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1.
Rev. Soc. Bras. Med. Trop ; 53: e20180533, 2020. tab
Article in English | LILACS | ID: biblio-1057270

ABSTRACT

Abstract INTRODUCTION: HBV and HIV have identical transmission routes. The aim of this study was to determine the prevalence of HBV in HIV patients and to detect the presence of occult HBV infection. METHODS: All samples were tested for serology markers and using qPCR. RESULTS: This study included 232 individuals, out of which 36.6% presented with HBV markers and 11.8% presented with HBsAg or HBV-DNA, including 3 patients that showed OBI. CONCLUSIONS: We observed a high prevalence of HBV among HIV patients. In addition, the results suggest that OBI can occur in patients with serological profiles that are indicative of past infection. Therefore, the application of molecular tests may enable the identification of infections that are not evident solely based on serology.


Subject(s)
Humans , HIV Infections/epidemiology , Hepatitis B virus/immunology , Hepatitis B/epidemiology , Hepatitis B Antibodies/blood , Hepatitis B Core Antigens/blood , Hepatitis B Surface Antigens/blood , Brazil/epidemiology , DNA, Viral/blood , HIV Infections/complications , Prevalence , Real-Time Polymerase Chain Reaction , Hepatitis B/complications , Hepatitis B/diagnosis
2.
Braz. j. infect. dis ; 23(6): 441-450, Nov.-Dec. 2019. tab, graf
Article in English | LILACS | ID: biblio-1089314

ABSTRACT

ABSTRACT Background: Antiretroviral therapy (ART) has decreased AIDS incidence and mortality, rendering comorbidities, such as hepatitis B more relevant for people living with human immunodeficiency virus (HIV). Since antiretroviral drugs may also inhibit hepatitis B virus (HBV) replication, analyzing the impact of ART on management of hepatitis B in this population is important. Objective: To assess HBV viremia among HIV/HBV coinfected individuals on ART and its associated factors. Method: For this cross-sectional study, HIV/HBV-coinfected individuals, aged over 18 years, who were on ART for over six months and receiving care at an outpatient clinic in São Paulo were recruited. Sociodemographic characteristics, information about viral exposure, clinical and laboratory data, including evaluation of liver fibrosis were obtained. Plasma HBV DNA was measured by polymerase chain reaction. Viral genome sequencing was conducted for genotyping and identification of drug resistance-conferring mutations if viral load exceeded 900 IU/mL. Results: Out of 2,946 patients who attended the clinic in 2015, 83 were eligible and 56 evaluated. Plasma HBV DNA was detected in 16 (28.6%) (95% CI: 18.0-41.3%), all on lamivudine and tenofovir treatment. HBV DNA detection was associated with lower education (p = 0.015), higher international normalized ratios (p = 0.045), history of an AIDS-defining illness [OR: 3.43 (95% CI: 1.10-11.50)], and HBeAg detection [OR: 6.60 (95% CI: 1.84-23.6)]. In contrast, a last CD4+ count above 500 cells/mm3 in the year prior to inclusion [OR: 0.18 (95% CI: 0.04-0.71)] and detection of anti-HBe [OR: 0.21 (95% CI: 0.04-0.99)] were negatively associated. Patients with HBV DNA above 900 IU/mL were infected with subgenotypes A1 (n = 3) and D2 (n = 1), and exhibited viral mutations associated with total resistance to lamivudine and partial resistance to entecavir. Conclusions: Despite being on ART, a significant proportion of HIV/HBV-coinfected individuals present HBV viremia. Characterization of factors that are associated with this finding may help professionals provide better management to these patients.


Subject(s)
Humans , Male , Female , Middle Aged , HIV Infections/virology , Anti-HIV Agents/therapeutic use , Viral Load/drug effects , Antiretroviral Therapy, Highly Active , Coinfection/virology , Hepatitis B/virology , Viremia , DNA, Viral/blood , HIV Infections/complications , HIV Infections/drug therapy , Hepatitis B virus/isolation & purification , Cross-Sectional Studies , Risk Factors , CD4 Lymphocyte Count , Educational Status , Hepatitis B/complications
3.
Rev. Soc. Bras. Med. Trop ; 52: e20180457, 2019. tab, graf
Article in English | LILACS | ID: biblio-1041557

ABSTRACT

Abstract INTRODUCTION: We defined the cut-off values of the antigenemia and cytomegalovirus (CMV) DNA tests in HIV/AIDS patients to identify CMV disease. METHODS: A total of 97 samples from 68 patients with and without CMV disease were analyzed by viral DNA detection and antigenemia assay. RESULTS: Qualitative and quantitative results significantly differed between assays. The cut-off values for the antigenemia and qPCR assays were 1.5 positive cells/200,000 leukocytes and 3.715 log/mL, respectively. CONCLUSIONS: Antigenemia and qPCR are suitable for monitoring CMV disease in HIV patients, however, the threshold values should be determined within the centers where the patients are monitored.


