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Delghandi S, Raoufinia R, Shahtahmasbi S, Meshkat Z, Gouklani H, Gholoobi A. An overview of occult hepatitis B infection (OBI) with emphasis on HBV vaccination. Heliyon 2024; 10:e37097. [PMID: 39281486 PMCID: PMC11402251 DOI: 10.1016/j.heliyon.2024.e37097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Revised: 08/25/2024] [Accepted: 08/27/2024] [Indexed: 09/18/2024] Open
Abstract
Background The prevalence of chronic hepatitis B virus (HBV) poses a significant threat to the lives of 257 million individuals globally, potentially resulting in severe outcomes such as liver cirrhosis or hepatocellular carcinoma. Among the existing preventive measures, yeast-derived vaccines have proven to be the most efficacious approach in combatting hepatitis B. Nonetheless, as scientific inquiries focus more on occult HBV infection (OBI) in vaccinated persons and the lingering risk of vertical transmission affecting 10-30 % of babies born to HBsAg-positive mothers, there is a growing apprehension regarding the inability of HBV vaccines to ensure complete immunity. This study aims to offer a more comprehensive understanding of the implications of widespread HBV vaccination initiatives on OBI while tackling the primary limitations associated with current vaccine formulations. Methods The exploration was conducted on PubMed, Scopus, and Web of Science databases to pinpoint research on OBI within vaccinated cohorts. A sum of 76 suitable studies was recognized. Discussion Multiple studies have documented the occurrence of OBI in fully vaccinated individuals, including both the general population and high-risk groups, such as newborns born to HBsAg-positive mothers. Factors contributing to vaccine failures include low-level anti-HBs antibodies, high maternal viral loads in mother-to-child transmission cases, as well as the presence of vaccine escape mutants and heterologous HBV genotypes. However, further research is needed to precisely understand the impact of active immunization on the emergence of OBI in vaccinated populations. Nonetheless, it is apparent that the advancement of more effective HBV vaccines could potentially lead to the extinction of HBV.
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Affiliation(s)
- Sara Delghandi
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Division of Immunology and Genomic Medicine, Center for Cancer Immunotherapy and Immunobiology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Ramin Raoufinia
- Noncommunicable Diseases Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Sahar Shahtahmasbi
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Zahra Meshkat
- Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hamed Gouklani
- Infectious and Tropical Diseases Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Aida Gholoobi
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
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Han Y, Li Y, Wang S, Chen J, Zhang J. Temporal trend analysis of acute hepatitis B virus infection in China, 1990-2019. Epidemiol Infect 2024; 152:e48. [PMID: 38468382 DOI: 10.1017/s095026882400044x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/13/2024] Open
Abstract
China faces challenges in meeting the World Health Organization (WHO)'s target of reducing hepatitis B virus (HBV) infections by 95% using 2015 as the baseline. Using Global Burden of Disease (GBD) 2019 data, joinpoint regression models were used to analyse the temporal trends in the crude incidence rates (CIRs) and age-standardized incidence rates (ASIRs) of acute HBV (AHBV) infections in China from 1990 to 2019. The age-period-cohort model was used to estimate the effects of age, period, and birth cohort on AHBV infection risk, while the Bayesian age-period-cohort (BAPC) model was applied to predict the annual number and ASIRs of AHBV infections in China through 2030. The joinpoint regression model revealed that CIRs and ASIRs decreased from 1990 to 2019, with a faster decline occurring among males and females younger than 20 years. According to the age-period-cohort model, age effects showed a steep increase followed by a gradual decline, whereas period effects showed a linear decline, and cohort effects showed a gradual rise followed by a rapid decline. The number of cases of AHBV infections in China was predicted to decline until 2030, but it is unlikely to meet the WHO's target. These findings provide scientific support and guidance for hepatitis B prevention and control.
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Affiliation(s)
- Ying Han
- Department of Epidemiology and Health Statistics, School of Public Health, Southwest Medical University, Luzhou, P. R. China
| | - Yuansheng Li
- Department of Epidemiology and Health Statistics, School of Public Health, Southwest Medical University, Luzhou, P. R. China
| | - Shuyuan Wang
- Department of Epidemiology and Health Statistics, School of Public Health, Southwest Medical University, Luzhou, P. R. China
| | - Jialu Chen
- Department of Epidemiology and Health Statistics, School of Public Health, Southwest Medical University, Luzhou, P. R. China
| | - Junhui Zhang
- Department of Epidemiology and Health Statistics, School of Public Health, Southwest Medical University, Luzhou, P. R. China
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Demissie M, Weldekidan HA, Yosef Y, Sori SA, Tsega D, Jiru HD, Derribow AB, Tetema MD, Jima GB, Zeleke FT, Endeshew F, Abeje S. Timing of Hepatitis B Vaccine Birth Dose in Exposed Newborns, Southwest Ethiopia: A Cross-Sectional Study. SAGE Open Nurs 2023; 9:23779608231187258. [PMID: 37457619 PMCID: PMC10345928 DOI: 10.1177/23779608231187258] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2023] [Revised: 06/19/2023] [Accepted: 06/24/2023] [Indexed: 07/18/2023] Open
Abstract
Introduction Hepatitis B virus disease is a global acute and chronic communicable disease. Mother-to-child transmission is the reason for high carrier rates. Unvaccinated newborns infected through mother-to-child transmission are at >95% risk of developing chronic hepatitis B virus disease. Vaccination is the most effective measure to reduce the global incidence of hepatitis B virus disease. Despite the World Health Organization's target to achieve 90% of the hepatitis B vaccine birth dose by 2030, little is known about the vaccination status of exposed newborns. Objective The present study aimed to determine the timing of the hepatitis B vaccine birth dose in exposed newborns in Southwest Ethiopia. Methods An institution-based cross-sectional study was employed on 422 systematically selected exposed newborns from April 2, 2022, to August 28, 2022. A pretested, interviewer-administered questionnaire was used for data collection. Data were entered into Epi data 3.1 and exported into SPSS version 23 software for analysis. Both bivariable and multivariable binary logistic regressions were performed. Variables with a p-value <.05 at a 95% confidence interval (CI) were considered statistically significant. Results The proportion of neonates who received their first dose of the hepatitis B vaccine on time was 57 (42.5%) (95% CI: 38.3-46.1%). A higher likelihood of vaccinating their exposed newborns on time was associated with formal education (adjusted odds ratio [AOR] = 3.01, 95% CI: 2.21-7.09), four or more ANC visits (AOR = 2.33, 95% CI: 2.05-6.21), and husband engagement (AOR = 4.31, 95% CI: 2.03-6.34). Conclusion The proportion of timely initiation of the hepatitis B vaccine birth dose in Southwest Ethiopia was low. Thus, strengthening health education on the hepatitis B vaccine, encouraging women to have at least four ANC visits, and encouraging male involvement help improve the timely administration of the hepatitis B vaccine.
