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Background: It has been reported that hepatitis B virus (HBV) double mutations (A1762T, G1764A) are an aetiological factor of hepatocellular carcinoma (HCC). However, it is unclear who is prone to develop HCC, among those infected with the mutant. Exploring HBV quasispecies, which are strongly influenced by host immune pressure, may provide more information about the association of viral factors and HCC. Materials and methods: Nine HCC cases and 10 controls were selected from the Long An cohort. Serum samples were collected in 2004 and 2019 from subjects with HBV double mutations and the complete genome of HBV was amplified and sequenced using next-generation sequencing (NGS). Results: The Shannon entropy values increased from 2004 to 2019 in most cases and controls. There was no significant difference in mean intrahost quasispecies genetic distances between cases and controls. The change in the values of mean intrahost quasispecies genetic distances of the controls between 2004 and 2019 was significantly higher than that of the cases (P<0.05). The viral loads did not differ significantly between cases and controls in 2004(p=0.086) but differed at diagnosed in 2019 (p=0.009). Three mutations occurring with increasing frequency from 2004 to 2019 were identified in the HCC cases, including nt446 CâG, nt514 AâC and nt2857TâC. Their frequency differed significantly between the cases and controls (P<0.05). Conclusions: The change in the values of mean intrahost quasispecies genetic distances in HCC was smaller, suggesting that HBV in HCC cases may be subject to low host immune pressure. Increasing viral loads during long-term infection are associated with the development of HCC. The novel mutations may increase the risk for HCC.
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Genotype I of hepatitis B virus (HBV) was proposed recently following sequencing of complete HBV genomes from Vietnam and Laos. However, its long-term molecular evolution is unknown. The objectives of this study were to study the molecular evolution of this genotype from an asymptomatic HBsAg carrier from the Long An cohort over a 15-year period was studied using both NGS and clone-based sequencing. The number of complete genome sequences obtained in 2004, 2007, 2013, and 2019 are 17, 20, 19, and 10, respectively. All strains belong to subgenotype I1, except for six (five from 2007 and one from 2019) and 8 further strains from 2007 which form a cluster branching out from other subgenotype I sequences, supported by a 100% bootstrap value. Based on complete genome sequences, all of the estimated intragroup nucleotide divergence values between these strains and HBV subgenotypes I1-I2 exceed 4%. These strains are recombinants between genotype I1 and subgenotype C but the breakpoints vary. The median intrahost viral evolutionary rate in this carrier was 3.88E-4 substitutions per site per year. The Shannon entropy (Sn) ranged from 0.55 to 0.88 and the genetic diversity, D, ranged from 0.0022 to 0.0041. In conclusion, our data provide evidence of novel subgenotypes. Considering that the 8 strains disappeared after 2007, while one of the 6 strains appears again in 2019, we propose these 6 strains as a new subgenotype, provisionally designated HBV subgenotype I3 and the 8 strains as aberrant genotype.
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Vírus da Hepatite B , Hepatite B , Humanos , Vírus da Hepatite B/genética , Seguimentos , Filogenia , Genoma Viral/genética , Análise de Sequência de DNA , China/epidemiologia , DNA Viral/genética , Análise por Conglomerados , GenótipoRESUMO
It has been reported that some mutations in the genome of hepatitis B virus (HBV) may predict the outcome of the virus infection. However, evolutionary data derived from long-term longitudinal analysis of entire HBV genomes using next generation sequencing (NGS) remain rare. In this study, serum samples were collected from asymptomatic hepatitis B surface antigen (HBsAg) carriers from a long-term prospective cohort. The entire HBV genome was amplified by polymerase chain reaction (PCR) and sequenced using NGS. Twenty-eight time series serum samples from nine subjects were successfully analysed. The Shannon entropy (Sn) ranged from 0 to 0.89, with a median value of 0.76, and the genetic diversity (D) ranged from 0 to 0.013, with a median value of 0.004. Intrahost HBV viral evolutionary rates ranged from 2.39E-04 to 3.11E-03. Double mutations at nt1762(A â T) and 1764(G â A) and a stop mutation at nt1896(G â A) were seen in all sequences from subject BO129 in 2007. However, in 2019, most sequences were wild type at these positions. Deletions between nt 2920-3040 were seen in all sequences from subject TS115 in 2007 and 2013 but these were not present in 2004 or 2019. Some sequences from subject CC246 had predicted escape substitutions (T123N, G145R) in the surface protein in 2004, 2013 and 2019 but none of the sequences from 2007 had these changes. In conclusion, HBV mutations may revert to wild type in natural infection. Clinicians should be wary of predicting long-term prognoses on the basis of the presence of mutations.
