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1.
FASEB J ; 35(6): e21680, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34042225

RESUMO

Hepatitis B virus (HBV) is a human hepatotropic pathogen causing hepatocellular carcinoma. We recently obtained HBV-susceptible immortalized human hepatocyte NKNT-3 by exogenously expressing NTCP and its derived cell clones, #28.3.8 and #28.3.25.13 exhibiting different levels of HBV susceptibility. In the present study, we showed that HBV infection activated the ATM-Chk2 signaling pathway in #28.3.25.13 cells but not in #28.3.8 cells. Both the cell culture supernatant and extracellular vesicles (EVs) derived from HBV-infected #28.3.25.13 cells also activated the ATM-Chk2 signaling pathway in naïve #28.3.25.13 cells. Interestingly, EVs derived from HBV-infected #28.3.25.13 cells included higher level of mitochondrial DNA (mtDNA) than those from HBV-infected #28.3.8 cells. Based on our results, we propose the novel model that EVs mediate the activation of ATM-Chk2 signaling pathway by the intercellular transfer of mtDNA in HBV-infected human hepatocyte.


Assuntos
Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Quinase do Ponto de Checagem 2/metabolismo , DNA Mitocondrial/genética , Vesículas Extracelulares/metabolismo , Hepatite B/patologia , Hepatócitos/patologia , Replicação Viral , Proteínas Mutadas de Ataxia Telangiectasia/genética , Quinase do Ponto de Checagem 2/genética , DNA Mitocondrial/metabolismo , Células Hep G2 , Hepatite B/genética , Hepatite B/metabolismo , Hepatite B/microbiologia , Vírus da Hepatite B/fisiologia , Hepatócitos/metabolismo , Hepatócitos/microbiologia , Humanos
2.
Front Immunol ; 12: 636803, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33841420

RESUMO

Commensal gut microbiota protects the immune defense of extra-intestinal organs. Gut microbiota depletion by antibiotics can impair host antiviral immune responses and alter hepatitis B virus (HBV) infection outcomes. However, how gut microbiota modulates antiviral immune response in the liver remains unclear. Here, mice were treated with broad-spectrum antibiotics to deplete gut microbiota. Gut integrity was evaluated, and translocation of live commensal gut bacteria and their components into the liver was investigated. An HBV infection model was established to evaluate impairment of antiviral immune response in the liver after gut microbiota depletion. We found that gut microbiota depletion was associated with impairment of colon epithelial integrity, and live commensal gut microbiota could translocate to the liver. Further, T cell antiviral function in the liver was impaired, partially relying on enhanced PD-1 expression, and HBV immune clearance was hampered. In conclusion, gut microbiota depletion by antibiotics can impair gut barrier function and suppress T cell antiviral immune response in the liver.


Assuntos
Colo/patologia , Microbioma Gastrointestinal/fisiologia , Vírus da Hepatite B/fisiologia , Hepatite B/imunologia , Mucosa Intestinal/fisiologia , Fígado/imunologia , RNA Ribossômico 16S/genética , Linfócitos T/imunologia , Animais , Antibacterianos/administração & dosagem , Translocação Bacteriana , Células Cultivadas , Modelos Animais de Doenças , Fezes/microbiologia , Hepatite B/microbiologia , Humanos , Imunidade , Fígado/virologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Receptor de Morte Celular Programada 1/metabolismo , Regulação para Cima , Carga Viral
3.
Front Immunol ; 12: 755890, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35069530

RESUMO

Hepatitis B virus (HBV) co-infection is fairly common in people living with HIV (PLWH) and affects millions of people worldwide. Identical transmission routes and HIV-induced immune suppression have been assumed to be the main factors contributing to this phenomenon. Moreover, convergent evidence has shown that people co-infected with HIV and HBV are more likely to have long-term serious medical problems, suffer more from liver-related diseases, and have higher mortality rates, compared to individuals infected exclusively by either HIV or HBV. However, the precise mechanisms underlying the comorbid infection of HIV and HBV have not been fully elucidated. In recent times, the human gastrointestinal microbiome is progressively being recognized as playing a pivotal role in modulating immune function, and is likely to also contribute significantly to critical processes involving systemic inflammation. Both antiretroviral therapy (ART)-naïve HIV-infected subjects and ART-treated individuals are now known to be characterized by having gut microbiomic dysbiosis, which is associated with a damaged intestinal barrier, impaired mucosal immunological functioning, increased microbial translocation, and long-term immune activation. Altered microbiota-related products in PLWH, such as lipopolysaccharide (LPS) and short-chain fatty acids (SCFA), have been associated with the development of leaky gut syndrome, favoring microbial translocation, which in turn has been associated with a chronically activated underlying host immune response and hence the facilitated pathogenesis of HBV infection. Herein, we critically review the interplay among gut microbiota, immunity, and HIV and HBV infection, thus laying down the groundwork with respect to the future development of effective strategies to efficiently restore normally diversified gut microbiota in PLWH with a dysregulated gut microbiome, and thus potentially reduce the prevalence of HBV infection in this population.


