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McFadden WM, Sarafianos SG. Biology of the hepatitis B virus (HBV) core and capsid assembly modulators (CAMs) for chronic hepatitis B (CHB) cure. Glob Health Med 2023; 5:199-207. [PMID: 37655181 PMCID: PMC10461335 DOI: 10.35772/ghm.2023.01065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Revised: 06/03/2023] [Accepted: 06/30/2023] [Indexed: 09/02/2023]
Abstract
Hepatitis B virus (HBV) is a hepadnavirus, a small DNA virus that infects liver tissue, with some unusual replication steps that share similarities to retroviruses. HBV infection can lead to chronic hepatitis B (CHB), a life-long infection associated with significant risks of liver disease, especially if untreated. HBV is a significant global health problem, with hundreds of millions currently living with CHB. Currently approved strategies to prevent or inhibit HBV are highly effective, however, a cure for CHB has remained elusive. To achieve a cure, elimination of the functionally integrated HBV covalently closed chromosomal DNA (cccDNA) genome is required. The capsid core is an essential component of HBV replication, serving roles when establishing infection and in creating new virions. Over the last two and a half decades, significant efforts have been made to find and characterize antivirals that target the capsid, specifically the HBV core protein (Cp). The antivirals that interfere with the kinetics and morphology of the capsid, termed capsid assembly modulators (CAMs), are extremely potent, and clinical investigations indicate they are well tolerated and highly effective. Several CAMs offer the potential to cure CHB by decreasing the cccDNA pools. Here, we review the biology of the HBV capsid, focused on Cp, and the development of inhibitors that target it.
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Affiliation(s)
- William M. McFadden
- Center for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA
- Children's Healthcare of Atlanta, Atlanta, GA, USA
| | - Stefan G. Sarafianos
- Center for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA
- Children's Healthcare of Atlanta, Atlanta, GA, USA
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Fazlalipour M, Ghoreshi ZAS, Molaei HR, Arefinia N. The Role of DNA Viruses in Human Cancer. Cancer Inform 2023; 22:11769351231154186. [PMID: 37363356 PMCID: PMC10286548 DOI: 10.1177/11769351231154186] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Accepted: 01/03/2023] [Indexed: 06/28/2023] Open
Abstract
This review discusses the possible involvement of infections-associated cancers in humans, with virus infections contributing 15% to 20% of total cancer cases in humans. DNA virus encoded proteins interact with host cellular signaling pathways and control proliferation, cell death and genomic integrity viral oncoproteins are known to bind cellular Deubiquitinates (DUBs) such as cyclindromatosis tumor suppressor, ubiquitin-specific proteases 7, 11, 15 and 20, and A-20 to improve their intracellular stability and cellular signaling pathways and finally transformation. Human papillomaviruses (cervical carcinoma, oral cancer and laryngeal cancer); human polyomaviruses (mesotheliomas, brain tumors); Epstein-Barr virus (B-cell lymphoproliferative diseases and nasopharyngeal carcinoma); Kaposi's Sarcoma Herpesvirus (Kaposi's Sarcoma and primary effusion lymphomas); hepatitis B (hepatocellular carcinoma (HCC)) cause up to 20% of malignancies around the world.
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Affiliation(s)
- Mehdi Fazlalipour
- WHO Collaborating Center for Reference and Research on Rabies, Pasteur Institute of Iran (IPI), Tehran, Iran
- Research Center for Emerging and Reemerging Infectious diseases, Pasteur Institute of Iran (IPI), Tehran, Iran
| | | | - Hamid Reza Molaei
- Department of Medical Bacteriology and Virology, Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | - Nasir Arefinia
- Student Research Committee, Jiroft University of Medical Sciences, Jiroft, Iran
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Bezerra CS, Portilho MM, Barbosa JR, de Azevedo CP, Mendonça ACDF, da Cruz JNM, Frota CC, do Lago BV, Villar LM. Dried blood spot sampling for hepatitis B virus quantification, sequencing and mutation detection. Sci Rep 2022; 12:1651. [PMID: 35102169 PMCID: PMC8803841 DOI: 10.1038/s41598-022-05264-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Accepted: 01/10/2022] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) diagnosis is performed on serum samples, but the access to this diagnosis is difficult in low-income regions. The use of dried blood spot (DBS) samples does not require special structure for collection, storage or transport. This study evaluates the use of DBS for detection, quantification and sequencing of HBV DNA using in-house techniques. Two study groups were included: 92 HBsAg + individuals and 49 negative controls. Serum and DBS samples were submitted to quantitative and qualitative in-house PCR for S/pol genes, sequencing and phylogenetic analyses. Total of 84 serum samples were successfully amplified. Of them, 63 paired DBS were also positive in qualitative PCR. Qualitative PCR in DBS presented a sensitivity of 75% and specificity of 100% (Kappa = 0.689). Quantitative PCR in DBS presented a detection limit of 852.5 copies/mL (250 IU/mL), sensitivity of 77.63% and specificity of 100% (Kappa = 0.731). A total of 63 serum samples and 36 DBS samples were submitted to sequencing, revealing the circulation of genotypes A (65.08%), D (4.8%), E (3.2%) and F (27%) with 100% of correspondence between serum and DBS. All sequenced samples displayed polymorphisms in HBsAg gene. An HIV-coinfected patient presented the rtM204V/I-rtL180M double resistance mutation in serum and DBS. In conclusion, DBS is an alternative to detect, quantify and characterize HBV DNA, being a possibility of increasing diagnosis in low-income settings, closing gaps in HBV control.