Subject(s)
Humans , DNA, Viral/analysis , AIDS-Related Opportunistic Infections/diagnosis , Cytomegalovirus Infections/diagnosis , Cytomegalovirus/isolation & purification , Brazil/epidemiology , DNA, Viral/blood , Predictive Value of Tests , Prospective Studies , ROC Curve , Sensitivity and Specificity , AIDS-Related Opportunistic Infections/blood , Cytomegalovirus Infections/blood , Viral Load , Cytomegalovirus/genetics , Real-Time Polymerase Chain Reaction , Antigens, Viral/blood
4.
Rev. Soc. Bras. Med. Trop ; 52: e20190304, 2019. tab, graf
Article in English | LILACS | ID: biblio-1020443

ABSTRACT

Abstract INTRODUCTION: Human parvovirus B19 (B19V) is a common pathogen, which on infection causes variety of clinical conditions from benign self-limiting exanthematous disease and other similar pathologies to fetal death. METHODS: We collected 341 serum samples between the first and fourth day after the onset of symptoms from all patients suspected of dengue fever who were attended at Regional Hospital of Tefé. Initially, patients were screened for malaria by blood smear test and negative samples were sent to Fundação de Medicina Tropical Doutor Heitor Vieira Dourado (FMT-HVD) situated in Manaus (AM) for dengue testing using semi-nested multiplex PCR. Further, we investigated 44 malaria and dengue-negative samples of children for B19V DNA by nested-PCR. Positive samples were analyzed by BLAST against entire public non-redundant nucleotide database and genotyped by phylogenetic analyses using neighbor-joining clustering method. RESULTS: Eight samples (18.2%) were found to be PCR positive. Fever, headache, ocular pain, and/or muscle pain were reported as the most frequent symptoms by the patients and none were diagnosed with rash at the time of sample collection. Phylogenetic analysis of major capsid protein 2 (VP2) and VP3 coding region showed high similarity with B19V genotype 1. CONCLUSIONS: Our results reveal the spread of B19V genotype 1 in Tefé. Moreover, our results emphasize the significance of laboratorial differential diagnosis using molecular techniques in patients with acute febrile, and thereby aid the health surveillance system in improving patient care even in the remote areas of Amazon.


Subject(s)
Humans , Male , Female , Adolescent , Adult , Aged , Young Adult , DNA, Viral/blood , Parvovirus B19, Human/genetics , Parvoviridae Infections/diagnosis , Parvoviridae Infections/virology , Dengue/diagnosis , Phylogeny , Brazil , Polymerase Chain Reaction , Genotype , Middle Aged
5.
Rev. Soc. Bras. Med. Trop ; 52: e20180432, 2019. tab
Article in English | LILACS | ID: biblio-1003137

ABSTRACT

Abstract By decreasing the pre-seroconversion window period, nucleic acid testing (NAT) has improved the safety of blood products and reduced the risk of transfusion-transmitted infections. Between 2011 and 2017, NAT determinations for approximately 898,202 donations were performed at Fundação Pró-Sangue/Hemocentro de São Paulo (FPS-HSP). Three seronegative HIV-viremic donations were detected. The NAT yield rate per million donations was 3.34 for HIV, and the acute HIV-1 infections detected are described, followed by a brief review of the situation in Brazil.


Subject(s)
Humans , Male , Adult , Blood Donors , DNA, Viral/blood , RNA, Viral/blood , HIV Infections/diagnosis , HIV-1/genetics , Nucleic Acid Amplification Techniques
6.
Mem. Inst. Oswaldo Cruz ; 113(1): 62-65, Jan. 2018. tab, graf
Article in English | LILACS | ID: biblio-1040579

ABSTRACT

In occult hepatitis B infection (OBI), hepatitis B virus DNA (HBV DNA) can be detected in serum samples; however, oral fluid collection for detection of HBV DNA has not yet been explored, despite the availability of collection devices. Serum and oral fluid samples from 45 hepatitis B core antibody (anti-HBc)-positive patients were collected for the amplification of the HBV polymerase gene. HBV DNA was detected in five serum and four oral fluid samples (the detection limit for oral fluid was 1.656 log IU/mL in paired serum). In conclusion, simple methodologies of sample collection and in-house polymerase chain reaction (PCR) allowed detection of HBV DNA, and these could be used to improve the diagnosis of OBI, especially in locations with limited resources.


Subject(s)
Humans , Male , Female , Adult , Aged , Saliva/virology , DNA, Viral/analysis , Hepatitis B/diagnosis , Hepatitis B Antibodies/analysis , Hepatitis B Surface Antigens/analysis , DNA, Viral/blood , Hepatitis B virus/isolation & purification , Hepatitis B virus/genetics , Polymerase Chain Reaction , Viral Load , Middle Aged
7.
Rev. bras. epidemiol ; 21: e180018, 2018. tab, graf
Article in Portuguese | LILACS | ID: biblio-958832

