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1.
BMJ ; 370: m2200, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32873599

RESUMO

Hepatitis B virus (HBV) infection causes chronic hepatitis and has long term complications. Individuals ever infected with HBV are at risk of viral reactivation under certain circumstances. This review summarizes studies on HBV persistence and reactivation with a focus on the definitions and mechanisms. Emphasis is placed on the interplay between HBV replication and host immunity as this interplay determines the patterns of persistence following viral acquisition. Chronic infections exhibit as overt persistence when a defective immune response fails to control the viral replication. The HBV genome persists despite an immune response in the form of covalently closed circular DNA (cccDNA) and integrated DNA, rendering an occult state of viral persistence in individuals whose infection appears to have been resolved. We have described HBV reactivation that occurs because of changes in the virus or the immune system. This review aims to raise the awareness of HBV reactivation and to understand how HBV persists, and discusses the risks of HBV reactivation in a variety of clinical settings.


Assuntos
Vírus da Hepatite B/imunologia , Hepatite B Crônica/virologia , Replicação Viral/imunologia , Animais , DNA Viral/sangue , Saúde Global , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/imunologia , Humanos , Imunossupressão , Imunossupressores/uso terapêutico , Fatores de Risco
2.
PLoS One ; 15(8): e0238062, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32841308

RESUMO

This retrospective multicenter cohort study investigated the kinetics (ascending and descending phases) of cytomegalovirus (CMV) and Epstein-Barr virus (EBV)-DNA in whole blood (WB) and plasma samples collected from adult kidney transplant (KT) recipients. CMV-DNA kinetics according to antiviral therapy were investigated. Three hundred twenty-eight paired samples from 42 episodes of CMV infection and 157 paired samples from 26 episodes of EBV infection were analyzed by a single commercial molecular method approved by regulatory agencies for both matrices. CMV-DNAemia followed different kinetics in WB and plasma. In the descending phase of infection, a slower decay of viral load and a higher percentage of CMV-DNA positive samples were observed in plasma versus WB. In the 72.4% of patients receiving antiviral therapy, monitoring with plasma CMV-DNAemia versus WB CMV-DNAemia could delay treatment interruption by 7-14 days. Discontinuation of therapy based on WB monitoring did not result in relapsed infection in any patients. Highly different EBV-DNA kinetics in WB and plasma were observed due to lower positivity in plasma; EBV positive samples with a quantitative result in both blood compartments were observed in only 11.5% of cases. Our results emphasize the potential role of WB as specimen type for post-KT surveillance of both infections for disease prevention and management.


Assuntos
Citomegalovirus/genética , DNA Viral/sangue , Herpesvirus Humano 4/genética , Transplante de Rim , Adulto , Antivirais/farmacologia , Estudos de Coortes , Citomegalovirus/efeitos dos fármacos , Citomegalovirus/fisiologia , Herpesvirus Humano 4/efeitos dos fármacos , Herpesvirus Humano 4/fisiologia , Humanos , Imunossupressores/farmacologia , Cinética , Estudos Retrospectivos
3.
BMC Infect Dis ; 20(1): 509, 2020 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-32664850

RESUMO

BACKGROUND: Complete clearance of intracellular viruses depends on effector cells of innate and adaptive immune systems. This study aimed to identify the relationships among antiviral cytokines produced by natural killer (NK) and T cells and clinical-virological characteristics in untreated chronic hepatitis B (CHB) patients. METHODS: We measured antiviral cytokines interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and interleukin-2 (IL-2) produced by T, NK and natural killer T (NKT) cells, respectively, in a cohort with chronic hepatitis B virus (HBV) infection (CHB). We also correlated these cytokines with clinical-virological characteristics using a linear regression model. RESULTS: levels of IFN-γ+ and TNF-α+ CD4+ and CD8+ T cells were significantly higher in immune active (IA) phase than in other phases. Immune tolerant (IT) patients showed the lowest expression of IFN-γ by NK and NKT cells, and TNF-α by NK cells. IFN-γ+, TNF-α+ and IL-2+ CD4+ and CD8+ T cells frequencies were similar between IA and gray zone (GZ) phases. Principal component analysis based on cytokines confirmed that most IT patients significantly differed from inactive carriers (IC) and IA patients, while GZ patients were widely scattered. Multivariate analysis showed both T and NK cells producing IFN-γ and TNF-α, but not IL-2, had significant association with serum alanine aminotransferase (ALT). Moreover, IFN-γ+ NKT cells were associated with HBV DNA, while IFN-γ+ CD4+ and CD8+ T cells were correlated with age. CONCLUSION: HBV clinical phases are characterized by distinct cytokine signatures, which showed relationship to viral features in these untreated CHB patients.