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Genoma Viral , Vírus da Hepatite B/genética , Hepatite B/virologia , Mutação , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
BACKGROUND: Serum osteopontin (OPN) concentrations were found to be significantly increased in patients infected with hepatitis B virus (HBV) and patients with hepatocellular carcinoma (HCC). OBJECTIVE: The aim of this study was to determine the association among HCC, OPN, and HBV. METHODS: Two hundred and forty-one subjects were recruited and divided into 6 groups: healthy controls, asymptomatic HBsAg carriers, HBsAg (-) patients with other tumors, HBsAg (+) chronic liver disease patients, HBsAg (+) patients with HCC, and HBsAg (-) patients with HCC or liver cirrhosis (LC). Serum concentrations of OPN and HBsAg were measured and analyzed. RESULTS: OPN concentrations in the HBsAg (+) HCC group were significantly higher than the healthy control group and the HBsAg (-) patients with other cancers (both p = 0.0001). The OPN concentrations of the HBsAg (-) patients with HCC or LC also did not differ significantly from those of the healthy control group (p = 0.075). There is a correlation between the titer of HBsAg and concentrations of OPN in all 3 HBsAg (+) groups (all p values <0.05). CONCLUSIONS: Infection with HBV may increase the serum concentrations of OPN. The association of OPN and HCC may be not attributable to tumor development per se but, rather, to HBV infection.
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Carcinoma Hepatocelular , Hepatite B Crônica , Hepatite B , Neoplasias Hepáticas , Antígenos de Superfície da Hepatite B , Vírus da Hepatite B , Hepatite B Crônica/complicações , Humanos , OsteopontinaRESUMO
Recommendations promoted worldwide have suggested a period of protection lasting more than 20 years against hepatitis B (HB) following primary immunization. Starting in 1987, universal HB vaccinations were carried out in Long An County, Guangxi Province, one of the earliest counties in which plasma-derived HB vaccine was delivered to newborns across China. Data collection targeted toward understanding the long term (26-33 years since primary immunization) immune effects of the plasma-derived HB vaccine was conducted in 2015; a second data collection was carried out in 2019 to assess seroconversion in the same cohort. This study qualitatively compared positive vs negative results and quantitatively assessed HB biomarkers - HB surface antigen (HBsAg), antibody to HBsAg (anti-HBs), HB e-antigen (HBeAg), antibody to HBeAg (anti-HBe), and antibody to HB core antigen (anti-HBc) - in serum 26-33 years after the full initial course of HB vaccination, then analyzed anti-HBs seroconversion using the two-phase sampling method in the same cohort and calculated the anti-HBs seroconversion rate from 2015 to 2019. The protective sero-conversion rate (anti-HBs ≥10mIU/mL) was 37.6% (192/511); the HBsAg-positive rate was 5.3% (27/511); the anti-HBs mean geometric titer (GMT) was 11.1 mIU/mL. Among the 143 participants involved in both 2015 and 2019 data collections, the seroconversion rate was 3.5% (5/143); two individuals had protective anti-HBs levels in 2015. These findings indicate that anti-HBs status can be seroconverted to a protective concentration level 4 years earlier in a high HBV epidemic region. The role of genomic mutations and the disappearance of immune memory and seroconversion should be investigated.