ABSTRACT

RESUMO: Introdução: A disseminação da infecção pelo vírus linfotrópico-T humano (HTLV) em famílias da área metropolitana de Belém, Pará, Brasil, e a ausência de estudos na população em geral requisitam investigações que esclareçam melhor a sua prevalência na região. Metodologia: Foi realizada pesquisa de anticorpos anti-HTLV-1/HTLV-2 em indivíduos adultos transeuntes de logradouros públicos de Belém, entre novembro de 2014 e novembro de 2015. A infecção foi confirmada por pesquisa de DNA proviral e foi realizada avaliação clínica e investigação intrafamiliar dos infectados. Resultados: Dos 1.059 indivíduos investigados, 21 (2,0%) apresentaram amostras sororeagentes, 15 (1,4%) confirmados para HTLV-1, 5 (0,5%) para HTLV-2 e o DNA proviral foi indetectável em 1 caso. A média de idade dos infectados (57,2) foi maior que a dos não infectados (46,2) (p = 0,0010). A infecção aumentou com a idade e se destacou nos indivíduos com renda familiar menor ou igual a um salário mínimo. A transmissão intrafamiliar parece ter ocorrido em todas as famílias investigadas. Dentre os portadores de HTLV-1, 30% (3/10) já apresentavam algum sintoma relacionado à infecção. Discussão: O aumento da infecção de acordo com a idade pode ocorrer por soroconversão tardia de infecção pré-adquirida ou pelo risco cumulativo de novas infecções, sobretudo em mulheres. Conclusão: A infecção por HTLV demonstrou moderada prevalência na população estudada, com predomínio do HTLV-1. Essa mostrou-se associada à baixa renda e ao aumento da idade das mulheres. Também apresentou disseminação intrafamiliar e negligência no diagnóstico das doenças associadas.


ABSTRACT: Introduction: The spread of the HTLV infection in families living in the metropolitan area of Belém, Pará, Brazil, and the lack of studies in the general population requires studies to better understand its prevalence in the region. Methods: An anti-HTLV-1/HTLV-2 antibodies test was carried out on random adults in public places in Belém between November 2014 and November 2015. A proviral DNA test detected if the person was infected, and then a clinical evaluation and an intrafamilial investigation were carried out. Results: Of the 1059 individuals being investigated, 21 (2.0%) had seroreagent samples, 15 (1.4%) had HTLV-1, 5 (0.5%) had HTLV-2, and proviral DNA was undetectable in one case. The mean age of the infected people (57.2) was higher than that of those that were uninfected (46.2) (p = 0.0010). The prevalence of infection increased with age, especially in individuals with a family income equal to or less than a minimum wage. Intrafamilial transmission seems to have occurred in all of the families being studied. Among the patients with HTLV-1, 30% (3/10) already had some symptom related to the infection. Discussion: The increase in prevalence rates according to age may be due to late seroconversion of a previously acquired infection, or the cumulative risk of new infections, especially in women. Conclusion: There was a moderate prevalence of the HTLV infection among adult individuals from the metropolitan area of Belém, with a predominance of HTLV-1. This infection was associated with low income and increasingly older women. It also presented intrafamily spread and negligence in the diagnosis of associated diseases.


Subject(s)
Humans , Adolescent , Adult , Aged , Aged, 80 and over , Young Adult , Deltaretrovirus Infections/epidemiology , Socioeconomic Factors , Urban Population , Brazil/epidemiology , DNA, Viral/blood , Human T-lymphotropic virus 1/genetics , Human T-lymphotropic virus 1/immunology , HTLV-I Antibodies/blood , Human T-lymphotropic virus 2/genetics , Human T-lymphotropic virus 2/immunology , HTLV-II Antibodies/blood , Deltaretrovirus Infections/diagnosis , Prevalence , Cross-Sectional Studies , Prospective Studies , Endemic Diseases , Middle Aged
8.
Ann. hepatol ; 16(3): 358-365, May.-Jun. 2017. tab, graf
Article in English | LILACS | ID: biblio-887247

ABSTRACT

ABSTRACT Introduction. Chronic hepatitis B (CHB) is associated with high burden and healthcare costs. Virologic response achieved with antivirals is associated with progression avoidance. This study aimed to estimate the efficiency and clinical impact of antiviral strategies in CHB patients. Material and methods. A Markov model estimated lifetime complications and direct costs in both, HBeAg-positive and HBeAg-negative cohorts. Strategy 1 (71% of treated population) and strategy 2 (100%), both based on pegylated interferon (peg-IFN) followed by oral tenofovir or entecavir, were compared to no treatment. Progression was based on HBV-DNA levels. Rescue therapy with oral antivirals was applied for peg-IFN failure. Disease costs (€, 2014) and utilities were obtained from literature. Results. Compared to natural history, strategy 1 increased QALY (3.98 in HBeAg-positive, 2.16 in -negative cohort). With strategy 2, survival was up to 5.60 (HBeAg-positive) and 3.05 QALY (in HBeAg-negative). The model predicted avoidance of 128 and 86 carcinomas in HBeAg-positive and -negative patients with strategy 1, and up to 181 and 121 in HBeAg-positive and -negative for strategy 2. Total cost increased up to €102,841 (strategy 1) and €105,408 (strategy 2) in HBeAg-positive, and €85,858 and €93,754 in HBeAg-negative. A€1,581/QALY gained ratio was estimated versus the natural history for both strategies. In conclusion, increasing antiviral coverage would be efficient, reducing complications.


