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ABSTRACT BACKGROUND: Occult hepatitis B virus infection (OBI) is defined as the presence of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) in the liver of individuals with undetectable hepatitis B virus surface antigen (HBsAg) in the serum. The actual prevalence of OBI and its clinical relevance are not yet fully understood. OBJECTIVE: To evaluate the prevalence of HBV DNA in liver biopsies of HBsAg-negative patients with chronic liver disease of different etiologies in a referral center in Brazil and compare two different HBV DNA amplification protocols to detect HBV. DESIGN AND SETTING: This cross-sectional observational study was conducted at the Liver Outpatient Clinic, Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil, between January 2016 and December 2019. METHODS: HBV DNA was investigated in 104 liver biopsy samples from individuals with chronic liver disease of different etiologies, in whom HBsAg was undetectable in serum by nested-polymerase chain reaction (nested-PCR), using two different protocols. RESULTS: OBI, diagnosed by detecting HBV DNA using both protocols, was detected in 6.7% of the 104 individuals investigated. Both protocols showed a good reliability. CONCLUSION: In addition to the differences in the prevalence of HBV infection in different regions, variations in the polymerase chain reaction technique used for HBV DNA amplification may be responsible for the large variations in the prevalence of OBI identified in different studies. There is a need for better standardization of the diagnostic methods used to diagnose this entity.
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Argentina exhibits low serological prevalence for Hepatitis B virus (HBV); however, occult hepatitis B infection (OBI) has been reported in blood donors, Amerindians and individuals coinfected with hepatitis C virus (HCV), and/or human immunodeficiency virus (HIV). The aim of this study was to analyze the genetic diversity of HBV and to evaluate serological marker associations and coinfections with HCV and HIV in patients attending and treated in a public hospital in the province of Buenos Aires, Argentina. A total of 189 HBV reactive samples (HBsAg and/or anti-HBc) were analyzed for HBV DNA characterization. All reactive samples were tested for anti-HCV and HIV-antigen/antibody using CMIA assays. Thirty-six samples exhibited detectable HBV DNA, 7 of which were OBI. HBV sequences were classified as subgenotypes A1, A2, B2, D3, F1b, F3 and F4. Mutations related to the ability to escape the host's immune response, resistance to antiviral therapy and progression to disease were found in patients, partly due to the variable sensitivity of HBsAg, the reverse transcriptase, the basal core promoter and the preCore. HCV and HIV prevalence was 10% and most of the genotypes found in the sequences were genotype 1 and B/F recombinant subtype, respectively. Of the total samples analyzed, 7 exhibited coinfections. This study shows the frequency of OBI, subgenotype distribution, HBV mutations and coinfections, which may have important clinical implications in public hospital patients. Planned prevention, detection and treatment adherence are needed to reduce transmission and morbidity in vulnerable populations.
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Coinfecção/genética , Hepatite B Crônica/genética , Hepatite B/genética , Hepatite C/genética , Adolescente , Adulto , Idoso , Argentina/epidemiologia , Doadores de Sangue , Coinfecção/sangue , Coinfecção/tratamento farmacológico , Coinfecção/virologia , Farmacorresistência Viral/genética , Feminino , Genótipo , Infecções por HIV/sangue , Infecções por HIV/genética , Infecções por HIV/virologia , Hepacivirus/genética , Hepacivirus/patogenicidade , Hepatite B/sangue , Hepatite B/tratamento farmacológico , Hepatite B/virologia , Anticorpos Anti-Hepatite B/sangue , Anticorpos Anti-Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/sangue , Antígenos de Superfície da Hepatite B/genética , Antígenos de Superfície da Hepatite B/imunologia , Vírus da Hepatite B/genética , Vírus da Hepatite B/patogenicidade , Hepatite B Crônica/sangue , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/virologia , Hepatite C/sangue , Hepatite C/tratamento farmacológico , Hepatite C/virologia , Hospitais Públicos , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Sangue Oculto , Adulto JovemRESUMO
BACKGROUND: The hepatitis B virus (HBV) is one of the leading causes of acute, chronic and occult hepatitis (OBI) representing a serious public health threat. Cytokines are known to be important chemical mediators that regulate the differentiation, proliferation and function of immune cells. Accumulating evidence indicate that the inadequate immune responses are responsible for HBV persistency. The aim of this study were to investigate the cytokines IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-10 and IL-17A in patients with OBI and verify if there is an association between the levels of these cytokines with the determination of clinical courses during HBV occult infection. METHODS: 114 patients with chronic hepatitis C were investigated through serological and molecular tests, the OBI coinfected patients were subjected to the test for cytokines using the commercial human CBA kit. As controls, ten healthy donors with no history of liver disease and 10 chronic HBV monoinfected patients of similar age to OBI patients were selected. RESULTS: Among 114 HCV patients investigated, 11 individuals had occult hepatitis B. The levels of cytokines were heterogeneous between the groups, most of the cytokines showed higher levels of production detection among OBI/HCV individuals when compared to control group and HBV monoinfected pacients. We found a high level of IL-17A in the HBV monoinfected group, high levels of TNF-α, IL-10, IL-6, IL-4 and IL-2 in OBI/HCV patients. CONCLUSION: These cytokines could be involved in the persistence of HBV DNA in hepatocytes triggers a constant immune response, inducing continuous liver inflammation, which can accelerate liver damage and favor the development of liver cirrhosis in other chronic liver diseases.
