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1.
Medicine (Baltimore) ; 99(33): e20877, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32871973

RESUMO

OBJECTIVE: The purpose of this study was to evaluate the efficacy of different nucleos(t)ide analogues in the prognosis of HBV-related hepatocellular carcinoma (HCC) patients after curative treatment by network meta-analysis. METHODS: Literature retrieval was conducted in globally recognized databases, namely, PubMed, EMBASE, Cochrane Library databases, and Science Citation Index Expanded, to address relative studies investigating nucleot(s)ide analogues for HBV-related HCC patients after curative resection. Relative parametric data, including 1-, 3-, and 5-year overall survival rate and 1-, 3-, and 5-year recurrence-free survival rate were quantitatively pooled and estimated. The inconsistency factor, the cumulative ranking curve, and the publication bias were evaluated. RESULTS: Fourteen observational studies of 2481 adults performed between 2000 and 2019 were eligible. In terms of overall survival, ADV (Adefovir dipivoxil) (Odds ratio (OR): 2.35, 95% confidence interval (CI): 1.17-4.73), Lamivudine (OR: 2.08, 95% CI: 1.78-5.58), and Entecavir (OR: 2.14, 95% CI: 1.59-2.88) were found to be more beneficial than control group while ADV has the highest probability of having the most efficacious treatment (SCURA values 66.3) for 5-year overall survival. In late recurrence-free survival, ADV (OR = 1.88, 95% CI: 1.77-4.60), Entecavir (OR = 1.96, 95% CI: 1.36-2.55), and Lamivudine (OR = 1.73, 95% CI: 1.06-2.82) all had better significant prognosis than patients without antiviral therapy postoperatively and patients with ADV as postoperative antiviral therapy has significantly recurrence-free survival benefit at 5-year follow-up compared to those undertaking Entecavir (OR = 1.96, 95% CI: 1.52-7.38) and Lamivudine (OR = 1.39, 95% CI: 1.09-3.01). Moreover, the application of ADV possessed the highest possibility of having the best clinical effects on 1- (surface under the cumulative ranking probabilities (SUCRA), 64.7), 3- (SUCRA, 64.7), and 5-year (SUCRA, 70.4) recurrence survival rate for HBV-related HCC patients. CONCLUSIONS: Patients with postoperative nucleos(t)ide analogues antiviral therapy had better survival benefit than those without antiviral therapy for HBV-related HCC patients after curative treatment. Additionally, nucleotide analogues like ADV and Tenofovir disoproxil fumarate has better impact on early and late recurrence-free survival of patients after curative treatment than those undertaking nucleoside analogues.


Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/terapia , Hepatite B/complicações , Hepatite B/tratamento farmacológico , Neoplasias Hepáticas/terapia , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/epidemiologia , Hepatite B/epidemiologia , Vírus da Hepatite B , Humanos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/epidemiologia , Metanálise em Rede
3.
J Immunother Cancer ; 8(2)2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32611687

RESUMO

The present review summarizes up-to-date evidence addressing the frequently discussed clinical controversies regarding the use of immune checkpoint inhibitors (ICIs) in cancer patients with viral infections, including AIDS, hepatitis B and C, progressive multifocal leukoencephalopathy, influenza, and COVID-19. In detail, we provide available information on (1) safety regarding the risk of new infections, (2) effects on the outcome of pre-existing infections, (3) whether immunosuppressive drugs used to treat ICI-related adverse events affect the risk of infection or virulence of pre-existing infections, (4) whether the use of vaccines in ICI-treated patients is considered safe, and (5) whether there are beneficial effects of ICIs that even qualify them as a therapeutic approach for these viral infections.


Assuntos
Imunossupressores/uso terapêutico , Neoplasias/complicações , Viroses/terapia , Betacoronavirus , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Hepatite B/complicações , Hepatite B/tratamento farmacológico , Hepatite B/imunologia , Hepatite B/terapia , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Hepatite C/imunologia , Hepatite C/terapia , Humanos , Influenza Humana/complicações , Influenza Humana/tratamento farmacológico , Influenza Humana/imunologia , Influenza Humana/terapia , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Viroses/complicações , Viroses/tratamento farmacológico , Viroses/imunologia
4.
PLoS One ; 15(7): e0228302, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32628668