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Antígenos de Superfície da Hepatite B , Hepatite B , China/epidemiologia , Hepatite B/prevenção & controle , Anticorpos Anti-Hepatite B , Vacinas contra Hepatite B , Humanos , Memória Imunológica , Recém-Nascido , SoroconversãoRESUMO
BACKGROUND: LongAn, Guangxi, was the first county in China to implement universal childhood hepatitis B virus (HBV) immunization. We aimed to determine its long-term effects in preventing hepatocellular carcinoma (HCC) 32 years after the immunization programme was launched. METHODS: Information on HCC deaths for LongAn and its neighbouring county, BinYang (where universal hepatitis B vaccination was not started till 2002), were obtained from the national mortality surveillance system. The data were analysed using Poisson regression. RESULTS: The overall age-adjusted mortalities of HCC in LongAn and BinYang during 2017-2018 were 53.3/100,000 and 45.4/100,000, respectively. The mortality of males aged 20-29 years in LongAn, who were vaccinated at birth, was lower (2.7/100,000, 95%CI 0.8-4.5) than that of males in BinYang, who were not vaccinated (4.7/100,000, 95%CI 3.2-6.3). In LongAn, the HCC mortality in adults aged 20-29 years declined significantly from 7.9/100,000 (95%CI 4.4-11.4) in 2004 to 1.4/100,000 (95%CI 0.4-2.4) in 2017-2018 (χ2 = 5.554, p = 0.018). Among those vaccinated at birth, the HCC mortality in mountainous areas, where dietary exposure to aflatoxins is more common, is higher (9.0/100,000, 95%CI 4.5-13.5) than in low-lying areas (6.5/100,000, 95%CI 3.6-9.4) (χ2 = 0.2393, p = 0.618). CONCLUSION: Immunization of infants against HBV has reduced their risk of developing HCC as children and young adults but could not prevent all cases of HCC, suggesting that the major risk factor for HCC in hyperendemic regions is shifting from HBV to other factors. Additional prevention strategies for HCC will be needed in the future.
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Carcinoma Hepatocelular/epidemiologia , Hepatite B/terapia , Neoplasias Hepáticas/epidemiologia , Vacinação/métodos , Adolescente , Adulto , Criança , Pré-Escolar , China , Feminino , Hepatite B/virologia , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto JovemRESUMO
Hepatitis B virus has been classified into 10 genotypes and 48 subgenotypes worldwide. We found previously, through polymerase chain reaction (PCR) amplification of a sample collected in 2011, that an HBsAg carrier was infected with two genotypes (B and D) of HBV. We carried out cloning, sequencing and phylogenetic analysis of the complete genomes and, for confirmation, analysed a sample collected from the same individual in 2018. Fifteen complete sequences were obtained from each sample. The carrier was infected in 2011 by genotypes B and D and by various recombinants, but only genotype D was present in 2018. The major and minor parents of the recombinants are genotypes B and D, respectively, although the recombination breakpoints vary among them. All 23 genotype D isolates form a cluster, branching out from other subgenotype D sequences and supported by a 100â% bootstrap value. Based on complete genome sequences, almost all of the estimated intragroup nucleotide divergence values between our isolates and HBV subgenotypes D1-D10 exceed 4â%. Compared to the other subgenotypes (D1-D10), 35 unique amino acids were present in our isolates. Our data provide evidence for a novel subgenotype, provisionally designated HBV subgenotype D11.
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Vírus da Hepatite B/genética , Vírus da Hepatite B/isolamento & purificação , Hepatite B/virologia , China , Análise por Conglomerados , DNA Viral/genética , Genoma Viral/genética , Genótipo , Humanos , Filogenia , Análise de Sequência de DNA/métodos , VietnãRESUMO
The long-term persistence of immunity following universal infant immunization against hepatitis B virus (HBV) and the need for a subsequent booster dose in adolescence remain under debate. With data derived from Long'an County, Guangxi, China, we reported previously that the prevalence of hepatitis B surface antigen (HBsAg) among adults born from 1987 to 1993 increases with age, although these individuals had received a first dose of the vaccine within 24 hours of birth. Here, we sought the source of transmission by comparison of genotypes among their family members using phylogenetic analysis of complete HBV S gene sequences. For comparison, we screened 2199 vaccinated individuals aged 5 to 17 in Cang Wu County and 1592 vaccinated individuals aged 3 to 7 in Ling Shan County in Guangxi for HBsAg carriers and investigate their family members. In total, 50 asymptomatic HBsAg carriers who were vaccinated at birth and 152 family members were analyzed. The results showed that 25% (95% CI: 6.0-44.0) of the HBsAg-positive children had not acquired their HBV infection from their mothers. This phenomenon showed a trend that increases with age. Antibody escape mutations were detected in 22.9% (95% CI: 11.0-34.8) of the isolates. In conclusion, a booster dose may be necessary for adolescence who were vaccinated at birth in highly endemic countries.
