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BACKGROUND: Hepatitis B virus (HBV) infection is a major concern regarding blood safety in countries with a high HBV prevalence, such as China. We aimed to understand the prevalence of HBV infection among blood donors in Chongqing and provide an important basis for developing appropriate blood screening strategies. METHODS: Dual enzyme-linked immunosorbent assays (ELISAs) for hepatitis B surface antigen (HBsAg) were conducted in parallel with nucleic acid testing (NAT) of donors. All HBsAg-reactive and/or HBV DNA-positive blood samples were tested for HBsAg and hepatitis B DNA levels. RESULTS: A total of 117,927 blood donor samples were collected from the Chongqing Blood Center between April 2020 and November 2020. In total, 473 HBV-ineligible samples were retained for HBsAg and DNA confirmation. A total of 272 samples were confirmed to be HBsAg+, including 2 HBV DNA - and 270 HBV DNA + samples. A total of 201 donations were HBsAg-, including 72 HBV DNA - samples. The rate of HBV infection was 65.33% (309/473) in men, which was significantly higher than that in women (p < 0.001). The HBV failure rate was higher among the first-time donors (p < 0.05). Of the 182 NAT R/HBsAg N/N samples (Nucleic acid test reactivity/2 anti-HBsAg tests negative), 37.91% (69/182) were false positives. The proportion of hepatitis B infections in the 18 NAT R/HBsAg N/R (Nucleic acid test reactivity/1 anti-HBsAg tests negative) samples was 94.44% (17/18), of which 50% (9/18) were occult HBV infection. A total of 95.83% (69/72) of the false positives were from the NAT R/HBsAg N/N group, and 58.33% (42/72) were first-time donors. CONCLUSION: Our data showed a strikingly high HBV infection rate among blood donors in Chongqing. Double ELISA and single NAT can effectively prevent HBV leakage and improve blood safety. First-time donors have a high rate of HBV transplant failure; therefore, donors should be retained and recruited from low-risk groups.
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Donantes de Sangre , ADN Viral , Ensayo de Inmunoadsorción Enzimática , Antígenos de Superficie de la Hepatitis B , Virus de la Hepatitis B , Hepatitis B , Humanos , Donantes de Sangre/estadística & datos numéricos , China/epidemiología , Femenino , Masculino , Hepatitis B/epidemiología , Hepatitis B/diagnóstico , Hepatitis B/sangre , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/aislamiento & purificación , Virus de la Hepatitis B/inmunología , Antígenos de Superficie de la Hepatitis B/sangre , Adulto , ADN Viral/sangre , Persona de Mediana Edad , Prevalencia , Adulto Joven , AdolescenteRESUMEN
Mixed cryoglobulinemia vasculitis (MCV) is caused in ~90% of cases by chronic hepatitis C virus (HCVposMCV) and more rarely by hepatitis B virus (HBV) infection, or apparently noninfectious. HCVposMCV develops in only ~5% of patients with chronic hepatitis C (CHC), but risk factors other than female gender have not been identified so far. We conducted a retrospective case control study investigating whether past active HBV infection, defined by hepatitis B surface antigen (HBsAg) seroclearance and anti-core antibody (HBcAb) positivity, could be a risk factor for developing HCVposMCV. The prevalence of HBsAg seroclearance was 48% within 123 HCVposMCV patients and 29% within 257 CHC patients (p=0.0003). Multiple logistic regression including as variables gender, birth year, age at HBV testing, cirrhosis, and hepatocellular carcinoma, confirmed an association of HBsAg seroclearance with HCVposMCV [adjusted odds ratio (OR) 2.82, 95% confidence interval (95% CI) 1.73-4.59, p<0.0001]. Stratification by gender, however, showed that HBsAg seroclearance was associated with HCVposMCV in male [OR 4.63, 95% CI 2.27-9.48, p<0.0001] and not in female patients [OR 1.85, 95% 95% CI 0.94-3.66, p=0.076]. HBsAg seroclearance, and more likely occult HBV infection, is an independent risk factor for HCVposMCV in male CHC patients.