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Affiliation(s)
- Mebratu Demissie
- Department of Midwifery, College of Medicine and Health Science, Wolkite University, Wolkite, Ethiopia
| | - Haregwa Asnake Weldekidan
- Department of Midwifery, College of Medicine and Health Science, Wolkite University, Wolkite, Ethiopia
| | - Yirgalem Yosef
- Department of Midwifery, College of Medicine and Health Science, Wolkite University, Wolkite, Ethiopia
| | - Seboka Abebe Sori
- Department of Midwifery, College of Medicine and Health Science, Wolkite University, Wolkite, Ethiopia
| | - Daniel Tsega
- Department of Midwifery, College of Medicine and Health Science, Wolkite University, Wolkite, Ethiopia
| | - Hirut Dinku Jiru
- Department of Midwifery, College of Medicine and Health Science, Wolkite University, Wolkite, Ethiopia
| | - Aberash Beyene Derribow
- Department of Midwifery, College of Medicine and Health Science, Wolkite University, Wolkite, Ethiopia
| | - Mesfin Difer Tetema
- Department of Midwifery, College of Medicine and Health Science, Wolkite University, Wolkite, Ethiopia
| | - Gudeta Beriso Jima
- Department of Midwifery, College of Medicine and Health Science, Wolkite University, Wolkite, Ethiopia
| | - Fentahun Temene Zeleke
- Department of Midwifery, College of Medicine and Health Science, Wolkite University, Wolkite, Ethiopia
| | - Fikremariam Endeshew
- Department of Midwifery, College of Medicine and Health Science, Wolkite University, Wolkite, Ethiopia
| | - Seblework Abeje
- Department of Biochemistry, College of Medicine and Health Science, Wolkite University, Wolkite, Ethiopia
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4
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Liang Z, Huang Y, Li H, Zhang X, Shi K, Zang N, Wang M, Liang T, Wei W. Synthesis and evaluation of 3-phenylisoxazoline derivatives as non-nucleoside hepatitis B virus inhibitors. Tetrahedron 2022. [DOI: 10.1016/j.tet.2022.133177] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2022]
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Wirsching S, Machtakova M, Borgans F, Pretsch L, Fichter M, Cacicedo ML, Thérien-Aubin H, Landfester K, Gehring S. OVA-PEG-R848 nanocapsules stimulate neonatal conventional and plasmacytoid dendritic cells. Front Pediatr 2022; 10:966113. [PMID: 36177449 PMCID: PMC9513203 DOI: 10.3389/fped.2022.966113] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Accepted: 08/17/2022] [Indexed: 12/04/2022] Open
Abstract
Childhood mortality represents a major issue with 5. 3 million worldwide deaths of children under 5 years of age in 2019. Approximately half of those deaths can be attributed to easily preventable, infectious diseases. Currently approved neonatal vaccines are typically effective only after multiple doses leaving infants especially vulnerable during the first 6 months of life. Survival rates could be improved significantly by developing new and more potent vaccines that are capable of overcoming inherently tolerogenic neonatal immune systems. TLR agonists have garnered a great deal of attention in recent years due to their extensive capacities to activate innate immunity. Herein, the superior capacity of the TLR7/8 agonist, resiquimod (R848), to activate adult and neonatal primary peripheral blood dendritic cells is demonstrated. Moreover, R848 can be conjugated to polyethylene glycol and encapsulated in ovalbumin nanocapsules to efficiently co-deliver antigen and adjuvant in vitro. This study is among the first to demonstrate the capacity of encapsulated R848 to activate neonatal dendritic cells. These findings support the potential incorporation of R848 as adjuvant in neonatal vaccines, making them more effective in eliciting a robust immune response.
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Affiliation(s)
- Sebastian Wirsching
- Children's Hospital, University Medical Center of the Johannes Gutenberg University, Mainz, Germany
| | | | - Frauke Borgans
- Children's Hospital, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.,Department of Infectious Diseases, University Hospital Frankfurt, Frankfurt, Germany
| | - Leah Pretsch
- Children's Hospital, University Medical Center of the Johannes Gutenberg University, Mainz, Germany
| | - Michael Fichter
- Children's Hospital, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.,Max Planck Institute for Polymer Research, Mainz, Germany.,Department of Dermatology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany
| | - Maximiliano L Cacicedo
- Children's Hospital, University Medical Center of the Johannes Gutenberg University, Mainz, Germany
| | - Héloïse Thérien-Aubin
- Max Planck Institute for Polymer Research, Mainz, Germany.,Department of Chemistry, Memorial University of Newfoundland, St. John's, NL, Canada
| | | | - Stephan Gehring
- Children's Hospital, University Medical Center of the Johannes Gutenberg University, Mainz, Germany
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Abstract
Vaccinology has come a long way from early, empirically developed vaccines to modern vaccines rationally designed and produced. Vaccines are meant to cooperate with the human immune system, the later largely unknown in the early years of vaccine development. In the recent years, a tremendous depth of knowledge has been accumulated in the field of immunology that has provided an opportunity to understand the mechanisms of action of the vaccine components. In parallel, our knowledge in microbiology, molecular biology, infectiology, epidemiology, and furthermore in bioinformatics has fostered our understanding of the interaction of microorganisms with the human immune system. Strategies engaged by pathogens strongly determine the targets of a vaccine, which should be formulated to stimulate potent and efficiently protective immune responses. The improved knowledge of immune response mechanisms has facilitated the development of new vaccines with the capacity to selectively address the key pathogenic mechanisms. The primary goal of a vaccine design might no longer be to mimic the pathogen but to identify the relevant processes of the pathogenic mechanisms to be effectively interrupted by a highly specific immune response, eventually surpassing natural limitations. Vaccines have become complex sets of components meant to orchestrate the fine-tuning of the immune processes leading to a lasting and specific immune memory. In addition to antigenic materials, which are comprised of the most critical immunogenic epitopes, adjuvant components are frequently added to induce a favorable immunological activation. Furthermore, for reasons of production and product stability preservatives, stabilizers, inactivators, antibiotics, or diluents could be present, but need to be evaluated. While on the one hand vaccine effectiveness is a primary goal, on the other hand side effects need to be excluded due to safety and tolerability. Further challenges in vaccinology include variability of the vaccinees, the variability of the pathogen, the population-based settings of vaccine application, and the process technology in vaccine production. Vaccine design has become more tailored and in turn has opened up the potential of extending its application to hitherto not accessible complex microbial pathogens plus providing new immunotherapies to tackle diseases such as cancer, Alzheimer's disease, and autoimmune disease. This chapter gives an overview of the key considerations and processes involved in vaccine design and development. It also describes the basic principles of normal immune responses and in their function in defense of infectious agents by vaccination.
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Affiliation(s)
- Claudius U Meyer
- Department of Pediatrics, University Medical Center Mainz, Mainz, Germany
| | - Fred Zepp
- Department of Pediatrics, University Medical Center Mainz, Mainz, Germany.
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Hepatitis B Virus Infection in Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation. J Pers Med 2021; 11:jpm11111108. [PMID: 34834460 PMCID: PMC8619006 DOI: 10.3390/jpm11111108] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Revised: 10/20/2021] [Accepted: 10/25/2021] [Indexed: 01/12/2023] Open
Abstract
Considering a steady increase in the number of allogeneic hematopoietic stem cell transplantations (allo-HSCT) worldwide and the significant proportion of the world’s population that has been exposed to hepatitis B virus (HBV) infection, HBV reactivation following allo-HSCT remains an important issue for post-transplant morbidity and mortality. Antiviral prophylaxis can reduce HBV replication, severity of HBV-related hepatitis, and mortality; therefore, identification of patients at risk is crucial. It is recommended that all recipients and donors should be screened for active or prior HBV infection, including HBsAg, antiHBc, and antiHBs. Adoptive immunity transfer from the donor seems to have protective effects against HBV reactivation. Antiviral prophylaxis should be initiated in all HBsAg-positive patients. HBsAg-negative, antiHBc-positive patients remain at risk; therefore, antiviral prophylaxis should be considered if baseline serum HBV DNA is detectable. In HBsAg-negative, antiHBc-positive patients without detectable HBV DNA, close monitoring of viral load with an on-demand therapy is necessary. Entecavir or tenofovir rather than lamivudine are more appropriate for the emergence of lamivudine resistance. The treatment duration remains unclear, with 6- to 12-month therapy after cessation of immunosuppressive therapy commonly recommended. Here we review the updated evidence and recent recommendations regarding HBV reactivation in patients undergoing allo-HSCT for individualized therapy.
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Gharbharan A, Jordans CCE, GeurtsvanKessel C, den Hollander JG, Karim F, Mollema FPN, Stalenhoef-Schukken JE, Dofferhoff A, Ludwig I, Koster A, Hassing RJ, Bos JC, van Pottelberge GR, Vlasveld IN, Ammerlaan HSM, van Leeuwen-Segarceanu EM, Miedema J, van der Eerden M, Schrama TJ, Papageorgiou G, Te Boekhorst P, Swaneveld FH, Mueller YM, Schreurs MWJ, van Kampen JJA, Rockx B, Okba NMA, Katsikis PD, Koopmans MPG, Haagmans BL, Rokx C, Rijnders BJA. Effects of potent neutralizing antibodies from convalescent plasma in patients hospitalized for severe SARS-CoV-2 infection. Nat Commun 2021; 12:3189. [PMID: 34045486 PMCID: PMC8160346 DOI: 10.1038/s41467-021-23469-2] [Citation(s) in RCA: 123] [Impact Index Per Article: 30.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Accepted: 03/31/2021] [Indexed: 02/08/2023] Open
Abstract
In a randomized clinical trial of 86 hospitalized COVID-19 patients comparing standard care to treatment with 300mL convalescent plasma containing high titers of neutralizing SARS-CoV-2 antibodies, no overall clinical benefit was observed. Using a comprehensive translational approach, we unravel the virological and immunological responses following treatment to disentangle which COVID-19 patients may benefit and should be the focus of future studies. Convalescent plasma is safe, does not improve survival, has no effect on the disease course, nor does plasma enhance viral clearance in the respiratory tract, influence SARS-CoV-2 antibody development or serum proinflammatory cytokines levels. Here, we show that the vast majority of patients already had potent neutralizing SARS-CoV-2 antibodies at hospital admission and with comparable titers to carefully selected plasma donors. This resulted in the decision to terminate the trial prematurely. Treatment with convalescent plasma should be studied early in the disease course or at least preceding autologous humoral response development.