Subject(s)
Humans , Hepatitis B virus/drug effects , Drug Costs , Hepatitis B, Chronic/economics , Hepatitis B, Chronic/drug therapy , Hepatitis B e Antigens/blood , Computer Simulation , DNA, Viral/blood , Biomarkers/blood , Cost-Benefit Analysis , Models, Economic , Disease Progression , Viral Load , Drug Resistance, Viral , Drug Therapy, Combination
9.
Rev. Assoc. Med. Bras. (1992) ; 63(3): 224-228, Mar. 2017. tab, graf
Article in English | LILACS | ID: biblio-956436

ABSTRACT

Summary Introduction: Virus surveillance strategies and genetic characterization of human parvovirus B19 (B19V) are important tools for regional and global control of viral outbreak. In São Paulo, Brazil, we performed a study of B19V by monitoring the spread of this virus, which is an infectious agent and could be mistakenly reported as a rash and other types of infection. Method: Serum samples were subjected to enzyme immunoassay, real time polymerase chain reaction, and sequencing. Results: From the 462 patients with suspected cases of exanthematic infections, the results of the 164 serum samples were positive for B19V immunoglobulin M. Among these cases, there were 38 patients with erythema infections and B19-associated with other infections such as encephalitis, hydrops fetalis, chronic anemia, hematological malignancies. These samples were sequenced and identified as genotype 1. Conclusion: This study showed patients with infections caused by B19V and sequencing genotype 1. Continuous monitoring is necessary to detect all known genotypes, and the emergence of new genotypes of these viruses for case management in public health control activities.


Resumo Introdução: Estratégias de vigilância para o parvovírus humano B19 e caracterização genética são ferramentas importantes para o controle regional e global do surto viral. Em São Paulo, Brasil, foi realizado um estudo de parvovírus B19, monitorando a disseminação desse vírus, que é um agente infeccioso e poderia ser erroneamente relatado como uma erupção cutânea e outros tipos de infecções. Método: As amostras de soro foram submetidas ao ensaio imunoenzimático, PCR quantitativo em tempo real e sequenciamento. Resultados: Dos 462 pacientes com casos suspeitos de infecções exantemáticas, os resultados das 164 amostras de soro foram positivos para parvovírus B19 imunoglobulina M. Entre eles, 38 pacientes com eritema infeccioso apresentaram B19 associado com outras infecções, como encefalite, hidropisia fetal, anemia crônica, doenças hematológicas malignas. Essas amostras foram sequenciadas e identificadas como genótipo 1. Conclusão: Os pacientes foram infectados com parvovírus B19 e apresentaram genótipo 1. Monitoração contínua é necessária para detectar todos os genótipos conhecidos e o surgimento de novos genótipos para o controle de casos em saúde pública.


Subject(s)
Humans , Male , Female , Infant , Child, Preschool , Child , Adolescent , Adult , Young Adult , Parvovirus B19, Human/isolation & purification , Parvovirus B19, Human/genetics , Erythema Infectiosum/virology , Genotype , Brazil , DNA, Viral/blood , Immunoglobulin G/blood , Immunoglobulin M/blood , Immunoassay , Hydrops Fetalis/virology , Population Surveillance , Erythema Infectiosum/blood , Reverse Transcriptase Polymerase Chain Reaction , Anemia/virology , Middle Aged , Antibodies, Viral/blood
10.
Article in English | WPRIM | ID: wpr-8650

ABSTRACT

BACKGROUND: Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) are increasingly important in immunocompromised patients. Nucleic acid extraction methods could affect the results of viral nucleic acid amplification tests. We compared two automated nucleic acid extraction systems for detecting CMV and EBV using real-time PCR assays. METHODS: One hundred and fifty-three whole blood (WB) samples were tested for CMV detection, and 117 WB samples were tested for EBV detection. Viral nucleic acid was extracted in parallel by using QIAsymphony RGQ and QIAcube (Qiagen GmbH, Germany), and real-time PCR assays for CMV and EBV were performed with a Rotor-Gene Q real-time PCR cycler (Qiagen). Detection rates for CMV and EBV were compared, and agreements between the two systems were analyzed. RESULTS: The detection rate of CMV and EBV differed significantly between the QIAsymphony RGQ and QIAcube systems (CMV, 59.5% [91/153] vs 43.8% [67/153], P=0.0005; EBV, 59.0% [69/117] vs 42.7% [50/117], P=0.0008). The two systems showed moderate agreement for CMV and EBV detection (kappa=0.43 and 0.52, respectively). QIAsymphony RGQ showed a negligible correlation with QIAcube for quantitative EBV detection. QIAcube exhibited EBV PCR inhibition in 23.9% (28/117) of samples. CONCLUSIONS: Automated nucleic acid extraction systems have different performances and significantly affect the detection of viral pathogens. The QIAsymphony RGQ system appears to be superior to the QIAcube system for detecting CMV and EBV. A suitable sample preparation system should be considered for optimized nucleic acid amplification in clinical laboratories.