Assuntos
Imunidade Adaptativa , Citocinas/metabolismo , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Hepatite B Crônica/sangue , Hepatite B Crônica/imunologia , Imunidade Inata , Adulto , Alanina Transaminase/sangue , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Estudos de Coortes , DNA Viral/sangue , Feminino , Antígenos de Superfície da Hepatite B/sangue , Hepatite B Crônica/virologia , Humanos , Células Matadoras Naturais/imunologia , Masculino , Células T Matadoras Naturais/imunologia , Adulto Jovem
4.
Anticancer Res ; 40(7): 3983-3990, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620641

RESUMO

BACKGROUND/AIM: Few studies have studied micro hepatic vein invasion in hepatocellular carcinoma (HCC). We explored the correlation between hepatic vein invasion and hepatitis B/C virus infection. PATIENTS AND METHODS: Between April 2000 and February 2018, 869 patients underwent liver resection for HCC at a single center. The patients were divided into two groups: those with micro hepatic vein invasion (VV+) and those without (VV-). The clinical data, overall survival (OS) and correlations with the presence of hepatitis B and C viruses were investigated. RESULTS: There were 817 VV- patients and 43 VV+ patients. OS was 66.2 months for VV- patients and 9.9 months for VV+ patients (p=0.0010). VV+ patients had significantly higher levels of serum HBV DNA (p=0.016). CONCLUSION: HCC patients with micro hepatic vein invasion showed significantly shorter OS. A higher level of HBV DNA appears to be a risk factor for micro hepatic vein invasion.


Assuntos
Carcinoma Hepatocelular/patologia , Veias Hepáticas/patologia , Neoplasias Hepáticas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos Virais/sangue , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/virologia , DNA Viral/sangue , Feminino , Hepacivirus/genética , Hepacivirus/imunologia , Hepatite B/patologia , Hepatite B/virologia , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Hepatite C/patologia , Hepatite C/virologia , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
5.
Proc Natl Acad Sci U S A ; 117(31): 18692-18700, 2020 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-32690683

RESUMO

A scalable approach for quantifying intact HIV-1 proviruses is critical for basic research and clinical trials directed at HIV-1 cure. The intact proviral DNA assay (IPDA) is a novel approach to characterizing the HIV-1 reservoir, focusing on the genetic integrity of individual proviruses independent of transcriptional status. It uses multiplex digital droplet PCR to distinguish and separately quantify intact proviruses, defined by a lack of overt fatal defects such as large deletions and APOBEC3G-mediated hypermutation, from the majority of proviruses that have such defects. This distinction is important because only intact proviruses cause viral rebound on ART interruption. To evaluate IPDA performance and provide benchmark data to support its implementation, we analyzed peripheral blood samples from 400 HIV-1+ adults on ART from several diverse cohorts, representing a robust sample of treated HIV-1 infection in the United States. We provide direct quantitative evidence that defective proviruses greatly outnumber intact proviruses (by >12.5 fold). However, intact proviruses are present at substantially higher frequencies (median, 54/106 CD4+ T cells) than proviruses detected by the quantitative viral outgrowth assay, which requires induction and in vitro growth (∼1/106 CD4+ T cells). IPDA amplicon signal issues resulting from sequence polymorphisms were observed in only 6.3% of individuals and were readily apparent and easily distinguished from low proviral frequency, an advantage of the IPDA over standard PCR assays which generate false-negative results in such situations. The large IPDA dataset provided here gives the clearest quantitative picture to date of HIV-1 proviral persistence on ART.


Assuntos
DNA Viral/sangue , Infecções por HIV , Provírus/genética , Latência Viral/genética , Adulto , Feminino , Infecções por HIV/sangue , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase/métodos
6.
PLoS One ; 15(6): e0234773, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32559248

RESUMO

Hepatocellular carcinoma (HCC) is among the leading causes of cancer-related death worldwide. Patients with hepatitis B virus (HBV) pre-S mutants in liver tissues or blood have been regarded as a high-risk population for HCC development and recurrence. Detection of pre-S mutants in clinical specimens is thus important for early diagnosis and prognosis of HCC to improve patient survival. Recently, we have developed a next-generation sequencing (NGS)-based platform that can quantitatively detect pre-S mutants in patient plasma with superior sensitivity and accuracy. In this study, we compared the pre-S genotyping results from plasma by the NGS-based analysis with those from liver tissues by the immunohistochemistry (IHC)-based analysis in 30 HBV-related HCC patients. We demonstrated that the detection rate of pre-S mutants was significantly higher by NGS- than by IHC-based analysis. There was a moderate to good agreement between both analyses in detection of pre-S mutants. Compared with the IHC, the NGS-based detection of pre-S mutants in patient plasma could determine the patterns of pre-S mutants in liver tissues more efficiently in a noninvasive manner. Our data suggest that the NGS-based platform may represent a promising approach for detection of pre-S mutants as biomarkers of HBV-related HCC in clinical practice.