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Coinfecção/imunologia , Coinfecção/virologia , Citocinas/sangue , Vírus da Hepatite B/imunologia , Hepatite B Crônica/imunologia , Hepatite C Crônica/virologia , Idoso , Estudos Transversais , Citocinas/classificação , Citocinas/imunologia , DNA Viral/análise , DNA Viral/genética , Feminino , Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B/genética , Vírus da Hepatite B/genética , Hepatite C Crônica/complicações , Hepatócitos/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
OBJECTIVES: To identify blood donors with occult hepatitis B infections (OBIs), determine the prevalence of antibody to hepatitis B core antigen (anti-HBc) positivity and estimate the impact of anti-HBc screening on donor deferral at CETS-Veracruz (Mexico). BACKGROUND: Hepatitis B virus infection is a major concern in transfusion medicine. Mexican regulations only mandate screening for hepatitis B surface antigen (HBsAg), and there are no requirements regarding testing for anti-HBc or use of a nucleic acid test (NAT). There is, therefore, limited information about the prevalence of anti-HBc positivity and occult hepatitis B among blood donors in Mexico. METHODS: This retrospective study examined individuals who donated blood to CETS-Veracruz from June 2014 to June 2017. All donors were serologically examined according to Mexican health regulations, and the prevalence of anti-HBc positivity was determined. A NAT was used to identify individuals with OBIs. RESULTS: We analysed the data of 28 016 blood donors. Over 4 years, the average prevalence of anti-HBc positivity was 1.05%. The risk factors for anti-HBc positivity were low education and age over 50 years. There were nine donors with OBIs. CONCLUSION: The presence of donors with OBIs in CETS-Veracruz and other Mexican blood banks highlights the need to mandate the implementation of anti-HBc screening in Mexico.
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Bancos de Sangue , Doadores de Sangue , Hepatite B , Adolescente , Adulto , Fatores Etários , Feminino , Hepatite B/sangue , Hepatite B/epidemiologia , Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores SocioeconômicosRESUMO
BACKGROUND: Occult hepatitis B virus infection (OBI) is defined as the presence of hepatitis B virus (HBV) DNA in serum and/or liver from HBsAg-negative subjects. Our aim was to determine OBI frequency in serum and genomic DNA in patients undergoing renal transplant and their cognate donors in a selected population from Western Mexico. METHODS: Blood samples were obtained from 94 donors and their cognate recipients (188 participants) before kidney transplantation. Identification of HBV DNA was carried-out by nested (S-region) and semi-nested (Pol-region) PCR in both genomic and serum DNA samples from 188 participants at pre-surgical stage and from a subset of 73 recipients at three-month follow-up. RESULTS: HBV-DNA was not detected in either genomic or serum DNA samples from recipients or donors prior to transplantation. After three-months of follow-up, 2 out of 73 (2.7%, 95% CI: 0.9-11.9%) recipients were positive to HBV-DNA (Pol-region) in genomic DNA samples using a high sensitivity Taq DNA polymerase. CONCLUSIONS: OBI incidence in recipients of kidney transplant may be higher than previously recognized. Detection of HBV-DNA was higher in genomic DNA than in serum samples using a high sensitivity Taq DNA polymerase. To the best of our knowledge, this is the first report regarding this specific topic in Mexicans.
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DNA Viral/sangue , Hepatite B/epidemiologia , Transplante de Rim , Adulto , Feminino , Hepatite B/sangue , Hepatite B/virologia , Vírus da Hepatite B/genética , Hepatite B Crônica , Humanos , Masculino , México , Reação em Cadeia da Polimerase , Doadores de TecidosRESUMO
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.