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Crioglobulinemia , Antígenos de Superficie de la Hepatitis B , Hepatitis C Crónica , Vasculitis , Humanos , Masculino , Crioglobulinemia/inmunología , Crioglobulinemia/etiología , Crioglobulinemia/sangre , Persona de Mediana Edad , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/inmunología , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/inmunología , Estudios Retrospectivos , Factores de Riesgo , Femenino , Anciano , Vasculitis/inmunología , Vasculitis/epidemiología , Vasculitis/etiología , Hepatitis B/complicaciones , Hepatitis B/inmunología , Hepatitis B/epidemiología , Estudios de Casos y Controles , Virus de la Hepatitis B/inmunología , Adulto , Factores Sexuales , Hepacivirus/inmunologíaRESUMEN
BACKGROUND: Occult HBV infection (OBI) is a special form of hepatitis B virus (HBV) infection that may cause Liver cirrhosis and hepatocellular carcinoma, causing significant harm to patients. Given the insidious nature of OBI, it is usually not easy to be detected. Most of the samples currently studied are concentrated on blood donors, however, patients in this special state have not been fully studied. This project aimed to study the effect of HBV S region mutations on HBsAg in patients with clinical OBI. METHODS: Collect 107 HBsAg-/HBV DNA + blood samples from Beijing Youan Hospital, Capital Medical University from August 2022 to April 2023. Next, the successfully extracted and amplified HBV DNA S regions were sequenced. Construct mutant plasmids to verify the cell function of the high-frequency mutation sites and explore the possible molecular mechanism. RESULTS: Sixty-eight HBsAg-negative samples were sequenced, revealing high-frequency amino acid substitution sites in the HBV S protein, including immune escape mutations (i.e., sY100CãsK122RãsI126TãsT131Pãand sS114T) and TMD (Transmembrane domain) region substitutions (i.e., sT5AãsG10DãsF20Sãand sS3N). We constructed a portion of the mutant plasmids and found that sT5A, sF20S, sG10D, sS3N, sI68T, and sI126T single point mutations or combined mutations may decrease HBsAg expression or change the antigenicity of HBsAg leading to detection failure. CONCLUSIONS: HBsAg-negative patients may show various mutations and amino acid replacement sites at high frequency in the HBV S-region, and these mutations may lead to undetectable Hepatitis B surface antigen (HBsAg), HBsAg antigenic changes or secretion inhibition.
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ADN Viral , Antígenos de Superficie de la Hepatitis B , Virus de la Hepatitis B , Hepatitis B , Mutación , Humanos , Antígenos de Superficie de la Hepatitis B/genética , Antígenos de Superficie de la Hepatitis B/inmunología , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/inmunología , Femenino , ADN Viral/genética , Masculino , Adulto , Persona de Mediana Edad , Hepatitis B/virología , Sustitución de Aminoácidos , Genotipo , Adulto Joven , AncianoRESUMEN
Occult HBV infection (OBI) remains a potential threat for blood safety. The prevalence of OBI was investigated in a blood donation center of Chinese PLA General Hospital to improve HBV blood safety. 229446 samples from blood donors were screened by two different enzyme-linked immunosorbent assay (ELISA) kits. 78 samples were HBV DNA positive among 212134 ELISA nonreactive donor samples. The prevalence of OBI was 0.04% (76/212134). Ten samples of OBI were permitted by the donors' content for further research, and all of these were below 200IU/mL, and six of these were below 20IU/mL(6/10,60%). Genotype B and genotype C was 20% (2/10) and 80% (8/10), respectively. 16 amino acid mutations were detected in the S region of OBI, included three mutations in MHR region of S. The prevalence of OBI is rare in this donation center. These mutations we found may contribute to the multifactorial occurrence of OBI.
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Donantes de Sangre , ADN Viral , Genotipo , Virus de la Hepatitis B , Hepatitis B , Humanos , Donantes de Sangre/estadística & datos numéricos , Hepatitis B/epidemiología , Hepatitis B/virología , Prevalencia , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/aislamiento & purificación , Beijing/epidemiología , Masculino , Adulto , Femenino , ADN Viral/genética , ADN Viral/sangre , Persona de Mediana Edad , Mutación , Adulto Joven , Ensayo de Inmunoadsorción Enzimática , China/epidemiología , AdolescenteRESUMEN
INTRODUCTION AND OBJECTIVES: Occult hepatitis B virus (HBV) infection (OBI) is characterised by low levels of hepatitis B virus (HBV) DNA in the blood/liver of patients with negative hepatitis B surface antigen (HBsAg). This study aimed to determine the OBI prevalence and virological characteristics (viral genotypes and HBsAg mutants) in patients with an "anti-HBc only" serological profile. MATERIALS AND METHODS: A total of 24 900 serum samples were routinely screened for hepatitis B markers over a five-year period. All anti-HBc-positive/HBsAg-negative/anti-HBs-negative sera were selected and analysed for the presence of HBV DNA. Mutational analyses of the HBs gene and polymerase gene sequences were performed. RESULTS: 1749 (7.02%) sera were anti-HBc positive, and 113 (0.45%) sera had an "anti-HBc only" serological profile (HBsAg/anti-HBs negative). HBV DNA was detected in 12/113 (10.61%) "anti-HBc only" positive sera, representing 0.048% of all routinely tested samples. Due to extremely low viremia, HBV genome was successfully sequenced in only two sera where subgenotype D3 was confirmed. Mutational analyses of the S gene revealed multiple missense mutations. In addition to the M133I, Y134F, and G145R mutations, already associated with diagnostic escape, we also found nine novel OBI-related S-gene mutations - S136Y, F158L, K160N, E164G, S167L, A168V, L175S, S210I and F212C. CONCLUSIONS: We detected multiple known and novel S gene mutations in 2/12 (16.6%) OBI cases, nevertheless, further studies are required to determine their role in the pathogenesis of OBI. Understanding the frequencies of clinically relevant HBV mutations may contribute to improvement of diagnostic protocols.
