeng Yang, Xiaofeng Wen, Maorong Wang, Zhansheng Jia, Bo Ning, Yongping Chen, Yue Qi, Jie Du, Jianning Jiang, Lixin Tong, Yao Xie and Jinzi J. Wu . 221 Hepatitis C Screening: Barriers to Linkage to Care Sammy Saab, Youssef P. Challita, Lisa M. Najarian, Rong Guo, Satvir S. Saggi and Gina Choi . 226 TIPS Is Not Associated with a Higher Risk of Developing HCC in Cirrhotic Patients: A Systematic Review and Meta-analysis Bin Chen, Long Pang, Hao-Bin Chen, Dong-Bo Wu, Yong-Hong Wang and En-Qiang Chen . 232 Effect of Autologous Bone Marrow Stem Cell Therapy in Patients with Liver Cirrhosis: A Meta-analysis Chuan-Xin Wu, Deng Wang, Ying Cai, Ao-Ran Luo and Hang Sun . 238 A Potential Functional Cure in Chinese HBeAg-negative Chronic Hepatitis B Patients Treated with Peg-interferon Alpha-2a Xinyue Chen, Qianguo Mao, Yao Xie, Xiaoguang Dou, Qing Xie, Jifang Sheng, Zhiliang Gao, Xiaoling Zhou, Yingxia Liu, Huanwei Zheng, Shuqin Zhang, Shibo Li, Fusheng Zhu, Yuqin Xu, Mingxiang Zhang, Yaoren Hu, Xiaoping Chen, Yan Huang, Hong Ren and Jidong Jia . 249 Review Articles HBV cccDNA and Its Potential as a Therapeutic Target Anjing Zhu, Xinzhong Liao, Shuang Li, Hang Zhao, Limin Chen, Min Xu and Xiaoqiong Duan . 258 Complementary and Alternative Medicine-related Drug-induced Liver Injury in Asia Cyriac Abby Philips, Philip Augustine, Sasidharan Rajesh, Praveen Kumar Y and Deepak Madhu . 263 Obesity Paradox in Chronic Liver Diseases: Product of Bias or a Real Thing? Ines Bilic Curcic, Maja Cigrovski Berkovic, Lucija Kuna, Hrvoje Roguljic, Robert Smolic, Silvija Canecki Varzic, Lucija Virovic Jukic and Martina Smolic . 275 Case Report Amoxicillin-clavulanate-induced Granulomatous Hepatitis: Case Report and Review of the Literature Avin Aggarwal, Neha Jaswal, Richa Jain and Hussien Elsiesy . 280 Editorial HBV cccDNA: The Stumbling Block for Treatment of HBV Infection Shousheng Liu1 and Yongning Xin*2 1Central Laboratories, Qingdao Municipal Hospital, Qingdao, China; 2Department of Infectious Disease, Qingdao Municipal Hospital, Qingdao, China Citation of this article: Liu S, Xin Y. HBV cccDNA: The stum- After the HBV infection, the innate immune and adaptive bling block for treatment of HBV infection. J Clin Transl Hepatol immune systems are activated and initiate antiviral 2019;7(3):195–196. doi: 10.14218/JCTH.2019.00047. responses, like those involving interferon (IFN)-g and TNF-a that are produced by T cells, thereby decreasing the levels of Hepatitis B virus (HBV) infection leads to severe liver disease HBV cccDNA, but the elimination of HBV cccDNA is difficult to and is one of the main causes of hepatocellular carcinoma- achieve.7 As the intermediate of HBV replication, cccDNA con- related mortality. Although the prevalence of HBV infection tributes to the persistence of HBV replication due to the bio- has decreased markedly with the effective application of logical mechanism of cccDNA formation, which itself remains ’ vaccines, it s still an arduous task to clear the hepatitis B unclear. Eliminating the cccDNA is critical to cure the HBV surface antigen after routine antiviral therapy, as the viral infection.8 rebound often occurs after therapy withdrawal. Therefore, the Recently, Zhu et al.9 conducted a systemic review of HBV 1 situation of dealing with HBV infection is still challenging. As cccDNA and its potential role as the therapeutic target of HBV such, eliminating HBV infection has become an important task infection. Pegylated-IFNa and nucleotide analogues (NAs) are for governments all over the world. In 2016, the Global Health the standard therapy methods, currently. Tang et al.10 Sector Strategy on Viral Hepatitis was approved by the World reported that IFNa exerts a significant effect on the long- Health Assembly to eliminate the HBV infection by 2030.2 term and sustainable suppression of cccDNA transcription, Accumulated studies have illuminated the processes which may due to the alteration of epigenetic modifications underlying the HBV replication cycle, which has provided the of cccDNA minichromosomes. NAs can inhibit HBV replication important insight into the detailed action of the HBV lifestyle by targeting the viral RNA-dependent DNA polymerase, and that has promoted development of therapeutic strategies several NAs, such as lamivudine, entecavir, telbivudine and so against HBV infection. HBV infection begins with the low- on, have been approved for clinical use. Although an effective affinity interaction between HBV and the heparin sulfate antiviral response has been observed with the use of IFNa and proteoglycans located on the host hepatocytes, followed by NAs, the cccDNA still could not be cleared completely, at HBV binding to the sodium taurocholate cotransporting poly- 10 3 present. peptide and then its entry into the hepatocytes. The HBV 9 genome is a relaxed circular DNA with a length of 3.2 kb, Zhu et al. reviewed several gene therapy strategies that which can be transported into the nuclear compartment in have been proposed
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