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Doenças Assintomáticas/epidemiologia , Portador Sadio/epidemiologia , Saúde da Família , Vírus da Hepatite B/isolamento & purificação , Hepatite B/epidemiologia , Adolescente , Adulto , Animais , Portador Sadio/transmissão , Criança , Pré-Escolar , China/epidemiologia , Transmissão de Doença Infecciosa , Feminino , Genótipo , Técnicas de Genotipagem , Hepatite B/transmissão , Vírus da Hepatite B/classificação , Vírus da Hepatite B/genética , Humanos , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular , Filogenia , Prevalência , Análise de Sequência de DNARESUMO
Our study aims to estimate the burden of hepatitis C virus (HCV) infection among the general population in Mainland China. We searched 4 databases for studies of the prevalence of anti-HCV antibody among the general population. Studies that met the selection criteria were included in the meta-analysis. Ninety-four studies with 10729 929 individuals were finally included. Overall, the prevalence of anti-HCV antibody among the general population in Mainland China is 0.91% (95% confidence interval, 0.81%-1.03%). The prevalence rates of anti-HCV antibody were geographically different, with a range of 0.32%-6.51%, and the East and South of China had a relatively lower prevalence. The prevalence of anti-HCV antibody increased successively from 0.16% to 3.95% with advancing age. It was noteworthy that the prevalence of anti-HCV antibody decreased continuously from 2.09% to 0.45% during 1991-2010, whereas it increased to 0.58% during 2011-2015.
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OBJECTIVES: We aimed to determine the prevalence of hepatitis B virus (HBV) drug-resistant mutations in patients co- infected with HBV/human immunodeficiency virus (HIV), including both drug-naïve subjects and those who received antiretroviral therapy (ART) in Guangxi, where the prevalence of HIV/HBV co-infection is highest in China. METHODS: Two hundred and three subjects co-infected with HBV/HIV were recruited, including 123 drug-naïve patients (group 1) and 80 who received ART (group 2). The polymerase gene of HBV in the serum of all study subjects was analysed. RESULTS: The results showed that the prevalence of HBV drug-resistant mutations in group 2 (76.5%, 95% CI 56.3-96.7) was significantly higher than that in group 1 (1.4%, 95% CI -1.4 to 4.2; χ2 = 50.955, p < 0.05). The major pattern of lamivudine (3TC)-resistant mutations is L180M+M204I+L80I (35.7%). In total, 95% of subjects with resistant mutations had cross-resistance to telbivudine and entecavir. No putative tenofovir disoproxil fumarate (TDF) resistance change was found. Five subjects (6.5%) in group 2 had HBV viral loads over 10 × 106 copies/mL. Four of them had 3TC-resistant mutations. Multivariate analysis showed that ART was the only factor associated with the development of drug-resistant mutations. CONCLUSION: Treating HIV in HIV/HBV co-infection with antiretroviral agents may result in a very high prevalence of HBV 3TC-resistant mutations. TDF could not completely suppress HBV replication.