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Hepatitis B Crónica , Hepatitis B , Adulto , Humanos , Virus de la Hepatitis B/genética , Antígenos de Superficie de la Hepatitis B , ADN Viral/genética , Prevalencia , Croacia/epidemiología , Hepatitis B/diagnóstico , Hepatitis B/epidemiología , Anticuerpos contra la Hepatitis BRESUMEN
Occult hepatitis B (HBV) infection (OBI), characterized by low viral loads, accounts for much of the risk of HBV transfusion-transmitted infection. With anticore antibodies (anti-HBc) screening introduced in England, the imperative to identify OBI donors has increased. We aimed to develop an ultra-sensitive PCR system and investigate risk factors for HBV DNA presence in blood donations. Seven extraction methods and three PCR assays were compared. The optimal system was sought to determine HBV DNA presence in anti-HBc-positive donations. Predictors of DNA positivity were subsequently investigated. Extraction from 5 mL of plasma increased sample representation and resulted in HBV DNA detection in low viral load samples (~0.5 IU/mL). Screening of 487 763 donations in 2022 identified two OBI donors and 2042 anti-HBc-positive donors, 412 of the latter with anti-HBs < 100 mIU/mL. Testing of 134 anti-HBc-positive donations utilizing the 5 mL extraction method identified two further HBV DNA-positive donations. Higher anti-HBc titer and anti-HBs negativity were significant predictors of DNA detectability in anti-HBc-positive donations. An ultrasensitive PCR assay identified potentially infectious donations increasing HBV DNA detection in anti-HBc-positive donors from 0.5% to 1.9%. Anti-HBc titers may further complement the risk stratification for DNA positivity in anti-HBc screening and minimize unnecessary donor deferral.
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Hepatitis B Crónica , Hepatitis B , Humanos , Virus de la Hepatitis B/genética , ADN Viral , Donantes de Sangre , Antígenos del Núcleo de la Hepatitis B , Anticuerpos contra la Hepatitis B , Antígenos de Superficie de la Hepatitis B , Reacción en Cadena de la Polimerasa/métodos , Medición de RiesgoRESUMEN
BACKGROUND: In Japan, 41 million blood donations have been screened for hepatitis B virus (HBV) during the past 8.4 years using individual donation nucleic acid amplification testing (ID-NAT) and antibody to hepatitis B core antigen (anti-HBc) screening. STUDY DESIGN AND METHODS: Transfusion-transmitted HBV infection (TT-HBV) incidence was examined. Donated blood implicated in TT-HBV was analyzed for infection stage and DNA levels. Causative HBV strains were phylogenetically analyzed. RESULTS: Among 5162 (0.013%) ID-NAT positives, window period (WP) and occult HBV infection (OBI) accounted for 3.4% (176) and 11.5% (594), respectively. No OBI-related TT-HBV occurred. Seven blood donations caused eight TT-HBV cases, six of which were in the pre-ID-NAT WP, leaving one with an unresolved infection stage. Seven cases were caused by platelet concentrate (180 mL plasma) and one case by fresh-frozen plasma (200 mL plasma), which contained estimated infectious doses varying between 2 and 2300 HBV virions. HBV subgenotypes in five cases were HBV/A2. Complete genome sequences of the transmitting A2 strains were nearly identical (99.6%-100%) and clustered in a group that included HBV/HIV-1 coinfections and a higher proportion of donors in the acute infection phase (69%) than the other group of HBV/A2 sequences (5%). DISCUSSION: The incidence of observed TT-HBV cases has significantly reduced to 0.19 per million in the ID-NAT screening period. OBI-related TT-HBV was eliminated by anti-HBc screening. Established TT-HBV cases were caused by blood products with large plasma volumes containing extremely low HBV concentrations derived from blood donors at a very early infection stage.