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Affiliation(s)
| | | | | | | | - Faiz Karim
- Groene Hart Hospital, Gouda, The Netherlands
| | | | | | | | | | | | | | | | | | | | | | | | - Jelle Miedema
- Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | | | - Thijs J Schrama
- Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | | | | | - Francis H Swaneveld
- Unit of Transfusion Medicine, Sanquin Blood Supply, Amsterdam, The Netherlands
| | - Yvonne M Mueller
- Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | | | | | - Barry Rockx
- Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - Nisreen M A Okba
- Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - Peter D Katsikis
- Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | | | - Bart L Haagmans
- Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - Casper Rokx
- Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
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Maraolo AE. Choosing the appropriate pharmacotherapy for hepatitis B during pregnancy: what are the considerations? Expert Opin Pharmacother 2021; 22:1083-1086. [PMID: 33797300 DOI: 10.1080/14656566.2021.1909571] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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10
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Hepatitis B vaccination response of treatment-naive patients with juvenile idiopathic arthritis. Rheumatol Int 2021; 42:1199-1205. [PMID: 33738550 DOI: 10.1007/s00296-021-04833-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Accepted: 03/02/2021] [Indexed: 10/21/2022]
Abstract
To evaluate the vaccine response of treatment-naive juvenile idiopathic arthritis (JIA) patients who were fully vaccinated against Hepatitis B Virus (HBV) and then compare their antibody status with healthy controls. In this multicenter study, initial visit hepatitis B surface antigen (HbsAg) and anti-hepatitis B surface antibody (anti-Hbs) titers of 262 treatment-naive JIA patients who were followed up regularly between May 2015 and October 2019 were evaluated retrospectively from patients' medical records and compared with 276 healthy peers. Both HbsAg and anti-Hbs antibody titers were tested by the ELISA technique. Anti-HBs titers ≥ 10 IU/L were considered as reactive indicating seroprotection against HBV. In the JIA group, seropositivity rate was 59.1% while 72.9% of the control group were immune against HBV (p = 0.002). The median titer for anti-Hbs was 14 (range: 0-1000) IU/L in the patient group and 43.3 (range: 0-1000) IU/L in the control group (p = 0.01). Neither JIA patients nor healthy controls were positive for HbsAg. Patients with JIA vaccinated according to the national vaccination schedule were evaluated at their first visit in pediatric rheumatology outpatient clinics for anti-Hbs presence and it was found that they have lesser seroprotectivity than their age and sex-matched routinely vaccinated, healthy peers. So, to complete missing vaccines and booster vaccine doses, assessing the immune status of the patients at the time of diagnosis against HBV should be in the check-list of physicians dealing with pediatric rheumatic diseases.
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11
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Shen XX, Qiu FZ, Shen LP, Yan TF, Zhao MC, Qi JJ, Chen C, Zhao L, Wang L, Feng ZS, Ma XJ. A rapid and sensitive recombinase aided amplification assay to detect hepatitis B virus without DNA extraction. BMC Infect Dis 2019; 19:229. [PMID: 30836947 PMCID: PMC6402085 DOI: 10.1186/s12879-019-3814-9] [Citation(s) in RCA: 67] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2018] [Accepted: 02/13/2019] [Indexed: 12/13/2022] Open
Abstract
Background Hepatitis B virus (HBV) infection is the major public health problem worldwide. In clinical practice, serological and molecular assays are the most commonly used diagnostic methods to detect HBV infection in clinical practices. Methods Here we present a rapid and sensitive recombinase aided amplification assay (RAA) to detect HBV at 39.0 °C for 30 min without DNA extraction from serum samples. The analytical sensitivity of RAA assay was 100 copies per reaction and showed no cross reaction with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). The universality of RAA assay was validated by testing of 41 archived serum samples with predefined HBV genotypes (B, C and D). Results A total of 130 archived suspected HBV infected serum samples were detected by commercial qPCR with DNA extraction and RAA assay without DNA extraction (heat-treatment). Compared with qPCR assay as a reference, the RAA assay obtained 95.7% sensitivity and 100% specificity and a kappa value of 0.818. Conclusions We developed a rapid, convenient, highly sensitive and specific method to detect HBV without DNA extraction in clinical samples. This RAA method of HBV detection is very suitable for clinical testing.
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Affiliation(s)
- Xin-Xin Shen
- NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, China
| | - Fang-Zhou Qiu
- NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, China.,Hebei Medical University, Shijiazhuang, 050031, Hebei, China
| | - Li-Ping Shen
- NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, China
| | - Ten-Fei Yan
- Myasthenia Gravis Research Institute, The First Hospital of Shijiazhuang, Shijiazhuang, 050011, Hebei, China
| | - Meng-Chuan Zhao
- Children's Hospital of Hebei Province, Shijiazhuang, 050031, Hebei, China
| | - Ju-Ju Qi
- NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, China.,Hebei Medical University, Shijiazhuang, 050031, Hebei, China
| | - Chen Chen
- NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, China
| | - Li Zhao
- NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, China.,Hebei Medical University, Shijiazhuang, 050031, Hebei, China
| | - Le Wang
- Children's Hospital of Hebei Province, Shijiazhuang, 050031, Hebei, China
| | - Zhi-Shan Feng
- Children's Hospital of Hebei Province, Shijiazhuang, 050031, Hebei, China.
| | - Xue-Jun Ma
- NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, China.
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12
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Pan T, Ding Y, Wu L, Liang L, He X, Li Q, Bai C, Zhang H. Design and synthesis of aminothiazole based Hepatitis B Virus (HBV) capsid inhibitors. Eur J Med Chem 2019; 166:480-501. [DOI: 10.1016/j.ejmech.2019.01.059] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2018] [Revised: 12/30/2018] [Accepted: 01/18/2019] [Indexed: 12/22/2022]
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13
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Hong Y, Mao D, Wu R, Gao Z, Meng T, Wang R, Liu L, Miao J. Hepatitis B virus S gene therapy with 10-23 DNAzyme delivered by chitosan-g-stearic acid micelles. RSC Adv 2019; 9:15196-15204. [PMID: 35514820 PMCID: PMC9064198 DOI: 10.1039/c9ra00330d] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2019] [Accepted: 05/05/2019] [Indexed: 12/21/2022] Open
Abstract
DrzBS, which targets HBV S gene expression, has important research significance and potential application value. CSO-SA is a safe and efficient non-viral gene carrier and CSO-SA/DrzBS micelles are a promising application for anti-HBV gene therapy.