Assuntos
Antígenos de Superfície da Hepatite B/genética , Vírus da Hepatite B/metabolismo , Fígado/virologia , Precursores de Proteínas/genética , Adulto , Idoso , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/virologia , DNA Viral/sangue , DNA Viral/metabolismo , Feminino , Genótipo , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/complicações , Hepatite B Crônica/patologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imuno-Histoquímica , Fígado/patologia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Mutação , Precursores de Proteínas/sangue , Análise de Sequência de DNA
7.
Zhonghua Liu Xing Bing Xue Za Zhi ; 41(6): 902-907, 2020 Jun 10.
Artigo em Chinês | MEDLINE | ID: mdl-32564557

RESUMO

Objective: To analyze the relationship between maternal mutations in basal core promoter region of hepatitis B virus (HBV) genotype C and intrauterine transmission. Methods: We collected information on general demographic characteristics and process of delivery among 399 pairs of consecutive HBsAg-positive mothers and their neonates, from the Third People's Hospital of Taiyuan in Shanxi province, China. Fluorescence quantitative polymerase chain reaction (FQ-PCR) and Electro-chemiluminescence immuno-assay (ECLIA) kits were used to detect both maternal and neonatal HBV DNA and serological markers in the peripheral blood. From 113 mothers with HBV DNA load ≥10(6) IU/ml, we selected 22 mothers whose neonates were with intrauterine transmission and randomly selected the same number of mothers whose neonates were without intrauterine transmission, as controls. The whole-length HBV DNA were extracted, amplified, cloned, sequenced and genotyped. Finally, a total of 39 mothers with genotype C of HBV were selected for mutation analysis. Results: Thirty-nine cases of genotype C (88.63%) were finally included in the study, with 19 cases in the intrauterine transmission group and 20 cases as controls. Rates of A1762T/G1764A double mutations were significantly different between the intrauterine transmission group and the control group (7.53% vs. 27.72%, P<0.001). Results from the multivariate analysis showed that the A1762T/G1764A double mutations had reduced the risk of intrauterine transmission (aOR=0.065, 95%CI: 0.006-0.746, P=0.028). Maternal A1762T/G1764A double mutations appeared to be possibly associated with neonatal HBeAg (P=0.050). Conclusion: A1762T/G1764A double mutations of HBV DNA from the genotype C of those HBsAg-positive mothers could reduced the risk of HBV intrauterine transmission during pregnancy.


Assuntos
Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/genética , Hepatite B/transmissão , Transmissão Vertical de Doença Infecciosa , Mutação , Complicações Infecciosas na Gravidez/virologia , Regiões Promotoras Genéticas/genética , China , DNA Viral/sangue , Feminino , Genótipo , Humanos , Recém-Nascido , Gravidez
8.
Int J Infect Dis ; 97: 126-130, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32497807

RESUMO

OBJECTIVE: The aim of this study was to determine the OBI in plasma and urine samples from renal transplant patients using Multiplex Nested PCR. METHOD: A total of 100 samples (plasma and urine) were collected from renal transplant patients admitted to the renal transplant center in Khartoum north, Sudan in 2019. For each sample, HBsAg, HBeAg and anti HBcAg were detected using Enzyme linked Immune sorbent assay (ELISA). The viral DNA was then extracted using viral DNA extraction kit and were then tested for HBV DNA by using multiplex nested PCR. Statistical analysis was done using statistical package of social science (IBM SPSS version 20.0) considering a P value ≤ 0.05 as a level of significance. RESULTS: HBsAg were not detected in al patient but, HBeAg were 14 (14%) and anti HBcAg were 36 (36%)were detect by using ELISA. A total 18 (18%) and 3 out of 100 were found positive in plasma and urine samples, respectively. Regarding the virus genotypes, D, E and mixed D/E genotypes were detected in all positive samples. Females were significantly (P value=0.013) higher detectable with HBV than males in plasma samples CONCLUSION: OBI incidence in renal transplant patients is high in Sudan. The multiplex nested PCR had identified OBI with a high rate supporting the efficiency of using molecular techniques in detecting of HBV. This will lead to an appropriate diagnosis and minimizing the risk to be infected by HBV.


Assuntos
Vírus da Hepatite B/isolamento & purificação , Hepatite B/virologia , Transplante de Rim , Adulto , Estudos Transversais , DNA Viral/sangue , Feminino , Genótipo , Hepatite B/sangue , Hepatite B/urina , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/sangue , Antígenos E da Hepatite B/imunologia , Vírus da Hepatite B/genética , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Sudão
9.
J Med Microbiol ; 69(6): 812-816, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32469303