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Hepatitis B , Reacción a la Transfusión , Humanos , Antígenos del Núcleo de la Hepatitis B , Incidencia , Japón/epidemiología , Reacción a la Transfusión/epidemiología , Hepatitis B/diagnóstico , Hepatitis B/epidemiología , Hepatitis B/prevención & control , Virus de la Hepatitis B/genética , Anticuerpos contra la Hepatitis B , Antígenos de Superficie de la Hepatitis B , Donantes de Sangre , ADN Viral , Técnicas de Amplificación de Ácido NucleicoRESUMEN
Objective: This study aimed to assess the efficacy of individual-donation nucleic acid testing (ID-NAT) in detecting occult hepatitis B virus infection (OBI) among anti-HBc positive blood donors, compared to minipool nucleic acid testing (MP-NAT). Methods: The present study analyzed data from the Shandong Blood Center in China during the period from January 2018 to June 2022, where HBsAg-negative blood donors were screened using the 6-sample minipool nucleic acid testing (6-sample MP NAT) method. NAT-positive samples underwent subsequent anti-HBc and anti-HBs testing. Approximately 5000 samples that passed the nucleic acid mixing test were randomly selected for anti-HBc testing, and over 100 anti-HBc positive samples underwent individual donor nucleic acid testing (ID-NAT). Any HBV DNA positive samples detected by ID-NAT were subsequently confirmed using alternative nucleic acid testing methods. Results: Among 220,445 HBsAg-negative blood donors, the positivity rate of HBV DNA detection using the 6-sample minipool nucleic acid testing (MP NAT) method was found to be 0.031% (69/220,445). Of the 67 HBV DNA positive samples, 55 (82.09%) and 25 (37.31%) were found to be positive for anti-HBc and anti-HBs, respectively, using the supplementary chemiluminescent microparticle immunoassay (CMIA). Among the 4797 HBsAg-negative/MP NAT-negative samples, 909 (18.95%) tested positive for anti-HBc. Further NAT testing was performed on 164 arbitrarily selected anti-HBc-positive/MP HBV DNA-negative samples, revealing a HBV DNA positivity rate of 1.22% (2/164). Conclusion: Using individual donation nucleic acid testing can significantly increase the detection rate of occult hepatitis B virus infection in anti-HBc-positive blood donors, resulting in a detection rate of 0.22% (1.22 × 0.1895). This rate is 8.10 times higher than the detection rate achieved by mixed testing methods (0.031%) [calculated as (0.22 + 0.031)/0.031]. Therefore, it is recommended to perform single HBV DNA testing on anti-HBc-positive blood donors, discard plasma with weakly positive or negative anti-HBs but positive anti-HBc, or avoid transfusing anti-HBc-positive plasma to recipients with weakly positive or negative anti-HBs to prevent HBV infection.
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Occult hepatitis B virus (HBV) infection (OBI) is a condition in which replication-competent viral DNA is detected in the liver (with detectable or undetectable HBV DNA in serum) of individual testing negative for HBV surface antigen (HBsAg). It is a risk factor for transfusion or transplant transmission, reactivation after immunosuppression or chemotherapy, and progression of chronic liver disease and hepatocarcinogenesis. The long-term stable presence of covalently closed circular DNA (cccDNA), which is fully replicative in the nucleus of infected hepatocytes is the molecular basis for the formation of OBI. HBV genome in liver tissue, HBV DNA and anti-HBc test in serum are the gold standard, common method and alternative markers for OBI diagnosis, respectively. Due to the stability of covalently closed circular DNA (cccDNA) and the long half-life of hepatocytes, the existence of OBI is extensive and prolonged. The low and/or intermittent replication of HBV in OBI patients, the limitations of the sensitivity of serological tests, and the non-standardized and invasive nature of liver histology render the "commonly used" serological tests are unreliable and the "gold standard" liver histology is impractical, thus the findings from studies on the formation, diagnosis and transplantation or transfusion transmission of HBV in OBI strongly suggest that the "alternative" marker, the anti-HBc test, may be the most reliable and practical approach for OBI diagnosis.
