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1.
Microbiol Spectr ; 12(7): e0023924, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38785430

ABSTRACT

Hepatitis B virus (HBV), a common blood transmission pathogen worldwide, can lead to viral hepatitis, cirrhosis, liver cancer, and other liver diseases. In particular, occult hepatitis B virus infection (OBI) may be caused by an immune response leading to suppressed virus replication. Gut microbiota can change the immunity status of the human body and, therefore, affect the replication of HBV. Thus, to identify whether there are differences in gut microbiota between HBV carriers and OBI carriers, we collected fecal samples from 18 HBV carriers, 24 OBI blood donors, and also 20 healthy blood donors as negative control. After 16S sequencing, we found that the abundance of Faecalibacterium was significantly reduced in samples from OBI blood donors compared with those from healthy blood donors. Compared with samples from HBV carriers, the samples from OBI blood donors had a significantly increased abundance of Subdoligranulum, which might stimulate immune activation, thus inhibiting HBV replication and contributing to the formation of occult infection. Our findings revealed the potential role of gut microbiota in the formation of OBI and further provided a novel strategy for the treatment of HBV infection.IMPORTANCEOccult hepatitis B virus infection (OBI) is a special form of hepatitis B virus infection with hepatitis B surface antigen (HBsAg) positive and hepatitis B virus (HBV) DNA negative. Gut microbiota may contribute to the immune response leading to suppressed virus replication and, thus, participates in the development of OBI. The study on gut microbiota of OBI blood donors provides novel data considerably advancing our understanding of the immune mechanism for the determination of occult hepatitis B virus infection, which is helpful for improving the strategy of the treatment of HBV infection.


Subject(s)
Feces , Gastrointestinal Microbiome , Hepatitis B virus , Hepatitis B , Humans , Hepatitis B virus/genetics , Hepatitis B virus/physiology , Male , Hepatitis B/virology , Hepatitis B/microbiology , Hepatitis B/immunology , Adult , Female , Feces/microbiology , Feces/virology , Middle Aged , Carrier State/microbiology , Carrier State/virology , DNA, Viral/genetics , Virus Replication , Hepatitis B Surface Antigens/blood , RNA, Ribosomal, 16S/genetics , Young Adult , Blood Donors , Bacteria/classification , Bacteria/isolation & purification , Bacteria/genetics
2.
FASEB J ; 35(6): e21680, 2021 06.
Article in English | MEDLINE | ID: mdl-34042225

ABSTRACT

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.


Subject(s)
Ataxia Telangiectasia Mutated Proteins/metabolism , Checkpoint Kinase 2/metabolism , DNA, Mitochondrial/genetics , Extracellular Vesicles/metabolism , Hepatitis B/pathology , Hepatocytes/pathology , Virus Replication , Ataxia Telangiectasia Mutated Proteins/genetics , Checkpoint Kinase 2/genetics , DNA, Mitochondrial/metabolism , Hep G2 Cells , Hepatitis B/genetics , Hepatitis B/metabolism , Hepatitis B/microbiology , Hepatitis B virus/physiology , Hepatocytes/metabolism , Hepatocytes/microbiology , Humans
3.
Front Immunol ; 12: 636803, 2021.
Article in English | MEDLINE | ID: mdl-33841420

ABSTRACT

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.


Subject(s)
Colon/pathology , Gastrointestinal Microbiome/physiology , Hepatitis B virus/physiology , Hepatitis B/immunology , Intestinal Mucosa/physiology , Liver/immunology , RNA, Ribosomal, 16S/genetics , T-Lymphocytes/immunology , Animals , Anti-Bacterial Agents/administration & dosage , Bacterial Translocation , Cells, Cultured , Disease Models, Animal , Feces/microbiology , Hepatitis B/microbiology , Humans , Immunity , Liver/virology , Male , Mice , Mice, Inbred C57BL , Programmed Cell Death 1 Receptor/metabolism , Up-Regulation , Viral Load
4.
Front Immunol ; 12: 755890, 2021.
Article in English | MEDLINE | ID: mdl-35069530

ABSTRACT

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.


Subject(s)
Coinfection , Gastrointestinal Microbiome , HIV Infections , HIV-1/immunology , Hepatitis B virus/immunology , Hepatitis B , Coinfection/drug therapy , Coinfection/immunology , Coinfection/microbiology , Coinfection/virology , Gastrointestinal Microbiome/drug effects , Gastrointestinal Microbiome/immunology , HIV Infections/drug therapy , HIV Infections/immunology , HIV Infections/microbiology , Hepatitis B/drug therapy , Hepatitis B/immunology , Hepatitis B/microbiology , Humans
5.
Front Immunol ; 11: 578801, 2020.
Article in English | MEDLINE | ID: mdl-33329547

ABSTRACT

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.


