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Liver damage can progress through different stages, resulting in cirrhosis or hepatocellular carcinoma (HCC), conditions that are often associated with viral infections. Globally, 42% and 21% of cirrhosis cases correlate with HBV and HCV, respectively. In the Americas, the prevalence ranges from 1% to 44%. The WHO has the goal to eliminate viral hepatitis, but it is important to consider occult HBV infection (OBI), a clinical condition characterized by the presence of HBV genomes despite negative surface antigen tests. This review aims to provide an overview of recent data on OBI, focusing on its role in the development of hepatic diseases and its significance in the WHO Viral Hepatitis Elimination Plan. Specific HBV gene mutations have been linked to HCC and other liver diseases. Factors related to the interactions between OBI and mutated viral proteins, which induce endoplasmic reticulum stress and oxidative DNA damage, and the potential role of HBV integration sites (such as the TERT promoter) have been identified in HCC/OBI patients. Health initiatives for OBI research in Latin American countries are crucial to achieving the WHO's goal of eradicating viral hepatitis by 2030, given the difficulty in diagnosing OBI and its unclear association with hepatic diseases.
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INTRODUCTION AND OBJECTIVES: Occult HBV infection (OBI) is a specific form of hepatitis B virus (HBV) infection and has the possibility of developing into hepatocellular carcinoma (HCC) in adults. This study aimed to estimate the global prevalence of occult HBV infection in children and adolescents. MATERIALS AND METHODS: We systematically searched PubMed, Embase, Web of Science, and Cochrane databases for relevant studies on the prevalence of OBI in children and adolescents. Meta-analysis was performed using STATA 16 software. RESULTS: Fifty studies were included. The overall prevalence of OBI in children and adolescents was 7.5% (95% CI: 0.050-0.103). In different risk populations, OBI prevalence was remarkably high in the HIV-infected population (24.2%, 95% CI: 0.000-0.788). The OBI prevalence was 0.8% (95% CI:0.000-0.029) in the healthy population, 3.8% (95% CI:0.012-0.074) in the general population, and 6.4% (95% CI: 0.021-0.124) in children born to HBsAg-positive mothers. Based on different serological profiles, the prevalence of OBI in HBsAg-negative and anti-HBc-positive patients was 6.6% (95% CI: 0.016-0.136), 3.0% (95% CI: 0.009-0.059) in HBsAg-negative and anti-HBc-negative patients, 4.6% (95% CI: 0.015-0.088) in HBsAg-negative and anti-HBs-positive patients, and 3.7% (95% CI: 0.001-0.102) in HBsAg-negative and anti-HBs-negative patients. CONCLUSIONS: Despite HBV vaccination and hepatitis B immunoglobulin (HBIG), OBI is common in children and adolescents in high-risk groups.
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Carcinoma Hepatocelular , Hepatite B , Neoplasias Hepáticas , Adolescente , Criança , Humanos , DNA Viral , Hepatite B/diagnóstico , Hepatite B/epidemiologia , Anticorpos Anti-Hepatite B , Antígenos de Superfície da Hepatite B , Vírus da Hepatite B/genética , Neoplasias Hepáticas/epidemiologia , PrevalênciaRESUMO
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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The goal of this study was to investigate the prevalence of occult HBV infection in a reference center for the Northern Brazil from 2005 to 2015 and to identify mutations associated with occult hepatitis B. Molecular analysis was performed on 110 serum samples in which anti-HBc was the only positive serological marker. Regions of the HBV genome were amplified by polymerase chain reaction to detect HBV DNA. A prevalence of 4.1% (793/18,889) for anti-HBc alone was identified. Molecular analysis revealed a prevalence of occult HBV infection of 0.04%. HBV DNA detected were identified in individuals who underwent hemodialysis, infected with the hepatitis C virus and from area of high endemicity for HBV. Direct DNA nucleotide sequencing and phylogenetic analysis identified that genotypes A and D and mutations E164D, I195M, P217L and P120S were associated with occult HBV infection in the S gene. This study contributed with epidemiological and molecular information on Northern Brazil samples with a suggestive profile of occult HBV infection in addition to reinforcing the importance of molecular diagnosis in this type of infection.