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Milestones in Hepatology. Ann Hepatol 2021; 21:100324. [PMID: 33640104 DOI: 10.1016/j.aohep.2021.100324] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Accepted: 01/27/2021] [Indexed: 02/04/2023]
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Prifti GM, Moianos D, Giannakopoulou E, Pardali V, Tavis JE, Zoidis G. Recent Advances in Hepatitis B Treatment. Pharmaceuticals (Basel) 2021; 14:417. [PMID: 34062711 PMCID: PMC8147224 DOI: 10.3390/ph14050417] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 04/22/2021] [Accepted: 04/23/2021] [Indexed: 01/10/2023] Open
Abstract
Hepatitis B virus infection affects over 250 million chronic carriers, causing more than 800,000 deaths annually, although a safe and effective vaccine is available. Currently used antiviral agents, pegylated interferon and nucleos(t)ide analogues, have major drawbacks and fail to completely eradicate the virus from infected cells. Thus, achieving a "functional cure" of the infection remains a real challenge. Recent findings concerning the viral replication cycle have led to development of novel therapeutic approaches including viral entry inhibitors, epigenetic control of cccDNA, immune modulators, RNA interference techniques, ribonuclease H inhibitors, and capsid assembly modulators. Promising preclinical results have been obtained, and the leading molecules under development have entered clinical evaluation. This review summarizes the key steps of the HBV life cycle, examines the currently approved anti-HBV drugs, and analyzes novel HBV treatment regimens.
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Affiliation(s)
- Georgia-Myrto Prifti
- Department of Pharmacy, Division of Pharmaceutical Chemistry, School of Health Sciences, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, 15771 Athens, Greece; (G.-M.P.); (D.M.); (E.G.); (V.P.)
| | - Dimitrios Moianos
- Department of Pharmacy, Division of Pharmaceutical Chemistry, School of Health Sciences, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, 15771 Athens, Greece; (G.-M.P.); (D.M.); (E.G.); (V.P.)
| | - Erofili Giannakopoulou
- Department of Pharmacy, Division of Pharmaceutical Chemistry, School of Health Sciences, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, 15771 Athens, Greece; (G.-M.P.); (D.M.); (E.G.); (V.P.)
| | - Vasiliki Pardali
- Department of Pharmacy, Division of Pharmaceutical Chemistry, School of Health Sciences, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, 15771 Athens, Greece; (G.-M.P.); (D.M.); (E.G.); (V.P.)
| | - John E. Tavis
- Molecular Microbiology and Immunology, Saint Louis University, Saint Louis, MO 63104, USA;
| | - Grigoris Zoidis
- Department of Pharmacy, Division of Pharmaceutical Chemistry, School of Health Sciences, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, 15771 Athens, Greece; (G.-M.P.); (D.M.); (E.G.); (V.P.)
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Tompa DR, Immanuel A, Srikanth S, Kadhirvel S. Trends and strategies to combat viral infections: A review on FDA approved antiviral drugs. Int J Biol Macromol 2021; 172:524-541. [PMID: 33454328 PMCID: PMC8055758 DOI: 10.1016/j.ijbiomac.2021.01.076] [Citation(s) in RCA: 131] [Impact Index Per Article: 32.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Revised: 01/10/2021] [Accepted: 01/12/2021] [Indexed: 12/12/2022]
Abstract
The infectious microscopic viruses invade living cells to reproduce themselves, and causes chronic infections such as HIV/AIDS, hepatitis B and C, flu, etc. in humans which may lead to death if not treated. Different strategies have been utilized to develop new and superior antiviral drugs to counter the viral infections. The FDA approval of HIV nucleoside reverse transcriptase inhibitor, zidovudine in 1987 boosted the development of antiviral agents against different viruses. Currently, there are a number of combination drugs developed against various viral infections to arrest the activity of same or different viral macromolecules at multiple stages of its life cycle; among which majority are targeted to interfere with the replication of viral genome. Besides these, other type of antiviral molecules includes entry inhibitors, integrase inhibitors, protease inhibitors, interferons, immunomodulators, etc. The antiviral drugs can be toxic to human cells, particularly in case of administration of combination drugs, and on the other hand viruses can grow resistant to the antiviral drugs. Furthermore, emergence of new viruses like Ebola, coronaviruses (SARS-CoV, SARS-CoV-2) emphasizes the need for more innovative strategies to develop better antiviral drugs to fight the existing and the emerging viral infections. Hence, we reviewed the strategic enhancements in developing antiviral drugs for the treatment of different viral infections over the years.
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Affiliation(s)
- Dharma Rao Tompa
- Biomolecular Crystallography Laboratory, Department of Bioinformatics, School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur 613 401, Tamil Nadu, India
| | - Aruldoss Immanuel
- Biomolecular Crystallography Laboratory, Department of Bioinformatics, School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur 613 401, Tamil Nadu, India
| | - Srimari Srikanth
- Biomolecular Crystallography Laboratory, Department of Bioinformatics, School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur 613 401, Tamil Nadu, India
| | - Saraboji Kadhirvel
- Biomolecular Crystallography Laboratory, Department of Bioinformatics, School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur 613 401, Tamil Nadu, India.