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Affiliation(s)
- Yun Hong
- Department of Pharmacy
- the First Affiliated Hospital
- College of Medicine
- Zhejiang University
- Hangzhou 310003
| | - Dongsen Mao
- Zhejiang Center of Laboratory Animals
- Zhejiang Academy of Medical Sciences
- Hangzhou 310007
- P. R. China
| | - Rui Wu
- College of Pharmaceutical Sciences
- Zhejiang University
- Hangzhou 310058
- P. R. China
| | - Zhe Gao
- Department of Pharmacy
- the First Affiliated Hospital
- College of Medicine
- Zhejiang University
- Hangzhou 310003
| | - Tingting Meng
- College of Pharmaceutical Sciences
- Zhejiang University
- Hangzhou 310058
- P. R. China
| | - Rongrong Wang
- Department of Pharmacy
- the First Affiliated Hospital
- College of Medicine
- Zhejiang University
- Hangzhou 310003
| | - Lin Liu
- Department of Pharmacy
- the First Affiliated Hospital
- College of Medicine
- Zhejiang University
- Hangzhou 310003
| | - Jing Miao
- Department of Pharmacy
- the First Affiliated Hospital
- College of Medicine
- Zhejiang University
- Hangzhou 310003
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14
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Maraolo AE, Buonomo AR, Zappulo E, Scotto R, Pinchera B, Gentile I. Unsolved Issues in the Treatment of Spontaneous Peritonitis in Patients with Cirrhosis: Nosocomial Versus Community-acquired Infections and the Role of Fungi. Rev Recent Clin Trials 2019; 14:129-135. [PMID: 30514194 DOI: 10.2174/1574887114666181204102516] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2018] [Revised: 11/26/2018] [Accepted: 11/27/2018] [Indexed: 06/09/2023]
Abstract
INTRODUCTION Historically, spontaneous bacterial peritonitis (SBP) has represented one of the most frequent and relevant infectious complications of advanced liver disease, and this is still valid today. Nevertheless, in recent years the role of fungi as causative pathogens of primary peritonitis in patients with cirrhosis has become not negligible. Another issue is linked with the traditional distinction, instrumental in therapeutic choice, between community-acquired and nosocomial forms, according to the onset. Between these two categories, another one has been introduced: the so-called "healthcare-associated infections". OBJECTIVE To discuss the most controversial aspects in the management of SBP nowadays in the light of best available evidence. METHODS A review of recent literature through MEDLINE was performed. RESULTS The difference between community-acquired and nosocomial infections is crucial to guide empiric antibiotic therapy, since the site of acquisition impact on the likelihood of multidrug-resistant bacteria as causative agents. Therefore, third-generation cephalosporins cannot be considered the mainstay of treatment in each episode. Furthermore, the distinction between healthcare-associated and nosocomial form seems very subtle, especially in areas wherein antimicrobial resistance is widespread, warranting broad-spectrum antibiotic regimens for both. Finally, spontaneous fungal peritonitis is a not common but actually underestimated entity, linked to high mortality. Especially in patients with septic shock and/or failure of an aggressive antibiotic regimen, the empiric addition of an antifungal agent might be considered. CONCLUSION Spontaneous bacterial peritonitis is one of the most important complications in patients with cirrhosis. A proper empiric therapy is crucial to have a positive outcome. In this respect, a careful assessment of risk factors for multidrug-resistant pathogens is crucial. Likewise important, mostly in nosocomial cases, is not to overlook the probability of a fungal ascitic infection, namely a spontaneous fungal peritonitis.
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Affiliation(s)
- Alberto Enrico Maraolo
- Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, 80131, Naples, Italy
| | - Antonio Riccardo Buonomo
- Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, 80131, Naples, Italy
| | - Emanuela Zappulo
- Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, 80131, Naples, Italy
| | - Riccardo Scotto
- Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, 80131, Naples, Italy
| | - Biagio Pinchera
- Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, 80131, Naples, Italy
| | - Ivan Gentile
- Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, 80131, Naples, Italy
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15
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Momin B, Millman AJ, Nielsen DB, Revels M, Steele CB. Promising practices for the prevention of liver cancer: a review of the literature and cancer plan activities in the National Comprehensive Cancer Control Program. Cancer Causes Control 2018; 29:1265-1275. [PMID: 30506129 DOI: 10.1007/s10552-018-1094-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2018] [Accepted: 11/02/2018] [Indexed: 01/23/2023]
Abstract
INTRODUCTION Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are risk factors for hepatocellular carcinoma, a type of primary liver cancer, and are most prevalent in people born 1945-1965. Relatively little information is available for liver cancer prevention, compared to other cancers. In this review, we provide a summary of current promising public health practices for liver cancer prevention from the literature, as well as liver cancer-related initiatives in the National Comprehensive Cancer Control Program (NCCCP). METHODS Two types of source materials were analyzed for this review: published literature (2005-present), and current cancer plans from the NCCCP (2005-2022). A search strategy was developed to include a review of several scientific databases. Of the 73 articles identified as potentially eligible, 20 articles were eligible for inclusion in the review. Eligible articles were abstracted using a data abstraction tool. Three independent keyword searches on 65 NCCCP plans were conducted. Keyword searches within each of the plans to identify activities related to liver cancer were conducted. Relevant information was abstracted from the plans and saved in a data table. RESULTS Of the 20 eligible articles, 15 articles provided information on interventions related to liver cancer and hepatitis B or hepatitis C prevention. All 15 of the intervention articles were related to hepatitis; 13 were hepatitis B-focused, two were hepatitis C-focused, and 14 focused on Asian/Pacific Islander American populations. The independent keyword search of NCCCP plans produced 46 results for liver, 27 results for hepatitis, and 52 results for alcohol. Two plans included activities related to liver cancer. Twenty-four plans included activities related to hepatitis. DISCUSSION A majority of the intervention articles published focused on HBV infection in Asian/Pacific Islander American populations, and a small percentage of NCCCP plans included liver-related content. The findings from this review will inform the development of an Action Plan on liver cancer prevention for the NCCCP, which will assist programs with the adoption and uptake of promising practices for the prevention of liver cancer.
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Affiliation(s)
- Behnoosh Momin
- Division of Cancer Prevention and Control, U.S. Centers for Disease Control and Prevention, 4770 Buford Highway, MS F-76, Atlanta, GA, 30341, USA.
| | - Alexander J Millman
- Division of Viral Hepatitis, U.S. Centers for Disease Control and Prevention, Atlanta, GA, USA
| | | | | | - C Brooke Steele
- Division of Cancer Prevention and Control, U.S. Centers for Disease Control and Prevention, 4770 Buford Highway, MS F-76, Atlanta, GA, 30341, USA
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Maraolo AE, Gentile I, Buonomo AR, Pinchera B, Borgia G. Current evidence on the management of hepatitis B in pregnancy. World J Hepatol 2018; 10:585-594. [PMID: 30310536 PMCID: PMC6177570 DOI: 10.4254/wjh.v10.i9.585] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Revised: 04/26/2018] [Accepted: 06/09/2018] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) infection is one of the main public health problems across the globe, since almost one third of the world population presents serological markers of contact with the virus. A profound impact on the epidemiology has been exerted by universal vaccination programmes in many countries, nevertheless the infection is still widespread also in its active form. In the areas of high endemicity (prevalence of hepatitis B surface antigen positivity > 7%), mother-to-child transmission represents the main modality of infection spread. That makes the correct management of HBV in pregnancy a matter of utmost importance. Furthermore, the infection in pregnancy needs to be carefully assessed and handled not only with respect to the risk of vertical transmission but also with respect to gravid women health. Each therapeutic or preventive choice deserves to be weighed upon attentively. On many aspects evidence is scarce or controversial. This review will highlight the latest insights into the paramount steps in managing HBV in pregnancy, with particular attention to recommendations from recent guidelines and data from up-do-date research syntheses.
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Affiliation(s)
- Alberto Enrico Maraolo
- Section of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples 80131, Italy
| | - Ivan Gentile
- Section of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples 80131, Italy
| | - Antonio Riccardo Buonomo
- Section of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples 80131, Italy
| | - Biagio Pinchera
- Section of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples 80131, Italy
| | - Guglielmo Borgia
- Section of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples 80131, Italy
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Decreasing prevalence of Hepatitis B and absence of Hepatitis C Virus infection in the Warao indigenous population of Venezuela. PLoS One 2018; 13:e0197662. [PMID: 29799873 PMCID: PMC5969771 DOI: 10.1371/journal.pone.0197662] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2018] [Accepted: 05/07/2018] [Indexed: 12/12/2022] Open
Abstract
Prevalence and molecular epidemiology studies for hepatitis B (HBV) and C (HCV) virus are scarce in Warao Amerindians from Venezuela, where an epidemic of human immunodeficiency virus type 1 (HIV-1) has recently been documented. To carry out a molecular epidemiology analysis of hepatitis B (HBV) and C (HCV) virus in Warao individuals from the Delta Amacuro State of Venezuela. A total of 548 sera were tested for serological and molecular markers for HBV and HCV. The prevalence of active infection (presence of HBV surface antigen, HBsAg), exposure to HBV (presence of Antibody to HBV core antigen, anti-HBc) and anti-HCV, was 1.8%, 13% and 0% respectively. HBV exposure was significantly lower in men below 18 years old and also lower than rates previously reported in other Amerindian communities from Venezuela. Thirty one percent (31%, 25/80) of individuals without evidence of HBV infection exhibited anti-HBs titer ≥ 10U.I / ml, being significantly more frequent in individuals younger than 20 years. A higher HBV exposure was observed among HIV-1 positive individuals (33% vs 11%, p <0.005). A high prevalence of occult HBV infection was also observed (5.6%, 11/195). Phylogenetic analysis of S gene and complete HBV genomes showed that F3 is the only circulating subgenotype, different from the F2 subgenotype found in 1991 in this population. These results suggest a recent introduction of subgenotype F3, with a low divergence among the isolates. These results highlight the importance of molecular epidemiology studies for viral control, and support the effectiveness of vaccination in reducing transmission of HBV.