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Hepatite B Crônica , Hepatite B , Brasil/epidemiologia , DNA Viral/genética , Hepatite B/complicações , Hepatite B/diagnóstico , Hepatite B/epidemiologia , Anticorpos Anti-Hepatite B , Antígenos de Superfície da Hepatite B/genética , Vírus da Hepatite B/genética , Hepatite B Crônica/complicações , Humanos , Filogenia , PrevalênciaRESUMO
Occult hepatitis B infection (OBI) is characterized by the detection of hepatitis B virus (HBV) DNA in serum or liver but negativity for hepatitis B surface antigen. OBI, which is thought to be maintained by host, immunological, viral and/or epigenetic factors, is one of the most challenging clinical features in the study of viral hepatitis. Currently, there is no validated detection test for OBI. It is believed that OBI is widely distributed throughout the world, with a higher prevalence in populations at high-risk HBV, but the detailed worldwide prevalence patterns are unknown. We conducted a survey of recently published studies on OBI rates across all continents. High prevalence rates of OBI are observed in some specific groups, including patients with hepatitis C virus, human immunodeficiency virus co-infection or hepatocellular carcinoma. In 2016, the World Health Organization adopted strategies to eliminate viral hepatitis by 2030, but the difficulties in detecting and treating OBI currently challenge this goal. Subjects with OBI can transmit HBV, and episodes of reactivation can occur. Further studies to understanding the mechanisms that drive the development of OBI are needed and can contribute to efforts at eliminating viral hepatitis.
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Hepatite B Crônica , Hepatite B , Neoplasias Hepáticas , DNA Viral/genética , Hepatite B/diagnóstico , Hepatite B/epidemiologia , Hepatite B/prevenção & controle , Vírus da Hepatite B/genética , Hepatite B Crônica/epidemiologia , Humanos , PrevalênciaRESUMO
ABSTRACT The goal of this study was to investigate the prevalence of occult HBV infection in a reference center for the Northern Brazil from 2005 to 2015 and to identify mutations associated with occult hepatitis B. Molecular analysis was performed on 110 serum samples in which anti-HBc was the only positive serological marker. Regions of the HBV genome were amplified by polymerase chain reaction to detect HBV DNA. A prevalence of 4.1% (793/18,889) for anti-HBc alone was identified. Molecular analysis revealed a prevalence of occult HBV infection of 0.04%. HBV DNA detected were identified in individuals who underwent hemodialysis, infected with the hepatitis C virus and from area of high endemicity for HBV. Direct DNA nucleotide sequencing and phylogenetic analysis identified that genotypes A and D and mutations E164D, I195M, P217L and P120S were associated with occult HBV infection in the S gene. This study contributed with epidemiological and molecular information on Northern Brazil samples with a suggestive profile of occult HBV infection in addition to reinforcing the importanceof molecular diagnosis in this type of infection.
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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 present study determined the HBV antigen, antibody, and DNA status in blood donations deemed to be HBV positive. Individuals with an occult HBV infection (OBI), defined as being positive for HBV DNA but negative for HBV surface antigen (HBsAg), as well as those with active infection (HBsAg-positive), were identified and characterized. STUDY DESIGN AND METHODS: From a total pool if 198,363 blood donations, we evaluated in a cross-sectional study, 1106 samples that were positive in screening tests for antibody to HBV core antigen (HBcAb), HBsAg, and/or HBV DNA by nucleic acid testing (NAT-HBV). The presence of genetic variants in the HBV pol/S gene in individuals with an active HBV infection was also determined. RESULTS: OBIs were detected in six of 976 samples (0.6%) that were positive only for HBcAb. The rate of HBV active infection was 0.024% (48/198,363) and there was a predominance of HBV sub-genotype A1 (62.2%, 28/45), followed by D3 (17.8%, 8/45). Mutations in the S gene were found in 57.8% (26/45) and immune escape mutations in 37.8% (17/45) of active HBV-infected donors. Among them, T123N, G145A, and D144G high-impact immune escape mutations were identified. CONCLUSION: Highly sensitive molecular tests improve the capacity to detect OBIs. When NAT is performed in pooled samples, HBcAb test has value in the detection of donors with OBI and improves transfusion safety. Mutations in the S gene are frequent in HBsAg-positive blood, including those associated with diagnostic failure and vaccine escape mutations.