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Patton LL. Viral pandemics and oral health: Lessons learned from HIV to SARS-CoV-2. Oral Surg Oral Med Oral Pathol Oral Radiol 2021; 131:149-153. [PMID: 33309265 PMCID: PMC7642737 DOI: 10.1016/j.oooo.2020.10.022] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2020] [Accepted: 10/26/2020] [Indexed: 01/06/2023]
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Therapeutic potential of bicyclol in liver diseases: Lessons from a synthetic drug based on herbal derivative in traditional Chinese medicine. Int Immunopharmacol 2020; 91:107308. [PMID: 33383448 DOI: 10.1016/j.intimp.2020.107308] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2020] [Revised: 12/06/2020] [Accepted: 12/14/2020] [Indexed: 12/19/2022]
Abstract
Bicyclol, an innovative chemical drug with proprietary intellectual property rights in China, is based on derivative of traditional Chinese medicine (TCM) Schisandra chinensis (Wuweizi) of North. Mounting data has proved that bicyclol has therapeutic potential in various pathological conditions in liver. In this narrative review, we provide the first summary of pharmacological activities, pharmacokinetic characteristics and toxicity of bicyclol, and discuss future research perspectives. Our results imply that bicyclol has a wide spectrum of pharmacological properties, including anti-viral, anti-inflammatory, immuno-regulatory, anti-oxidative, antisteatotic, anti-fibrotic, antitumor, cell death regulatory effects and modulation of heat shock proteins. Pharmacokinetic studies have indicated that bicyclol is the main substrate of CYP3A/2E1. Additionally, no obvious drug interactions have been found when bicyclol is administered simultaneously with other prescriptions. Furthermore, the results of chronic toxicity have strongly addressed that bicyclol has no noticeable toxic effects on all biochemical indices and pathological examinations of the main organs. In view of good pharmacological actions and safety, bicyclol is anticipated to be a potential candidate for various liver diseases, including acute liver injury, fulminant hepatitis, non-alcoholic fatty liver disease, fibrosis and hepatocellular carcinoma. Further studies are therefore required to delineate its molecular mechanisms and targets to confer this well-designed drug a far greater potency. We hope that bicyclol-based therapeutics for liver diseases might be broadly used in clinical practice worldwide.
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Choga WT, Anderson M, Zumbika E, Phinius BB, Mbangiwa T, Bhebhe LN, Baruti K, Kimathi PO, Seatla KK, Musonda RM, Bell TG, Moyo S, Blackard JT, Gaseitsiwe S. In Silico Prediction of Human Leukocytes Antigen (HLA) Class II Binding Hepatitis B Virus (HBV) Peptides in Botswana. Viruses 2020; 12:E731. [PMID: 32640609 PMCID: PMC7412261 DOI: 10.3390/v12070731] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Accepted: 07/03/2020] [Indexed: 02/07/2023] Open
Abstract
Hepatitis B virus (HBV) is the primary cause of liver-related malignancies worldwide, and there is no effective cure for chronic HBV infection (CHB) currently. Strong immunological responses induced by T cells are associated with HBV clearance during acute infection; however, the repertoire of epitopes (epi) presented by major histocompatibility complexes (MHCs) to elicit these responses in various African populations is not well understood. In silico approaches were used to map and investigate 15-mers HBV peptides restricted to 9 HLA class II alleles with high population coverage in Botswana. Sequences from 44 HBV genotype A and 48 genotype D surface genes (PreS/S) from Botswana were used. Of the 1819 epi bindings predicted, 20.2% were strong binders (SB), and none of the putative epi bind to all the 9 alleles suggesting that multi-epitope, genotype-based, population-based vaccines will be more effective against HBV infections as opposed to previously proposed broad potency epitope-vaccines which were assumed to work for all alleles. In total, there were 297 unique epi predicted from the 3 proteins and amongst, S regions had the highest number of epi (n = 186). Epitope-densities (Depi) between genotypes A and D were similar. A number of mutations that hindered HLA-peptide binding were observed. We also identified antigenic and genotype-specific peptides with characteristics that are well suited for the development of sensitive diagnostic kits. This study identified candidate peptides that can be used for developing multi-epitope vaccines and highly sensitive diagnostic kits against HBV infection in an African population. Our results suggest that viral variability may hinder HBV peptide-MHC binding, required to initiate a cascade of immunological responses against infection.
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Affiliation(s)
- Wonderful Tatenda Choga
- Research Laboratory, Botswana Harvard AIDS Institute Partnership, Gaborone 0000, Botswana; (W.T.C.); (M.A.); (B.B.P.); (T.M.); (L.N.B.); (K.B.); (K.K.S.); (R.M.M.); (S.M.)
- Division of Human Genetics, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa
| | - Motswedi Anderson
- Research Laboratory, Botswana Harvard AIDS Institute Partnership, Gaborone 0000, Botswana; (W.T.C.); (M.A.); (B.B.P.); (T.M.); (L.N.B.); (K.B.); (K.K.S.); (R.M.M.); (S.M.)
| | - Edward Zumbika
- Department of Applied Biology and Biochemistry, Faculty of Applied Sciences, National University of Science and Technology, Bulawayo 0000, Zimbabwe;
| | - Bonolo B. Phinius
- Research Laboratory, Botswana Harvard AIDS Institute Partnership, Gaborone 0000, Botswana; (W.T.C.); (M.A.); (B.B.P.); (T.M.); (L.N.B.); (K.B.); (K.K.S.); (R.M.M.); (S.M.)
| | - Tshepiso Mbangiwa
- Research Laboratory, Botswana Harvard AIDS Institute Partnership, Gaborone 0000, Botswana; (W.T.C.); (M.A.); (B.B.P.); (T.M.); (L.N.B.); (K.B.); (K.K.S.); (R.M.M.); (S.M.)