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Miller-Handley H, Paulsen G, Hooper DK, Lake M, Lazear D, Danziger-Isakov L. Durability of the hepatitis B vaccination in pediatric renal transplant recipients. Clin Transplant 2018; 32:e13247. [DOI: 10.1111/ctr.13247] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/21/2018] [Indexed: 12/14/2022]
Affiliation(s)
- Hilary Miller-Handley
- Department of Internal Medicine; Pediatrics at University of Cincinnati and Cincinnati Children's Hospital; Cincinnati OH USA
- Division of Pediatric Infection Disease; Cincinnati Children's Hospital; Cincinnati OH USA
| | - Grant Paulsen
- Division of Pediatric Infection Disease; Cincinnati Children's Hospital; Cincinnati OH USA
| | - David K. Hooper
- Division of Nephrology; Cincinnati Children's Hospital; Cincinnati OH USA
| | - Michael Lake
- Division of Pharmacy; Cincinnati Children's Hospital; Cincinnati OH USA
| | - Danielle Lazear
- Division of Pharmacy; Cincinnati Children's Hospital; Cincinnati OH USA
| | - Lara Danziger-Isakov
- Division of Pediatric Infection Disease; Cincinnati Children's Hospital; Cincinnati OH USA
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Stanley M. Tumour virus vaccines: hepatitis B virus and human papillomavirus. Philos Trans R Soc Lond B Biol Sci 2018; 372:rstb.2016.0268. [PMID: 28893935 DOI: 10.1098/rstb.2016.0268] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/09/2017] [Indexed: 12/11/2022] Open
Abstract
Two of the most important human oncogenic viruses are hepatitis B virus (HBV) and human papillomavirus (HPV). HBV infection has been preventable by vaccination since 1982; vaccination of neonates and infants is highly effective, resulting already in decreased rates of new infections, chronic liver disease and hepato-cellular carcinoma. Nonetheless, HBV remains a global public health problem with high rates of vertical transmission from mother to child in some regions. Prophylactic HPV vaccines composed of virus-like particles (VLPs) of the L1 capsid protein have been licensed since 2006/2007. These target infection by the oncogenic HPVs 16 and 18 (the cause of 70% of cervical cancers); a new vaccine licensed in 2014/2015 additionally targets HPVs 31, 33, 45, 52, 58. HPV vaccines are now included in the national immunization programmes in many countries, with young adolescent peri-pubertal girls the usual cohort for immunization. Population effectiveness in women is now being demonstrated in countries with high vaccine coverage with significant reductions in high-grade cervical intra-epithelial neoplasia (a surrogate for cervical cancer), genital warts and vaccine HPV type genoprevalence. Herd effects in young heterosexual men and older women are evident. Cancers caused by HBV and HPV should, in theory, be amenable to immunotherapies and various therapeutic vaccines for HPV in particular are in development and/or in clinical trial.This article is part of the themed issue 'Human oncogenic viruses'.
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Affiliation(s)
- Margaret Stanley
- Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK
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20
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Fiore M, Leone S, Maraolo AE, Berti E, Damiani G. Liver Illness and Psoriatic Patients. BIOMED RESEARCH INTERNATIONAL 2018; 2018:3140983. [PMID: 29546055 PMCID: PMC5818942 DOI: 10.1155/2018/3140983] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 08/31/2017] [Revised: 10/30/2017] [Accepted: 01/04/2018] [Indexed: 12/12/2022]
Abstract
Psoriasis is a chronic inflammatory disease of the skin affecting approximately 2% of the world's population. Systemic treatments, including methotrexate and cyclosporin, are associated with potential hepatotoxicity, due to either direct liver damage or immunosuppression or both immunomediated and a direct liver injury; therefore, treatment of patients with psoriasis poses a therapeutic challenge. The aim of this minireview is to help clinicians in the management of psoriatic patients who develop signs of liver dysfunction. To find relevant articles, a comprehensive search was performed on PubMed, EMBASE, and Cochrane with appropriate combinations of the following keywords being considered: viral hepatitis, nonalcoholic fatty liver disease, psoriasis, hepatotoxicity, drug toxicity, cholestasis, and autoimmune liver diseases.
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Affiliation(s)
- Marco Fiore
- Department of Anaesthesiological, Surgical and Emergency Sciences, University of Campania “Luigi Vanvitelli”, Naples, Italy
| | - Sebastiano Leone
- Department of Medicine, Division of Infectious Diseases, “San Giuseppe Moscati” Hospital, Avellino, Italy
| | - Alberto Enrico Maraolo
- Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, Naples, Italy
| | - Emilio Berti
- Department of Pathophysiology and Transplantation, Dermatology Unit, IRCCS Ca' Granda, University of Milan, Milan, Italy
| | - Giovanni Damiani
- Department of Pathophysiology and Transplantation, Dermatology Unit, IRCCS Ca' Granda, University of Milan, Milan, Italy
- Study Center of Young Dermatologists Italian Network (YDIN), Bergamo, Italy
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21
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Active immunization in patients transplanted for hepatitis B virus related liver diseases: A prospective study. PLoS One 2017; 12:e0188190. [PMID: 29145470 PMCID: PMC5690662 DOI: 10.1371/journal.pone.0188190] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2017] [Accepted: 10/29/2017] [Indexed: 02/07/2023] Open
Abstract
Introduction Prophylactic administration of hepatitis B immunoglobulin (HBIG) and nucleos(t)ide analogues (NAs) is the standard treatment for controlling hepatitis B virus (HBV) recurrence after liver transplantation (LT). Since lifelong use of HBIG is expensive and inconvenient and the antibodies level in anti-hepatitis B surface (HBs) is not sustainable and stable, an alternative strategy is to produce anti-HBs antibodies by active immunization. Our present study aimed to prospectively investigate the efficacy and safety of procedural HBV vaccination in transplanted patients. Methods Recipients who had undergone LT for hepatitis B related liver diseases more than one year before, with no evidence of HBV recurrence or rejection and normal liver function were enrolled. All subjects received the hepatitis B vaccine (40 μg) by intramuscular injection at months 0, 1, 2, 6 and 12 after enrollment with continuous administration of NAs. The liver function and anti-HBs titers were measured before each vaccination and HBIG (400U) was administrated intramuscularly when anti-HBs titer was lower than 30 IU/L during the course. The results of routine blood tests, liver function, concentration of immunosuppressant, and HBV-DNA copies were monitored during the research. After completion of the vaccination procedure, recipients were regarded as responders if their anti-HBs greater than 30 IU/L were maintained for up to six months without using HBIG and vaccine. Results Twenty-seven patients were enrolled in this study and the average anti-HBs titer before vaccination was 19.86±14.80 IU/L. The average anti-HBs titer of the nine responders at the end of the follow-up was 57.14±22.75 IU/L, giving an overall response rate of 33.3% (9/27). There were no reports of reactivation of HBV, rejection, severe anaphylaxis or other adverse events. Responders and non-responders showed their significant difference in anti-HBs titers after the fourth vaccination (P<0.01). Moreover, the majority of non-responders (11/18, 63.64%) had high LY/EO rates (lymphocyte number/eosinophil number>15) while most responders (8/9, 88.89%) had low LY/EO rates at the beginning of vaccination (P = 0.019). Conclusions Active immunization is an effective, cost-saving, and safe method for the prevention of HBV reactivation in patients transplanted for hepatitis B virus related liver diseases. The LY/EO rate may be a valuable indicator in selecting potential recipients for vaccination.
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Quantifying perinatal transmission of Hepatitis B viral quasispecies by tag linkage deep sequencing. Sci Rep 2017; 7:10168. [PMID: 28860476 PMCID: PMC5578979 DOI: 10.1038/s41598-017-10591-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2017] [Accepted: 08/11/2017] [Indexed: 02/07/2023] Open
Abstract
Despite full immunoprophylaxis, mother-to-child transmission (MTCT) of Hepatitis B Virus still occurs in approximately 2–5% of HBsAg positive mothers. Little is known about the bottleneck of HBV transmission and the evolution of viral quasispecies in the context of MTCT. Here we adopted a newly developed tag linkage deep sequencing method and analyzed the quasispecies of four MTCT pairs that broke through immunoprophylaxis. By assigning unique tags to individual viral sequences, we accurately reconstructed HBV haplotypes in a region of 836 bp, which contains the major immune epitopes and drug resistance mutations. The detection limit of minor viral haplotypes reached 0.1% for individual patient sample. Dominance of “a determinant” polymorphisms were observed in two children, which pre-existed as minor quasispecies in maternal samples. In all four pairs of MTCT samples, we consistently observed a significant overlap of viral haplotypes shared between mother and child. We also demonstrate that the data can be potentially useful to estimate the bottleneck effect during HBV MTCT, which provides information to optimize treatment for reducing the frequency of MTCT.