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Doadores de Sangue , Segurança do Sangue , Seleção do Doador , Vírus da Hepatite B/isolamento & purificação , Hepatite B/sangue , Adulto , Brasil , Estudos Transversais , DNA Viral/sangue , Feminino , Anticorpos Anti-Hepatite B/sangue , Antígenos do Núcleo do Vírus da Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
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
INTRODUCTION AND AIM: Occult hepatitis B virus infection (OBI) is characterized by the presence of replication-competent hepatitis B virus (HBV) DNA in the liver and/or serum of patients with undetectable levels of the HBV surface antigen (HBsAg). Due to the shared infection routes HIV positive patients are at higher risk of developing OBI, thus, the aim of this study was to determine the frequency of OBI in Mexican HIV-infected patients and to identify mutations in the HBV S gene that could be associated to the development of OBI. MATERIALS AND METHODS: Plasma samples from 50 HIV-infected patients with undetectable levels of the HBsAg were obtained and analyzed. The Core, PreS and S genes were amplified by nested PCR and sequenced by the Sanger method. To analyze HBV diversity in the OBI-positive patients, ten sequences of 762bp from the HBV S gene were selected, cloned, and subsequently sequenced for mutational analyses. RESULTS: OBI infection was found with a frequency of 36% (18/50). All the HBV sequences corresponded to the H genotype. The most common mutations were: C19Y, Q129H, E164D, and I195M, with a frequency of 44%, 36%, 39% and 48% respectively. CONCLUSIONS: In this study, we report the presence of OBI in a cohort of Mexican HIV-infected patients with an overall prevalence of 36%. Mutational analyses revealed that four non-silent mutations were frequent in different regions of the HBsAg gene, suggesting that they might be associated to the development of OBI in this population, nevertheless, further studies are required to determine their role in the pathogenesis of OBI.
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Coinfecção , Infecções por HIV/virologia , Antígenos de Superfície da Hepatite B/genética , Vírus da Hepatite B/genética , Hepatite B/virologia , Mutação , Adulto , Idoso , Análise Mutacional de DNA , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/etnologia , Hepatite B/sangue , Hepatite B/diagnóstico , Hepatite B/etnologia , Antígenos de Superfície da Hepatite B/sangue , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Epidemiologia Molecular , Taxa de Mutação , Fatores de Risco , Carga ViralRESUMO
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 Occult hepatitis B virus (HBV) - characterized by the absence of detectable HBsAg in the presence of HBV DNA - represents a potential threat for blood safety. OBJECTIVES This study was conducted with the aim to investigate the serological and molecular characterization of occult HBV infection (OBI) among blood donors in Mozambique. METHODS 1,502 blood donors were tested for HBsAg. All HBsAg-negative individuals were tested for HBV DNA. Antibodies against HBV core, surface and HBe antigen (anti-HBc, anti-HBs, HBeAg) were measured in HBV DNA positive individuals. FINDINGS 1435 serum samples were HBsAg negative and 16 positive for HBV DNA, 14 confirmed to have OBI, corresponding to a frequency of 0.98%. Of the 14 OBI infections identified, 13/14 (92.8%) were positive for anti-HBc, 4/14 (28.5%) for anti-HBs, and no samples were reactive for HBeAg. Of the 14 OBI cases, nine samples (64.2%) were sequenced for the S/P region. Eight samples (88.9%) belonged to genotype A1 and one (11.1%) to genotype E. One escape mutation (T123A) associated with OBI and various amino acid substitutions for genotype A1 and E were observed. MAIN CONCLUSIONS Our results show the importance of using nucleic acid amplification test to detect occult hepatitis B infection in blood donors in Mozambique.
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Humanos , Masculino , Feminino , Adulto , Doadores de Sangue , Vírus da Hepatite B/isolamento & purificação , Vírus da Hepatite B/genética , Técnicas de Amplificação de Ácido Nucleico/métodos , Hepatite B/diagnóstico , Antígenos de Superfície da Hepatite B/genética , Filogenia , DNA Viral , Reação em Cadeia da Polimerase , Estudos Transversais , MoçambiqueRESUMO
Leprosy patients may present with immune system impairment and have a higher hepatitis B virus (HBV) seroprevalence, justifying the investigation of occult HBV infection in these individuals. The aim of this study was to verify the frequency and the clinical factors associated with occult HBV infection in leprosy patients. Between 2015 and 2016, leprosy patients from a reference center in Brazil were interviewed to assess clinical data. Blood samples were collected for the screening of HBV serological markers using enzyme-linked immunosorbent assay. Patients with negative hepatitis B surface antigen (HBsAg) that had positive anti-HBc and/or anti-HBs were selected for HBV DNA detection using real-time polymerase chain reaction. SPSS was used for data analysis. Among 114 selected patients, six were identified with occult infection (5.3%) and five of them with multibacillary leprosy. Three patients with occult infection had a history of a type 2 reaction (P = 0.072; OR, 4.97; 95% CI, 0.87-28.52). Only two patients with occult infection had isolated anti-HBc, while three had isolated anti-HBs, including those with the highest HBV DNA titers. In conclusion, in leprosy patients with negative HBsAg and positive anti-HBc and/or anti-HBs, occult HBV infection occurs in 5.3% and can be found even in patients with isolated anti-HBs.