Subject(s)
Genomics , Hepatitis B Vaccines/therapeutic use , Hepatitis B/prevention & control , Immunogenicity, Vaccine , Systems Biology , Vaccination , Adult , Aged , Epigenesis, Genetic , Epigenomics , Feces/microbiology , Female , Gastrointestinal Microbiome , Gene Expression Profiling , Gene Regulatory Networks , Hepatitis B/genetics , Hepatitis B/metabolism , Hepatitis B/microbiology , Hepatitis B Antibodies/blood , Humans , Male , Middle Aged , Prospective Studies , Protein Interaction Maps , Proteomics , Time Factors , Transcriptome , Treatment Outcome
7.
Front Immunol ; 10: 927, 2019.
Article in English | MEDLINE | ID: mdl-31114580

ABSTRACT

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.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , Hepatitis B virus/immunology , Hepatitis B/immunology , Hepatitis B/microbiology , Immunity, Cellular , Microbiota/immunology , Animals , B-Lymphocytes/immunology , B-Lymphocytes/pathology , CD4-Positive T-Lymphocytes/pathology , Hepatitis B/drug therapy , Hepatitis B/pathology , Hepatitis B Antibodies/immunology , Hepatitis B Antibodies/pharmacology , Hepatitis B Surface Antigens/immunology , Male , Mice , Mice, Knockout , Toll-Like Receptors/immunology
8.
Hepatobiliary Pancreat Dis Int ; 18(1): 19-27, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30527903

ABSTRACT

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.


Subject(s)
Carcinoma, Hepatocellular/microbiology , Dysbiosis , Gastrointestinal Microbiome , Liver Neoplasms/microbiology , Liver/microbiology , Animals , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/virology , Cell Transformation, Neoplastic/metabolism , Cell Transformation, Neoplastic/pathology , Hepatitis B/microbiology , Hepatitis B/virology , Host-Pathogen Interactions , Humans , Liver/metabolism , Liver/pathology , Liver/virology , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Liver Neoplasms/virology , Prognosis , Risk Factors , Signal Transduction , Toll-Like Receptor 4/metabolism
9.
Am J Trop Med Hyg ; 98(1): 221-226, 2018 01.
Article in English | MEDLINE | ID: mdl-29342404

ABSTRACT

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.


Subject(s)
Coinfection/pathology , Helicobacter Infections/complications , Hepatitis B/complications , Stomach/pathology , Adult , Case-Control Studies , Coinfection/microbiology , Coinfection/virology , Egypt , Female , Helicobacter Infections/pathology , Helicobacter Infections/virology , Helicobacter pylori , Hepatitis B/microbiology , Hepatitis B/pathology , Humans , Liver/pathology , Liver/virology , Male , Severity of Illness Index , Stomach/microbiology
10.
Enferm. infecc. microbiol. clín. (Ed. impr.) ; 35(supl.3): 9-14, oct. 2017. tab
Article in Spanish | IBECS | ID: ibc-170745

ABSTRACT

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)


Subject(s)
Humans , Quality Control , Viral Load/methods , Hepatitis B virus/isolation & purification , Hepacivirus/isolation & purification , HIV-1/isolation & purification , Viral Load/standards , Hepatitis C/epidemiology , Hepatitis C/microbiology , Hepatitis B/epidemiology , Hepatitis B/microbiology , Acquired Immunodeficiency Syndrome/microbiology , Biomarkers , Societies, Medical/organization & administration , Societies, Medical/standards
11.
Article in English | MEDLINE | ID: mdl-28382278

ABSTRACT

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.


Subject(s)
CRISPR-Cas Systems , Gene Targeting , Hepatitis B virus/physiology , Hepatitis B/microbiology , Virus Integration , Base Sequence , Cell Line , DNA, Circular , Genome, Viral , High-Throughput Nucleotide Sequencing , Humans , Virus Replication
12.
Sci Rep ; 5: 15413, 2015 Dec 04.
Article in English | MEDLINE | ID: mdl-26634436

ABSTRACT

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.


Subject(s)
Bacterial Infections/microbiology , Coinfection/blood , Hepatitis B virus/isolation & purification , Hepatitis B/microbiology , Adult , Aged , Aged, 80 and over , Bacterial Infections/blood , Bacterial Infections/virology , Coinfection/microbiology , Coinfection/virology , Escherichia coli/isolation & purification , Escherichia coli/pathogenicity , Female , Hepatitis B/blood , Hepatitis B/complications , Hepatitis B/virology , Hepatitis B e Antigens/blood , Hepatitis B virus/pathogenicity , Humans , Klebsiella pneumoniae/isolation & purification , Klebsiella pneumoniae/pathogenicity , Male , Middle Aged , Pseudomonas aeruginosa/isolation & purification , Pseudomonas aeruginosa/pathogenicity , Retrospective Studies , Staphylococcus aureus/isolation & purification , Staphylococcus aureus/pathogenicity
13.
Int J Mol Sci ; 16(11): 26263-79, 2015 Nov 03.
Article in English | MEDLINE | ID: mdl-26540050

ABSTRACT

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.