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Hepatitis B Crónica , Hepatitis B , Humanos , Virus de la Hepatitis B/fisiología , ADN Viral , Hepatitis B/diagnóstico , Antígenos de Superficie de la Hepatitis B/genética , Anticuerpos contra la Hepatitis B/genética , ADN Circular/genéticaRESUMEN
BACKGROUND: The impact of hepatitis B surface antigen (HBsAg)-negative/hepatitis B virus (HBV) DNA-positive occult HBV infection (OBI) on the severity of liver fibrosis remains unclear. METHODS: A total of 1772 patients negative for HBsAg but positive for antibody to hepatitis B core antigen (HBcAg), stratified by the presence or absence of OBI, were selected for long-term carriage leading to elevation of ≥2 of 4 liver fibrosis indexes-hyaluronic acid (HA), laminin, type III procollagen peptide (PCIII), and type IV collagen (CIV)-at testing in a Chinese hospital. Patients were tested for serum viral load, HBV markers, and histopathological changes in liver biopsy specimens. RESULTS: OBI was identified in 148 patients with liver fibrosis (8.4%), who had significantly higher levels of HA, laminin, PCIII, and CIV than 1624 fibrotic patients without OBI (P < .05). In 36 patients with OBI who underwent liver biopsy, significant correlations were observed between OBI viral load and serum HA levels (P = .01), PCIII levels (P = .01), and pathological histological activity index (HAI) scores (P < .001), respectively; HAI scores and PCIII levels (P = .04); HBcAg immunohistochemical scores and HA levels (P < .001); and HBcAg immunohistochemical scores and PCIII levels (P = .03). Positive fluorescent in situ hybridization results were significantly more frequent in patients with OBIs (80.6% vs 37.5% in those without OBIs). Among patients with OBIs, HBcAg was detected in the liver tissue in 52.8% and HBsAg in 5.6%. CONCLUSIONS: OBI status appears to be associated with liver fibrosis severity.
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Hepatitis B Crónica , Hepatitis B , Humanos , Virus de la Hepatitis B , Antígenos de Superficie de la Hepatitis B , Antígenos del Núcleo de la Hepatitis B , Laminina , Hibridación Fluorescente in Situ , Hepatitis B/complicaciones , Cirrosis Hepática/patología , Ácido HialurónicoRESUMEN
BACKGROUND: Occult hepatitis B virus (HBV) infection (OBI) is primarily characterized by the persistence of HBV-DNA in the liver tissues and/or in the serum without detectable HBsAg. Human leukocyte antigen (HLA) polymorphisms have been found to be strongly associated with HBV in different ethnic backgrounds. The association of HLA-DRB1-DQB1 haplotypes with OBI has not been previously reported in China. The aim of this study was to identify the potential association of HLA-DRB1-DQB1 haplotypes that may be involved in OBI genetic susceptibility. METHODS: A case-control study was conducted between 107 OBI subjects and 280 healthy controls from the blood donors in the Shaanxi Province Blood Center. The HLA-DRB1, DQB1 loci were genotyped using polymerase chain reaction-sequence based typing (PCR-SBT). Based on the genotype data of the two loci, haplotype estimation was performed. RESULTS: HLA-DRB1*07:01-DQB1*02:02 (pc = 0.344 × 10-3 , OR = 3.489, 95%CI = 2.000-6.088) and HLA-DRB1*09:01-DQB1*03:03 (pc = 0.02, OR = 2.370, 95%CI = 1.450-3.873) serve as the possible risk and susceptibility haplotypes for OBI in Xi'an Han after Bonferroni correction. CONCLUSIONS: This study demonstrated that HLA II haplotypes were significantly associated with OBI in the Xi'an Han population. To the best of our knowledge, this is the first study to associate HLA-DRB1-DQB1 haplotypes with OBI, which can provide valuable insights into the relationship between the various genetic factors and immune responses in the Xi'an population. The findings can also form the basis for future studies about the role of HLA in OBI.
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Cadenas beta de HLA-DQ , Cadenas HLA-DRB1 , Hepatitis B Crónica , Hepatitis B , Humanos , Estudios de Casos y Controles , Frecuencia de los Genes , Haplotipos , Hepatitis B/genética , Virus de la Hepatitis B , Cadenas HLA-DRB1/genética , Cadenas beta de HLA-DQ/genéticaRESUMEN
Despite the availability of an effective hepatitis B virus (HBV) vaccine and universal immunization schedules, HBV has remained a health problem in various stages such as occult hepatitis B infection (OBI), chronic hepatitis B (CHB), and hepatocellular carcinoma (HCC), which is considered one of the possible phases during chronic HBV infection. OBI is defined as the persistence of HBV genomes in hepatocytes of patients with a negative HBV surface antigen (HBsAg) test and detectable or undetectable HBV DNA in the blood. OBI is occasionally associated with infection caused by mutant viruses that produce a modified HBsAg that is undetected by diagnostic procedures or with replication-defective variations. Many aspects of HBV (OBI more than any other stage) including prevalence, pathobiology, and clinical implications has remained controversial. According to a growing body of research, non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have been linked to the development and progression of a number of illnesses, including viral infectious disorders. Despite a shortage of knowledge regarding the expression and biological activities of lncRNAs and miRNAs in HBV infection, Hepatitis B remains a major global public health concern. This review summarizes the role of lncRNAs in the diagnosis and treatment of different stages of hepatitis B infection.