- Division of Human Genetics, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa
| | - Lynnette N. Bhebhe
- Research Laboratory, Botswana Harvard AIDS Institute Partnership, Gaborone 0000, Botswana; (W.T.C.); (M.A.); (B.B.P.); (T.M.); (L.N.B.); (K.B.); (K.K.S.); (R.M.M.); (S.M.)
| | - Kabo Baruti
- Research Laboratory, Botswana Harvard AIDS Institute Partnership, Gaborone 0000, Botswana; (W.T.C.); (M.A.); (B.B.P.); (T.M.); (L.N.B.); (K.B.); (K.K.S.); (R.M.M.); (S.M.)
- Department of Biological Sciences, Faculty of Science, University of Botswana, Gaborone 0000, Botswana
| | | | - Kaelo K. Seatla
- Research Laboratory, Botswana Harvard AIDS Institute Partnership, Gaborone 0000, Botswana; (W.T.C.); (M.A.); (B.B.P.); (T.M.); (L.N.B.); (K.B.); (K.K.S.); (R.M.M.); (S.M.)
- Department of Medical Laboratory Sciences, Faculty of Health Sciences, University of Botswana, Gaborone 0000, Botswana
| | - Rosemary M. Musonda
- Research Laboratory, Botswana Harvard AIDS Institute Partnership, Gaborone 0000, Botswana; (W.T.C.); (M.A.); (B.B.P.); (T.M.); (L.N.B.); (K.B.); (K.K.S.); (R.M.M.); (S.M.)
- Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
| | - Trevor Graham Bell
- Independent Researcher, P.O. Box 497, Wits, Johannesburg 2050, South Africa;
| | - Sikhulile Moyo
- Research Laboratory, Botswana Harvard AIDS Institute Partnership, Gaborone 0000, Botswana; (W.T.C.); (M.A.); (B.B.P.); (T.M.); (L.N.B.); (K.B.); (K.K.S.); (R.M.M.); (S.M.)
- Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
| | - Jason T. Blackard
- Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA;
| | - Simani Gaseitsiwe
- Research Laboratory, Botswana Harvard AIDS Institute Partnership, Gaborone 0000, Botswana; (W.T.C.); (M.A.); (B.B.P.); (T.M.); (L.N.B.); (K.B.); (K.K.S.); (R.M.M.); (S.M.)
- Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
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Smith-Palmer J, Cerri K, Sbarigia U, Chan EKH, Pollock RF, Valentine WJ, Bonroy K. Impact of Stigma on People Living with Chronic Hepatitis B. PATIENT-RELATED OUTCOME MEASURES 2020; 11:95-107. [PMID: 32214859 PMCID: PMC7082540 DOI: 10.2147/prom.s226936] [Citation(s) in RCA: 48] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/12/2019] [Accepted: 02/14/2020] [Indexed: 12/17/2022]
Abstract
Background People with chronic infectious diseases such as hepatitis B can face stigma, which can influence everyday life as well as willingness to engage with medical professionals or disclose disease status. A systematic literature review was performed to characterize the level and type of stigma experienced by people infected with hepatitis B virus (HBV) as well as to identify instruments used to measure it. Methods A literature review was performed using the PubMed, Embase and Cochrane Library databases to identify studies describing HBV-related stigma. For inclusion, articles were required to be published in full-text form, in English and report quantitative or qualitative data on HBV-related stigma that could be extracted. Results A total of 23 (17 quantitative and 6 qualitative) articles examined HBV-related stigma. The scope of the review was global but nearly all identified studies were conducted in countries in the WHO Southeast Asia or Western Pacific regions or within immigrant communities in North America. Several quantitative studies utilized tools specifically designed to assess aspects of stigma. Qualitative studies were primarily conducted via patient interviews. Internalized and social stigma were common among people living with chronic HBV . Some people also perceived structural/institutional stigma, with up to 20% believing that they may be denied healthcare and up to 30% stating they may experience workplace discrimination due to HBV. Conclusion HBV-related stigma is common, particularly in some countries in Southeast Asia and the Western Pacific region and among Asian immigrant communities, but is poorly characterized in non-Asian populations. Initiatives are needed to document and combat stigma (particularly in settings/jurisdictions where it is poorly described) as well as its clinical and socioeconomic consequences.
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Affiliation(s)
- Stewart Sell
- Wadsworth Center, New York State Department of Health, Empire State Plaza, Albany, NY, USA
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12
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Sato N, Watanabe S, Miura K, Goka R, Morimoto N, Takaoka Y, Nomoto H, Tsukui M, Isoda N, Nagashima S, Takahashi M, Okamoto H, Yamamoto H. Acute Liver Failure Caused by the Transmission of Hepatitis B Virus from the Spouse after 38 Years of Marriage. Intern Med 2019; 58:2963-2968. [PMID: 31243227 PMCID: PMC6859391 DOI: 10.2169/internalmedicine.3028-19] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
A 65-year-old man presented with acute liver failure and grade IV coma caused by hepatitis B virus (HBV) infection in 2017. The patient died on day 12 from the disease onset. The HBV isolated from the patient was genotype/subgenotype B/B1 and had multiple genomic mutations. The patient's wife was hepatitis B surface antigen (HBsAg)-positive when she delivered her first daughter in 1979. The HBV isolates of the patient and the wife shared 100% similarity over the entire genome. Because the patient's HBsAg value had been negative one year earlier, we considered the source of HBV transmission to be his wife.