RESUMO

Programmed death ligand 1 (PD-L1) has been recently shown to be a major obstacle to antiviral immunity by binding to its receptor programmed death 1 (PD-1) on specific IFN-γ producing T cells in chronic hepatitis B. Currently, IFN-α is widely used to treat hepatitis B virus (HBV) infection, but its antiviral effect vary greatly and the mechanism is not totally clear. We found that IFN-α/γ induced a marked increase of PD-L1 expression in hepatocytes. Signal and activators of transcription (Stat1) was then identified as a major transcription factor involved in IFN-α/γ-mediated PD-L1 elevation both in vitro and in mice. Blockage of the PD-L1/PD-1 interaction by a specific mAb greatly enhanced HBV-specific T cell activity by the gp96 adjuvanted therapeutic vaccine, and promoted HBV clearance in HBV transgenic mice. Our results demonstrate the IFN-α/γ-Stat1-PD-L1 axis plays an important role in mediating T cell hyporesponsiveness and inactivating liver-infiltrating T cells in the hepatic microenvironment. These data raise further potential interest in enhancing the anti-HBV efficacy of IFN-α and therapeutic vaccines.


Assuntos
Antígeno B7-H1/metabolismo , Vírus da Hepatite B/imunologia , Interferon-alfa/farmacologia , Interferon gama/farmacologia , Fator de Transcrição STAT1/metabolismo , Linfócitos T/imunologia , Regulação para Cima/efeitos dos fármacos , Animais , Anticorpos Monoclonais/uso terapêutico , Antígeno B7-H1/química , Antígeno B7-H1/genética , Antígeno B7-H1/imunologia , Sítios de Ligação , Linhagem Celular , Hepatite B/tratamento farmacológico , Hepatite B/veterinária , Antígenos de Superfície da Hepatite B/sangue , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , Receptor de Morte Celular Programada 1/metabolismo , Regiões Promotoras Genéticas , Fator de Transcrição STAT1/química , Linfócitos T/metabolismo
5.
Brasília; CONITEC; jun. 2020.
Não convencional em Português | BRISA/RedTESA | ID: biblio-1121768

RESUMO

CONTEXTO: a hepatite B crônica, causada pela infecção decorrente do vírus da hepatite B, tem sido um importante problema de saúde no mundo, afetando cerca de 350 milhões de pessoas mundialmente. Estima-se que mais de 786 mil indivíduos morrem anualmente por conta de suas complicações. O transplante de fígado é considerado padrão-ouro no tratamento da insuficiência hepática e do carcinoma hepatocelular relacionados ao vírus da hepatite B. No entanto, a reativação viral pós-transplante pode ser prejudicial à função do aloenxerto, levando a uma baixa sobrevida e, consequentemente, se configura como grande desafio na prática clínica. A profilaxia da reinfecção pelo vírus da hepatite B pós-transplante hepático é preconizada pelo PCDT, do Ministério da Saúde, por meio da utilização de lamivudina e imunoglobulina humana anti-hepatite B, sendo esta última utilizada na dose de 800 UI ao dia, durante boa parte do tratamento. TECNOLOGIA: imunoglobulina humana anti-hepatite B, na apresentação de 1.000 UI. JUSTIFICATIVA DA DEMANDA: atualmente faz-se a composição de dose por meio de um frasco contendo imunoglobulina humana anti-hepatite B 600 UI ou 500 UI juntamente com frascos de 100 UI. Contudo, devido a questões contratuais com a fabricante, a Coordenação-Geral do Componente Especializado da Assistência Farmacêutica (CGCEAF/DAF/SCTIE/MS) distribuirá a apresentação de 1.000 UI, de forma excepcional. No entanto, atualmente, esta apresentação não consta na Relação Nacional de Medicamentos Essenciais (Rename). Desse modo, apesar da imunoglobulina humana anti-hepatite B já estar incorporada no SUS, foi solicitada a inclusão da apresentação de 1.000 UI do medicamento. DELIBERAÇÃO FINAL: o Plenário da Conitec, em sua 87ª Reunião Ordinária, realizada nos dias 03 e 04 de junho de 2020, deliberou por unanimidade recomendar a incorporação da apresentação de 1.000 UI do medicamento imunoglobulina humana anti-hepatite B no SUS. Assim, foi assinado o registro de deliberação nº 524/2020. DECISÃO: Incorporar a apresentação de 1.000 UI do medicamento imunoglobulina humana anti-hepatite B, no âmbito do Sistema Único de Saúde - SUS, conforme Portaria nº 30, publicada no Diário Oficial da União nº 160, seção 1, página 118, em 20 de agosto de 2020.