RESUMO

HIV prevalence in Oman is low (<5 %); however, 45 % of the population are expatriates, including a portion originating from countries with high HIV prevalence (>5 %). HIV screening is performed at regional public health laboratories as part of a medical fitness programme for residency applicants. We conducted a retrospective evaluation of indeterminate serology results from 11 females of African origin, aged 21-43 years. Serology testing for HIV was conducted according to the national Oman algorithm: fourth-generation immunoassays (Bio-Rad GS HIV Combo Ag/Ab EIA, Siemens Enzygnost HIV Integral 4, Abbott ARCHITECT HIV Ag/Ab Combo, Roche Elecsys HIV Combi PT, bioMérieux VIDAS HIV DUO QUICK), confirmatory assays (Geenius HIV 1/2 Confirmatory, INNO-LIA HIV I/II Score) and PCR testing. Confirmatory testing to resolve indeterminate results was conducted with available samples for five patients using a combination of immunoassays, confirmatory assays, PCR/PERT and pro-viral DNA levels, at three external laboratories; Roche Diagnostics (Germany), Swiss National Laboratory (Switzerland) and Barts Health NHS Trust (UK). Nineteen serum, 15 plasma and two whole-blood samples were analysed. Nine of ten patients analysed on Bio-Rad and Siemens immunoassays were highly reactive; seven were highly reactive on the Abbott assay. Eight of nine patients tested with the Roche assay were negative. Three of four patients tested on the bioMérieux assay were negative. Five patients underwent confirmatory testing at external laboratories; all were negative by HIV-RNA or pro-viral DNA testing. In conclusion, HIV-RNA and pro-viral DNA testing is recommended for HIV screening of individuals from high-prevalence regions coming to low-prevalence regions.


Assuntos
DNA Viral/sangue , Infecções por HIV/diagnóstico , RNA Viral/sangue , Adulto , Reações Falso-Positivas , Feminino , Infecções por HIV/sangue , Humanos , Estudos Retrospectivos , Adulto Jovem
10.
J Virol ; 94(14)2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32350073

RESUMO

Antiretroviral therapy (ART) cannot eradicate human immunodeficiency virus (HIV) and a rapid rebound of virus replication follows analytical treatment interruption (ATI) in the vast majority of HIV-infected individuals. Sustained control of HIV replication without ART has been documented in a subset of individuals, defined as posttreatment controllers (PTCs). The key determinants of post-ART viral control remain largely unclear. Here, we identified 7 SIVmac239-infected rhesus macaques (RMs), defined as PTCs, who started ART 8 weeks postinfection, continued ART for >7 months, and controlled plasma viremia at <104 copies/ml for up to 8 months after ATI and <200 copies/ml at the latest time point. We characterized immunologic and virologic features associated with post-ART SIV control in blood, lymph node (LN), and colorectal (RB) biopsy samples compared to 15 noncontroller (NC) RMs. Before ART initiation, PTCs had higher CD4 T cell counts, lower plasma viremia, and SIV-DNA content in blood and LN compared to NCs, but had similar CD8 T cell function. While levels of intestinal CD4 T cells were similar, PTCs had higher frequencies of Th17 cells. On ART, PTCs had significantly lower levels of residual plasma viremia and SIV-DNA content in blood and tissues. After ATI, SIV-DNA content rapidly increased in NCs, while it remained stable or even decreased in PTCs. Finally, PTCs showed immunologic benefits of viral control after ATI, including higher CD4 T cell levels and reduced immune activation. Overall, lower plasma viremia, reduced cell-associated SIV-DNA, and preserved Th17 homeostasis, including at pre-ART, are the main features associated with sustained viral control after ATI in SIV-infected RMs.IMPORTANCE While effective, antiretroviral therapy is not a cure for HIV infection. Therefore, there is great interest in achieving viral remission in the absence of antiretroviral therapy. Posttreatment controllers represent a small subset of individuals who are able to control HIV after cessation of antiretroviral therapy, but characteristics associated with these individuals have been largely limited to peripheral blood analysis. Here, we identified 7 SIV-infected rhesus macaques that mirrored the human posttreatment controller phenotype and performed immunologic and virologic analysis of blood, lymph node, and colorectal biopsy samples to further understand the characteristics that distinguish them from noncontrollers. Lower viral burden and preservation of immune homeostasis, including intestinal Th17 cells, both before and after ART, were shown to be two major factors associated with the ability to achieve posttreatment control. Overall, these results move the field further toward understanding of important characteristics of viral control in the absence of antiretroviral therapy.