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Affiliation(s)
- Naoto Sato
- Division of Gastroenterology, Department of Medicine, Jichi Medical University, Japan
| | - Shunji Watanabe
- Division of Gastroenterology, Department of Medicine, Jichi Medical University, Japan
| | - Kouichi Miura
- Division of Gastroenterology, Department of Medicine, Jichi Medical University, Japan
| | - Rie Goka
- Division of Gastroenterology, Department of Medicine, Jichi Medical University, Japan
| | - Naoki Morimoto
- Division of Gastroenterology, Department of Medicine, Jichi Medical University, Japan
| | - Yoshinari Takaoka
- Division of Gastroenterology, Department of Medicine, Jichi Medical University, Japan
| | - Hiroaki Nomoto
- Division of Gastroenterology, Department of Medicine, Jichi Medical University, Japan
| | - Mamiko Tsukui
- Division of Gastroenterology, Department of Medicine, Jichi Medical University, Japan
| | - Norio Isoda
- Division of Gastroenterology, Department of Medicine, Jichi Medical University, Japan
| | - Shigeo Nagashima
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Japan
| | - Masaharu Takahashi
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Japan
| | - Hiroaki Okamoto
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Japan
| | - Hironori Yamamoto
- Division of Gastroenterology, Department of Medicine, Jichi Medical University, Japan
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The association of lncRNA-HULC polymorphisms with hepatocellular cancer risk and prognosis. Gene 2018; 670:148-154. [PMID: 29803923 DOI: 10.1016/j.gene.2018.05.096] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2018] [Revised: 05/10/2018] [Accepted: 05/23/2018] [Indexed: 02/09/2023]
Abstract
BACKGROUND Genetic polymorphisms in lncRNA HULC may affect the susceptibility and clinical outcome of cancer. We aimed to investigate the association of HULC tagSNPs with the risk and prognosis of hepatocellular cancer, as well as the influence of the SNPs on lncRNA expression level. METHODS A total of 1338 samples were recruited in the risk study. Among them, 351 HCC patients were involved in the prognosis study. SNP genotyping was performed using KASP method and lncRNA expression was detected by Real-time PCR. RESULTS We found a promoter SNP, rs1041279, was associated with a 1.41-fold increased HCC risk (P = 0.032). In the stratified analysis, rs1041279 had greater ORs for the increased HCC risk in the male subgroup (P = 0.014, OR = 1.54). Furthermore, multi-logistic regression analysis revealed a two-way interaction effect of smoking-rs2038540 SNP on HCC risk (OR = 4.20). And MDR analysis consistently demonstrated a SNP-environmental interaction among smoking-drinking-rs2038540 SNP as the best model for predicting HCC risk (P = 0.0107). In our study, no significant association was found between HULC SNPs and the overall survival (P > 0.05), and no significant effect was observed of rs1041279 SNP on lncRNA-HULC expression (P > 0.05). CONCLUSION lncRNA-HULC rs1041279 SNP and the interaction of rs2038540 SNP with environmental factors could enhance HCC risk.
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Dusheiko G. Current and future directions of management of hepatitis B: steps toward a cure. Future Virol 2018. [DOI: 10.2217/fvl-2017-0103] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Universal hepatitis B virus vaccination has been effective in reducing incident chronic hepatitis B but will not have the requisite effect on the prevalence of end-stage liver disease in chronically infected persons. The natural history and immunological stages of hepatitis B virus infection are still being defined. Over three decades, current therapies have reduced morbidity from chronic hepatitis B. The majority require nucleoside analog maintenance therapy. The preferential preservation of covalently closed circular DNA (cccDNA), and capsid reverse transcriptase–cccDNA interactions currently precludes cure in most. A functional cure in the host may require several synergistic antiviral and immunological intercessions. The correct sequencing and combinations of treatment with either host or viral targeting agents have yet to be determined. Proven surrogates for cccDNA for clinical trials are required. Different strategies may become apparent for patients at different stages of the disease. Curative therapies will require affordability. This review focuses on steps toward a cure.
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Affiliation(s)
- Geoffrey Dusheiko
- Kings College Hospital & University College London Medical School, Denmark Hill, London SE5 9RS, UK
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Taheri Ezbarami Z, Hassani P, Zagheri Tafreshi M, Alavi Majd H. A qualitative study on individual experiences of chronic hepatitis B patients. Nurs Open 2017; 4:310-318. [PMID: 29085657 PMCID: PMC5653392 DOI: 10.1002/nop2.100] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2016] [Accepted: 08/29/2017] [Indexed: 12/26/2022] Open
Abstract
Aim The aim of this study was to explain the perception of patients with chronic hepatitis B regarding problems in the Iranian society. Design Descriptive qualitative research. Methods In this qualitative study, 27 patients with chronic hepatitis B in Iran were selected through purposive sampling. The data were collected over 22 months, in 2015–2016, by means of semi‐structured interviews and field notes. The interview transcripts were coded using MAXQDA10 software®. To extract categories and themes, the thematic analysis approach was used. Results The participants’ age ranged from 25–52 years. Analysis of the data revealed seven themes: insufficient self‐care, misperceptions, stigmatization, psychological consequences, failure, spiritual struggle and post‐traumatic growth.