Subject(s)
Communicable Diseases/microbiology , Communicable Diseases/virology , Host-Pathogen Interactions , Metagenomics , Microbial Interactions , Microbiota , Acquired Immunodeficiency Syndrome/microbiology , Acquired Immunodeficiency Syndrome/virology , Animals , HIV Infections/microbiology , HIV Infections/virology , Hepatitis B/microbiology , Hepatitis B/virology , High-Throughput Nucleotide Sequencing , Humans , Influenza, Human/microbiology , Influenza, Human/virology , Metagenomics/methods , Microbiota/genetics , Tuberculosis/microbiology
14.
BMC Infect Dis ; 14: 94, 2014 Feb 21.
Article in English | MEDLINE | ID: mdl-24555665

ABSTRACT

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.


Subject(s)
Hepatitis B virus/genetics , Hepatitis B/epidemiology , Hepatitis D/epidemiology , Hepatitis Delta Virus/genetics , Adolescent , Adult , Blood Donors , Brazil/epidemiology , Coinfection/virology , Cross-Sectional Studies , Female , Genotype , Hepatitis B/microbiology , Hepatitis B Surface Antigens/blood , Hepatitis D/microbiology , Humans , Male , Middle Aged , Molecular Epidemiology , Phylogeny , Polymorphism, Restriction Fragment Length , Young Adult
15.
BMC Gastroenterol ; 13: 175, 2013 Dec 26.
Article in English | MEDLINE | ID: mdl-24369878

ABSTRACT

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.


Subject(s)
Colon/microbiology , DNA, Bacterial/analysis , Hepatitis B/microbiology , Liver Cirrhosis/microbiology , Metagenome , Microbiota/genetics , Adult , Case-Control Studies , Feces/microbiology , Female , Hepatitis B/complications , Humans , Liver Cirrhosis/etiology , Male , Microbiota/physiology , Middle Aged
16.
Hepatology ; 58(2): 538-45, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23505059

ABSTRACT

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.


Subject(s)
Coinfection/epidemiology , Hepacivirus/pathogenicity , Hepatitis B virus/pathogenicity , Hepatitis B/epidemiology , Hepatitis C/epidemiology , Adult , Cohort Studies , Female , Hepatitis B/microbiology , Hepatitis C/microbiology , Humans , Logistic Models , Male , Middle Aged , Models, Statistical , Prevalence , Registries , Retrospective Studies , Risk Factors , United States/epidemiology , United States Department of Veterans Affairs
17.
West Indian Med J ; 61(2): 139-44, 2012 Mar.
Article in English | MEDLINE | ID: mdl-23155958

ABSTRACT

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.


Subject(s)
Carrier State/microbiology , Hepatitis B/microbiology , Hepatitis C/microbiology , Nasal Cavity/microbiology , Renal Dialysis , Staphylococcus aureus/isolation & purification , Aged , Female , Hepatitis B/complications , Hepatitis C/complications , Humans , Male , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Middle Aged , Socioeconomic Factors
18.
Int J STD AIDS ; 23(9): 639-43, 2012 Sep.
Article in English | MEDLINE | ID: mdl-23033517

ABSTRACT

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.


Subject(s)
HIV Infections/microbiology , Hepatitis B/epidemiology , Hepatitis C/epidemiology , Syphilis/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Bacterial/blood , Antibodies, Viral/blood , Child , Child, Preschool , China/epidemiology , Female , HIV Infections/epidemiology , HIV Infections/virology , Hepatitis B/blood , Hepatitis B/microbiology , Hepatitis C/blood , Hepatitis C/microbiology , Humans , Infant , Logistic Models , Male , Middle Aged , Multivariate Analysis , Risk Factors , Seroepidemiologic Studies , Syphilis/blood , Syphilis/virology
19.
Int J STD AIDS ; 23(6): 435-8, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22807539

ABSTRACT

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.


Subject(s)
Anti-Retroviral Agents/therapeutic use , Coinfection/epidemiology , HIV Infections/epidemiology , Hepatitis B/epidemiology , Syphilis/epidemiology , Adult , Alanine Transaminase/blood , Antibodies, Bacterial/blood , CD4 Lymphocyte Count , Cameroon/epidemiology , Chi-Square Distribution , Coinfection/microbiology , Coinfection/virology , Female , HIV Infections/drug therapy , HIV Infections/microbiology , HIV Infections/virology , Hepatitis B/microbiology , Hepatitis B/virology , Hepatitis B Surface Antigens/blood , Humans , Male , Retrospective Studies , Risk Factors , Statistics, Nonparametric , Syphilis/complications , Syphilis/virology
20.
West Indian med. j ; 61(2): 139-144, Mar. 2012. graf, tab
Article in English | LILACS | ID: lil-672871

ABSTRACT

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.


Subject(s)
Aged , Female , Humans , Male , Middle Aged , Carrier State/microbiology , Hepatitis B/microbiology , Hepatitis C/microbiology , Nasal Cavity/microbiology , Renal Dialysis , Staphylococcus aureus/isolation & purification , Hepatitis B/complications , Hepatitis C/complications , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Socioeconomic Factors
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