Assuntos
Antirretrovirais/farmacologia , Síndrome de Imunodeficiência Adquirida dos Símios , Vírus da Imunodeficiência Símia , Células Th17 , Animais , Relação CD4-CD8 , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , DNA Viral/sangue , DNA Viral/imunologia , Macaca mulatta , Síndrome de Imunodeficiência Adquirida dos Símios/sangue , Síndrome de Imunodeficiência Adquirida dos Símios/tratamento farmacológico , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Vírus da Imunodeficiência Símia/imunologia , Vírus da Imunodeficiência Símia/metabolismo , Células Th17/imunologia , Células Th17/metabolismo , Fatores de Tempo
11.
Lancet HIV ; 7(5): e359-e365, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32386722

RESUMO

Several assays have been developed to measure and characterise the replication-competent HIV-1 reservoir, which constitutes the barrier to cure. To date, the application of these assays to studies in children and in limited-resource settings has been minimal, primarily because of their expense, the large required blood volumes, and labour-intensive technologies. For children vertically infected with HIV-1 who initiated suppressive antiretroviral therapy (ART) regimens in infancy, HIV-1-specific antibody concentrations are associated with viral persistence and could be used to estimate the size of the residual latent reservoir on ART. This strategy could be particularly useful for screening children on suppressive ART for enrolment into therapeutic vaccine trials and other protocols aimed at achieving HIV-1 remission.


Assuntos
Anticorpos Anti-HIV/sangue , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/imunologia , Transmissão Vertical de Doença Infecciosa , Carga Viral , Fármacos Anti-HIV/uso terapêutico , DNA Viral/sangue , Infecções por HIV/tratamento farmacológico , Infecções por HIV/transmissão , Humanos , Lactente
12.
J Oral Pathol Med ; 49(7): 693-700, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32428250

RESUMO

INTRODUCTION: The role of viral infections in the pathogenesis of autoimmune diseases has long been suggested, but little evidence is available. OBJECTIVE: This study aimed to evaluate an association between EBV and CMV and the presence of rheumatoid arthritis and its association with Sjögren's Syndrome. PATIENTS AND METHOD: A case-control study was performed with 227 patients divided in RA (n = 99), RA/SS (n = 20), and C (n = 128). Resting salivary flow rate and Schirmer's test were performed; minor salivary gland biopsy was indicated in the case of suspected Sjögren's syndrome. CMV and EBV viral loads were quantified in peripheral blood, and their presence in glandular tissue samples was evaluated by in situ hybridization (EBV) and immunohistochemistry (CMV). RESULTS: EBV was more frequent in RA and RA/SS than in C (P < .000007). No correlation with clinical markers (P > .05) or between RA and RA/SS was found (P > .05). A higher number of EBV/DNA copies were found in RA (158.52 copies/µL) and RA/SS (99.24 copies/µL) (P = .739). EBV/DNA was associated with the Schirmer test (P = .0231). CMV was detected in one patient of the RA group. None of the viruses were detected in biopsies of minor salivary glands. CONCLUSIONS: Detection of EBV/DNA in peripheral blood was associated with RA regardless of the presence of SS.


Assuntos
Artrite Reumatoide/virologia , Infecções por Citomegalovirus/complicações , Infecções por Vírus Epstein-Barr/complicações , Síndrome de Sjogren/virologia , Carga Viral , Artrite Reumatoide/complicações , Estudos de Casos e Controles , DNA Viral/sangue , Herpesvirus Humano 4 , Humanos , Síndrome de Sjogren/complicações
13.
Int J Hematol ; 112(2): 193-199, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32472530

RESUMO

Posttransplant lymphoproliferative disorder (PTLD) after allogeneic hematopoietic cell transplantation (HCT) is usually donor derived, associated with Epstein-Barr virus (EBV), and of B-cell origin. T-cell PTLD (T-PTLD) after allogeneic HCT is extremely rare. Four of 1015 (0.39%) allogeneic HCT patients were diagnosed with T-PTLD; peripheral T-cell lymphoma-not otherwise specified, anaplastic large cell lymphoma, monomorphic T-cell PTLD and polymorphic PTLD with chronic active EBV infection-like symptoms. Three of the four patients developed T-PTLD within 6 months after HCT from HLA-mismatched unrelated donor. Three (75%) and 4 (100%) cases were positive for EBV-encoded small RNA in situ hybridization and EBV-DNA load in peripheral blood, respectively. Chimerism analysis showed that 75% of T-PTLD tissues (3/4) were recipient derived. T-PTLD was refractory to salvage chemotherapy and fatal in all four patients. Including the 10 patients in the literature, the median interval from HCT to diagnosis of T-PTLD was 5 months (range 1-72 months), 55% were negative for EBV, and 56% were recipient-derived. T-PTLD, which often occurred early after allogeneic HCT, was more likely to be EBV negative and recipient derived than B-cell PTLD after allogeneic HCT. Like T-PTLD after solid organ transplant, T-PTLD after allogeneic HCT demonstrated morphological heterogeneity and poor prognosis.