Subject(s)
Automation , Cytomegalovirus/genetics , Cytomegalovirus Infections/diagnosis , DNA, Viral/blood , Herpesvirus 4, Human/genetics , Humans , Reagent Kits, Diagnostic , Real-Time Polymerase Chain Reaction
11.
Article in English | WPRIM | ID: wpr-8648

ABSTRACT

There has been increasing interest in standardized and quantitative Epstein-Barr virus (EBV) DNA testing for the management of EBV disease. We evaluated the performance of the Real-Q EBV Quantification Kit (BioSewoom, Korea) in whole blood (WB). Nucleic acid extraction and real-time PCR were performed by using the MagNA Pure 96 (Roche Diagnostics, Germany) and 7500 Fast real-time PCR system (Applied Biosystems, USA), respectively. Assay sensitivity, linearity, and conversion factor were determined by using the World Health Organization international standard diluted in EBV-negative WB. We used 81 WB clinical specimens to compare performance of the Real-Q EBV Quantification Kit and artus EBV RG PCR Kit (Qiagen, Germany). The limit of detection (LOD) and limit of quantification (LOQ) for the Real-Q kit were 453 and 750 IU/mL, respectively. The conversion factor from EBV genomic copies to IU was 0.62. The linear range of the assay was from 750 to 10⁶ IU/mL. Viral load values measured with the Real-Q assay were on average 0.54 log₁₀ copies/mL higher than those measured with the artus assay. The Real-Q assay offered good analytical performance for EBV DNA quantification in WB.


Subject(s)
DNA, Viral/blood , Epstein-Barr Virus Infections/diagnosis , Herpesvirus 4, Human/genetics , Humans , Limit of Detection , Reagent Kits, Diagnostic , Real-Time Polymerase Chain Reaction
12.
Säo Paulo med. j ; 134(3): 187-192, tab
Article in English | LILACS | ID: lil-785811

ABSTRACT

CONTEXT AND OBJECTIVE: Kaposi's sarcoma (KS) is a common neoplastic disease in AIDS patients. The aim of this study was to evaluate the frequency of human herpesvirus 8 (HHV-8) infection in human immunodeficiency virus (HIV)-infected patients, with or without KS manifestations and correlate HHV-8 detection with KS staging. DESIGN AND SETTING: Analytic cross-sectional study conducted in a public tertiary-level university hospital in Ribeirão Preto, São Paulo, Brazil. METHODS: Antibodies against HHV-8 lytic-phase antigens were detected by means of the immunofluorescence assay. HHV-8 DNA was detected in the patient samples through a nested polymerase chain reaction (nested PCR) that amplified a region of open reading frame (ORF)-26 of HHV-8. RESULTS: Anti-HHV-8 antibodies were detected in 30% of non-KS patients and 100% of patients with KS. Furthermore, the HHV-8 DNA detection rates observed in HIV-positive patients with KS were 42.8% in serum, 95.4% in blood samples and 100% in skin biopsies; and in patients without KS, the detection rate was 4% in serum. Out of the 16 serum samples from patients with KS-AIDS who were classified as stage II, two were positive (12.5%); and out of the 33 samples from patients in stage IV, 19 (57.6%) were positive. CONCLUSION: We observed an association between HHV-8 detection and disease staging, which was higher in the serum of patients in stage IV. This suggests that detection of HHV-8 DNA in serum could be very useful for clinical assessment of patients with KS and for monitoring disease progression.


CONTEXTO E OBJETIVO: Sarcoma de Kaposi (SK) é uma doença neoplásica comum em pacientes com aids. O objetivo deste estudo foi avaliar a frequência da infecção por herpesvírus humano 8 (HHV-8) em pacientes infectados por HIV, com ou sem SK e associar a detecção do HHV-8 com o estadiamento do SK. TIPO DE ESTUDO E LOCAL: Estudo transversal analítico realizado em hospital universitário público terciário de Ribeirão Preto, São Paulo, Brasil. MÉTODOS: Anticorpos contra antígenos de fase lítica do HHV-8 foram detectados por imunofluorescência. O DNA viral de HHV-8 foi detectado em amostras de pacientes pela reação em cadeia da polimerase do tipo nested (nested PCR), que amplificou uma região do fragmento de leitura aberta (ORF)-26 do HHV-8. RESULTADOS: Anticorpos anti-HHV-8 foram detectados em 30% dos pacientes sem SK e 100% dos com SK. Além disso, a detecção de HHV-8 DNA observada em pacientes HIV-positivos com SK foi de 42,8% no soro, 95,4% em amostras de sangue e 100% em biópsias de pele, e em pacientes sem SK foi de 4% no soro. Das 16 amostras de soro de pacientes com SK-AIDS classificados como estádio II, duas foram positivas (12,5%) e, das 33 amostras de pacientes no estádio IV, 19 (57,6%) foram positivas. CONCLUSÃO: Observamos associação entre a detecção do HHV-8 e o estadiamento da doença, que foi maior no soro de pacientes no estágio IV. Isso sugere que a detecção do HHV-8 no soro poderia ser muito útil para a avaliação clínica de pacientes com SK e para o monitoramento da progressão da doença.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Young Adult , AIDS-Related Opportunistic Infections/virology , Herpesvirus 8, Human/isolation & purification , Sarcoma, Kaposi/blood , Skin Neoplasms/blood , Biopsy , Brazil/epidemiology , DNA, Viral/blood , Polymerase Chain Reaction , Prevalence , Cross-Sectional Studies , Reproducibility of Results , Fluorescent Antibody Technique , Acquired Immunodeficiency Syndrome/blood , Acquired Immunodeficiency Syndrome/epidemiology , HIV Seropositivity/virology , AIDS-Related Opportunistic Infections/pathology , AIDS-Related Opportunistic Infections/blood , AIDS-Related Opportunistic Infections/epidemiology , Disease Progression , Antibodies, Viral/blood , Neoplasm Staging
13.
Article in English | WPRIM | ID: wpr-215525