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Carcinoma Hepatocelular , Hepatitis B Crónica , Hepatitis B , Neoplasias Hepáticas , MicroARNs , ARN Largo no Codificante , Humanos , Antígenos de Superficie de la Hepatitis B , Neoplasias Hepáticas/patología , ADN Viral , Virus de la Hepatitis B/genética , Hepatitis B Crónica/complicacionesRESUMEN
This study was performed to determine the prevalence, genotype distribution and risk factors of hepatitis B virus (HBV) infection among ß-thalassemia patients. ELISA was used to detect HBsAg and HBcAb. Molecular evaluation of HBV infection was performed by nested PCR, targeting S, X and pre-C regions of the genome, and sequencing. Of 126 thalassemia patients, 4 cases (3.17%) were positive for HBsAg, 23 cases (18.25%) were positive for HBcAb, and 6 cases (4.76%) had HBV viremia with genotype D, sub-genotype D3 and subtype ayw2. HBV prevalence among thalassemia patients was not statistically associated with gender distribution, place of residency, marital status and frequency of blood transfusion. HBsAg seroprevalence was significantly higher in Afghan immigrants and patients with ALT levels of 41-80 IU/L. The prevalence of HBV viremia was significantly higher among thalassemia patients aged >20 years compared to the patients aged <20 years. Moreover, 1.59% of thalassemia patients had seropositive occult HBV infection, which was positive for HBV-DNA and HBcAb but negative for HBsAg. Considering the relatively high prevalence of occult HBV infection among thalassemia patients, there is a possibility of their contamination through donated blood. Therefore, screening of donated blood based on detection of HBsAg cannot abolish HBV transmission through blood transfusion.
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Hepatitis B Crónica , Hepatitis B , Talasemia beta , Humanos , Antígenos de Superficie de la Hepatitis B , Irán , Viremia/complicaciones , Estudios Seroepidemiológicos , Hepatitis B/epidemiología , Virus de la Hepatitis B , Anticuerpos contra la Hepatitis B , PrevalenciaRESUMEN
Introduction: Occult hepatitis B virus infection (OBI) is an HBsAg negative state in HBV infection with usually inactive HBV replication. However, there were a minority of individuals with positive HBeAg and anti-HBs among OBI blood donors and few studies have focused on this unusual serological pattern. Methods: 2022 plasma of blood donors that preliminary screened reactive for HBV DNA and non-reactive for HBsAg were collected from 16 provinces in China from 2015 to 2018. HBV DNA and HBsAg in these samples were retested using the Cobas TaqScreen MPX test and ARCHITECT HBsAg Quantitative II assay. Lumipulse HBsAg-HQ assay and polyethylene glycol (PEG)-double precipitation following HCl and trypsin digestion were performed to detect HBsAg from HBsAg-anti-HBs circulating immune complexes (CICs). Results: 1487 of 2022 samples were positive for Cobas HBV DNA test and non-reactive for ARCHITECT HBsAg assay, while 404 of them were positive using Lumipulse HBsAg-HQ assay. 10 HBsAg-/anti-HBs+/HBeAg+ OBI blood donor samples were further dissociated and HBsAg-CICs were detected in 7 samples. Sequencing analysis showed that D44N, N98T, G73S, Del 56-116, and I161T occurred in the pre-S region, and immune escape mutations such as P127T, F134L, G145R, V168A, and I126T/S in the S region were found. Discussion: In conclusion, there were a minority of HBsAg-/anti-HBs+/HBeAg+ individuals in OBI blood donors. The undetectable HBsAg in these individuals was mainly due to HBsAg-CICs. Immune escape-associated mutations also happened under the host's selective pressure. HBsAg dissociation methods or Lumipulse HBsAg-HQ assay is recommended to distinguish these individuals.
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Despite being vaccine-preventable, hepatitis B virus (HBV) infection remains the seventh leading cause of mortality in the world. In South Africa (SA), over 1.9 million people are chronically infected with HBV, and 70% of all Black chronic carriers are infected with HBV subgenotype A1. The virus remains a significant burden on public health in SA despite the introduction of an infant immunization program implemented in 1995 and the availability of effective treatment for chronic HBV infection. In addition, the high prevalence of HIV infection amplifies HBV replication, predisposes patients to chronicity, and complicates management of the infection. HBV research has made significant progress leading to better understanding of HBV epidemiology and management challenges in the SA context. This has led to recent revision of the national HBV infection management guidelines. Research on developing new vaccines and therapies is underway and progress has been made with designing potentially curative gene therapies against HBV. This review summarizes research carried out in SA on HBV molecular biology, epidemiology, treatment, and vaccination strategies.