Assuntos
Humanos , Imunoglobulinas/uso terapêutico , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B/tratamento farmacológico , Avaliação da Tecnologia Biomédica , Sistema Único de Saúde , Brasil , Análise Custo-Benefício/economia
8.
Medicine (Baltimore) ; 99(16): e19886, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32312015

RESUMO

BACKGROUND: This study aims at evaluating the benefits and harms of hepatitis B immune globulin (HBIG) and hepatitis B vaccine (HBVac) in preventing mother to child transmission in HBV surface antigen (HBsAg) positive pregnant women during antenatal period. METHODS: Seven electronic databases including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), WanFang Database, Chinese Biomedical Literature Database (CBM), VIP Database for Chinese Technical Periodicals (VIP), and 3 clinical trial registry platforms were searched from inception date to December 2017. Only randomized controlled trials (RCTs) were included in this study. The Cochrane risk of bias tool was applied to assessing the risk of bias. The outcomes were analyzed by Review Manager 5.3 software. RESULTS: Sixteen RCTs involving 2440 HBsAg positive pregnant women were included in the meta-analysis. Compared with placebo group, HBIG and HBVac group had a significant decrease in the number of newborns who were HBsAg positive (relative risks [RR]: 0.2, 95% confidence interval [CI] [0.18, 0.40], P < .00001) and HBV-DNA positive (RR: 0.25, 95% CI [0.09, 0.71], P = .010), and had a significant increase in the number of anti-HBs positive newborns (RR: 3.95, 95% CI [3.11, 5.00], P < .00001). After 1-year follow up, the number of HBsAg positive newborns continued to decline (RR: 0.09, 95% CI [0.04, 0.20], P < .00001) and the number of anti-HBs positive newborns continued to increase in HBIG and HBVac group (RR: 1.30, 95% CI [1.22, 1.38], P < .00001). Compared with HBIG group, HBIG and HBVac group had no significant difference in the number of HBsAg positive newborns (RR: 1.68, 95% CI [0.66, 4.30], P = .28), and had a significant decrease in the number of HBsAg positive newborns (RR: 0.31, 95% CI [0.12, 0.84], P = .02). Additionally, only 1 study reported 2 swelling cases, 4 studies were reported no adverse events, and 11 studies were not report adverse reaction. CONCLUSIONS: HBIG and HBVac could be an effective alternative for HBsAg positive pregnant women to prevent mother to child transmission. However, due to the limitations of the study, the long-term efficacy and safety of HBIG and HBVac still need long-term and high-quality research to confirm.


Assuntos
Vacinas contra Hepatite B/administração & dosagem , Hepatite B/tratamento farmacológico , Imunoglobulinas/administração & dosagem , Transmissão Vertical de Doença Infecciosa/prevenção & controle , China/epidemiologia , DNA Viral/genética , Feminino , Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/imunologia , Vacinas contra Hepatite B/uso terapêutico , Vírus da Hepatite B/imunologia , Humanos , Imunoglobulinas/uso terapêutico , Recém-Nascido , Gravidez , Complicações Infecciosas na Gravidez/virologia , Cuidado Pré-Natal/normas , Ensaios Clínicos Controlados Aleatórios como Assunto
9.
Nat Rev Drug Discov ; 19(3): 149-150, 2020 03.
Artigo em Inglês | MEDLINE | ID: covidwho-606
11.
BMC Infect Dis ; 20(1): 230, 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32188424