Assuntos
Coinfecção , Microbioma Gastrointestinal , Infecções por HIV , HIV-1/imunologia , Vírus da Hepatite B/imunologia , Hepatite B , Coinfecção/tratamento farmacológico , Coinfecção/imunologia , Coinfecção/microbiologia , Coinfecção/virologia , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/imunologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Infecções por HIV/microbiologia , Hepatite B/tratamento farmacológico , Hepatite B/imunologia , Hepatite B/microbiologia , Humanos
4.
Front Immunol ; 11: 578801, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33329547

RESUMO

Background: Vaccination remains one of the most effective means of reducing the burden of infectious diseases globally. Improving our understanding of the molecular basis for effective vaccine response is of paramount importance if we are to ensure the success of future vaccine development efforts. Methods: We applied cutting edge multi-omics approaches to extensively characterize temporal molecular responses following vaccination with hepatitis B virus (HBV) vaccine. Data were integrated across cellular, epigenomic, transcriptomic, proteomic, and fecal microbiome profiles, and correlated to final HBV antibody titres. Results: Using both an unsupervised molecular-interaction network integration method (NetworkAnalyst) and a data-driven integration approach (DIABLO), we uncovered baseline molecular patterns and pathways associated with more effective vaccine responses to HBV. Biological associations were unravelled, with signalling pathways such as JAK-STAT and interleukin signalling, Toll-like receptor cascades, interferon signalling, and Th17 cell differentiation emerging as important pre-vaccination modulators of response. Conclusion: This study provides further evidence that baseline cellular and molecular characteristics of an individual's immune system influence vaccine responses, and highlights the utility of integrating information across many parallel molecular datasets.


Assuntos
Genômica , Vacinas contra Hepatite B/uso terapêutico , Hepatite B/prevenção & controle , Imunogenicidade da Vacina , Biologia de Sistemas , Vacinação , Adulto , Idoso , Epigênese Genética , Epigenômica , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Hepatite B/genética , Hepatite B/metabolismo , Hepatite B/microbiologia , Anticorpos Anti-Hepatite B/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Mapas de Interação de Proteínas , Proteômica , Fatores de Tempo , Transcriptoma , Resultado do Tratamento
6.
Front Immunol ; 10: 927, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31114580

RESUMO

The ability of the host to clear hepatitis B virus (HBV) is closely correlated to the establishment of commensal microbiota. However, how microbiota affects anti-HBV immunity is still unclear. Using a well-known hydrodynamical HBV transfection mouse model and treatment with antibiotics (Atb), we explored the change in adaptive immunity (CD4+ cells, germinal center B cells and anti-HBs Ab). In our setting, normal mice exhibited complete clearance of HBV within 6 weeks post-hydrodynamic injection (HDI) of HBV-containing plasmid, whereas Atb-treated mice lost this capacity, showing high serum level of hepatitis B surface antigen (HBsAg) without hepatitis B surface antibodies (anti-HBs), similar as what happened in Rag1-/- mice or CD4-/- mice, suggesting that microbiota may influence the function of CD4+ T cells. Furthermore, the numbers of splenic and hepatic effector CD4+ T cells (CD44hiCD62L-CD4+ T cells) both decreased with impaired function (IFN-γ synthesis), resulting in lower frequency of germinal center B cells and CD4+ follicular helper T cells, and impaired anti-HBs production. We further tried to find the bacterial species responsible for maintaining anti-HBV immunity, and found that each antibiotic alone could not significantly influence HBV clearance compared to antibiotic combination, suggesting that global commensal microbial load is critical for promoting HBV clearance. We also confirmed that TLRs (e.g., TLR2, 4, 9) are not major players in immune clearance of HBV using their agonists and knock-out mice. These results suggest that commensal microbiota play an important role in maintaining CD4+ T cell immunity against HBV infection.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Vírus da Hepatite B/imunologia , Hepatite B/imunologia , Hepatite B/microbiologia , Imunidade Celular , Microbiota/imunologia , Animais , Linfócitos B/imunologia , Linfócitos B/patologia , Linfócitos T CD4-Positivos/patologia , Hepatite B/tratamento farmacológico , Hepatite B/patologia , Anticorpos Anti-Hepatite B/imunologia , Anticorpos Anti-Hepatite B/farmacologia , Antígenos de Superfície da Hepatite B/imunologia , Masculino , Camundongos , Camundongos Knockout , Receptores Toll-Like/imunologia
7.
Hepatobiliary Pancreat Dis Int ; 18(1): 19-27, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30527903

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world. Gut microbiota has been demonstrated to play a critical role in liver inflammation, chronic fibrosis, liver cirrhosis, and HCC development through the gut-liver axis. DATA SOURCES: Recently there have been several innovative studies investigating gut microbial dysbiosis-mediated enhancement of HCC through the gut-liver axis. Literatures from January 1998 to January 2018 were searched in the PubMed database using the keywords "gut microbiota" and "hepatocellular carcinoma" or "liver cancer", and the results of experimental and clinical studies were analyzed. RESULTS: Gut microbial dysbiosis accompanies the progression of alcoholic liver disease, non-alcoholic fatty liver disease and liver cirrhosis, and promotes HCC progression in an experimental mouse model. The immune system and key factors such as Toll-like receptor 4 are involved in the process. There is evidence for gut microbial dysbiosis in hepatitis virus-related HCC patients. CONCLUSIONS: Gut microbial dysbiosis is closely associated with hepatic inflammation disease and HCC through the gut-liver axis. With the enhanced understanding of the interactions between gut microbiota and liver through the gut-liver axis, new treatment strategies for HCC are being developed.


