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Jianjun Niu, Yong Lin, Pingguo Liu, Yiwen Yu, Chenghao Su, Xiaomin Wang
Long non-coding RNAs are involved with development and progression of cancer, and the advance of microarray technology allows the researchers to investigate the complete expression profile of lncRNA in various kinds of sample. We enrolled 5 male primary HCC cases with chronic HBV infection and the HCC and normal tissues have been obtained during the resection surgery. After total RNA extraction, the lncRNA microarray analysis was conducted to determine the lncRNA and mRNA expression signals. 612 lncRNAs and 1,064 mRNAs were significantly up-regulated in HCC tissue while 656 lncRNAs and 1,532 mRNAs were down-regulated in HCC tissues...
October 18, 2016: Oncotarget
Frank Tacke, Daniela C Kroy
Persistent hepatitis B virus (HBV) infections affect about 240 million patients worldwide that are at risk of developing liver cirrhosis or hepatocellular carcinoma. HBV is a small, partially double stranded DNA virus with four overlapping genes and a unique life cycle, which involves the generation of an RNA template for replication via reverse transcription. Mutations occur frequently during chronic infection, and particular selection pressures select distinct mutants. Nucleoside and nucleotide analogues like lamivudine (LMV), entecavir (ETV), telbivudine (LdT), adefovir dipivoxil (ADV) and tenofovir (TDF) are used to achieve long-term suppression of viral replication...
September 2016: Annals of Translational Medicine
Natali Abeywickrama-Samarakoon, Jean-Claude Cortay, Paul Dény
PURPOSE OF REVIEW: To highlight new concepts and therapeutic approaches concerning hepatitis D virus (HDV) infection. RECENT FINDINGS: Common receptor for hepatitis B virus (HBV) and HDV has been elucidated, deciphering of HDV replication is still in progress, preliminary results of phase II proof-of-concept clinical assays for entry inhibitors and cellular farnesyl transferase inhibitors are now available. SUMMARY: Hepatitis D infection remains a severe acute and chronic liver illness with the only currently approved therapy (Peg-αIFN) achieving disappointingly low rates of sustained viral response and clinical improvement...
October 7, 2016: Current Opinion in Infectious Diseases
Qing Wang, Andrea De Luca, Colette Smith, Robert Zangerle, Helen Sambatakou, Fabrice Bonnet, Colette Smit, Philipp Schommers, Alicia Thornton, Juan Berenguer, Lars Peters, Vincenzo Spagnuolo, Adriana Ammassari, Andrea Antinori, Eugenia Quiros Roldan, Cristina Mussini, Jose M Miro, Deborah Konopnicki, Jan Fehr, Maria A Campbell, Monique Termote, Heiner C Bucher
Background: Non-Hodgkin lymphoma (NHL) is the most common AIDS-defining condition in the era of antiretroviral therapy (ART). Whether chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection promote NHL in HIV-infected patients is unclear. Objective: To investigate whether chronic HBV and HCV infection are associated with increased incidence of NHL in HIV-infected patients. Design: Cohort study. Setting: 18 of 33 cohorts from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE)...
October 18, 2016: Annals of Internal Medicine
Jian Huang, Lei Zhao, Ping Yang, Zhen Chen, Ni Tang, Xiong Z Ruan, Yaxi Chen
Hepatitis B virus (HBV) is a hepatocyte-specific DNA virus whose gene expression and replication are closely associated with hepatic metabolic processes. Thus, a potential anti-viral strategy is to target the host metabolic factors necessary for HBV gene expression and replication. Recent studies revealed that fatty acid translocase CD36 is involved in the replication, assembly, storage, and secretion of certain viruses, such as hepatitis C virus (HCV) and human immunodeficiency virus (HIV). However, the relationship between CD36 and the HBV life cycle remains unclear...
2016: PloS One
Yuchen Xia, Arnaud Carpentier, Xiaoming Cheng, Peter Daniel Block, Yao Zhao, Zhensheng Zhang, Ulrike Protzer, T Jake Liang
BACKGROUND AND AIMS: One major obstacle of hepatitis B virus (HBV) research is the lack of efficient cell culture system permissive for viral infection and replication. The aim of our study was to establish a robust HBV infection model by using hepatocyte-like cells (HLCs) derived from human pluripotent stem cells. METHODS: HLCs were differentiated from human embryonic stem cells and induced pluripotent stem cells. Maturation of hepatocyte functions was determined...