ABSTRACT

With recent advances in molecular and genomic investigations, the impact of hepatitis B viral and host factors on the progression of chronic HBV infection has been explored. For viral factors, hepatitis B viral load is a strong predictor for liver disease progression. Hepatitis B viral kinetics appear to be important for successful anti-viral therapy. Serum HBsAg level serves as a complementary marker to viral load for the prediction of HBV-related adverse outcomes in patients with low viral load. In those with low viral load, high serum HBsAg level is associated with higher risks of cirrhosis and HCC. Hepatitis B core-related antigen (HBcrAg) induces host immune responses, and the reduction of the HBcrAg level as well as the increment of total anti-HBc level are significantly associated with favorable outcomes. HBV genotypes (genotype C/D) and mutants (basal core promoter and deletion mutation in pre-S genes) are well known viral genetic markers to predict disease progression. For host factors, serum inflammatory biomarkers have been developed to evaluate the HBV-associated hepatic necroinflammation and fibrosis. Host single nucleotide polymorphism on sodium taurocholate cotransporting polypeptide (NTCP, an HBV entry receptor) may be associated with a decreased risk for cirrhosis and HCC. In conclusion, patients with chronic hepatitis B should be evaluated with relevant viral and host markers to identify those who are at a higher risk of liver disease progression and then receive timely antiviral therapy.


Subject(s)
Biomarkers/blood , DNA, Viral/blood , Hepatitis B Surface Antigens/blood , Hepatitis B e Antigens/blood , Hepatitis B virus/genetics , Hepatitis B, Chronic/complications , Humans , Liver Cirrhosis/etiology , Organic Anion Transporters, Sodium-Dependent/genetics , Polymorphism, Single Nucleotide , Risk Factors , Symporters/genetics
14.
Article in English | WPRIM | ID: wpr-215522

ABSTRACT

BACKGROUND/AIMS: It remains to be determined whether switching from adefovir (ADV) to tenofovir (TDF) provides better virological outcomes in patients exhibiting suboptimal responses to ADV plus nucleoside analogue (ADV+NA) therapy for NA-resistant chronic hepatitis B (CHB). METHODS: In this prospective trial, patients who showed partial responses (defined as serum hepatitis B virus [HBV] DNA >60 IU/mL) to ADV+NA therapy for NA resistance were randomly allocated to receive TDF plus NA (TDF+NA group, n=16) or to continue their current therapy (ADV+NA group, n=16). The primary end point was the proportion of patients with complete virological response (CVR, defined as serum HBV DNA 2log10 IU/mL was more likely in the TDF+NA group at both 24 and 48 weeks (68.8% vs. 56.3%, P=0.014 vs. 81.3% vs. 56.3%, P=0.001, respectively). During the follow-up, the rate of HBeAg seroconversion was higher in the TDF+NA group than the ADV+NA group (12.5% vs. 6.25%, P=0.640), as was that for the hepatitis B surface antigen (6.25% vs. 0%, P=0.080). No serious adverse events due to antiviral agents occurred. CONCLUSIONS: In patients exhibiting suboptimal responses to ADV+NA therapy for NA-resistant CHB, switching from ADV to TDF might provide better virological outcomes.


Subject(s)
Adenine/analogs & derivatives , Alanine Transaminase/blood , Antiviral Agents/therapeutic use , DNA, Viral/blood , Drug Resistance, Viral , Drug Therapy, Combination , Female , Genotype , Hepatitis B e Antigens/blood , Hepatitis B virus/genetics , Hepatitis B, Chronic/drug therapy , Humans , Lamivudine/therapeutic use , Male , Middle Aged , Organophosphonates/therapeutic use , Prospective Studies , Tenofovir/therapeutic use , Treatment Outcome
15.
Article in English | WPRIM | ID: wpr-188161

ABSTRACT

BACKGROUND/AIMS: Clear indicators for stopping antiviral therapy in chronic hepatitis B (CHB) patients are not yet available. Since the level of hepatitis B surface antigen (HBsAg) is correlated with covalently closed circular DNA, the HBsAg titer might be a good indicator of the off-treatment response. This study aimed to determine the relationship between the HBsAg titer and the entecavir (ETV) off-treatment response. METHODS: This study analyzed 44 consecutive CHB patients (age, 44.6±11.4 years, mean±SD; men, 63.6%; positive hepatitis B envelope antigen (HBeAg) at baseline, 56.8%; HBV DNA level, 6.8±1.3 log₁₀ IU/mL) treated with ETV for a sufficient duration and in whom treatment was discontinued after HBsAg levels were measured. A virological relapse was defined as an increase in serum HBV DNA level of >2000 IU/mL, and a clinical relapse was defined as a virological relapse with a biochemical flare, defined as an increase in the serum alanine aminotransferase level of >2 × upper limit of normal. RESULTS: After stopping ETV, virological relapse and clinical relapse were observed in 32 and 24 patients, respectively, during 20.8±19.9 months of follow-up. The cumulative incidence rates of virological relapse were 36.2% and 66.2%, respectively, at 6 and 12 months, and those of clinical relapse were 14.3% and 42.3%. The off-treatment HBsAg level was an independent factor associated with clinical relapse (hazard ratio, 2.251; 95% confidence interval, 1.076–4.706; P=0.031). When patients were grouped according to off-treatment HBsAg levels, clinical relapse did not occur in patients with an off-treatment HBsAg level of ≤2 log10 IU/mL (n=5), while the incidence rates of clinical relapse at 12 months after off-treatment were 28.4% and 55.7% in patients with off-treatment HBsAg levels of >2 and ≤3 log₁₀ IU/mL (n=11) and >3 log₁₀ IU/mL (n=28), respectively. CONCLUSION: The off-treatment HBsAg level is closely related to clinical relapse after treatment cessation. A serum HBsAg level of <2 log₁₀ IU/mL is an excellent predictor of a sustained off-treatment response in CHB patients who have received ETV for a sufficient duration.