Assuntos
Carcinoma Hepatocelular/microbiologia , Disbiose , Microbioma Gastrointestinal , Neoplasias Hepáticas/microbiologia , Fígado/microbiologia , Animais , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/virologia , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Hepatite B/microbiologia , Hepatite B/virologia , Interações Hospedeiro-Patógeno , Humanos , Fígado/metabolismo , Fígado/patologia , Fígado/virologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Prognóstico , Fatores de Risco , Transdução de Sinais , Receptor 4 Toll-Like/metabolismo
8.
Am J Trop Med Hyg ; 98(1): 221-226, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29342404

RESUMO

The relationship between hepatitis B virus (HBV) infection, severity of liver disease, frequency of Helicobacter pylori infection, and degree of gastric lesions was not yet fully investigated in Egyptian patients. The present work was performed on 100 Egyptian patients with HBV from the National Hepatology and Tropical Medicine Institute and 70 healthy volunteers as control group. The participants were subjected to full medical history taking, clinical examination, and laboratory investigations. All patients were positive for HBV surface antigen (HBV sAg), HBV DNA, and negative for hepatitis C virus antibodies. The severity of the liver disease was assessed using Child-Pugh scoring system. Screening of all participants for H. pylori Ag in stool was performed. Biopsy specimens were taken from the gastric lesions of H. pylori-infected patients for histopathological examination. The mean age of the patients and control group were 34.9 and 33.4 years, respectively. The levels of the liver enzymes were statistically higher in HBV patients than the control group. Helicobacter pylori Ag in stool was detected in 45.7% of the control group, and a higher percentage (60%) was detected in the patients group. Chronic gastritis with glandular atrophy and metaplasia was found in 15.6% of patients of Child-Pugh A, 70% of Child-Pugh B, and 100% of Child-Pugh C. It could be concluded that the prognosis of the liver disease significantly influences the severity of the gastric pathology in H. pylori infection.


Assuntos
Coinfecção/patologia , Infecções por Helicobacter/complicações , Hepatite B/complicações , Estômago/patologia , Adulto , Estudos de Casos e Controles , Coinfecção/microbiologia , Coinfecção/virologia , Egito , Feminino , Infecções por Helicobacter/patologia , Infecções por Helicobacter/virologia , Helicobacter pylori , Hepatite B/microbiologia , Hepatite B/patologia , Humanos , Fígado/patologia , Fígado/virologia , Masculino , Índice de Gravidade de Doença , Estômago/microbiologia
9.
Enferm. infecc. microbiol. clín. (Ed. impr.) ; 35(supl.3): 9-14, oct. 2017. tab
Artigo em Espanhol | IBECS | ID: ibc-170745

RESUMO

Fundamentos: Las determinaciones de la carga viral de los virus de la inmunodeficiencia humana tipo 1 (VIH-1), de la hepatitis C (VHC) y de la hepatitis B (VHB) son marcadores microbiológicos fundamentales para el seguimiento y control de los pacientes infectados por estos virus. Los laboratorios de microbiología disponen de herramientas que garantizan la fiabilidad de sus resultados, entre ellas se encuentran los programas de intercomparación externos, como es el Programa de Control de Calidad de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (SEIMC). En el presente número se muestra el análisis de resultados del Programa de Control de Calidad SEIMC de carga viral de estos virus, incluyendo el genotipado del VHC, realizado durante el año 2015. Métodos y resultados: En el control del VIH-1 se remitieron 5 estándares, de los que 1 (plasma humano seronegativo) no contenía el virus y los otros 4 consistían en plasma de 3 pacientes virémicos distintos en un intervalo de concentraciones entre 2-5 log10 copias/ml; 2 de ellos eran idénticos, con el fin de analizar la repetibilidad. Una parte significativa de los laboratorios obtuvo de uno a varios resultados fuera de los límites aceptables (media ± 0,25 log10 copias/ml), dependiendo del estándar y del método empleado, en promedio el 26,6% de los centros. La repetibilidad fue excelente, y el 97,9% de los laboratorios obtuvo resultados aceptables (D < 0,5 log10 copias/ml). En los controles del VHC y del VHB se remitieron 2 estándares con diferente contenido del virus. La mayor parte de los participantes, un 88,5% en el caso del VHC y un 85,5% en el del VHB, obtuvo ambos resultados dentro de los límites de la media ± 1,96 DE log10 UI/ml. Conclusiones: Los resultados obtenidos ponen de manifiesto la utilidad de los controles externos para asegurar la calidad de los resultados analíticos, incluyendo la fase postanalítica. Debido a la variabilidad interlaboratorio es aconsejable utilizar un mismo método y el mismo laboratorio en el seguimiento de los pacientes (AU)