RESUMO

BACKGROUND: Hepatitis B virus (HBV) infection is a major public health problem worldwide. More than 2 billion people have been exposed to HBV, and about 257 million individuals are chronic carriers of HBV. HBV reactivation has been increasingly reported in HBV carriers who have undergone immunosuppression or chemotherapy, resulting in mortality. Treatment of hypothalamic/pituitary tumors in HBV carriers requires extensive care to avoid HBV reactivation as steroid therapy is required after surgery for hypothalamic/pituitary tumors. CASE PRESENTATION: This retrospective review identified 5 patients, who were HBV carriers positive for hepatitis B surface antigen among 1352 patients with surgically treated hypothalamic/pituitary tumor in Kohnan Hospital between February 2007 and April 2017. Transsphenoidal surgery was performed with particular attention to prevent damage to the pituitary gland, with delicate manipulation to minimize postoperative steroid coverage. All patients received nucleot(s)ide analogue to control HBV-DNA levels before the surgery. As a result, all patients had a good clinical course. Blood examinations found a transient increase of liver enzymes and HBV-DNA levels in all patients, which started to decrease within 2 weeks after surgery. No specific treatment other than nucleot(s)ide analogues was needed to maintain liver function, and all patients returned to their previous activities including reinstatement. CONCLUSION: Initiation of nucleot(s)ide analogues administration prior to the surgery for hypothalamic/pituitary tumors can be an effective strategy for preventing reactivation in HBV carriers. Appropriate screening of the patient's HBV phase, optimal timing of nucleot(s)ide analogues -administration, and administration period of nucleot(s)ide analogues need to be established.


Assuntos
Antivirais/uso terapêutico , Hepatite B/tratamento farmacológico , Neoplasias Hipotalâmicas/cirurgia , Neoplasias Hipofisárias/cirurgia , Idoso , DNA Viral/sangue , Feminino , Guanina/análogos & derivados , Guanina/uso terapêutico , Hepatite B/virologia , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/patogenicidade , Vírus da Hepatite B/fisiologia , Humanos , Neoplasias Hipotalâmicas/virologia , Imunossupressão , Lamivudina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/virologia , Estudos Retrospectivos , Esteroides/uso terapêutico , Ativação Viral/efeitos dos fármacos
12.
Artigo em Inglês | MEDLINE | ID: mdl-32164970

RESUMO

Emtricitabine (Emtriva, FTC) is an antiviral medicine which decreases the body's amount of HIV. Emtricitabine on of Anti-HIV drugs slow down or protect the immune system against damage and reduce the risk of diseases related to developing of AIDS. Emtricitabine use also for treatment of hepatitis B virus. Emtricitabine is a drug class known as nucleoside reversing transcriptase inhibitors (NRTIs). In view of Emtricitabine's clinical significance, a thorough review of the physical and pharmaceutical characteristics and details of the multiple analytical techniques used to test the drug in pharmaceutical and biological systems was conducted. The methods investigated include identification test, Spectroscopy, chromatography, electrochemicals, and Thermal. Beside the analytical profile, the degradation and stability of Emtricitabine, its pharmacology and pharmacokinetics, Pharmaceutical Applications, Mechanism of Action, dosage forms and dose, ADME profile, and interactions have been debated.


Assuntos
Fármacos Anti-HIV/farmacologia , Emtricitabina/farmacologia , Inibidores da Transcriptase Reversa/farmacologia , Infecções por HIV/tratamento farmacológico , Hepatite B/tratamento farmacológico , Humanos
13.
Nat Rev Drug Discov ; 19(3): 149-150, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32127666
14.
Artigo em Inglês | MEDLINE | ID: mdl-32074216

RESUMO

For pregnant women with high viral load, antiviral therapy has been administered in addition to active and passive immune prophylaxis as a crucial adjunctive therapy to interrupt mother-to-child hepatitis B virus (HBV) transmission (MTCT). However, the time of antiviral therapy onset remains controversial. A systematic review and meta-analysis was conducted to compare the efficacy of antiviral therapy during the second or the third trimester for prevention of HBV vertical transmission. We searched nine databases for observational studies and randomized controlled trials that enrolled pregnant women with positive HBsAg treated with antivirals. The outcomes of interest were maternal HBV-DNA levels prior to delivery and the rates of HBV MTCT. We included nine studies that enrolled 1,502 pregnant women. The average HBV-DNA level before treatment was approximately 8 log10 copies/mL. Compared to the onset of antiviral intervention in the third trimester, the beginning of treatment in the second trimester distinctly reduced maternal predelivery HBV-DNA levels. However, no significant difference in HBV MTCT was found between the second and third trimester groups. Furthermore, the subgroup analysis showed that there were no significant differences between groups beginning treatment at different times (second or third trimester) with regard to HBV MTCT or other evaluated endpoints. For pregnant women with HBV-DNA levels less than or equal to 8 log10 copies/mL, the beginning of antiviral treatment can be delayed until the third trimester.