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Patel DP, Treat JR, Castelo-Socio L. Decreased Hepatitis B vaccine response in pediatric patients with atopic dermatitis, psoriasis, and morphea. Vaccine 2017; 35:4499-4500. [PMID: 28736199 DOI: 10.1016/j.vaccine.2017.07.025] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2017] [Revised: 07/03/2017] [Accepted: 07/10/2017] [Indexed: 01/29/2023]
Abstract
Multiple groups of patients have been recognized for having high rates of non-responders to the Hepatitis B vaccine including those with HIV, inflammatory bowel disease, and chronic kidney disease. These patients are at increased risk for infection due to both the nature of their underlying diseases and the immunosuppressive drugs they are commonly prescribed. Identification of groups with high non-response rates is essential in order to establish vaccination guidelines and prevent serious infections in already susceptible patients. We thus aimed to assess the rate of antibody response to the HBV vaccine in patients with psoriasis, atopic dermatitis, or morphea prior to starting immunosuppressive therapy.
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Affiliation(s)
- Deepa P Patel
- Section of Pediatric Dermatology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, United States; The University of Louisville School of Medicine, Louisville, Kentucky 40206, United States.
| | - James R Treat
- Section of Pediatric Dermatology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, United States
| | - Leslie Castelo-Socio
- Section of Pediatric Dermatology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, United States
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Choudhuri G, Ojha R, Negi TS, Gupta V, Saxena S, Choudhuri A, Pal S, Choudhuri J, Sangam A. A school-based intervention of screening a movie to increase hepatitis B vaccination levels among students in Uttar Pradesh, India: impact on knowledge, awareness, attitudes and vaccination levels. HEPATOLOGY, MEDICINE AND POLICY 2017; 2:10. [PMID: 30288323 PMCID: PMC6171006 DOI: 10.1186/s41124-017-0027-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/05/2016] [Accepted: 06/05/2017] [Indexed: 01/21/2023]
Abstract
BACKGROUND India is home to one in 14 of all chronic hepatitis B virus (HBV) cases, meaning that it is important to develop HBV interventions that are applicable in the Indian context. Vaccination is the foremost tool for interrupting the HBV infection cycle. HBV vaccination was not included in India's government-sponsored expanded immunisation program until 2011, and many children born earlier remain unvaccinated. This study sought to observe the impact of the HOPE Initiative's school-based intervention to increase vaccination coverage by increasing HBV awareness among students in Lucknow, Uttar Pradesh. METHODS At 430 schools in the administrative areas within and surrounding Lucknow, students viewed an educational documentary film on HBV and completed two questionnaires, one immediately before the screening and the other six weeks later. Both questionnaires asked the same 14 questions, which were organized into five domains: knowledge of the magnitude of the problem of HBV; knowledge of modes of HBV transmission; knowledge of consequences of HBV infection; awareness of HBV; and attitudes regarding HBV. The baseline questionnaire also asked students whether they had been vaccinated against HBV. At two-year follow-up, researchers measured vaccination levels at a subset of 30 intervention schools and six non-intervention schools to further assess the impact of the intervention. RESULTS Baseline questionnaires were completed by 11,250 students, and post-intervention questionnaires, by 9698 students. Scores for knowledge about the magnitude of the HBV problem improved from 41% at baseline to 74% at follow-up, and scores for knowledge about modes of transmission, from 38% to 75% (p < 0.05 for both). The baseline HBV vaccination level among students receiving the intervention was 21%. Two years after the intervention, 45% of students (N = 4284) reported being vaccinated at intervention schools compared to 22% (N = 1264) at non-intervention schools. CONCLUSIONS The observed increases in HBV awareness, knowledge and vaccination levels in this study indicate that school-based interventions can be used to achieve higher vaccination coverage among Indian children. The documentary film was found to be an affordable tool for reaching large audiences. More studies are needed to validate the impact of this intervention and to explore its applicability to other social causes.
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Affiliation(s)
- Gourdas Choudhuri
- HOPE (Health Oriented Programs and Education) Initiative, www.hope.org.in, 422, Aradhana, Eldeco 2, Rae Bareli Road, Lucknow, UP 226025 India
- Department of Gastroenterology and Hepatobiliary Sciences, Fortis Memorial Research Institute, Sector 44, Gurgaon, Haryana 122002 India
| | - Rajesh Ojha
- HOPE (Health Oriented Programs and Education) Initiative, www.hope.org.in, 422, Aradhana, Eldeco 2, Rae Bareli Road, Lucknow, UP 226025 India
| | - T. S. Negi
- HOPE (Health Oriented Programs and Education) Initiative, www.hope.org.in, 422, Aradhana, Eldeco 2, Rae Bareli Road, Lucknow, UP 226025 India
| | - Varun Gupta
- HOPE (Health Oriented Programs and Education) Initiative, www.hope.org.in, 422, Aradhana, Eldeco 2, Rae Bareli Road, Lucknow, UP 226025 India
- Department of Gastroenterology and Hepatobiliary Sciences, Fortis Memorial Research Institute, Sector 44, Gurgaon, Haryana 122002 India
| | - Shipra Saxena
- HOPE (Health Oriented Programs and Education) Initiative, www.hope.org.in, 422, Aradhana, Eldeco 2, Rae Bareli Road, Lucknow, UP 226025 India
| | - Arundhati Choudhuri
- HOPE (Health Oriented Programs and Education) Initiative, www.hope.org.in, 422, Aradhana, Eldeco 2, Rae Bareli Road, Lucknow, UP 226025 India
| | - Sanjoy Pal
- HOPE (Health Oriented Programs and Education) Initiative, www.hope.org.in, 422, Aradhana, Eldeco 2, Rae Bareli Road, Lucknow, UP 226025 India
| | - Jui Choudhuri
- HOPE (Health Oriented Programs and Education) Initiative, www.hope.org.in, 422, Aradhana, Eldeco 2, Rae Bareli Road, Lucknow, UP 226025 India
| | - Alok Sangam
- HOPE (Health Oriented Programs and Education) Initiative, www.hope.org.in, 422, Aradhana, Eldeco 2, Rae Bareli Road, Lucknow, UP 226025 India
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Gehring S, Pietrzak-Nguyen A, Fichter M, Landfester K. Novel strategies in vaccine design: can nanocapsules help prevent and treat hepatitis B? Nanomedicine (Lond) 2017; 12:1205-1207. [DOI: 10.2217/nnm-2016-0064] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Affiliation(s)
- Stephan Gehring
- Children's Hospital, University Medical Center, Johannes Gutenberg University, 55128 Mainz, Germany
| | - Anette Pietrzak-Nguyen
- Children's Hospital, University Medical Center, Johannes Gutenberg University, 55128 Mainz, Germany
| | - Michael Fichter
- Children's Hospital, University Medical Center, Johannes Gutenberg University, 55128 Mainz, Germany
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Borgia G, Maraolo AE, Gentile I. Hepatitis B mother-to-child transmission and infants immunization: we have not come to the end of the story yet. Infect Dis (Lond) 2017; 49:584-587. [PMID: 28316268 DOI: 10.1080/23744235.2017.1303746] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Affiliation(s)
- Guglielmo Borgia
- a Department of Clinical Medicine and Surgery, Section of Infectious Diseases , University of Naples 'Federico II' , Naples , Italy
| | - Alberto Enrico Maraolo
- a Department of Clinical Medicine and Surgery, Section of Infectious Diseases , University of Naples 'Federico II' , Naples , Italy
| | - Ivan Gentile
- a Department of Clinical Medicine and Surgery, Section of Infectious Diseases , University of Naples 'Federico II' , Naples , Italy
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Narciso-Schiavon JL, Schiavon LL. To screen or not to screen? Celiac antibodies in liver diseases. World J Gastroenterol 2017; 23:776-791. [PMID: 28223722 PMCID: PMC5296194 DOI: 10.3748/wjg.v23.i5.776] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2016] [Revised: 11/28/2016] [Accepted: 12/08/2016] [Indexed: 02/06/2023] Open
Abstract
Celiac disease (CD) is a systemic immune-mediated disorder triggered by dietary gluten in genetically predisposed individuals. The typical symptoms are anemia, diarrhea, fatigue, weight loss, and abdominal pain. CD has been reported in patients with primary sclerosing cholangitis, primary biliary cholangitis, autoimmune hepatitis, aminotransferase elevations, nonalcoholic fatty liver disease, hepatitis B, hepatitis C, portal hypertension and liver cirrhosis. We evaluate recommendations for active screening for CD in patients with liver diseases, and the effect of a gluten-free diet in these different settings. Active screening for CD is recommended in patients with liver diseases, particularly in those with autoimmune disorders, steatosis in the absence of metabolic syndrome, noncirrhotic intrahepatic portal hypertension, cryptogenic cirrhosis, and in the context of liver transplantation. In hepatitis C, diagnosis of CD can be important as a relative contraindication to interferon use. Gluten-free diet ameliorates the symptoms associated with CD; however, the associated liver disease may improve, remain the same, or progress.