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Hepatite B/epidemiologia , Hanseníase/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Criança , Estudos Transversais , DNA Viral/sangue , Feminino , Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Reação em Cadeia da Polimerase em Tempo Real , Carga Viral , Adulto JovemRESUMO
INTRODUCTION: Hepatitis B virus (HBV) infection in children is a health problem worldwide. In Mexico, a high prevalence rate of HBV infection and occult HBV infection have been reported in high-risk adults and children. However, studies regarding HBV infection transmitted from HBV-infected parents to children are limited. This study aimed to determine the risk factors associated with HBV transmission of HBV from parents to children in Mexico. METHODOLOGY: A retrospective case-control study was carried out in 24 pediatric patients with clinical HBV infection and 48 healthy controls. Bivariate and forward conditional logistic regression analysis was used to compare demographic variables, the status of HBV vaccination, and risk factors for HBV infection transmission among children and their parents. RESULTS: No newborns were diagnosed with HBV infection, and no significant differences were found in age (p = 0.209) or gender (p = 0.612) compared to the control group. The independent risk factor associated with HBV transmission was the presence of a parent with a history of promiscuity (OR = 30.95, 95%CI = 3.382-283.326; p = 0.002), whereas having completed the HBV vaccination schedule for their age was a protective factor against HBV infection in the children (OR = 0.245, 95%CI = 0.079-0.764; p = 0.015). CONCLUSIONS: HBV infection in Mexican children is associated with close interpersonal contact with a parent engaged in high-risk sexual practices suggesting that the horizontal route could be the primary mode of infection. Child and adult vaccination campaigns should be reinforced to avoid HBV infection in Mexico.
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Transmissão de Doença Infecciosa , Saúde da Família , Hepatite B/transmissão , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Hepatite B/epidemiologia , Humanos , Lactente , Recém-Nascido , Masculino , México/epidemiologia , Prevalência , Estudos Retrospectivos , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
INTRODUCTION AND AIM: Occult hepatitis B virus (HBV) infection (OBI) represents a state without detectable hepatitis B surface antigen, but positive for HBV DNA. The correlation between OBI and hepatocellular carcinoma (HCC) carcinogenesis is controversial. We studied the frequency and characteristics of OBI among HCC patients and metastatic liver cancer patients. MATERIAL AND METHODS: DNA was obtained from tumor and non-tumor tissues from 75 HCC patients (15 chronic hepatitis B (CHB), 39 chronic hepatitis C (CHC), 21 cryptogenic) and 15 metastatic liver cancer patients who underwent liver resection. HBV DNA and covalentlyclosed circular (ccc) DNA were detected using real-time polymerase chain reaction (PCR), and four HBV DNA regions were detected by nested PCR. Clinicopathological factors were compared between patients with and without OBI. RESULTS: HBV DNA was detected in 14 (93.3%) CHB, five (22.7%) cryptogenic and four (10.3%) CHC patients. cccDNA was detected in 12 (80.0%) CHB, three (14.3%) cryptogenic and two (5.1%) CHC patients. All CHB, eight (38.1%) cryptogenic and ten (25.6%) CHC patients tested positive with nested PCR. No metastatic liver cancer patients were positive for any HBV DNA regions. OBI patients had shorter prothrombin times (P = 0.0055), and lower inflammation activity score in non-tumor liver (P = 0.0274). There were no differences in anti-HBV antibodies. CONCLUSIONS: OBI was detected in 38% of cryptogenic and 25.6% of CHC patients. There was no correlation between OBI and anti-HBV antibodies, but fewer patients with OBI had high inflammatory activity, suggesting that factors other than inflammation may be involved in HCC carcinogenesis in patients with OBI.