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Humanos , Infecções por HIV/epidemiologia , Vírus da Hepatite B/imunologia , Hepatite B/epidemiologia , Anticorpos Anti-Hepatite B/sangue , Antígenos do Núcleo do Vírus da Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Brasil/epidemiologia , DNA Viral/sangue , Infecções por HIV/complicações , Prevalência , Reação em Cadeia da Polimerase em Tempo Real , Hepatite B/complicações , Hepatite B/diagnósticoRESUMO
BACKGROUND Many studies have identified mutations in the hepatitis B surface antigen (HBsAg) as important factors limiting the ability of commercial serological assays to detect this viral antigen. However, an association between mutations in the HBsAg gene and the occurrence of occult HBV infection (OBI) in patients has not been established. OBJECTIVES To detect hepatitis B virus (HBV) DNA in patients with anti-HBc as a unique serological marker, a previously published, cost-effective TaqMan-based real-time polymerase chain reaction (PCR) test with minor groove binding probes was adapted for use in this study. The current study also aimed to investigate HBsAg mutations and genotypes of HBV in OBI at the Viral Hepatitis Ambulatory Clinic in Rio de Janeiro to determine any possible association. METHODS Intra-assay and inter-assay reproducibility were determined, and the mean coefficient of variation values obtained were 2.07 and 3.5, respectively. Probit analysis indicated that the 95% detection level was 25 IU/mL. The prevalence of OBI was investigated in 35 serum samples with an ‘anti-HBc alone’ profile from individuals who attended our clinic between 2011 and 2013. FINDINGS HBV DNA was detected in only one sample, resulting in an OBI rate of 2.9%. Nucleotide sequencing of the pre-S/S region was performed to genotype and analyse mutations within the HBsAg gene of this HBV DNA. The HBV in the OBI case was classified as sub-genotype A1, and a sequence analysis of the small S gene revealed 12 mutations in the major hydrophilic region compared to the consensus A1 sequence. Most of these mutations occurred in amino acid residues that have been reported as clinically relevant because they have been implicated in vaccine escape and/or inability to detect HBsAg by commercial serological assays. MAIN CONCLUSIONS Our study suggests the importance of specific HBsAg mutations, different from those in D, B, and C genotypes, in sub-genotype A1 HBV associated with OBI.
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DNA Viral/isolamento & purificação , DNA Viral/genética , Hepatite B/genética , Hepatite B/virologia , Antígenos de Superfície da Hepatite B/genética , Sensibilidade e Especificidade , Reação em Cadeia da Polimerase em Tempo RealRESUMO
Occult hepatitis B virus infection (OBI) is characterized by the absence of HBsAg and persistence of the virus genome (HBV-DNA) in liver tissue and/or blood. OBI has been reported in several clinical contexts. However, the clinical significance of OBI in tuberculosis (TB) treatment is unknown. We investigated the OBI prevalence and its impact on the risk of drug-induced liver injury (DILI) during TB treatment. This was a prospective cohort study with one hundred patients who were treated for TB from 2008 to 2015. Laboratory, clinical and demographic data of TB patients were extracted from medical records. Based on HBV-DNA testing of serum samples, an OBI prevalence of 12% was established; almost half of these patients had both anti-HBc and anti-HBs serological markers. Low CD4+ cell counts have been shown to be a risk factor for OBI among TB patients co-infected with HIV (P=.036). High DILI incidence was observed in this study. A multivariable Cox proportional hazard model was conducted and identified OBI (HR 2.98, 95% CI 1.30-6.86) as the strongest predictor for DILI when adjusted to CD4+ cell count (HR 0.38, 95% CI 0.17-0.90), ALT before TB treatment (HR 1.37, 95% CI 0.81-2.32) and TB extrapulmonary clinical form (HR 2.91, 95% CI 1.75-7.21). The main aim of this study was to highlight DILI as a clinical outcome during treatment of TB patients with OBI. Therefore, HBV-DNA testing should be considered routinely in monitoring DILI, and also in other clinical implications associated with OBI, reduce morbidity and mortality.