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Qiu J, Xu B, Gong Q, Pan W, Liu C, Huang Z, Gu X, Liang G. Synthesis and Biological Evaluation of Matijin-Su Derivatives as Potential Antihepatitis B Virus and Anticancer Agents. Chem Biodivers 2016; 13:1584-1592. [PMID: 27451105 DOI: 10.1002/cbdv.201600113] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2016] [Accepted: 06/23/2016] [Indexed: 01/06/2023]
Abstract
A series of Matijin-Su (MTS, (2S)-2-{[(2S)-2-benzamido-3-phenylpropanoyl]amino}-3-phenylpropyl acetate) derivatives were synthesized and evaluated for their anti-HBV and cytotoxic activities in vitro. Six compounds (4g, 4j, 5c, 5g, 5h and 5i) showed significant inhibition against HBV DNA replication with the IC50 values in range of 2.18 - 8.55 μm, which were much lower than that of positive control lamivudine (IC50 82.42 μm). In particular, compounds 5h (IC50 2.18 μm; SI 151.59) and 5j (IC50 5.65 μm; SI 51.16) displayed relatively low cytotoxicities, resulting in high SI values. Notably, besides the anti-HBV DNA replication activity, compound 4j also exhibited more potent in vitro cytotoxic activity than 5-fluorouracil in two hepatocellular carcinoma cell (HCC) lines (QGY-7701 and SMMC-7721), indicating that 4j may be a promising lead for the exploration of drugs with dual therapeutic effects on HBV infection and HBV-induced HCC.
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Affiliation(s)
- Jingying Qiu
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical College, 209 Tongshan Road, Xuzhou, 221004, P. R. China
| | - Bixue Xu
- The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, 202 Shachong South Road, Guiyang, 550002, P. R. China
| | - Qineng Gong
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical College, 209 Tongshan Road, Xuzhou, 221004, P. R. China
| | - Weidong Pan
- The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, 202 Shachong South Road, Guiyang, 550002, P. R. China
| | - Changxiao Liu
- Tianjin Institute of Pharmaceutical Research, 308 Anshan Xi Dao, Nankai District, Tianjin, 300193, P. R. China
| | - Zhengming Huang
- 302 Hospital of PLA, 100 Xisihuan Zhong Road, Fengtai Beijing, 100039, P. R. China
| | - Xiaoke Gu
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical College, 209 Tongshan Road, Xuzhou, 221004, P. R. China
| | - Guangyi Liang
- The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, 202 Shachong South Road, Guiyang, 550002, P. R. China
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Qiu Z, Lin X, Zhou M, Liu Y, Zhu W, Chen W, Zhang W, Guo L, Liu H, Wu G, Huang M, Jiang M, Xu Z, Zhou Z, Qin N, Ren S, Qiu H, Zhong S, Zhang Y, Zhang Y, Wu X, Shi L, Shen F, Mao Y, Zhou X, Yang W, Wu JZ, Yang G, Mayweg AV, Shen HC, Tang G. Design and Synthesis of Orally Bioavailable 4-Methyl Heteroaryldihydropyrimidine Based Hepatitis B Virus (HBV) Capsid Inhibitors. J Med Chem 2016; 59:7651-66. [PMID: 27458651 DOI: 10.1021/acs.jmedchem.6b00879] [Citation(s) in RCA: 56] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Targeting the capsid protein of hepatitis B virus (HBV) and thus interrupting normal capsid formation have been an attractive approach to block the replication of HBV viruses. We carried out multidimensional structural optimizations based on the heteroaryldihydropyrimidine (HAP) analogue Bay41-4109 (1) and identified a novel series of HBV capsid inhibitors that demonstrated promising cellular selectivity indexes, metabolic stabilities, and in vitro safety profiles. Herein we disclose the design, synthesis, structure-activity relationship (SAR), cocrystal structure in complex with HBV capsid proteins and in vivo pharmacological study of the 4-methyl HAP analogues. In particular, the (2S,4S)-4,4-difluoroproline substituted analogue 34a demonstrated high oral bioavailability and liver exposure and achieved over 2 log viral load reduction in a hydrodynamic injected (HDI) HBV mouse model.
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Affiliation(s)
- Zongxing Qiu
- Roche Innovation Center Shanghai, ‡Medicinal Chemistry, §Chemical Biology, ∥Pharmaceutical Sciences, and ⊥Discovery Virology, Roche Pharma Research and Early Development , 720 Cailun Road, Shanghai, 201203 China
| | - Xianfeng Lin
- Roche Innovation Center Shanghai, ‡Medicinal Chemistry, §Chemical Biology, ∥Pharmaceutical Sciences, and ⊥Discovery Virology, Roche Pharma Research and Early Development , 720 Cailun Road, Shanghai, 201203 China
| | - Mingwei Zhou
- Roche Innovation Center Shanghai, ‡Medicinal Chemistry, §Chemical Biology, ∥Pharmaceutical Sciences, and ⊥Discovery Virology, Roche Pharma Research and Early Development , 720 Cailun Road, Shanghai, 201203 China
| | - Yongfu Liu
- Roche Innovation Center Shanghai, ‡Medicinal Chemistry, §Chemical Biology, ∥Pharmaceutical Sciences, and ⊥Discovery Virology, Roche Pharma Research and Early Development , 720 Cailun Road, Shanghai, 201203 China
| | - Wei Zhu
- Roche Innovation Center Shanghai, ‡Medicinal Chemistry, §Chemical Biology, ∥Pharmaceutical Sciences, and ⊥Discovery Virology, Roche Pharma Research and Early Development , 720 Cailun Road, Shanghai, 201203 China
| | - Wenming Chen
- Roche Innovation Center Shanghai, ‡Medicinal Chemistry, §Chemical Biology, ∥Pharmaceutical Sciences, and ⊥Discovery Virology, Roche Pharma Research and Early Development , 720 Cailun Road, Shanghai, 201203 China
| | - Weixing Zhang
- Roche Innovation Center Shanghai, ‡Medicinal Chemistry, §Chemical Biology, ∥Pharmaceutical Sciences, and ⊥Discovery Virology, Roche Pharma Research and Early Development , 720 Cailun Road, Shanghai, 201203 China
| | - Lei Guo
- Roche Innovation Center Shanghai, ‡Medicinal Chemistry, §Chemical Biology, ∥Pharmaceutical Sciences, and ⊥Discovery Virology, Roche Pharma Research and Early Development , 720 Cailun Road, Shanghai, 201203 China
| | - Haixia Liu
- Roche Innovation Center Shanghai, ‡Medicinal Chemistry, §Chemical Biology, ∥Pharmaceutical Sciences, and ⊥Discovery Virology, Roche Pharma Research and Early Development , 720 Cailun Road, Shanghai, 201203 China
| | - Guolong Wu
- Roche Innovation Center Shanghai, ‡Medicinal Chemistry, §Chemical Biology, ∥Pharmaceutical Sciences, and ⊥Discovery Virology, Roche Pharma Research and Early Development , 720 Cailun Road, Shanghai, 201203 China
| | - Mengwei Huang
- Roche Innovation Center Shanghai, ‡Medicinal Chemistry, §Chemical Biology, ∥Pharmaceutical Sciences, and ⊥Discovery Virology, Roche Pharma Research and Early Development , 720 Cailun Road, Shanghai, 201203 China
| | - Min Jiang
- Roche Innovation Center Shanghai, ‡Medicinal Chemistry, §Chemical Biology, ∥Pharmaceutical Sciences, and ⊥Discovery Virology, Roche Pharma Research and Early Development , 720 Cailun Road, Shanghai, 201203 China
| | - Zhiheng Xu
- Roche Innovation Center Shanghai, ‡Medicinal Chemistry, §Chemical Biology, ∥Pharmaceutical Sciences, and ⊥Discovery Virology, Roche Pharma Research and Early Development , 720 Cailun Road, Shanghai, 201203 China
| | - Zheng Zhou
- Roche Innovation Center Shanghai, ‡Medicinal Chemistry, §Chemical Biology, ∥Pharmaceutical Sciences, and ⊥Discovery Virology, Roche Pharma Research and Early Development , 720 Cailun Road, Shanghai, 201203 China