Assuntos
Infecções por Vírus Epstein-Barr/complicações , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transtornos Linfoproliferativos/etiologia , Linfócitos T , Criança , Pré-Escolar , DNA Viral/sangue , Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/virologia , Feminino , Herpesvirus Humano 4 , Humanos , Hibridização In Situ , Lactente , Masculino , Prognóstico , Transplante Homólogo , Carga Viral
14.
Aliment Pharmacol Ther ; 52(1): 196-204, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32452564

RESUMO

BACKGROUND: Anti-viral therapy is not indicated for patients with chronic hepatitis B (CHB) in the immune-tolerant phase. AIMS: To investigate the cumulative incidence of phase change and hepatocellular carcinoma (HCC) and independent predictors for phase change in patients with CHB in immune-tolerant phase. METHODS: In total, 946 patients in immune-tolerant phase, defined as hepatitis B e antigen positivity, HBV-DNA >20 000 IU/mL and alanine aminotransferase (ALT) ≤40 IU/L, between 1989 and 2017 were enrolled from eight institutes. RESULTS: The mean age of study population (429 men and 517 women) was 36.7 years. The mean ALT and HBV-DNA levels were 24.6 IU/L and 8.50 log10 IU/mL, respectively. Of the study population, 476 (50.3%) patients remained in immune-tolerant phase throughout the study period (median: 63.6 months). The cumulative incidence rates of phase change and HCC at 10 years were 70.7% and 1.7%, respectively. Multivariate analyses revealed that HBV-DNA level >107  IU/mL was associated independently with a reduced risk of phase change (hazard ratio [HR] = 0.734, P = 0.008), whereas a high ALT level, above the cut-off recommended in the Korean Association for the Study of the Liver guidelines (34 IU/L for men and 30 IU/L for women), was associated independently with a greater risk of phase change (HR = 1.885, P < 0.001). CONCLUSIONS: The criterion of HBV-DNA level > 107  IU/mL may be useful to define immune-tolerant phase. In addition, an extremely low risk of HCC development was observed in patients with CHB in immune-tolerant phase.


Assuntos
Carcinoma Hepatocelular/epidemiologia , Hepatite B Crônica/epidemiologia , Neoplasias Hepáticas/epidemiologia , Adulto , Alanina Transaminase/sangue , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/virologia , DNA Viral/sangue , Feminino , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/genética , Hepatite B Crônica/complicações , Hepatite B Crônica/imunologia , Hepatite B Crônica/virologia , Humanos , Tolerância Imunológica , Incidência , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
15.
Medicine (Baltimore) ; 99(17): e19832, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32332630

RESUMO

BACKGROUND: Human parvovirus B19 (B19V) infection exhibits a broad range of clinical outcomes. Blood transfusion is a common route of B19V transmission. However, information about the overall prevalence of B19V infection and B19V genotypes among blood donors in mainland China is lacking. METHODS: This meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A literature search for studies reporting the B19V prevalence among blood donors in mainland China from 2000 to 2018 was performed. The prevalence of B19V was estimated through a meta-analysis of the relevant literature. A comprehensive meta-analysis program was used for data processing and statistical analysis. RESULTS: Twenty-one eligible articles were included, involving 48,923 participants assessed for B19V-DNA, 12,948 participants assessed for anti-B19V immunoglobulin M (IgM), and 8244 participants assessed for anti-B19V immunoglobulin G (IgG). The analysis revealed the pooled estimates of the prevalence rates of B19V-DNA, anti-B19V IgM, and anti-B19V IgG among blood donors to be 0.7% (95% confidence interval [CI] 0.2-2.4%), 2.7% (95% CI 1.7-4.3%), and 33.6% (95% CI 28.2-39.4%), respectively. Moreover, phylogenetic analyses indicated that 142 of 169 (84.0%) B19V isolates belonged to Genotype 1. CONCLUSIONS: The overall prevalence of B19V among blood donors is not high in mainland China, and most isolates belong to Genotype 1.


Assuntos
Doadores de Sangue , Genótipo , Infecções por Parvoviridae/epidemiologia , Infecções por Parvoviridae/virologia , Parvovirus B19 Humano/genética , Transfusão de Sangue , China/epidemiologia , DNA Viral/sangue , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Prevalência
16.
JAMA Netw Open ; 3(4): e203707, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32338753