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Infecciones por VIH , Hepatitis B , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Hepatitis B/complicaciones , Hepatitis B/epidemiología , Hepatitis B/prevención & control , Vacunas contra Hepatitis B/uso terapéutico , Virus de la Hepatitis B/genética , Humanos , Lactante , Sudáfrica/epidemiologíaRESUMEN
PURPOSE: Occult Hepatitis B virus infection (OBI) is of great significance to the transmission of Hepatitis B virus (HBV) and the evolution of the patient's clinical outcome. We conducted a systematic review and meta-analysis to estimate the prevalence of OBI in Asia. METHODS: Literature search was conducted in PubMed, Cochrane Library database, Web of Science and Embase with the keywords of 'Hepatitis B virus', 'occult infection', 'prevalence'. 70 studies were included in the meta-analysis. Meta-analysis was performed using random-effects models to calculate the pooled prevalence of OBI and 95% confidence interval (CI). The data were analyzed in R 4.1.2. RESULTS: The overall prevalence of OBI was 4% (95%CI: 0.03-0.06) in Asia. Subgroup analysis based on geographic region showed a prevalence of 3% (95%CI 0.02-0.06) in East Asia, 9% (95%CI 0.05-0.15) in West Asia, 3% (95%CI 0.01-0.11) in Southern Asia and 9% (95%CI 0.05-0.15) in Southeast Asia. Subgroup analysis demonstrated a prevalence of 1% (95%CI 0.00-0.02) in general population, 5% (95%CI: 0.03-0.08) in high-risk population, 9% (95%CI: 0.03-0.22) in the human immunodeficiency virus (HIV)-infected patient, 18% (95%CI: 0.09-0.32) in the hepatopathy patients. CONCLUSION: Based on the meta-analysis of the prevalence of OBI in different populations, we concluded that the prevalence of OBI in the high-risk population, hepatopathy patients, and HIV-infected patients was higher than that in the general population. A systematic review showed that OBI was associated with disease progression and prognosis. Therefore, these populations should be routinely screened for OBI and promptly intervened to avoid promoting disease progression.
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Infecciones por VIH , Hepatitis B Crónica , Hepatitis B , Humanos , Virus de la Hepatitis B , Antígenos de Superficie de la Hepatitis B , ADN Viral , Hepatitis B/complicaciones , Hepatitis B Crónica/complicaciones , Infecciones por VIH/complicaciones , Asia/epidemiología , Progresión de la EnfermedadRESUMEN
BACKGROUND: Some occult hepatitis B virus (HBV) infections are resulted from PreS mutations that reduce secretion of envelope protein (HBsAg). We investigated the ceramide amounts and species in hepatocytes infected with PreS variants that were isolated from HBsAg-seronegative patients with hepatocellular carcinoma (HCC) and the ceramide effects on autochthonous HCC development in murine models. METHODS: HBV PreS/S regions from 35 HBsAg-seronegative HCC patients were sequenced. Hepatocyte cell lines and male C57BL/6J mouse livers were transfected with two PreS variant representatives. The ceramides with variated lengths of fatty acyl chains were quantified. Tumour development was examined in the HBV-transfected mice fed different diet types. RESULTS: In HBsAg-seronegative HCC patients, nonneoplastic liver tissues harboured HBsAg and replication-competent HBV. The most frequently detected PreS/S variants carried mutations of altered amino acid properties in HBsAg compared with an isolate from one HBsAg-seronegative HCC patient. Hepatocyte infection with PreS variants caused HBsAg retention within the endoplasmic reticulum and generated more amounts of ceramides with C16:0 ceramide elevated the highest. Saturated fatty acids aggravated the PreS variant-infected hepatocytes to generate abnormal amounts and species of ceramides, which with HBV proteins synergistically activated NLRP3 inflammasome in liver inflammatory macrophages. Liver tumours were only detected in HBV-transfected mice fed high-fat diet, with higher tumour loads in the PreS variant-transfected, associated with abnormal ceramide generation. CONCLUSIONS: HBV PreS mutations which altered amino acid properties of envelope proteins inhibited HBsAg secretion. Hepatocyte infection with PreS variants generated abnormal ceramides which with HBV proteins coactivated NLRP3 inflammasome in liver macrophages to promote autochthonous HCC development.