Background: Human immunodeficiency virus type 1 (HIV-1) and hepatitis B (HBV) and C virus (HCV) viral load determinations are among the most relevant markers for the follow up of patients infected with these viruses. External quality assessment schemes are crucial to ensure the accuracy of results obtained by microbiology laboratories. This article summarises the results obtained in the 2015 SEIMC External Quality Assessment Scheme for HIV-1, HCV, and HBV viral loads. Methods and results: In the HIV-1 programme, a total of 5 standards were sent. One standard consisted of seronegative human plasma, while the remaining four contained plasma from three different viraemic patients, in the range of 2-5 log10 copies/mL; 2 of these standards were identical, aiming to determine repeatability. A significant proportion of the laboratories (26.6% on average) obtained values outside the accepted range (mean ± 0.25 log10 copies/mL), depending on the standard and method used for quantification. Repeatability was excellent, with up to 97.9% of laboratories reporting results within the limits (D < 0.5 log10 copies/mL). The HBV and HCV programmes consisted of two standards with different viral load contents. Most of the participants, 88.5% in the case of HCV and 85.5% in the case of HBV, obtained all results within the accepted range (mean ± 1.96 SD log10 IU/mL). Conclusions: Data from this analysis reinforce the utility of proficiency programmes to ensure the quality of the results obtained by a particular laboratory, as well as the importance of the post-analytical phase in the overall quality. Due to the notable interlaboratory variability, it is advisable to use the same method and the same laboratory for patient follow up (AU)


Assuntos
Humanos , Controle de Qualidade , Carga Viral/métodos , Vírus da Hepatite B/isolamento & purificação , Hepacivirus/isolamento & purificação , HIV-1/isolamento & purificação , Carga Viral/normas , Hepatite C/epidemiologia , Hepatite C/microbiologia , Hepatite B/epidemiologia , Hepatite B/microbiologia , Síndrome da Imunodeficiência Adquirida/microbiologia , Biomarcadores , Sociedades Médicas/organização & administração , Sociedades Médicas/normas
10.
Artigo em Inglês | MEDLINE | ID: mdl-28382278

RESUMO

The presence of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) and the permanent integration of HBV DNA into the host genome confers the risk of viral reactivation and hepatocellular carcinoma. Nucleoside/nucleotide analogs alone have little or no capacity to eliminate replicative HBV templates consisting of cccDNA or integrated HBV DNA. Recently, CRISPR/Cas9 technology has been widely applied as a promising genome-editing tool, and HBV-specific CRISPR-Cas9 systems were shown to effectively mediate HBV cccDNA disruption. However, the integrated HBV DNA fragments are considered as important pro-oncogenic properties and it serves as an important template for viral replication and expression in stable HBV cell line. In this study, we completely excised a full-length 3,175-bp integrated HBV DNA fragment and disrupted HBV cccDNA in a stable HBV cell line. In HBV-excised cell line, the HBV cccDNA inside cells, supernatant HBV DNA, HBsAg, and HBeAg remained below the negative critical values for more than 10 months. Besides, by whole genome sequencing, we analyzed off-target effects and excluded cell contamination. It is the first time that the HBV infection has been fully eradicated in a stable HBV cell line. These findings demonstrate that the CRISPR-Cas9 system is a potentially powerful tool capable of promoting a radical or "sterile" HBV cure.


Assuntos
Sistemas CRISPR-Cas , Marcação de Genes , Vírus da Hepatite B/fisiologia , Hepatite B/microbiologia , Integração Viral , Sequência de Bases , Linhagem Celular , DNA Circular , Genoma Viral , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Replicação Viral
11.
Sci Rep ; 5: 15413, 2015 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-26634436

RESUMO

Bacterial infections are common in patients suffering viral hepatitis and critical for prognosis. However, any correlation between HBV and concomitant bacterial infections is not well characterized. A retrospective study was conducted from Jan 2012 to Jan 2014 on 1333 hospitalized patients infected with bacteria. Among them, 491 HBV-infected patients were co-infected with E. coli (268), S. aureus (61), P. aeruginosa (64) or K. pneumoniae (98). A group of 300 complication-free chronically HBV-infected patients were controls. We found that HBV DNA levels were elevated in patients with each of the bacterial infections (all P < 0.05). ALT and HBeAg were strong determinants of high HBV DNA concentration. Patterns of determinants varied in infections by Gram-positive and Gram-negative bacteria. Patients with HBV DNA ≥ 2000 IU/mL had higher rates of all four concomitant bacterial infections (all P < 0.001). All types of strains isolated from HBV-positive patients showed less resistance to tested antimicrobials. The HBV DNA serum concentrations were inversely correlated to the number of ineffective antimicrobials in E. coli, P. aeruginosa and K. pneumoniae infections (P = 0.022, 0.017 and 0.016, respectively), but not S. aureus (P = 0.194). In conclusion, bacterial infections are associated with a high level of HBV replication, which, in turn, has a significant positive impact on bacterial resistance to antimicrobials. These correlations vary between Gram-negative and Gram-positive bacteria.