RESUMO

Importance: Antiviral treatment is important in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) comprehensive therapy. A high HBV DNA level is an independent risk factor for HBV-related HCC, but no quantifiable clinical index is available to date. Objective: To evaluate the feasibility and availability of the novel HBV DNA quantitation-time index (HDQTI), which includes HBV DNA quantitation and follow-up, to predict HBV-related HCC prognosis. Design, Setting, and Participants: This retrospective prognostic study of patients with HCC from multiple centers in China was performed from January 1, 2002, to December 31, 2016. The median follow-up time was 18 months, and the longest follow-up time was 147 months. Data analysis was performed from January 1, 2017, to December 31, 2018. Main Outcomes and Measures: Clinical characteristics, antitumor management, antiviral treatment, HDQTI scores, follow-up information, and overall survival were recorded and analyzed. A receiver operating characteristic curve and accompanying area under the curve were calculated for HDQTI. Results: A total of 842 patients (mean [SD] age, 61.80 [9.85] years; 513 [60.9%] male) were included in the study. Of all included patients, 734 received no antiviral therapy before diagnosis (no previous diagnosis of HBV infection), 43 underwent nonstandard antiviral therapy, and 65 received regular antiviral therapy. Compared with the group without antiviral treatment, the Barcelona Clinic Liver Cancer (BCLC) stage was earlier (A:B:C, 73.8%:26.2%:0% to 5.7%:65.5%:28.8%, P < .001), the mean (SD) tumor size was smaller (2.89 [1.26] to 7.56 [3.28] cm, P < .001), the ratio of baseline HBV DNA level of more than 105 copies/mL was lower (10.8% to 40.6%, P < .001), and the ratio of the α1-fetoprotein level more than 400 ng/mL was less (21.5% to 78.2%, P < .001) in the standard antiviral treatment group, whereas the nonstandard treatment group was between the 2 groups. Recurrence occurred in 39 of 109 BCLC stage A cases. Patients with HDQTI scores higher than 34 had high risk of recurrence; at this cutoff level, the sensitivity of the HDQTI was 76.9% and the specificity was 92.9%, with an area under curve of 0.928. Patients in various BCLC stages had similar trends in overall survival and HDQTI scores (BCLC stage A: HDQTI score <34, not applicable; HDQTI score ≥34, 44.0 months; 95% CI, 38.3-49.7 months; BCLC stage B: HDQTI score <34, 35.0 months; 95% CI, 33.3-36.7 months; HDQTI score ≥34, 17.0 months; 95% CI, 14.5-19.5 months; P = .002; BCLC stage C: HDQTI score <34, 18.0 months; 95% CI, 16.5-19.6 months; HDQTI scores ≥34, 10.0 months; 95% CI, 8.5-11.5 months; P = .005). Conclusions and Relevance: The findings suggest that the HDQTI can be used as an independent prognostic indicator of recurrence in HBV-related HCC. Shorter follow-up intervals and accurate imaging evaluation are recommended in patients with HDQTI scores of 34 or higher.


Assuntos
Carcinoma Hepatocelular/virologia , DNA Viral/sangue , Vírus da Hepatite B/genética , Hepatite B/diagnóstico , Neoplasias Hepáticas/virologia , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Estudos de Casos e Controles , Intervalo Livre de Doença , Estudos de Viabilidade , Feminino , Seguimentos , Hepatite B/complicações , Hepatite B/tratamento farmacológico , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/induzido quimicamente , Recidiva Local de Neoplasia/diagnóstico , Curva ROC , Estudos Retrospectivos
17.
Arch Virol ; 165(6): 1279-1288, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32240369

RESUMO

Mother-to-child transmission of hepatitis B virus (HBV) is the main route of transmission in Asia, and characterization of HBV quasispecies is needed to further understand virus evolution and adaptation. To understand changes in HBV during mother-to-child transmission, we enrolled nine pairs of mothers and children in the study, including a set of twins. Three groups were infected with HBV genotype C, and six groups were infected with HBV genotype B. The full-length HBV genome was amplified by PCR from serum samples before antiviral treatment, the whole viral genomes from each pair were sequenced, and the complexity and diversity of the quasispecies were analyzed. The entropy of transmitted HBV in children was found to be lower than their mothers, suggesting that there was a bottleneck effect during HBV transmission from the mother to the child. Selective evolution was shown by calculating πN and πS in the whole genomes, and the highest values were obtained for the X gene, which plays a role in viral replication and immune escape. All genotype C patients and only one genotype B pair had a πN/πS greater than 1 ratio, indicating that positive selection had occurred. In addition, quasispecies were found to be different between the twin children despite having the same mother, indicating that virus evolution is host-specific.


Assuntos
Vírus da Hepatite B/genética , Hepatite B Crônica/transmissão , Hepatite B Crônica/virologia , Transmissão Vertical de Doença Infecciosa , Quase-Espécies , Transativadores/genética , Adulto , Criança , Pré-Escolar , China , DNA Viral/sangue , Evolução Molecular , Feminino , Genoma Viral , Genótipo , Vírus da Hepatite B/classificação , Vírus da Hepatite B/isolamento & purificação , Especificidade de Hospedeiro/genética , Humanos , Lactente , Recém-Nascido , Masculino , Mães , Mutação , Filogenia , Reação em Cadeia da Polimerase , Gêmeos , Adulto Jovem
18.
Best Pract Res Clin Obstet Gynaecol ; 68: 103-108, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32278628

RESUMO

Chronic Hepatitis B virus (HBV) infection is endemic worldwide, and the prevalence is especially high in the Asia-Pacific regions. Despite its high prevalence, the literature regarding the impact of HBV infection on subfertility and fertility treatment remains limited and conflicting. Latest studies do not suggest any detrimental effect of HBV infection on the outcome of IVF/ICSI treatment in women having chronic HBV infection. There is evidence that HBV exists in ovarian tissue including oocyte and follicular fluid, and therefore has the potential risk of transmission to the embryo, which can explain the finding of vertical transmission despite immunoprophylaxis. Most recently, we have observed the evidence of HBV viral replication in female HBV carriers undergoing IVF/ICSI treatment. This raises the question of whether antiviral medication should be administered during ovarian stimulation in IVF/ICSI treatment cycles for women with chronic HBV infection to help reduce the chance of vertical transmission.