Asunto(s)
Carcinoma Hepatocelular , Hepatitis B Crónica , Neoplasias Hepáticas , Aminoácidos/genética , Animales , Carcinoma Hepatocelular/genética , Ceramidas , Dieta Alta en Grasa/efectos adversos , Antígenos de Superficie de la Hepatitis B/genética , Virus de la Hepatitis B/genética , Inflamasomas , Neoplasias Hepáticas/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Mutación , Proteína con Dominio Pirina 3 de la Familia NLR/genéticaRESUMEN
BACKGROUND: The prevalence of occult hepatitis B infection (OBI) among Iranian liver transplant recipient patients has not been explored yet. The present study aimed to determine the OBI prevalence among Iranian liver transplant recipients. METHODS: This study encompassed 97 patients having undergone liver transplantation due to several clinical backgrounds in the Liver Transplantation Center, Tehran, Iran. After serological evaluation, two different types of PCR methods were applied for amplification of HBV DNA, followed by the direct sequencing of whole hepatitis B virus (HBV) surface genes. RESULTS: At the time of admission, none of the patients were positive for HBsAg. However, 24 (25%), 12 (12.3%), and 5 (5.1%) cases were positive for anti-HBc, hepatitis C virus (HCV), and hepatitis delta virus (HDV) antibodies, respectively. Moreover, two males were positive for OBI (2.1%). Both were positive for anti-HBc and negative for anti-HBs, anti-HCV, and anti-HDV. HBV-related cirrhosis was the underlying reason for their liver transplantation. HBsAg sequences revealed no amino acid substitution. CONCLUSIONS: The prevalence of OBI in the Iranian liver transplantation patients was relatively low. Future longitudinal studies with a larger sample size are suggested to explore the significance of this clinical finding, including the reactivation of cryptic HBV DNA, in liver transplant subjects.
Asunto(s)
Hepatitis B Crónica , Hepatitis B , Trasplante de Hígado , ADN Viral/análisis , ADN Viral/genética , Hepatitis B/epidemiología , Anticuerpos contra la Hepatitis B , Antígenos de Superficie de la Hepatitis B , Virus de la Hepatitis B/fisiología , Humanos , Irán/epidemiología , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/métodos , Masculino , PrevalenciaRESUMEN
Occult hepatitis B virus (HBV) infection (OBI) refers to a condition in which replication-competent viral DNA is present in the liver (with detectable or undetectable HBV DNA in the serum) of individuals testing negative for the HBV surface antigen (HBsAg). In this peculiar phase of HBV infection, the covalently closed circular DNA (cccDNA) is in a low state of replication. Many advances have been made in clarifying the mechanisms involved in such a suppression of viral activity, which seems to be mainly related to the host's immune control and epigenetic factors. OBI is diffused worldwide, but its prevalence is highly variable among patient populations. This depends on different geographic areas, risk factors for parenteral infections, and assays used for HBsAg and HBV DNA detection. OBI has an impact in several clinical contexts: (a) it can be transmitted, causing a classic form of hepatitis B, through blood transfusion or liver transplantation; (b) it may reactivate in the case of immunosuppression, leading to the possible development of even fulminant hepatitis; (c) it may accelerate the progression of chronic liver disease due to different causes toward cirrhosis; (d) it maintains the pro-oncogenic properties of the "overt" infection, favoring the development of hepatocellular carcinoma.
Asunto(s)
Hepatitis B Crónica , Hepatitis B , Neoplasias Hepáticas , ADN Viral/genética , Hepatitis B/diagnóstico , Hepatitis B/epidemiología , Antígenos de Superficie de la Hepatitis B , Virus de la Hepatitis B/fisiología , HumanosRESUMEN
BACKGROUND AND AIM: This study aimed to detect mutations in the HBV S gene and evaluate their relationship to occult hepatitis B virus (HBV) infection (OBI). METHODS: The study included 32 patients with negative serum HBsAg and HBV DNA who underwent liver biopsy due to different clinical indications defined as the OBI group and 32 patients who underwent liver biopsy due to chronic hepatitis B (CHB) as the comparison group. The HBV S gene region was amplified by Nested PCR, and Sanger sequencing was performed. RESULTS: At least one amino acid (aa) mutation was detected in the major hydrophilic region (MHR) of the HBV S gene in 14/32 (43.75%) of the patients with OBI and 8/32 (25.0%) with CHB. The genotype of all patients with OBI and CHB was HBV/D. Although 9 (28.1%) of the cases with OBI had sub-genotype HBV/D3, none of the patients with CHB had sub-genotype HBV/D3. Unlike patients with CHB, L15*, D33N, Q51P, V63F, L91I, P108S, T115I, P120L, T125M, Q129H, T189I, L216F, P217L mutations were detected in the HBV S gene in OBI cases. Also, P127T aa polymorphism was frequently detected. Mutation frequency in the HBV S gene in the major hydrophilic region (MHR) was higher in patients with OBI with sub-genotypes HBV/D3 and D2 than those with HBV/D1 and those with serotype HBV/ayw3 compared to those with HBV/ayw2 (p < 0.05). CONCLUSIONS: Sub-genotypic-specific mutation patterns were seen in the "a" determinant region and T helper cell epitopes of HBsAg, especially in the C-terminus domain; this may be associated with OBI.