October 13, 2016: Journal of Hepatology
Meng-Hsuan Hsieh, Shu-Chi Wang, Ming-Yen Hsieh, Chung-Feng Huang, Ming-Lun Yeh, Jeng-Fu Yang, Ko Chang, Wei-Ru Lin, Chun-Yu Lin, Tun-Chieh Chen, Jee-Fu Huang, Chia-Yen Dai, Jih-Jin Tsai, Wan-Long Chuang, Ming-Lung Yu
In Taiwan, injecting drug use has been the main route of human immunodeficiency virus (HIV) transmission since 2005, with hepatitis B virus (HBV) and hepatitis D virus (HDV) also having similar transmission routes. This has now become an important public health issue. The aim of this study is to explore the conditions of HDV infections between injecting drug users (IDUs) with and without HIV infection in Southern Taiwan. In this study, 87 IDUs were enrolled, including 27 anti-HDV seronegative IDUs and 60 anti-HDV seropositive IDUs, and the results of their liver function tests, CD4 cell counts, and anti-HIV and HIV RNA levels were analyzed...
October 2016: Kaohsiung Journal of Medical Sciences
Thomas Schluep, Jason Lickliter, James Hamilton, David L Lewis, Ching-Lung Lai, Johnson Yn Lau, Stephen A Locarnini, Robert G Gish, Bruce D Given
ARC-520 Injection, an RNA interference drug for the treatment of hepatitis B that targets cccDNA-derived viral mRNA transcripts with high specificity, effectively reduces the production of viral proteins and HBV DNA. In this phase I, randomized, double-blind, placebo-controlled study, 54 healthy volunteers (half male, half female) received a single, intravenous dose of 0.01-4.0 mg/kg ARC-520 Injection (N = 36) or placebo (N = 18). Assessments included safety, tolerability, pharmacokinetics, and pharmacodynamics (cytokines and complement)...
October 14, 2016: Clinical Pharmacology in Drug Development
Jyun-Yuan Huang, Hung-Lin Chen, Chiaho Shih
Hepatitis B virus (HBV) is a major human pathogen. In this study, we found that miR-204 and miR-1236 were down-regulated in HBV-producing cells, and each could suppress HBV replication. Using a bioinformatic approach and a reporter assay, we identified miR-1236, which can reduce HBV replication and protein production by directly targeting at HBV specific mRNA. In contrast, miR-204 was identified by a microarray approach, and had no effect on HBV RNA and protein production. Surprisingly, miR-204 could inhibit HBV pregenomic RNA encapsidation and capsid assembly...
October 13, 2016: Scientific Reports
H Becker, J T Stahmeyer, M P Manns, C Krauth, M Cornberg
Infections with hepatitis B-, C- and D- viruses have a significant health burden. In Germany, the seroprevalence of HBs-Ag is calculated with 0.6 % and of HCV-antibodies with 0.3 %. However, most patients are not diagnosed. Sequelae are liver-cirrhosis and hepatocellular carcinoma. Several S3-guidelines for the diagnosis and treatment of viral hepatitis have been established. However, implementation of guidelines is not easy to evaluate. To estimate the changes of medical knowledge and diagnostic procedures about viral hepatitis, 7 parameters of liver-diagnostics were elected to analyze the requirements profile in the years 2005 - 2011 in 4 German federal states...