Subject(s)
Adult , Alanine Transaminase/blood , Antiviral Agents/therapeutic use , DNA, Viral/blood , Female , Follow-Up Studies , Guanine/analogs & derivatives , Hepatitis B Surface Antigens/blood , Hepatitis B virus/genetics , Hepatitis B, Chronic/drug therapy , Humans , Male , Middle Aged , Multivariate Analysis , Polymerase Chain Reaction , Recurrence , Treatment Outcome
16.
Article in English | WPRIM | ID: wpr-200494

ABSTRACT

Standardized cytomegalovirus (CMV) DNA quantification is important for managing CMV disease. We evaluated the performance of the Real-Q CMV Quantification Kit (Real-Q assay; BioSewoom, Korea) using whole blood (WB), with nucleic acid extraction using MagNA Pure 96 (Roche Diagnostics, Germany). Real-time PCR was performed on two platforms: the 7500 Fast real-time PCR (7500 Fast; Applied Biosystems, USA) and CFX96 real-time PCR detection (CFX96; Bio-Rad, USA) systems. The WHO international standard, diluted with CMV-negative WB, was used to validate the analytical performance. We used 90 WB clinical samples for comparison with the artus CMV RG PCR kit (artus assay; Qiagen, Germany). Limits of detections (LODs) in 7500 Fast and CFX96 were 367 and 479 IU/mL, respectively. The assay was linear from the LOD to 10(6) IU/mL (R2 ≥0.9886). The conversion factors from copies to IU in 7500 Fast and CFX96 were 0.95 and 1.06, respectively. Compared with the artus assay, for values 1,000 copies/mL, 73.3% and 80.6% of samples in 7500 Fast and CFX96, respectively, had <0.5 log10 copies/mL. The Real-Q assay is useful for quantifying CMV in WB with the two real-time PCR platforms.


Subject(s)
Cytomegalovirus/genetics , Cytomegalovirus Infections/diagnosis , DNA, Viral/blood , Humans , Limit of Detection , Reagent Kits, Diagnostic , Real-Time Polymerase Chain Reaction
17.
Article in English | WPRIM | ID: wpr-46329

ABSTRACT

BACKGROUND/AIMS: Tenofovir disoproxil fumarate (TDF) exhibits similar antiviral efficacy against treatment-naïve and lamivudine (LAM)-resistant chronic hepatitis B (CHB). However, there are few clinical reports on the antiviral effects of TDF-LAM combination therapy compared to TDF monotherapy in patients with LAM-resistant CHB. METHODS: We investigated the antiviral efficacy of TDF monotherapy vs. TDF-LAM combination therapy in 103 patients with LAM-resistant CHB. RESULTS: The study subjects were treated with TDF alone (n=40) or TDF-LAM combination therapy (n=63) for ≥6 months. The patients had previously been treated with TDF-based rescue therapy for a median of 30.0 months (range, 8-36 months). A virologic response (VR) was achieved in 99 patients (96.1%): 95.0% (38/40) of patients in the TDF monotherapy group and 96.8% (61/63) of patients in the TDF-LAM combination therapy group. The VR rates were not significantly different between the TDF monotherapy and TDF-LAM combination therapy groups (88.9 vs. 87.3% at month 12, and 94.4 vs. 93.7% at month 24, log-rank p=0.652). Univariate and multivariate analyses revealed that none of the pretreatment factors were significantly associated with VR. CONCLUSIONS: TDF monotherapy was as effective as TDF-LAM combination therapy for maintaining viral suppression in the vast majority of patients with LAM-resistant CHB, which suggests that TDF add-on therapy with LAM is unnecessary.


Subject(s)
Adult , Aged , Aged, 80 and over , Antiviral Agents/pharmacology , DNA, Viral/blood , Drug Administration Schedule , Drug Resistance, Viral/drug effects , Drug Therapy, Combination , Female , Hepatitis B virus/genetics , Hepatitis B, Chronic/drug therapy , Humans , Kidney Function Tests , Lamivudine/therapeutic use , Liver Function Tests , Male , Middle Aged , Polymerase Chain Reaction , Tenofovir/therapeutic use , Treatment Outcome
18.
Article in English | WPRIM | ID: wpr-46324

ABSTRACT

Recent studies suggest that liver cirrhosis is reversible after administering oral nucleos(t)ide analogue therapy to patients with hepatitis B virus (HBV) infection. However, few studies have addressed whether esophageal varices can regress after such therapy. We report a case of complete regression of esophageal varices during entecavir therapy in patients with HBV-related liver cirrhosis, suggesting that complications of liver cirrhosis such as esophageal varices can regress after the long-term suppression of HBV replication.