Assuntos
Fertilização In Vitro/métodos , Antígenos de Superfície da Hepatite B/análise , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/fisiopatologia , Hepatite B/complicações , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Infertilidade , Adulto , DNA Viral/sangue , Feminino , Fertilização In Vitro/estatística & dados numéricos , Hepatite B/epidemiologia , Vírus da Hepatite B/genética , Hepatite B Crônica/complicações , Hepatite B Crônica/transmissão , Humanos , Indução da Ovulação , Gravidez , Análise do Sêmen
19.
Aliment Pharmacol Ther ; 51(11): 1169-1179, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32291781

RESUMO

BACKGROUND: Studies have shown a higher risk of hepatocellular carcinoma (HCC) with higher baseline serum hepatitis B virus (HBV) DNA levels in chronic hepatitis B (CHB) patients. However, the association between very high HBV DNA levels (>6 log10 IU/mL) and HCC risk remains unclear, especially in middle-aged and old HBeAg-positive patients. AIM: To identify the association between broad-range HBV DNA levels and HCC risk. METHODS: We conducted a historical cohort study in Korea involving 6949 non-cirrhotic, treatment-naïve CHB patients with alanine aminotransferase (ALT) <2× upper limit of normal for >1 year. HBV DNA was >6 log10 IU/mL in 2029 (29.2%) patients. Follow-up was censored when the antiviral therapy was initiated. RESULTS: The mean age of the patients was 45 years. During 8.0 years of median follow-up, 363 patients (5.2%) developed HCC. By multivariable Cox regression analysis, HCC risk was highest with baseline HBV DNA levels of 6-7 log10 IU/mL (adjusted hazard ratio [aHR] 4.98; P < 0.001), and lowest with >8 log10 IU/mL (aHR 0.90; P = 0.71) and ≤4 log10 IU/mL (aHR 1.00; reference), which was independent of other predictive factors. The similar association between HBV DNA levels and HCC risk was consistently observed in all age subgroups (age <40, 40-49 and ≥ 50 years). CONCLUSIONS: HCC risk was highest with moderate serum HBV DNA levels of 6-7 log10 IU/mL in CHB patients without significant ALT elevation. Extending treatment indication to CHB patients with moderate levels of HBV DNA may be considered to further prevent HCC, regardless of ALT levels.


Assuntos
Carcinoma Hepatocelular/diagnóstico , DNA Viral/sangue , Vírus da Hepatite B/genética , Hepatite B Crônica/sangue , Neoplasias Hepáticas/diagnóstico , Adulto , Idoso , Alanina Transaminase/sangue , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/virologia , Transformação Celular Viral , Estudos de Coortes , Progressão da Doença , Feminino , Seguimentos , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/complicações , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/patologia , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , República da Coreia , Fatores de Risco
20.
Nat Biomed Eng ; 4(6): 601-609, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32284553

RESUMO

In organ transplantation, infection and rejection are major causes of graft loss. They are linked by the net state of immunosuppression. To diagnose and treat these conditions earlier, and to improve long-term patient outcomes, refined strategies for the monitoring of patients after graft transplantation are needed. Here, we show that a fast and inexpensive assay based on CRISPR-Cas13 accurately detects BK polyomavirus DNA and cytomegalovirus DNA from patient-derived blood and urine samples, as well as CXCL9 messenger RNA (a marker of graft rejection) at elevated levels in urine samples from patients experiencing acute kidney transplant rejection. The assay, which we adapted for lateral-flow readout, enables-via simple visualization-the post-transplantation monitoring of common opportunistic viral infections and of graft rejection, and should facilitate point-of-care post-transplantation monitoring.


Assuntos
Sistemas CRISPR-Cas , Rejeição de Enxerto/virologia , Infecções Oportunistas/diagnóstico , Patologia Molecular/métodos , Biomarcadores/sangue , Biomarcadores/urina , Quimiocina CXCL9/sangue , Quimiocina CXCL9/urina , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Citomegalovirus/genética , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/diagnóstico , DNA Viral/sangue , DNA Viral/genética , DNA Viral/urina , Humanos , Rim , Nefropatias/virologia , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Testes Imediatos , Polyomavirus/genética , Polyomavirus/isolamento & purificação , Infecções por Polyomavirus/diagnóstico , Complicações Pós-Operatórias/diagnóstico , RNA Mensageiro , Infecções Tumorais por Vírus/diagnóstico
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