October 6, 2016: Zeitschrift Für Gastroenterologie
Ling-Hao Zhao, Xiao Liu, He-Xin Yan, Wei-Yang Li, Xi Zeng, Yuan Yang, Jie Zhao, Shi-Ping Liu, Xue-Han Zhuang, Chuan Lin, Chen-Jie Qin, Yi Zhao, Ze-Ya Pan, Gang Huang, Hui Liu, Jin Zhang, Ruo-Yu Wang, Yun Yang, Wen Wen, Gui-Shuai Lv, Hui-Lu Zhang, Han Wu, Shuai Huang, Ming-Da Wang, Liang Tang, Hong-Zhi Cao, Ling Wang, T P Lee, Hui Jiang, Ye-Xiong Tan, Sheng-Xian Yuan, Guo-Jun Hou, Qi-Fei Tao, Qin-Guo Xu, Xiu-Qing Zhang, Meng-Chao Wu, Xun Xu, Jun Wang, Huan-Ming Yang, Wei-Ping Zhou, Hong-Yang Wang
Hepatitis B virus (HBV) can integrate into the human genome, contributing to genomic instability and hepatocarcinogenesis. Here by conducting high-throughput viral integration detection and RNA sequencing, we identify 4,225 HBV integration events in tumour and adjacent non-tumour samples from 426 patients with HCC. We show that HBV is prone to integrate into rare fragile sites and functional genomic regions including CpG islands. We observe a distinct pattern in the preferential sites of HBV integration between tumour and non-tumour tissues...
October 5, 2016: Nature Communications
Mateja M Jelen, Lea Hošnjak, Špela Štunf, Anja Zagožen, Kristina Fujs Komloš, Petra Markočič, Mario Poljak, Katja Seme
INTRODUCTION: Of the 350 million individuals chronically infected with hepatitis B virus (HBV) worldwide, approximately 15 to 20 million have been exposed to hepatitis D virus (HDV). This study determined for the first time the HDV prevalence in Slovenian patients with chronic HBV infection. In addition, a literature search was performed to identify all HDV prevalence studies from European countries. METHODS: A total of 1,305 HBsAg-positive serum samples, obtained from the same number of patients, were randomly selected from 2,337 patients referred to the Slovenian national reference laboratory for viral hepatitis between 1998 and 2015...
September 2016: Acta Dermatovenerologica Alpina, Panonica, et Adriatica
Ke-Qi Han, Hui Han, Xue-Qun He, Lei Wang, Xiao-Dong Guo, Xue-Ming Zhang, Jie Chen, Quan-Gang Zhu, Hua Nian, Xiao-Feng Zhai, Ma-Wei Jiang
The purpose of this study was to screen for changes in chemokine and chemokine-related genes that are expressed in hepatocellular carcinoma (HCC) as potential markers of HCC progression. Total RNA was extracted from tumor and peritumor tissues from mice with HCC and analyzed using a PCR microarray comprising 98 genes. Changes in gene expression of threefold or more were screened and subsequently confirmed by immunohistochemical analyses and western blotting. Furthermore, whether chemokine knockdown by RNA interference (RNAi) could significantly suppress tumor growth in vivo was also evaluated...
September 28, 2016: Cancer Medicine
Kübra Altinel, Kosuke Hashimoto, Yu Wei, Christine Neuveut, Ishita Gupta, Ana Maria Suzuki, Alexandre Dos Santos, Pierrick Moreau, Tian Xia, Soichi Kojima, Sachi Kato, Yasuhiro Takikawa, Isao Hidaka, Masahito Shimizu, Tomokazu Matsuura, Akihito Tsubota, Hitoshi Ikeda, Sumiko Nagoshi, Harukazu Suzuki, Marie-Louise Michel, Didier Samuel, Marie Annick Buendia, Jamila Faivre, Piero Carninci
: Hepatitis B virus (HBV) is a major cause of liver diseases including hepatocellular carcinoma (HCC), and more than 650,000 people die annually due to HBV-associated liver failure. Extensive studies of individual promoters have revealed that heterogeneous RNA 5' -ends contribute to the complexity of HBV transcriptome and proteome. Here we provide a comprehensive map of HBV transcription start sites (TSSs) in human liver, HCC and blood, as well as several experimental replication systems, at single nucleotide resolution...
September 28, 2016: Journal of Virology
Belinda K Mössner, Benjamin Staugaard, Janne Jensen, Søren Thue Lillevang, Peer B Christensen, Dorte Kinggaard Holm
AIM: To detect chronic hepatitis B (CHB), chronic hepatitis C (CHC) and human immunodeficiency virus (HIV) infections in dried blood spot (DBS) and compare these samples to venous blood sampling in real-life. METHODS: We included prospective patients with known viral infections from drug treatment centers, a prison and outpatient clinics and included blood donors as negative controls. Five drops of finger capillary blood were spotted on filter paper, and a venous blood sample was obtained...