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Affiliation(s)
- Zahra Taheri Ezbarami
- School of Nursing and Midwifery Shahid Beheshti University of Medical Sciences TehranIran
| | - Parkhideh Hassani
- School of Nursing and Midwifery Shahid Beheshti University of Medical Sciences TehranIran
| | | | - Hamid Alavi Majd
- School of Paramedical Sciences Faculty of Paramedical Sciences Department of Biostatistics Shahid Beheshti University of Medical Sciences TehranIran
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16
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Haban H, Benchekroun S, Sadeq M, Benjouad A, Amzazi S, Oumzil H, Elharti E. Assessment of the HBV vaccine response in a group of HIV-infected children in Morocco. BMC Public Health 2017; 17:752. [PMID: 28962610 PMCID: PMC5622525 DOI: 10.1186/s12889-017-4776-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2017] [Accepted: 09/20/2017] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND Since its development in the early 1980s, Hepatitis B virus (HBV) vaccine has been proven to be highly protective. However, its immunogenicity may be ineffective among HIV-infected children. In Morocco, HBV vaccine was introduced in 1999, and since then all infants, including vertically HIV-infected infants, have been following the vaccination schedule, implemented by the Moroccan ministry of health. An assessment of the immunization of these children is important to optimize efforts aimed at tackling Hepatitis B coinfection, within the country. METHODS Forty-nine HIV-infected children (HIV group) and 112 HIV uninfected children (control group) were enrolled in this study. Samples were tested by Elisa (Monolisa Anti-HBs, Biorad) to quantify the anti-HBs antibodies. The % of lymphocyte subsets i.e. CD4+ T cells, CD8+ T cells, B cells, and NK, was determined by flow cytometry, using CellQuest Pro software (Becton-Dickinson), and for HIV group, HIV viral load was measured by real time PCR assay (Abbott). All variables were statistically compared in the two groups. RESULTS The median age was 51 ± 35 months for the HIV group and 50 ± 36 months (p > 0.05) for the control group. Female represented 63% and 41% (p = 0.01), among the HIV group and the control group, respectively. Among HIV-infected children, 71.4% (35/49) were under HAART therapy at the enrollment in the study. Seroprotection titer i.e. anti-HBs ≥10mUI/ml among control group was 76% (85/112), and only 29% (14/49) among the perinatally HIV-infected children (p < 0.0001). Lower % of CD4 + T cells was observed in HIV-infected children with a poor anti-HBs response. CONCLUSION In this studied group, we have shown that despite the vaccination of HIV-children with HBV vaccine, 71% did not show any seroprotective response. These findings support the need for monitoring HBV vaccine response among HIV-infected children in Morocco, in order to revaccinate non-immunized children.
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Affiliation(s)
- Houda Haban
- National Reference Laboratory for HIV, Department of Virology, National Institute of Hygiene, Rabat, Morocco.,Immunology-Biochemistry Laboratory, Faculty of Sciences, University Mohammed Vth, Rabat, Morocco
| | - Soumia Benchekroun
- Pediatric Infectious Disease Clinic, Ibn Sina University Hospital, Rabat, Morocco
| | - Mina Sadeq
- Environmental Epidemiology Unit, National Institute of Hygiene, Rabat, Morocco
| | | | - Said Amzazi
- Immunology-Biochemistry Laboratory, Faculty of Sciences, University Mohammed Vth, Rabat, Morocco
| | - Hicham Oumzil
- National Reference Laboratory for HIV, Department of Virology, National Institute of Hygiene, Rabat, Morocco
| | - Elmir Elharti
- National Reference Laboratory for HIV, Department of Virology, National Institute of Hygiene, Rabat, Morocco.
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17
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Abstract
PURPOSE OF REVIEW A major focus in HIV vaccine research is the development of suitable antigens that elicit broadly neutralizing antibody responses targeting HIV's envelope protein (Env). Delivery of Env in a repetitive manner on particle-based carriers allows higher avidity interactions and is therefore expected to efficiently engage B cells, thus leading to affinity maturation that results in superior antibody responses characterized by improved breadth, potency, and durability. This review summarizes current work that is evaluating diverse types of such particulate carriers for Env delivery. RECENT FINDINGS Various types of particle scaffolds are being investigated, encompassing group-specific antigen-derived virus-like particles, bacteria-derived proteins that self-assemble into symmetrical nanoparticles, as well as liposomes assembled from membrane components and recombinantly produced Env isoforms. Env-derived antigens from peptides over selected isolates to improved, stabilized next-generation designer Envs have been attached to such carriers. Immunological evaluation in animal models showed that these structures often elicit superior humoral immune responses. SUMMARY The findings reviewed here emphasize the potential of particle-based delivery modalities to elicit better antibody responses. Together with advances in Env antigen design, these approaches may synergistically act together on the way to obtain vaccine candidates that potentially induce protective immune responses against HIV.
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18
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Wei X, Wang JP, Hao CQ, Yang XF, Wang LX, Huang CX, Bai XF, Lian JQ, Zhang Y. Notch Signaling Contributes to Liver Inflammation by Regulation of Interleukin-22-Producing Cells in Hepatitis B Virus Infection. Front Cell Infect Microbiol 2016; 6:132. [PMID: 27800305 PMCID: PMC5065963 DOI: 10.3389/fcimb.2016.00132] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2016] [Accepted: 09/29/2016] [Indexed: 12/28/2022] Open
Abstract
The mechanism of hepatitis B virus (HBV) induced liver inflammation is not fully elucidated. Notch signaling augmented interleukin (IL)-22 secretion in CD4+ T cells, and Notch-IL-22 axis fine-tuned inflammatory response. We previously demonstrated a proinflammatory role of IL-22 in HBV infection. Thus, in this study, we analyzed the role of Notch in development of IL-22-producing cells in HBV infection by inhibition of Notch signaling using γ-secretase inhibitor DAPT in both hydrodynamic induced HBV-infected mouse model and in peripheral blood cells isolated from patients with HBV infection. mRNA expressions of Notch1 and Notch2 were significantly increased in livers and CD4+ T cells upon HBV infection. Inhibition of Notch signaling in vivo leaded to the reduction in NKp46+ innate lymphoid cells 22 (ILC22) and lymphoid tissue inducer 4 (LTi4) cells in the liver. This process was accompanied by downregulating the expressions of IL-22 and related proinflammatory cytokines and chemokines in the liver, as well as blocking the recruitment of antigen-non-specific inflammatory cells into the liver and subsequent liver injury, but did not affect HBV antigens production and IL-22 secretion in the serum. Furthermore, IL-22 production in HBV non-specific cultured CD4+ T cells, but not HBV-specific CD4+ T cells, was reduced in response to in vitro inhibition of Notch signaling. In conclusion, Notch siganling appears to be an important mediator of the liver inflammation by modulating hepatic ILC22. The potential proinflammatory effect of Notch-mediated ILC22 may be significant for the development of new therapeutic approaches for treatment of hepatitis B.