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Antituberculosos/efeitos adversos , Antituberculosos/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , DNA Viral/sangue , Hepatite B Crônica/complicações , Tuberculose/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Antígenos de Superfície da Hepatite B/sangue , Hepatite B Crônica/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Tuberculose/tratamento farmacológico , Adulto JovemRESUMO
Studies on the prevalence of infection with hepatitis B virus (HBV) among children are scarce in Latin American countries, especially in Mexico. This study was aimed to investigate the prevalence of HBV infection, occult hepatitis B infection (OBI) and HBV genotypes among children with clinical hepatitis. In total, 215 children with clinical hepatitis were evaluated for HBV infection. HBV serological markers and HBV DNA were analysed. OBI diagnosis and HBV genotyping was performed. HBV infection was found in 11.2% of children with clinical hepatitis. Among these HBV DNA positive-infected children, OBI was identified in 87.5% (n = 21/24) of the cases and 12.5% (n = 3/24) were positive for both HBV DNA and hepatitis B surface antigen. OBI was more frequent among children who had not been vaccinated against hepatitis B (p < 0.05) than in those who had been vaccinated. HBV genotype H was prevalent in 71% of the children followed by genotype G (8%) and genotype A (4%). In conclusion, OBI is common among Mexican children with clinical hepatitis and is associated with HBV genotype H. The results show the importance of the molecular diagnosis of HBV infection in Mexican paediatric patients with clinical hepatitis and emphasise the necessity of reinforcing hepatitis B vaccination in children.
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Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Infecções Assintomáticas/epidemiologia , Vírus da Hepatite B/imunologia , Hepatite B Crônica/epidemiologia , Vacinação/métodos , Primers do DNA , DNA Viral/isolamento & purificação , Genótipo , Técnicas de Genotipagem , Hepatite A/diagnóstico , Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/classificação , Vírus da Hepatite B/genética , Hepatite B Crônica/prevenção & controle , Imunoglobulina M/sangue , México/epidemiologia , Reação em Cadeia da Polimerase , PrevalênciaRESUMO
In this cross-sectional study, 207 hepatitis B surface antigen (HBsAg)-negative kidney transplant recipients were evaluated based on demographic and epidemiological data and on the levels of serological markers of hepatitis B virus (HBV) and hepatitis C virus infection and liver enzymes. Patients with HBV or human immunodeficiency virus infection were excluded. Sera were analysed for the presence of HBV-DNA. HBV-DNA was detected in two patients (1%), indicating occult hepatitis B (OHB) infection (the HBV-DNA loads were 3.1 and 3.5 IU/mL in these patients). The results of the liver function tests were normal and no serological markers indicative of HBV infection were detected. The prevalence of OHB infection was low among kidney transplant recipients, most likely due to the low HBsAg endemicity in the general population of the study area.
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Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vírus da Hepatite B , Hepatite B/epidemiologia , Transplante de Rim , Brasil/epidemiologia , Estudos Transversais , DNA Viral/análise , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Hepatite B/diagnóstico , PrevalênciaRESUMO
A high prevalence of occult hepatitis B (OHB) genotype H infections has been observed in the native Mexican Nahua population. In addition, a low incidence of hepatitis B virus (HBV)-associated hepatocellular carcinoma has been described in Mexico. The immune response to infection among OHB-infected patients has been poorly evaluated in vivo. Therefore, we assessed the expression profiles of 23 cytokines in OHB genotype H-infected Nahua patients. A total of 41 sera samples from natives of the Nahua community were retrospectively analysed. Based on their HBV antibody profiles, patients were stratified into two groups: OHB patients (n = 21) and patients that had recovered from HBV infection (n = 20). Herein, we report distinctive cytokines profiles in OHB-infected individuals. Compared to healthy controls (n = 20) and patients who resolved HBV infection, OHB-infected patients displayed an increase in interleukin (IL)-2 secretion in addition to a characteristic inflammation profile (decrease in IL-8 and tumour necrosis factor-alpha levels and increased levels of tumour growth factor-beta). IL-15 and interferon-gamma levels were reduced in OHB-infected individuals when compared to those patients who resolved HBV infection. In contrast, OHB patients showed an increase in monocyte chemoattractant protein (MCP)-1 and MCP-2 compared to healthy controls and patients who resolved HBV infection. These findings suggest that cytokine expression can influence the severity of OHB disease and could lead to new investigation into the treatment of liver and other infectious diseases.