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Carcinoma Hepatocelular/virologia , DNA Viral/genética , Vírus da Hepatite B/genética , Hepatite B Crônica/virologia , Neoplasias Hepáticas/virologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/secundário , Transformação Celular Viral , DNA Viral/sangue , Feminino , Anticorpos Anti-Hepatite B/sangue , Vírus da Hepatite B/imunologia , Vírus da Hepatite B/patogenicidade , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/epidemiologia , Interações Hospedeiro-Patógeno , Humanos , Incidência , Japão/epidemiologia , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Carga ViralRESUMO
BACKGROUND: Revaccination after hematopoietic stem cell transplantation (HSCT) is necessary to compensate for the loss of immunological memory. The aims of this study were to evaluate the adherence to revaccination schedule and the humoral immune response to different vaccine antigens in HSCT pediatric and young adult patients. METHODS: Patients submitted to HSCT for over 3 years were recruited. After written informed consent, a questionnaire was filled in, the vaccination card was analyzed, a blood sample was collected and tested by ELISA for diphtheria, Haemophilus influenzae type b (Hib), hepatitis A, hepatitis B, tetanus, measles, rubella, and varicella antibodies. RESULTS: Sixty-three patients (mean age at HSCT, 10.7 years) were evaluated. Forty-one (65%) were male; 34 (54%) had allogeneic and 29 (46%), autologous HSCT. Complete adherence to diphtheria revaccination was found in 79.4% patients and seropositivity was found in 92% of those who completed the revaccination schedule; for Hib, 68.3% adherence and 95.3% seropositivity were observed; for hepatitis A, 63.5% adherence and 92.5% seropositivity; for 3 doses of hepatitis B, 86.8% adherence and 79.2% seropositivity; for tetanus, 79.4% adherence and 100% seropositivity; for measles and rubella, 17.5% adherence and 100% seropositivity; for varicella, 7.9% adherence and 100% seropositivity. The existence of a Vaccination Center for Special Immunobiologicals in patients' municipality was positively associated with completed vaccine schedule; on the other hand, chronic GVHD was negatively associated with revaccination adherence. CONCLUSION: Hematopoietic stem cell transplantation patients showed good seropositivity rates after complete vaccination schedule. However, a low coverage rate was observed for live attenuated antigens.
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Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Imunização Secundária/estatística & dados numéricos , Hospedeiro Imunocomprometido , Cooperação do Paciente/estatística & dados numéricos , Vacinação/estatística & dados numéricos , Adolescente , Adulto , Antígenos de Bactérias/sangue , Antígenos Virais/sangue , Infecções Bacterianas/imunologia , Infecções Bacterianas/prevenção & controle , Criança , Pré-Escolar , Feminino , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Esquemas de Imunização , Imunização Secundária/normas , Terapia de Imunossupressão/efeitos adversos , Masculino , Testes Sorológicos , Inquéritos e Questionários , Vacinação/normas , Viroses/imunologia , Viroses/prevenção & controle , Adulto JovemRESUMO
In the present study, we evaluated the prevalence of occult hepatitis B (OBI) in a population from the Brazilian Amazon region, identify circulating genotypes, and mutations in the S gene. One hundred eighty-one patients with negative serology for HBsAg and anti-HBs and positive serology for anti-HBc participated in the study. Detection of viral DNA, genotyping by sequencing, and analysis of nucleotide sequences to detect possible mutations were performed. HBV DNA was detected in 14.36% of the patients. Genotyping revealed genotype A in 88.46% of HBV DNA-positive subjects, with subgenotype A1 being the most prevalent (78.26%) followed by subgenotype A2 (21.74%). Genotype F was detected in 11.54% (all of them subgenotype F2). Amino acid substitutions were observed in the amplified S gene in individuals with OBI compared to HBsAg-positive individuals (evident infection). In conclusion, the results show a high prevalence of OBI in the population studied, with a pattern of genotypes A and F that circulate in the Brazilian Amazon region. Amino acid substitutions were detected in part of the S gene in patients with OBI. Further studies on the molecular epidemiology of HBV in this region are important to identify patients considered healthy but who are potential transmitters of the disease.
Assuntos
DNA Viral/sangue , Antígenos de Superfície da Hepatite B/genética , Hepatite B/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Substituição de Aminoácidos , Brasil/epidemiologia , Estudos Transversais , DNA Viral/genética , Feminino , Genótipo , Técnicas de Genotipagem , Hepatite B/patologia , Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/classificação , Vírus da Hepatite B/genética , Vírus da Hepatite B/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Análise de Sequência de DNA , Adulto JovemRESUMO
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.