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Affiliation(s)
- Xin Wei
- Center for Infectious Diseases, Tangdu Hospital, Fourth Military Medical UniversityXi'an, China
| | - Jiu-Ping Wang
- Department of Infectious Diseases, Xijing Hospital, Fourth Military Medical UniversityXi'an, China
| | - Chun-Qiu Hao
- Center for Infectious Diseases, Tangdu Hospital, Fourth Military Medical UniversityXi'an, China
| | - Xiao-Fei Yang
- Center for Infectious Diseases, Tangdu Hospital, Fourth Military Medical UniversityXi'an, China
| | - Lin-Xu Wang
- Center for Infectious Diseases, Tangdu Hospital, Fourth Military Medical UniversityXi'an, China
| | - Chang-Xing Huang
- Center for Infectious Diseases, Tangdu Hospital, Fourth Military Medical UniversityXi'an, China
| | - Xue-Fan Bai
- Center for Infectious Diseases, Tangdu Hospital, Fourth Military Medical UniversityXi'an, China
| | - Jian-Qi Lian
- Center for Infectious Diseases, Tangdu Hospital, Fourth Military Medical UniversityXi'an, China
| | - Ye Zhang
- Center for Infectious Diseases, Tangdu Hospital, Fourth Military Medical UniversityXi'an, China
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19
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Hadziyannis SJ. Predicting Outcomes of Patients With Chronic Hepatitis B Virus Infection Based on Quantification of the Hepatitis B Surface Antigen. Clin Gastroenterol Hepatol 2016; 14:1499-501. [PMID: 27339695 DOI: 10.1016/j.cgh.2016.06.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2016] [Revised: 06/15/2016] [Accepted: 06/15/2016] [Indexed: 02/07/2023]
Affiliation(s)
- Stephanos J Hadziyannis
- Second Department of Medicine of the School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
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20
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Gentile G, Micozzi A. Speculations on the clinical significance of asymptomatic viral infections. Clin Microbiol Infect 2016; 22:585-8. [PMID: 27450587 DOI: 10.1016/j.cmi.2016.07.016] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2016] [Revised: 07/01/2016] [Accepted: 07/05/2016] [Indexed: 12/12/2022]
Abstract
A detailed understanding of asymptomatic chronic viral infections is critical to analyse their pathogenesis, assess the severity and burden of disease and, where required, optimize public health control measures. Recent studies on herpesviruses showed that the host-virus interactions are modulated by co-infections, emphasizing the relevance of co-infections in determining the clinical expression (from asymptomatic to symptomatic infections) and the severity of herpesvirus-associated diseases (either neoplastic or infectious diseases). To demonstrate causality between viruses (virome) and diseases, Koch's postulates should be adapted adding new knowledge on host-microbe relationship and microbial interactions. In the present review we aim to provide an update on asymptomatic chronic infections and criteria for causality and on the virological, immunological and host-virus interactions in asymptomatic chronic infections in human hosts, focusing on herpetic infections.
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Affiliation(s)
- G Gentile
- Department of Cellular Biotechnologies and Haematology, Sapienza University, Rome, Italy.
| | - A Micozzi
- Department of Cellular Biotechnologies and Haematology, Sapienza University, Rome, Italy
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21
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Abstract
Since the first antiviral drug, idoxuridine, was approved in 1963, 90 antiviral drugs categorized into 13 functional groups have been formally approved for the treatment of the following 9 human infectious diseases: (i) HIV infections (protease inhibitors, integrase inhibitors, entry inhibitors, nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, and acyclic nucleoside phosphonate analogues), (ii) hepatitis B virus (HBV) infections (lamivudine, interferons, nucleoside analogues, and acyclic nucleoside phosphonate analogues), (iii) hepatitis C virus (HCV) infections (ribavirin, interferons, NS3/4A protease inhibitors, NS5A inhibitors, and NS5B polymerase inhibitors), (iv) herpesvirus infections (5-substituted 2'-deoxyuridine analogues, entry inhibitors, nucleoside analogues, pyrophosphate analogues, and acyclic guanosine analogues), (v) influenza virus infections (ribavirin, matrix 2 protein inhibitors, RNA polymerase inhibitors, and neuraminidase inhibitors), (vi) human cytomegalovirus infections (acyclic guanosine analogues, acyclic nucleoside phosphonate analogues, pyrophosphate analogues, and oligonucleotides), (vii) varicella-zoster virus infections (acyclic guanosine analogues, nucleoside analogues, 5-substituted 2'-deoxyuridine analogues, and antibodies), (viii) respiratory syncytial virus infections (ribavirin and antibodies), and (ix) external anogenital warts caused by human papillomavirus infections (imiquimod, sinecatechins, and podofilox). Here, we present for the first time a comprehensive overview of antiviral drugs approved over the past 50 years, shedding light on the development of effective antiviral treatments against current and emerging infectious diseases worldwide.