Assuntos
Infecções Bacterianas/microbiologia , Coinfecção/sangue , Vírus da Hepatite B/isolamento & purificação , Hepatite B/microbiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções Bacterianas/sangue , Infecções Bacterianas/virologia , Coinfecção/microbiologia , Coinfecção/virologia , Escherichia coli/isolamento & purificação , Escherichia coli/patogenicidade , Feminino , Hepatite B/sangue , Hepatite B/complicações , Hepatite B/virologia , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/patogenicidade , Humanos , Klebsiella pneumoniae/isolamento & purificação , Klebsiella pneumoniae/patogenicidade , Masculino , Pessoa de Meia-Idade , Pseudomonas aeruginosa/isolamento & purificação , Pseudomonas aeruginosa/patogenicidade , Estudos Retrospectivos , Staphylococcus aureus/isolamento & purificação , Staphylococcus aureus/patogenicidade
12.
Int J Mol Sci ; 16(11): 26263-79, 2015 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-26540050

RESUMO

Microbes have co-evolved with human beings for millions of years. They play a very important role in maintaining the health of the host. With the advancement in next generation sequencing technology, the microbiome profiling in the host can be obtained under different circumstances. This review focuses on the current knowledge of the alteration of complex microbial communities upon the infection of different pathogens, such as human immunodeficiency virus, hepatitis B virus, influenza virus, and Mycobacterium tuberculosis, at different body sites. It is believed that the increased understanding of the correlation between infectious disease and the alteration of the microbiome can contribute to better management of disease progression in the future. However, future studies may need to be more integrative so as to establish the exact causality of diseases by analyzing the correlation between microorganisms within the human host and the pathogenesis of infectious diseases.


Assuntos
Doenças Transmissíveis/microbiologia , Doenças Transmissíveis/virologia , Interações Hospedeiro-Patógeno , Metagenômica , Interações Microbianas , Microbiota , Síndrome da Imunodeficiência Adquirida/microbiologia , Síndrome da Imunodeficiência Adquirida/virologia , Animais , Infecções por HIV/microbiologia , Infecções por HIV/virologia , Hepatite B/microbiologia , Hepatite B/virologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Influenza Humana/microbiologia , Influenza Humana/virologia , Metagenômica/métodos , Microbiota/genética , Tuberculose/microbiologia
13.
BMC Infect Dis ; 14: 94, 2014 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-24555665

RESUMO

BACKGROUND: Hepatitis B virus (HBV) and hepatitis D virus (HDV) represent important public health problems in the Western Amazon region with reported cases of fulminant hepatitis. This cross sectional study describes HBV and HDV genotypes circulating in the Brazilian Amazon region. METHODS: HBsAg positive individuals (n = 224) were recruited in Manaus/Amazonas State (130 blood donors from the Hematology and Hemotherapy Foundation from Amazonas/HEMOAM; 60 subjects from outpatient clinic) and in Eirunepe city (n = 34) from 2003-2009. Most participants (n = 153) lived in Manaus, 63 were from 20 remote isolated municipalities, 8 lived outside Amazonas State. Genotyping was based on PCR products: HBV genotype A-F specific primers, restricted length polymorphism for HDV. HDV isolates were directly sequenced (delta antigen 405 nucleotide fragment) and phylogenetic analysis performed (MEGA; neighbor-joining, Kimura's two parameter). RESULTS: Most participants were young adult males and HBV mono-infection predominated (70.5%, 158/224). Among blood donors, outpatient subjects and individuals from Eirunepe, HBV/A prevailed followed by HBV/D and F (p > 0.05). HBV/A was more frequent in blood donors (p < 0.05). HBV-HDV coinfection rate was 8.5% in blood donors (11/130), 65.0% (39/60) in outpatient subjects and 47.0% (16/34) in individuals from Eirunepe. Compared to blood donors, coinfection was higher in outpatient subjects (65.0% versus 8.5%; RR = 5.0; CI 3.4-7.9; p < 0.0001) and in subjects from Eirunepe (47.0% versus 8.5%; RR = 5.5; CI 3.0-9.9; p < 0.0001). HBV-HDV coinfection rates were higher in patients from highly endemic remote cities. Only HDV genotype 3 was detected, HBV/F-HDV/3 predominated (20/38; 52.7%), followed by HBV/A-HDV/3 (31.6%; 12/38) and HBV/D-HDV/3 (15.8%; 6/38). CONCLUSIONS: The description of HBV and HDV genotypes circulating in the western Amazon can contribute to a better understanding of their relevance on the regional epidemics. These infections are highly endemic in the Amazon where their control is challenged by its vast territorial dimension with small, hard-to-reach municipalities dispersed into the jungle and populated by diverse ethnic groups.


Assuntos
Vírus da Hepatite B/genética , Hepatite B/epidemiologia , Hepatite D/epidemiologia , Vírus Delta da Hepatite/genética , Adolescente , Adulto , Doadores de Sangue , Brasil/epidemiologia , Coinfecção/virologia , Estudos Transversais , Feminino , Genótipo , Hepatite B/microbiologia , Antígenos de Superfície da Hepatite B/sangue , Hepatite D/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular , Filogenia , Polimorfismo de Fragmento de Restrição , Adulto Jovem
14.
BMC Gastroenterol ; 13: 175, 2013 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-24369878