September 7, 2016: World Journal of Gastroenterology: WJG
Vladimir S Trubetskoy, Jacob B Griffin, Anthony L Nicholas, Eric M Nord, Zhao Xu, Ryan M Peterson, Christine I Wooddell, David B Rozema, Darren H Wakefield, David L Lewis, Steven B Kanner
The RNA interference (RNAi)-based therapeutic ARC-520 for chronic hepatitis B virus (HBV) infection consists of a melittin-derived peptide conjugated to N-acetylgalactosamine for hepatocyte targeting and endosomal escape, and cholesterol-conjugated RNAi triggers, which together result in HBV gene silencing. To characterize the kinetics of RNAi trigger delivery and 5'-phosphorylation of guide strands correlating with gene knockdown, we employed a peptide-nucleic acid (PNA) hybridization assay. A fluorescent sense strand PNA probe binding to RNAi duplex guide strands was coupled with anion exchange high performance liquid chromatography to quantitate guide strands and metabolites...
September 19, 2016: Nucleic Acids Research
Marianoel Pereira-Gómez, Juan-Vicente Bou, Iván Andreu, Rafael Sanjuán
The high levels of genetic diversity shown by hepatitis B virus (HBV) are commonly attributed to the low fidelity of its polymerase. However, the rate of spontaneous mutation of human HBV in vivo is currently unknown. Here, based on the evolutionary principle that the population frequency of lethal mutations equals the rate at which they are produced, we have estimated the mutation rate of HBV in vivo by scoring premature stop codons in 621 publicly available, full-length, molecular clone sequences derived from patients...
2016: PloS One
Timokratis Karamitros, Dimitrios Paraskevis, Angelos Hatzakis, Mina Psichogiou, Ioannis Elefsiniotis, Tara Hurst, Anna-Maria Geretti, Apostolos Beloukas, John Frater, Paul Klenerman, Aris Katzourakis, Gkikas Magiorkinis
Endogenous retroviruses (ERVs) comprise 6-8% of the human genome. HERVs are silenced in most normal tissues, up-regulated in stem cells and in placenta but also in cancer and HIV-1 infection. Crucially, there are conflicting reports on detecting HERV RNA in non-cellular clinical samples such as plasma that suggest the study of HERV RNA can be daunting. Indeed, we find that the use of real-time PCR in a quality assured clinical laboratory setting can be sensitive to low-level proviral contamination. We developed a mathematical model for low-level contamination that allowed us to design a laboratory protocol and standard operating procedures for robust measurement of HERV RNA...
2016: Scientific Reports
Ching-Lung Lai, Danny Wong, Philip Ip, Malgorzata Kopaniszen, Wai-Kay Seto, James Fung, Fung-Yu Huang, Brian Lee, Giuseppe Cullaro, Chun Kong Chong, Ringo Wu, Charles Cheng, John Yuen, Vincent Ngai, Man-Fung Yuen
BACKGROUND AND AIMS: Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA), a minichromosome essential for HBV replication, is supposed to be resistant to nucleos(t)ide analogue treatment. We investigated the effect of long-term nucleos(t)ide analogue treatment on cccDNA. METHODS: Among 129 patients who had been enrolled in previous international nucleos(t)ide analogue clinical trials and had liver biopsies at baseline and one year after treatment, we recruited 43 patients on long-term continuous treatment for 72 to 145 months for a third liver biopsy...
September 14, 2016: Journal of Hepatology
Slim Fourati, Jean-Michel Pawlotsky
Hepatitis B virus (HBV) infects approximately 240 million individuals worldwide. Recent advances in the virology, immunopathogenesis, and diagnosis of HBV infection are summarized in this review article. The identification of a hepatocyte-specific cellular receptor for HBV, the sodium taurocholate co-transporting polypeptide (NTCP), made it possible to develop reliable cell culture systems and better understand the early steps of the viral lifecycle. Viral and host factors involved in covalently closed circular DNA synthesis, stability, and transcriptional regulation have also been identified and provide potential targets for new drugs...
2016: F1000Research
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