Assuntos
Antivirais/administração & dosagem , Hepatite B/tratamento farmacológico , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/virologia , Feminino , Hepatite B/prevenção & controle , Hepatite B/transmissão , Humanos , Recém-Nascido , Gravidez , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Carga Viral
15.
Public Health Rep ; 135(2): 202-210, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32027559

RESUMO

OBJECTIVE: Daily tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) use as HIV preexposure prophylaxis (PrEP) is monitored by identifying TDF/FTC prescriptions from pharmacy databases and applying diagnosis codes and antiretroviral data to algorithms that exclude TDF/FTC prescribed for HIV postexposure prophylaxis (PEP), HIV treatment, and hepatitis B virus (HBV) treatment. We evaluated the accuracy of 3 algorithms used by the Centers for Disease Control and Prevention (CDC), Gilead Sciences, and the New York State Department of Health (NYSDOH) using a reference population in Bronx, New York. METHODS: We extracted diagnosis codes and data on all antiretroviral prescriptions other than TDF/FTC from an electronic health record database for persons aged ≥16 prescribed TDF/FTC during July 2016-June 2018 at Montefiore Medical Center. We reviewed medical records to classify the true indication of first TDF/FTC use as PrEP, PEP, HIV treatment, or HBV treatment. We applied each algorithm to the reference population and compared the results with the medical record review. RESULTS: Of 2862 patients included in the analysis, 694 used PrEP, 748 used PEP, 1407 received HIV treatment, and 13 received HBV treatment. The algorithms had high specificity (range: 98.4%-99.0%), but the sensitivity of the CDC algorithm using a PEP definition of TDF/FTC prescriptions ≤30 days was lower (80.3%) than the sensitivity of the algorithms developed by Gilead Sciences (94.7%) or NYSDOH (96.1%). Defining PEP as TDF/FTC prescriptions ≤28 days improved CDC algorithm performance (sensitivity, 95.8%; specificity, 98.8%). CONCLUSIONS: Adopting the definition of PEP as ≤28 days of TDF/FTC in the CDC algorithm should improve the accuracy of national PrEP surveillance.


Assuntos
Algoritmos , Infecções por HIV/prevenção & controle , Profilaxia Pré-Exposição/estatística & dados numéricos , Adolescente , Adulto , Idoso , Fármacos Anti-HIV/uso terapêutico , Registros Eletrônicos de Saúde , Emtricitabina/uso terapêutico , Feminino , Infecções por HIV/tratamento farmacológico , Hepatite B/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque , Profilaxia Pós-Exposição/estatística & dados numéricos , Tenofovir/uso terapêutico
16.
Lancet Gastroenterol Hepatol ; 5(4): 406-417, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32057301

RESUMO

Chronic hepatitis B virus (HBV) infection follows a dynamic and variable course. At different stages in the disease, hepatitis flares might occur, which can be challenging to predict and manage. Flares are believed to be primarily immune-mediated and might mark transitions to inactive disease or clearance of infection, but in certain scenarios they might also lead to hepatic decompensation or death. As such, understanding of the clinical significance of flares in different patient populations and different scenarios is important for optimal management. In this Review, we summarise what is known about flares in different stages of chronic HBV infection; describe flares in the context of the natural history of chronic infection; summarise the immunological mechanisms underlying flares, and describe flares in different clinical scenarios. Each section reviews existing knowledge and highlights key unanswered questions that need to be addressed to improve the understanding of flares, hopefully providing insights into their pathogenesis that can be used to improve current clinical management and ideally to further develop new curative therapeutic approaches for HBV infection. We also propose a working definition of an ALT flare to facilitate future research.