RESUMO

BACKGROUND: Assessment and characterization of human colon microbiota is now a major research area in human diseases, including in patients with hepatitis B liver cirrhosis (HBLC). METHODS: We recruited 120 patients with HBLC and 120 healthy controls. The fecal microbial community and functions in the two groups were analyzed using high-throughput Solexa sequencing of the complete metagenomic DNA and bioinformatics methods. RESULTS: Community and metabolism-wide changes of the fecal microbiota in 20 HBLC patients and 20 healthy controls were observed and compared. A negative correlation was observed between the Child-Turcotte-Pugh scores and Bacteroidetes (P < 0.01), whereas a positive correlation was observed between the scores and Enterobacteriaceae and Veillonella (P < 0.01). Analysis of the additional 200 fecal microbiota samples demonstrated that these intestinal microbial markers might be useful for distinguishing liver cirrhosis microbiota samples from normal ones. The functional diversity was significantly reduced in the fecal microbiota of cirrhotic patients compared with in the controls. At the module or pathway levels, the fecal microbiota of the HBLC patients showed enrichment in the metabolism of glutathione, gluconeogenesis, branched-chain amino acid, nitrogen, and lipid (P < 0.05), whereas there was a decrease in the level of aromatic amino acid, bile acid and cell cycle related metabolism (P < 0.05). CONCLUSIONS: Extensive differences in the microbiota community and metabolic potential were detected in the fecal microbiota of cirrhotic patients. The intestinal microbial community may act as an independent organ to regulate the body's metabolic balance, which may affect the prognosis for HBLC patients.


Assuntos
Colo/microbiologia , DNA Bacteriano/análise , Hepatite B/microbiologia , Cirrose Hepática/microbiologia , Metagenoma , Microbiota/genética , Adulto , Estudos de Casos e Controles , Fezes/microbiologia , Feminino , Hepatite B/complicações , Humanos , Cirrose Hepática/etiologia , Masculino , Microbiota/fisiologia , Pessoa de Meia-Idade
15.
Hepatology ; 58(2): 538-45, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23505059

RESUMO

UNLABELLED: There are sparse epidemiologic data on coinfection of hepatitis B (HBV) and hepatitis C (HCV) in the United States. Therefore, the aim of this study was to determine the prevalence and predictors of HBV coinfection in a large U.S. population of HCV patients. We used the National Veterans Affairs HCV Clinical Case Registry to identify patients tested for HCV during 1997-2005. Patients were categorized based on HCV exposure (any two +HCV tests or one test with a diagnostic code), HCV infection (+RNA or genotype), HBV exposure (any +HBV test, excluding +HBsAb only), and HBV infection (+HBsAg, HBV DNA, or HBeAg). The prevalence of HBV exposure among patients with HCV exposure and that of HBV infection among patients with HCV infection were determined. Multivariate logistic regression evaluated potential demographic and clinical predictors of HBV coinfection. Among 168,239 patients with HCV exposure, 58,415 patients had HBV exposure for a prevalence of 34.7% (95% confidence interval [CI] 34.5-35.0). Among 102,971 patients with HCV infection, 1,431 patients had HBV coinfection for a prevalence of 1.4% (95% CI 1.3-1.5). Independent associations with HBV coinfection compared with HCV monoinfection were age ≤ 50 years, male sex, positive HIV status, history of hemophilia, sickle cell anemia or thalassemia, history of blood transfusion, cocaine and other drug use; there was decreased risk in patients of Hispanic ethnicity. CONCLUSION: This is the largest cohort study in the U.S. on the prevalence of HBV coinfection in HCV patients. Among veterans with HCV, exposure to HBV is common (~35%), but HBV coinfection is relatively low (1.4%). Several possible risk factors were identified.


Assuntos
Coinfecção/epidemiologia , Hepacivirus/patogenicidade , Vírus da Hepatite B/patogenicidade , Hepatite B/epidemiologia , Hepatite C/epidemiologia , Adulto , Estudos de Coortes , Feminino , Hepatite B/microbiologia , Hepatite C/microbiologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Prevalência , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Estados Unidos/epidemiologia , United States Department of Veterans Affairs
16.
West Indian Med J ; 61(2): 139-44, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23155958

RESUMO

AIM: To study the correlation of nasal Staphylococcus aureus carrier status in patients on haemodialysis, infected by hepatitis C virus (HCV), hepatitis B virus (HBV), and their sociodemographic features. SUBJECTS AND METHODS: A survey, including patients' sociodemographic features, was applied to patients by physicians in face to face interviews. Medical records regarding their serologic data were recorded from haemodialysis centres. Nasal swab samples of 2 cm depth from both nostrils of patients were obtained for nasal culture. Samples were inoculated in 5% sheep blood agar and incubated in an incubator at a temperature of 37 degrees C for 24 hours. The results were studied by the same microbiologist. RESULTS: A total of 185 patients were enrolled in the study. According to culture results, 14.1% of patients (n = 26) had methicillin sensitive Staphylococcus aureus (MSSA) and 1.1% (n = 2) had methicillin resistant Staphylococcus aureus (MRSA). Status of viral hepatitis was 3.8% (n = 8), 10.8% (n = 20) for HBV and HCV respectively. Forty per cent (n = 8) of patients with HBV (+) had MSSA carrier status. Statistically significant positive correlation between MSSA and HCV carrier was detected (r = 0.325, p = 0.001) but not between HBV carrier and MSSA (p = 0.255). CONCLUSION: In the present study, significant positivity was detected between MSSA carrier status and HCV in patients on haemodialysis and who have lived together with < or = 2 family members at home. Particularly, statistically significant correlation between HCV(+) and MSSA carrier was observed.