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Affiliation(s)
- Erik De Clercq
- KU Leuven-University of Leuven, Rega Institute for Medical Research, Department of Microbiology and Immunology, Leuven, Belgium
| | - Guangdi Li
- KU Leuven-University of Leuven, Rega Institute for Medical Research, Department of Microbiology and Immunology, Leuven, Belgium Department of Metabolism and Endocrinology, Metabolic Syndrome Research Center, Key Laboratory of Diabetes Immunology, Ministry of Education, National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
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22
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Li W, Urban S. Entry of hepatitis B and hepatitis D virus into hepatocytes: Basic insights and clinical implications. J Hepatol 2016; 64:S32-S40. [PMID: 27084034 PMCID: PMC7114860 DOI: 10.1016/j.jhep.2016.02.011] [Citation(s) in RCA: 84] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2015] [Revised: 02/05/2016] [Accepted: 02/07/2016] [Indexed: 12/30/2022]
Abstract
For almost three decades following the discovery of the human Hepatitis B Virus (HBV) the early events of virus infection (attachment to hepatocytes, specific binding to a receptor on hepatocytes) remained enigmatic. The gradual improvement of tissue culture systems for HBV has enabled the identification of viral determinants for viral infectivity and facilitated the discovery of the human sodium taurocholate co-transporting polypeptide (hNTCP) as a liver specific receptor of HBV and its satellite, the human Hepatitis Delta Virus (HDV). These findings are currently leading basic and clinical research activities in new directions. (1) Stable hNTCP-expressing cell lines have become a valuable platform to study the full HBV replication cycle from its native template, the cccDNA. (2) The suitability of NTCP complemented cell culture systems for high throughput screening approaches will facilitate identification of novel host factors involved in HBV replication (including those that determine the peculiar host specificity of HBV infection) and will enable identification and development of novel drug candidates for improved therapeutics. (3) Since NTCP is a major host-specific restriction factor for HBV and HDV, hNTCP-expressing animals provide the basis for future susceptible in vivo models. (4) The concept obtained with the entry inhibitor Myrcludex B demonstrates that NTCP is a suitable target for clinical interference with viral entry. This will foster further clinical approaches aiming at curative combination therapies.
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Affiliation(s)
- Wenhui Li
- National Institute of Biological Sciences, Beijing 102206, China.
| | - Stephan Urban
- Department of Infectious Diseases, Molecular Virology, University Hospital Heidelberg, Im Neuenheimer Feld 345, D-69120 Heidelberg, Germany; German Center of Infectious Diseases (DZIF), Heidelberg, Germany.
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23
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Mazzanti R, Arena U, Tassi R. Hepatocellular carcinoma: Where are we? World J Exp Med 2016; 6:21-36. [PMID: 26929917 PMCID: PMC4759352 DOI: 10.5493/wjem.v6.i1.21] [Citation(s) in RCA: 94] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2015] [Revised: 12/14/2015] [Accepted: 01/05/2016] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the second cause of death due to malignancy in the world, following lung cancer. The geographic distribution of this disease accompanies its principal risk factors: Chronic hepatitis B virus and hepatitis C virus infection, alcoholism, aflatoxin B1 intoxication, liver cirrhosis, and some genetic attributes. Recently, type II diabetes has been shown to be a risk factor for HCC together with obesity and metabolic syndrome. Although the risk factors are quite well known and it is possible to diagnose HCC when the tumor is less than 1 cm diameter, it remains elusive at the beginning and treatment is often unsuccessful. Liver transplantation is thus far considered the best treatment for HCC as it cures HCC and the underlying liver disease. Using the Milan criteria, overall survival after liver transplantation for HCC is about 70% after 5 years. Many attempts have been made to go beyond the Milan Criteria and according to recent works reasonably good results have been achieved by using a histochemical marker such as cytokeratine 19 and the so-called "up to seven criteria" to divide patients into categories according to their risk of relapse. In addition to liver transplantation other therapies have been proposed such as resection, tumor ablation by different means, embolization and chemotherapy. An important step in the treatment of advanced HCC has been the introduction of sorafenib, the first oral, systemic drug that has provided significant improvement in survival. Treatment of HCC patients must be multidisciplinary and by using the different approaches discussed in this review it is possible to offer prolonged survival and quite good and sometimes even excellent quality of life to many patients.
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24
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Abstract
Hepatitis B virus (HBV) infection affects 240 million people worldwide. A liver-specific bile acid transporter named the sodium taurocholate cotransporting polypeptide (NTCP) has been identified as the cellular receptor for HBV and its satellite, the hepatitis D virus (HDV). NTCP likely acts as a major determinant for the liver tropism and species specificity of HBV and HDV at the entry level. NTCP-mediated HBV entry interferes with bile acid transport in cell cultures and has been linked with alterations in bile acid and cholesterol metabolism in vivo. The human liver carcinoma cell line HepG2, complemented with NTCP, now provides a valuable platform for studying the basic biology of the viruses and developing treatments for HBV infection. This review summarizes critical findings regarding NTCP's role as a viral receptor for HBV and HDV and discusses important questions that remain unanswered.
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Affiliation(s)
- Wenhui Li
- National Institute of Biological Sciences, Zhongguancun Life Science Park, Beijing 102206, China;
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