Assuntos
Alanina Transaminase/sangue , DNA Viral/sangue , Vírus da Hepatite B/genética , Hepatite B Crônica/imunologia , Hepatite B/imunologia , Antivirais/uso terapêutico , Linfócitos B/imunologia , Quimiocinas/imunologia , Citocinas/imunologia , Feminino , Hepatite B/tratamento farmacológico , Hepatite B/virologia , Antígenos de Superfície da Hepatite B/sangue , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/virologia , Humanos , Células Matadoras Naturais/imunologia , Macrófagos do Fígado/imunologia , Masculino , Células Supressoras Mieloides/imunologia , Nucleosídeos/uso terapêutico , Exacerbação dos Sintomas , Linfócitos T/imunologia
17.
BMC Complement Med Ther ; 20(1): 37, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32024508

RESUMO

BACKGROUND: Yiganling (YGL) capsule is a traditional Chinese medicine preparation consisting of eight herbs that has been clinically proven to have a favorable treatment effect on Hepatitis B (HB). However, due to its multiple targets and multi-pharmacological effects, the mechanisms of YGL capsule in the treatment of HB are unknown. METHODS: First, the chemical constituents of YGL capsules were obtained from the Chinese medicine database, and YGL capsules were constructed. Second, active compounds were screened by the ADME model. The target fishing model was used to screen the corresponding targets of active compounds and to construct a compounds and compound targets network. Using human disease databases and literature mining, we systematically identified genes associated with HB, constructed disease-specific protein-protein interaction networks, and performed clustering and enrichment analyses of these networks. These networks were then merged to obtain a compound-disease target network, and cluster and enrichment analyses were performed on the compound-disease target network to acquire a compounds-disease targets-mechanism network and a clustering network. RESULTS: We successfully built eight pharmacological network diagrams, including four primary networks and other network maps. The four dominating network maps included a HB disease-associated protein-protein interaction network, a YGL capsule compounds-target network, a YGL capsule ingredient target-HB disease target network, and a YGL-HB disease mechanism network. Other networks included a pathway of HB disease targets, the HB disease protein-protein interaction cluster analysis network, and the YGL-HB target clustering network. CONCLUSION: This study successfully forecasted, illuminated, and confirmed the synergistic effects of HB disease molecules and discovered the potential of HB relevant targets, clusters, and target-related biological processes and signaling pathways. Our research not only provides theoretical support for the molecular and pharmacological mechanisms of YGL capsule in HB treatment, but also provides new research methods for the study of the other traditional Chinese medicinal compounds.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Hepatite B/tratamento farmacológico , Mapas de Interação de Proteínas , Cápsulas , Humanos , Medicina Tradicional Chinesa
18.
BMC Infect Dis ; 20(1): 84, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31996147

RESUMO

BACKGROUND: Hepatitis B virus (HBV) infection is a global health problem and interferon-alpha (IFN-α) is one of the effective therapies. However, little is known about the genetic background of the HBV infection or the genetic determinants of the IFN-α treatment response. Thus, we aim to explore the possible molecular mechanisms of HBV infection and its response to the IFN-α therapy with a comprehensive bioinformatics analysis. METHODS: The Gene Expression Omnibus datasets (GSE83148, GSE84044 and GSE66698) were collected and the differentially expressed genes (DEGs), key biological processes and intersecting pathways were analyzed. The expression of the co-expressed DEGs in the clinical samples was verified by quantitative real time polymerase chain reaction (qRT-PCR). RESULTS: Analysis of all the 3 datasets revealed that there were eight up-regulated and one down-regulated co-expressed DEGs following the HBV infection and after IFN-α treatment. In clinical samples, the mRNA level of HKDC1, EPCAM, GSN, ZWINT and PLD3 were significantly increased, while, the mRNA level of PLEKHA2 was significantly decreased in HBV infected liver tissues compared to normal liver tissues. PI3K-Akt signaling pathway, focal adhesion, HTLV-I infection, cytokine-cytokine receptor interaction, metabolic pathways, NF-κB signaling pathway were important pathways associated with the HBV infection and the response of IFN-α treatment. CONCLUSIONS: The co-expressed genes, common biological processes and intersecting pathways identified in the study might play an important role in HBV infection and response of IFN-α treatment. The dysregulated genes may act as novel biomarkers and therapeutic targets for HBV.