Assuntos
Portador Sadio/microbiologia , Hepatite B/microbiologia , Hepatite C/microbiologia , Cavidade Nasal/microbiologia , Diálise Renal , Staphylococcus aureus/isolamento & purificação , Idoso , Feminino , Hepatite B/complicações , Hepatite C/complicações , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Pessoa de Meia-Idade , Fatores Socioeconômicos
17.
Int J STD AIDS ; 23(9): 639-43, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23033517

RESUMO

To determine the seroprevalence of hepatitis C virus (HCV), hepatitis B virus (HBV) and syphilis in HIV-1-infected patients and related risk factors in Shandong province, China, we tested all eligible participants between 2000 and 2010 for the presence of anti-HCV antibody, hepatitis B surface antigen (HBsAg) and non-treponemal antibodies for syphilis after informed consent. Among 2087 HIV-infected patients, anti-HCV antibody was present in 41.2%, HBsAg in 12.6% and rapid plasma reagin (RPR) reactivity in 19.6%. In the multivariate logistic regression model, male gender (adjusted odds ratio [aOR] = 1.41), minority ethnicity (aOR = 1.72), syphilis infection (aOR = 1.40), former paid blood donors (aOR = 3.36), blood transfusion recipients (aOR = 2.91) and injection drug users (aOR = 1.98) were significantly associated with HCV infection. HCV infection (aOR = 1.40) and being men who have sex with men (aOR = 2.38) were significantly associated with syphilis infection. Co-infection with HCV, HBV and syphilis was observed frequently in all described subgroups of HIV infection. The results of this study suggest that it is necessary to screen for these viruses and syphilis in all Chinese HIV-infected patients.


Assuntos
Infecções por HIV/microbiologia , Hepatite B/epidemiologia , Hepatite C/epidemiologia , Sífilis/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antibacterianos/sangue , Anticorpos Antivirais/sangue , Criança , Pré-Escolar , China/epidemiologia , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Hepatite B/sangue , Hepatite B/microbiologia , Hepatite C/sangue , Hepatite C/microbiologia , Humanos , Lactente , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores de Risco , Estudos Soroepidemiológicos , Sífilis/sangue , Sífilis/virologia
18.
Int J STD AIDS ; 23(6): 435-8, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22807539

RESUMO

Hepatitis B virus (HBV) and syphilis co-infections contribute significantly to HIV-associated morbidity and mortality, but the burden of these diseases is not fully appreciated in sub-Saharan Africa, as prevalence data are scarce. Both infections often remain undiagnosed in resource-limited settings because routine testing is not a part of most of the national guidelines. Epidemiological studies provide important information on prevalence and risk factors for such co-infections and can provide guidance for clinical management and for the development of test strategies. We analysed data on baseline characteristics, CD4 cell counts, HBV and syphilis co-infection rates of 690 patients enrolling for antiretroviral therapy in rural Cameroon. The prevalence of both hepatitis B surface antigen (HBsAg, 12.6%, 95% CI 10.1-15.1) and treponemal antibodies (11.4%, 95% CI 8.9-13.7) was high, with significantly higher prevalences for both infections in men; detection of treponemal antibodies increased with age. Although liver enzyme elevations were common, they were not useful to identify HBsAg-positive patients. In this setting, routine serological screening for HBV and syphilis co-infection should be considered to avoid complications and ongoing transmission.


Assuntos
Antirretrovirais/uso terapêutico , Coinfecção/epidemiologia , Infecções por HIV/epidemiologia , Hepatite B/epidemiologia , Sífilis/epidemiologia , Adulto , Alanina Transaminase/sangue , Anticorpos Antibacterianos/sangue , Contagem de Linfócito CD4 , Camarões/epidemiologia , Distribuição de Qui-Quadrado , Coinfecção/microbiologia , Coinfecção/virologia , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/microbiologia , Infecções por HIV/virologia , Hepatite B/microbiologia , Hepatite B/virologia , Antígenos de Superfície da Hepatite B/sangue , Humanos , Masculino , Estudos Retrospectivos , Fatores de Risco , Estatísticas não Paramétricas , Sífilis/complicações , Sífilis/virologia
19.
West Indian med. j ; 61(2): 139-144, Mar. 2012. graf, tab
Artigo em Inglês | LILACS | ID: lil-672871