| | - Ning Qin
- Roche Innovation Center Shanghai, ‡Medicinal Chemistry, §Chemical Biology, ∥Pharmaceutical Sciences, and ⊥Discovery Virology, Roche Pharma Research and Early Development , 720 Cailun Road, Shanghai, 201203 China
| | - Shuang Ren
- Roche Innovation Center Shanghai, ‡Medicinal Chemistry, §Chemical Biology, ∥Pharmaceutical Sciences, and ⊥Discovery Virology, Roche Pharma Research and Early Development , 720 Cailun Road, Shanghai, 201203 China
| | - Hongxia Qiu
- Roche Innovation Center Shanghai, ‡Medicinal Chemistry, §Chemical Biology, ∥Pharmaceutical Sciences, and ⊥Discovery Virology, Roche Pharma Research and Early Development , 720 Cailun Road, Shanghai, 201203 China
| | - Sheng Zhong
- Roche Innovation Center Shanghai, ‡Medicinal Chemistry, §Chemical Biology, ∥Pharmaceutical Sciences, and ⊥Discovery Virology, Roche Pharma Research and Early Development , 720 Cailun Road, Shanghai, 201203 China
| | - Yuxia Zhang
- Roche Innovation Center Shanghai, ‡Medicinal Chemistry, §Chemical Biology, ∥Pharmaceutical Sciences, and ⊥Discovery Virology, Roche Pharma Research and Early Development , 720 Cailun Road, Shanghai, 201203 China
| | - Yi Zhang
- Roche Innovation Center Shanghai, ‡Medicinal Chemistry, §Chemical Biology, ∥Pharmaceutical Sciences, and ⊥Discovery Virology, Roche Pharma Research and Early Development , 720 Cailun Road, Shanghai, 201203 China
| | - Xiaoyue Wu
- Roche Innovation Center Shanghai, ‡Medicinal Chemistry, §Chemical Biology, ∥Pharmaceutical Sciences, and ⊥Discovery Virology, Roche Pharma Research and Early Development , 720 Cailun Road, Shanghai, 201203 China
| | - Liping Shi
- Roche Innovation Center Shanghai, ‡Medicinal Chemistry, §Chemical Biology, ∥Pharmaceutical Sciences, and ⊥Discovery Virology, Roche Pharma Research and Early Development , 720 Cailun Road, Shanghai, 201203 China
| | - Fang Shen
- Roche Innovation Center Shanghai, ‡Medicinal Chemistry, §Chemical Biology, ∥Pharmaceutical Sciences, and ⊥Discovery Virology, Roche Pharma Research and Early Development , 720 Cailun Road, Shanghai, 201203 China
| | - Yi Mao
- Roche Innovation Center Shanghai, ‡Medicinal Chemistry, §Chemical Biology, ∥Pharmaceutical Sciences, and ⊥Discovery Virology, Roche Pharma Research and Early Development , 720 Cailun Road, Shanghai, 201203 China
| | - Xue Zhou
- Roche Innovation Center Shanghai, ‡Medicinal Chemistry, §Chemical Biology, ∥Pharmaceutical Sciences, and ⊥Discovery Virology, Roche Pharma Research and Early Development , 720 Cailun Road, Shanghai, 201203 China
| | - Wengang Yang
- Roche Innovation Center Shanghai, ‡Medicinal Chemistry, §Chemical Biology, ∥Pharmaceutical Sciences, and ⊥Discovery Virology, Roche Pharma Research and Early Development , 720 Cailun Road, Shanghai, 201203 China
| | - Jim Z Wu
- Roche Innovation Center Shanghai, ‡Medicinal Chemistry, §Chemical Biology, ∥Pharmaceutical Sciences, and ⊥Discovery Virology, Roche Pharma Research and Early Development , 720 Cailun Road, Shanghai, 201203 China
| | - Guang Yang
- Roche Innovation Center Shanghai, ‡Medicinal Chemistry, §Chemical Biology, ∥Pharmaceutical Sciences, and ⊥Discovery Virology, Roche Pharma Research and Early Development , 720 Cailun Road, Shanghai, 201203 China
| | - Alexander V Mayweg
- Roche Innovation Center Shanghai, ‡Medicinal Chemistry, §Chemical Biology, ∥Pharmaceutical Sciences, and ⊥Discovery Virology, Roche Pharma Research and Early Development , 720 Cailun Road, Shanghai, 201203 China
| | - Hong C Shen
- Roche Innovation Center Shanghai, ‡Medicinal Chemistry, §Chemical Biology, ∥Pharmaceutical Sciences, and ⊥Discovery Virology, Roche Pharma Research and Early Development , 720 Cailun Road, Shanghai, 201203 China
| | - Guozhi Tang
- Roche Innovation Center Shanghai, ‡Medicinal Chemistry, §Chemical Biology, ∥Pharmaceutical Sciences, and ⊥Discovery Virology, Roche Pharma Research and Early Development , 720 Cailun Road, Shanghai, 201203 China
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Pietrzak-Nguyen A, Piradashvili K, Fichter M, Pretsch L, Zepp F, Wurm FR, Landfester K, Gehring S. MPLA-coated hepatitis B virus surface antigen (HBsAg) nanocapsules induce vigorous T cell responses in cord blood derived human T cells. NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE 2016; 12:2383-2394. [PMID: 27516081 DOI: 10.1016/j.nano.2016.07.010] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/17/2016] [Revised: 07/18/2016] [Accepted: 07/23/2016] [Indexed: 02/06/2023]
Abstract
Chronic hepatitis B virus (HBV) infection is the most prevalent serious liver infection in the world. A frequent route of infection represents mother-to-child transmission. Efficient control of HBV replication depends on antigen-specific cellular immune response mediated by dendritic cells (DCs). Aim of the present study was to evaluate optimized adjuvant combinations, efficiently maturing monocyte-derived neonatal and adult dendritic cells (moDCs). In addition, the potential of polymeric HBsAg-nanocapsules (HBsAg-NCs) was investigated regarding up-take by moDCs and the subsequent induction of specific T cell responses in a human co-culture model. Simultaneous stimulation of moDCs with MPLA and IFNγ induced up-regulation of CD80 and HLA-DR along with vigorous secretion of IL-12p70. MPLA-coating of HBsAg-NCs promoted NCs-uptake by moDCs. Finally, MPLA-HBsAg-NCs-pulsed moDCs with IFNγ increased T cell proliferation and induced antigen-specific IFNγ release by T cells. The herein presented vaccine approach provides a rational for neonatal and therapeutic immunization strategies against HBV.
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Affiliation(s)
- Anette Pietrzak-Nguyen
- Children's Hospital, University Medical Center, Johannes-Gutenberg University, Mainz, Germany
| | | | - Michael Fichter
- Children's Hospital, University Medical Center, Johannes-Gutenberg University, Mainz, Germany
| | - Leah Pretsch
- Children's Hospital, University Medical Center, Johannes-Gutenberg University, Mainz, Germany
| | - Fred Zepp
- Children's Hospital, University Medical Center, Johannes-Gutenberg University, Mainz, Germany
| | | | | | - Stephan Gehring
- Children's Hospital, University Medical Center, Johannes-Gutenberg University, Mainz, Germany.
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31
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Leng XJ, Yan XB. Status and development of anti-HBV drugs based on "HBF drug watch". Shijie Huaren Xiaohua Zazhi 2016; 24:2336-2346. [DOI: 10.11569/wcjd.v24.i15.2336] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) infection is a major public health threat globally. Present therapies can only suppress viral replication instead of viral elimination. With the application of direct anti-viral agents (DAAs) to hepatitis C virus (HCV) infection, many pharmaceutical industries pay their attention to investigating anti-HBV drugs. As a result, the update of anti-HBV drugs at the website http://www.hepb.org/professionals/hbf_drug_watch.htm speeds up. In this review, we summarize all the drugs available in the market and those in clinical trials based on this website.
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