Assuntos
Biologia Computacional , Redes Reguladoras de Genes , Vírus da Hepatite B/imunologia , Hepatite B/imunologia , Interferon-alfa/uso terapêutico , Transdução de Sinais , Conjuntos de Dados como Assunto , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Hepatite B/tratamento farmacológico , Hepatite B/virologia , Humanos , Fígado/imunologia , Fígado/virologia , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real
19.
BMC Infect Dis ; 20(1): 49, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31941464

RESUMO

BACKGROUND: Hepatitis B is a major concern in Africa, especially in HIV-infected patients. Unfortunately, access to hepatitis B virus (HBV) testing and adequate treatment remains a challenge in the continent. We investigated HBV testing, treatment, and virologic suppression in HIV-infected patients followed up as part of Cameroon's national antiretroviral programme. METHODS: A cross-sectional survey was performed in adult patients receiving antiretroviral therapy (ART) in 19 hospitals in the Centre and Littoral regions in Cameroon. The proportions of patients tested for hepatitis B surface antigen (HBsAg) prior to the study were compared among all study hospitals using the Chi-square test. The association of individual and hospital-related characteristics with HBV testing and virologic suppression was assessed using multilevel logistic regression models. RESULTS: Of 1706 patients (women 74%, median age 42 years, median time on ART 3.9 years), 302 (17.7%) had been tested for HBsAg prior to the study. The proportion of HBV-tested patients ranged from 0.8 to 72.5% according to the individual hospital (p < 0.001). HBV testing was lower in women (adjusted odds ratio [aOR] 0.64, 95% confidence interval [CI] 0.46-0.89, p = 0.010) and higher in patients who initiated ART in 2010 or later (aOR 1.66, 95% CI 1.23-2.27, p < 0.001). Of 159 HBsAg-positive patients at the time of the study (9.3%), only 97 (61.0%) received Tenofovir + Lamivudine (or Emtricitabine). Of 157 coinfected patients, 114 (72.6%) had a HBV viral load < 10 IU/mL. HBV suppression was higher in patients with a HIV viral load < 300 copies/mL (aOR 3.46, 95% CI 1.48-8.09, p = 0.004) and lower in patients with increased ALT level (aOR 0.86 per 10 IU/mL increase, 95% CI 0.75-0.97, p = 0.019). CONCLUSIONS: A substantial proportion of HIV/HBV coinfected patients were at higher risk of liver disease progression. Improving the management of HBV infection in the routine healthcare setting in Africa is urgently required in order to achieve the 2030 elimination targets. Micro-elimination of HBV infection in people living with HIV could be an easier and cost-effective component than more widely scaling up HBV policies.


Assuntos
Coinfecção/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Vírus da Hepatite B/genética , Hepatite B/tratamento farmacológico , Hepatite B/virologia , Resposta Viral Sustentada , Adulto , Antirretrovirais/uso terapêutico , Camarões , Estudos Transversais , Feminino , Seguimentos , Genótipo , Antígenos de Superfície da Hepatite B/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Saúde Pública , Carga Viral
20.
PLoS One ; 15(1): e0227231, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31923260

RESUMO

A platform capable of specifically delivering an antiviral drug to the liver infected with hepatitis B is a major concern in hepatology. Vaccination has had a major effect on decreasing the emerging numbers of new cases of infection. However, the total elimination of the hepatitis B virus from the body requires prolonged therapy. In this work, we aimed to target the liver macrophages with lipid polymer hybrid nanoparticles (LPH), combining the merit of polymeric nanoparticles and lipid vesicles. The hydrophilic antiviral drug, entecavir (E), loaded LPH nanoparticles were optimized and physicochemically characterized. A modulated lipidic corona, as well as, an additional coat with vitamin E were used to extend the drug release enhance the macrophage uptake. The selected vitamin E coated LPH nanoparticles enriched with lecithin-glyceryl monostearate lipid shell exhibited high entrapment for E (80.47%), a size ≤ 200 nm for liver passive targeting, extended release over one week, proven serum stability, retained stability after refrigeration storage for 6 months. Upon macrophage uptake in vitro assessment, the presented formulation displayed promising traits, enhancing the cellular retention in J774 macrophages cells. In vivo and antiviral activity futuristic studies would help in the potential application of the ELPH in hepatitis B control.


Assuntos
Antivirais/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Guanina/análogos & derivados , Hepatite B/metabolismo , Lipídeos/química , Macrófagos/efeitos dos fármacos , Nanopartículas/química , Polímeros/química , Vitamina E/química , Animais , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Eritrócitos/efeitos dos fármacos , Guanina/administração & dosagem , Guanina/farmacologia , Guanina/uso terapêutico , Hepatite B/tratamento farmacológico , Masculino , Camundongos , Ratos
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