RESUMO

AIM: To study the correlation of nasal Staphylococcus aureus carrier status in patients on haemodialysis, infected by hepatitis C virus (HCV), hepatitis B virus (HBV), and their sociodemographic features. SUBJECTS AND METHODS: A survey, including patients ' sociodemographic features, was applied to patients by physicians in face to face interviews. Medical records regarding their serologic data were recorded from haemodialysis centres. Nasal swab samples of 2 cm depth from both nostrils of patients were obtained for nasal culture. Samples were inoculated in 5% sheep blood agar and incubated in an incubator at a temperature of 37ºCfor 24 hours. The results were studied by the same microbiologist. RESULTS: A total of 185 patients were enrolled in the study. According to culture results, 14.1% of patients (n = 26) had methicillin sensitive Staphylococcus aureus (MSSA) and 1.1% (n = 2) had methicillin resistant Staphylococcus aureus (MRSA). Status of viral hepatitis was 3.8% (n = 8), 10.8% (n = 20) for HBV and HCV, respectively. Forty per cent (n = 8) of patients with HBV (+) had MSSA carrier status. Statistically significant positive correlation between MSSA and HCV carrier was detected (r = 0.325, p = 0.001) but not between HBV carrier and MSSA (p = 0.255). CONCLUSION: In the present study, significant positivity was detected between MSSA carrier status and HCV in patients on haemodialysis and who have lived together with < 2 family members at home. Particularly, statistically significant correlation between HCV (+) and MSSA carrier was observed.


OBJETIVO: Estudiar la correlación entre el portador del Estafilococo dorado (Staphylococcus aureus) nasal en pacientes de hemodiálisis infectados por el virus de la hepatitis C (VHC), el virus de la hepatitis B (VHB), y sus características sociodemográficas. SUJETOS Y MÉTODOS: Una encuesta que incluía características sociodemográficas de los pacientes fue aplicada a pacientes por médicos en entrevistas cara a cara. Historias clínicas contentivas de sus datos serológicos, fueron registradas a partir de los centros de hemodiálisis. Muestras defrotis nasales de 2 cm de profundidad de ambas fosas nasales, fueron obtenidas para un cultivo nasal. Se inocularon muestras en agar de sangre de oveja al 5%, e incubadas en una incubadora a una temperatura de 37ºC por 24 horas. Los resultados fueron examinados por el mismo microbiólogo. RESULTADOS: Un total de 185 pacientes fueron enrolados en el estudio. Según los resultados del cultivo, 14.1% pacientes (n = 26) tenían estafilococo dorado sensible a la meticilina (MSSA) y 1.1% (n = 2) tenían estafilococo dorado resistente a la meticilina (MRSA). El estatus de las hepatitis virales fue 3.8% (n = 8), y 10.8% (n = 20) para HVB y HVC respectivamente. Cuarentapor ciento (n = 8) de los pacientes con HVB (+) eran portadores del MSSA. Estadísticamente, se detectó una correlación positiva significativa (r = 0.325, p = 0.001), entre MSSA y el portador de VHC, no así entre el portador del VHByMSSA (p = 0.255). CONCLUSIÓN: En el estudio presente, se detectó una positividad significativa entre el estatus de; portador de MSSA y los pacientes de VHC en hemodiálisis, que vivían junto con [= dos o menos de dos] miembros de la familia en casa. En particular, se observó una correlación estadísticamente significativa entre HCV (+) y el portador MSSA.


Assuntos
Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Portador Sadio/microbiologia , Hepatite B/microbiologia , Hepatite C/microbiologia , Cavidade Nasal/microbiologia , Diálise Renal , Staphylococcus aureus/isolamento & purificação , Hepatite B/complicações , Hepatite C/complicações , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Fatores Socioeconômicos
20.
Transplant Proc ; 41(1): 250-2, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19249527

RESUMO

BACKGROUND: Bacterial and fungal infections are serious complications in patients with cirrhosis and are among the main causes of morbidity and mortality. The effects of pretransplantation infection on the outcome after orthotopic liver transplantation (OLT), however, have not been fully described. OBJECTIVE: To assess the influence of pretransplantation infection on OLT by analyzing the clinical profiles of liver recipients with preexisting bacterial or fungal infection. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 223 adult patients who underwent living donor OLT between October 1, 2005, and September 30, 2006. In all patients, routine blood culture, was performed, and in patients with suspected bacterial or fungal infection; sputum, urine, and ascitic fluid cultures were performed. RESULTS: Of 223 patients, 37 (16.6%) had a positive culture in one or more samples. Culture-positive and culture-negative groups differed significantly in end-stage liver disease score but showed no differences in Child-Turcotte-Pugh score, existence of spontaneous bacterial peritonitis, hemodialysis, or duration of stay in the intensive care unit or hospital. Six of 37 patients with positive cultures (16.2%) and 4 (2.2%) of 186 patients with negative cultures (2.2%) died during the first 90 days after OLT (P = .007). The causes of death among culture-positive patients were brain edema (n = 2), brain hemorrhage (n = 1), hepatic dysfunction (n = 1), and sepsis (n = 2), whereas all 4 culture-negative patients died of infectious complications. CONCLUSION: Prompt OLT accompanied by adequate antibiotic or antifungal therapy may be acceptable in patients with preexisting bacterial or fungal infection unless there are overt manifestations of active infection.


Assuntos
Infecções Bacterianas/complicações , Transplante de Fígado , Micoses/complicações , Adulto , Suscetibilidade a Doenças , Feminino , Hepatite B/microbiologia , Hepatite B/cirurgia , Hepatite C/microbiologia , Hepatite C/cirurgia , Humanos , Cirrose Hepática Alcoólica/microbiologia , Cirrose Hepática Alcoólica/cirurgia , Falência Hepática/microbiologia , Falência Hepática/cirurgia , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios , Resultado do Tratamento
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