Subject(s)
Abdomen/diagnostic imaging , Antiviral Agents/therapeutic use , DNA, Viral/blood , Esophageal and Gastric Varices/complications , Guanine/analogs & derivatives , Hepatitis B virus/genetics , Hepatitis B, Chronic/complications , Humans , Liver Cirrhosis/diagnosis , Male , Middle Aged , Polymerase Chain Reaction , Ultrasonography
19.
Article in English | WPRIM | ID: wpr-93970

ABSTRACT

BACKGROUND/AIMS: This study aimed to clarify the effect of obesity on the development of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients receiving antiviral treatment. METHODS: This study applied a retrospective analysis to a historical cohort in Bundang Jesaeng Hospital. In total, 102 CHB patients were treated with entecavir as an initial treatment for CHB and checked for obesity using a body composition analyzer. Hepatic steatosis was measured semiquantitatively using Hamaguchi’s scoring system in ultrasonography. Risk factors for the development of HCC were analyzed, including obesity-related factors (body mass index [BMI], waist circumference [WC], waist-to-hip ratio [WHR], visceral fat area [VFA], and hepatic steatosis). RESULTS: The median follow-up duration of the patients was 45.2 months (interquartile range: 36.0-58.3 months). The cumulative incidence rates of HCC at 1 year, 3 years, and 5 years were 0%, 5.3%, and 9.0%, respectively. Univariable analysis revealed that the risk factors for HCC development were a platelet count of <120,000 /mm² (hazard ratio [HR]=5.21, P=0.031), HBeAg negativity (HR=5.61, P=0.039), and liver cirrhosis (HR=10.26, P=0.031). Multivariable analysis showed that the significant risk factor for HCC development was liver cirrhosis (HR=9.07, P=0.042). However, none of the obesity-related risk factors were significantly associated with HCC: BMI ≥25 kg/m² (HR=0.90, P=0.894), WC ≥90 cm (HR=1.10, P=0.912), WHR ≥0.9 (HR=1.94, P=0.386), VFA ≥100 cm² (HR=1.69, P=0.495), and hepatic steatosis (HR=0.57, P=0.602). CONCLUSION: HCC development is associated with liver cirrhosis but not obesity-related factors in CHB patients receiving entecavir.


Subject(s)
Adult , Antiviral Agents/therapeutic use , Body Mass Index , Carcinoma, Hepatocellular/epidemiology , Cohort Studies , DNA, Viral/blood , Female , Guanine/analogs & derivatives , Hepatitis B virus/genetics , Hepatitis B, Chronic/complications , Humans , Incidence , Liver Cirrhosis/complications , Liver Neoplasms/epidemiology , Male , Middle Aged , Obesity/complications , Proportional Hazards Models , Retrospective Studies , Risk Factors , Viral Load
20.
Article in English | WPRIM | ID: wpr-93969

ABSTRACT

BACKGROUND/AIMS: To analyze the effects of preexisting lamivudine (LAM) resistance and applying antiviral treatment (adefovir [ADV] add-on LAM combination treatment) on long-term treatment outcomes, and comparing the clinical outcomes of antiviral-naïve chronic hepatitis B patients receiving entecavir (ETV) monotherapy. METHODS: This study enrolled 73 antiviral-naïve patients who received 0.5-mg ETV as an initial therapy and 54 patients who received ADV add-on LAM combination treatment as a rescue therapy from July 2006 to July 2010. RESULTS: During 24-month treatments, the decreases in serum log10HBV-DNA values (copies/mL) were significantly greater in the antiviral-naïve patients treated with ETV than the patients receiving ADV add-on LAM combination treatment. The biochemical response rates for alanine aminotransferase normalization at 6 months (ETV) and 12 months (ADV add-on LAM) were 90.4% (66/73) and 77.8% (42/54), respectively (P=0.048). A Kaplan-Meier analysis indicated that the rates of serologic response, viral breakthrough, and emergence of genotypic resistance did not differ significantly between the two patient groups. There were also no significant intergroup differences in the rates of disease progression (PD) and new development of hepatocellular carcinoma (HCC). CONCLUSION: The long-term clinical outcomes of antiviral-naïve patients treated with ETV and LAM-resistant patients receiving ADV add-on LAM combination treatment were comparable in terms of the emergence of HCC and disease progression.


Subject(s)
Adenine/analogs & derivatives , Adult , Alanine Transaminase/blood , Antibodies, Viral/blood , Antiviral Agents/therapeutic use , DNA, Viral/blood , Disease Progression , Drug Resistance, Viral/drug effects , Drug Therapy, Combination , Female , Follow-Up Studies , Genotype , Guanine/analogs & derivatives , Hepatitis B e Antigens/blood , Hepatitis B virus/drug effects , Hepatitis B, Chronic/drug therapy , Humans , Lamivudine/pharmacology , Male , Middle Aged , Organophosphonates/pharmacology , Treatment Outcome
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