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Adulto , Feminino , Humanos , Masculino , Citocinas/sangue , Vírus da Hepatite B/genética , Hepatite B/imunologia , Indígenas Centro-Americanos , Estudos de Casos e Controles , Estudos Transversais , Genótipo , Hepatite B/sangue , Hepatite B/etnologia , México/etnologiaRESUMO
La infección oculta por virus de hepatitis B es una forma reconocida de infección que ha ganado interés en la última década, por su significado clínico y las implicaciones frente a los crecientes estados de inmunosupresión. La hepatitis B oculta corresponde a un estado de infección que no presenta marcadores serológicos como antígeno de superficie de hepatitis b, o elevación de transaminasas; su diagnostico se basa en la presencia de DNA viral en población con o sin anticuerpos contra la partícula del core viral, siendo la población de mayor riesgo, los pacientes con trasplante hepático receptores de donante core +, pacientes con hepatocarcinoma, pacientes con cirrosis criptogénica pacientes con insuficiencia renal crónica, usuarios de drogas intravenosas y donantes de sangre frecuentes. Objetivo: Identificar pacientes con infección oculta por virus de hepatitis B en población con insuficiencia renal crónica en hemodiálisis con mayor riesgo, dados por la presencia de anticuerpo contra partícula core VHB y coinfección con virus de hepatitis C. Materiales y métodos: Pacientes con insuficiencia renal crónica en hemodiálisis en la unidad renal del hospital Militar central. Se describen las características demográficas básicas y se identifican los pacientes con anticuerpo core positivo de manera exclusiva, e infección por virus de hepatitis C. Teniendo en cuenta que esta es la población de mayor riesgo de infección oculta, se realiza cuantificacion del genoma viral por técnica de amplificación. Resultados: La serie corresponde a una población adulta mayor predominantemente masculina, con insuficiencia renal crónica secundaria a nefropatía diabética e hipertensiva en su mayoría; el 54 % de los pacientes vacunados contra hepatitis B presenta anticuerpos protectores, y el 13 % presenta anticuerpo contra partícula core del virus de hepatitis B como marcador exclusivo de enfermedad y un paciente con infección por virus de hepatitis C, sin encontrar la presencia de genoma viral en estos pacientes. Discusión: Los pacientes con insuficiencia renal crónica en hemodiálisis que están expuestos a hemoderivados y procedimientos invasivos; a pesar de las normas de bioseguridad, se encuentran en alto riesgo de infección oculta por virus de hepatitis B. Los estudios multinaciones realizados a nivel mundial muestran una gran variabiliadad en la prevalencia de Hepatitis B oculta, a razón de las características demográficas propias de las poblaciones estudiadas. Conclusiones: No se encontró genoma viral de virus de hepatitis B en pacientes con insuficiencia renal crónica en hemodiálisis mayor de seis meses con anticuerpo contra partícula core positivo exclusivo y coinfección con virus de hepatitis C en la unidad renal del hospital Militar central a noviembre de 2008.
Occult Hepatitis B infection is a very well known form of infection, which has gained attention during the last decade because of its clinical significance and the implications facing immunosuppression conditions. Occult hepatitis B corresponds to an infectious state with the absence of serological hepatitis B markers or transaminase elevation. Its diagnostic is based on viral DNA presence in people who may have or not antibodies against viral coreÊs particle, being the most risky population patients who have had hepatic transplant, receivers of positive core donor, patients with hepatocellular carcinoma, patients with cryptogenic cirrhosis, patients with chronic kidney failure, intravenous drug users and frequent blood donors. This studyÊs objective was to identify patients with occult hepatitis B infection in a population with chronic kidney failure on hemodialysis with higher risk given by the presence of the core particle antibody and co-infection with hepatitis C virus. Materials and methods: the current study takes as target a population of patients with chronic kidney failure in hemodialysis at the kidney unit of the "Hospital Militar Central". A survey which pretends to describe the basic demographic characteristics and to identify patients with exclusive positive core antibody and hepatitis C is applied taking into account that this population is at the highest risk for hidden infection; viral genome identification by the amplification technique was done. Results: the series correspond to a basically adult male population with secondary chronic kidney failure due to diabetic and hypertensive nephropathy; 54% of vaccined patients against hepatitis B had protective antibodies and, 13% presented antibodies against core particle of hepatitis B virus, and one patient was positive to Hepatitis C virus, without the presence of viral genome in this population. Discussion: patients with chronic kidney failure on hemodialysis who are exposed to blood derivatives and invasive procedures in spite of bio - safety policies are at high risk for occult hepatitis B infection. Multinational studies conducted worldwide, show a wide geographical variability in occult hepatitis B prevalence. Conclusions: No hepatitis B viral genome was detected in patients with chronic kidney failure on hemodialysis treatment longer than six months with antibody against core particle and co-infection with hepatitis C virus in the kidney unit of "Hospital Militar Central" by November 2008.