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Coinfecção/epidemiologia , Farmacorresistência Viral Múltipla/genética , Infecções por HIV/tratamento farmacológico , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B/tratamento farmacológico , Lamivudina/uso terapêutico , Adulto , Fármacos Anti-HIV/uso terapêutico , China/epidemiologia , Coinfecção/tratamento farmacológico , Coinfecção/virologia , DNA Polimerase Dirigida por DNA/genética , Feminino , HIV/efeitos dos fármacos , Infecções por HIV/epidemiologia , Hepatite B/epidemiologia , Vírus da Hepatite B/genética , Humanos , Masculino , Análise Multivariada , Mutação , Prevalência , Tenofovir/uso terapêutico , Carga ViralRESUMO
Immunogenicity of hepatitis B vaccine between 20 µg with 3-dose schedule and 60 µg with 2-dose regimens was compared 2 years after primary immunization. A total of 353 healthy adults aged 18-25 years were enrolled in the study and randomly assigned (1: 1: 1) into 3 vaccine groups: A (20 µg, 0-1-6 month), B (60 µg, 0-1 month) and C (60 µg, 0-2 month). Serum samples were collected at 1 month after a series vaccination and 12 months, 24 months after the first-dose. The GMC level of anti-HBs antibody was measured using Chemiluminescent Microparticle ImmunoAssay (CMIA). There were 59, 45 and 55 vaccinees available to follow-up with 2 year later in vaccine groups A, B and C, respectively. No significant differences existed in sex ratio, age and body mass index (BMI) among vaccinees at month 24 and the corresponding participants at baseline in each group (P > 0.05). The seroprotection rates in group A, B and C were 98.31%, 88.37% and 85.19%, respectively (P = 0.014), reflecting the fact that the rate of group A was significantly higher than that in group C (P = 0.026). Also, the GMC level of anti-HBs antibody in group A was significantly higher than those of other two groups (427.46 mIU/ml vs. 89.74 mIU/ml, 89.80 mIU/ml, respectively; all P < 0.01). This data suggested that the standard 20 µg (0-1-6 month) regimen of hepatitis B vaccine should be recommended as a priority on the premise of complete compliance in adults.
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Anticorpos Anti-Hepatite B/sangue , Vacinas contra Hepatite B/administração & dosagem , Vacinas contra Hepatite B/imunologia , Hepatite B/prevenção & controle , Esquemas de Imunização , Imunogenicidade da Vacina , Adolescente , Adulto , China , Feminino , Seguimentos , Voluntários Saudáveis , Humanos , Imunoensaio , Masculino , Soro/imunologia , Adulto JovemRESUMO
BACKGROUND: The accuracy of des-γ -carboxyprothrombin (DCP) in the detection of hepatocellular carcinoma (HCC) in those infected hepatitis B virus (HBV) from cross-sectional or case-control studies is contradictory. OBJECTIVE: To resolve this contradiction using a prospective study. METHODS: Three hundred male individuals persistently infected with HBV were recruited from the Chinese cohort and followed up once per year from 2012 to 2015. Each subject was screened for HCC by measurements of serum alpha-fetoprotein (AFP), lectin-bound α -fetoprotein (AFP-L3), DCP concentrations and ultrasonographic examinations. RESULTS: Nineteen HCC cases were identified. The area under receiver operating characteristic (AUROC) at first, second and third visit for AFP, AFP-L3 and DCP ranges from 0.710-0.897, 0.566-0.637 and 0.520-0.595, respectively. The rate of elevated DCP is not significantly different between the HCC cases and controls (52.6% vs. 47.4%) (P > 0.05). The incidence of HCC in subjects with elevated DCP is not significantly higher than that of those with normal DCP (9.5% vs. 4.6%) (P > 0.05). The AUROC of combinations of these biomarkers was higher than that of AFP alone at the first visit. However, it was reduced at the second visit. At the third visit, the AUROCs of AFP + DCP and AFP + AFP-L3 + DCP, but not that of AFP + AFP-L3, were higher than that of AFP alone. CONCLUSIONS: AFP but DCP or AFP-L3 remains a valuable biomarker for HCC in those chronically infected with HBV. The combination with AFP-L3 and DCP may not increase the accuracy of AFP in differentiating HCC cases from controls, among those infected with HBV.
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Biomarcadores Tumorais , Carcinoma Hepatocelular/etiologia , Hepatite B Crônica/complicações , Neoplasias Hepáticas/etiologia , Mutação , Regiões Promotoras Genéticas , Precursores de Proteínas/genética , Protrombina/genética , Adulto , Alelos , Biomarcadores , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/epidemiologia , Estudos de Casos e Controles , Feminino , Hepatite B Crônica/diagnóstico , Humanos , Incidência , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/epidemiologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Curva ROC , Reprodutibilidade dos TestesRESUMO
In the era of combination therapy for human immunodeficiency virus (HIV), liver disease including hepatocellular carcinoma (HCC), are the major causes of death for patients co-infected with hepatitis B virus (HBV) and HIV. However, the mechanisms remain obscure. We aimed to determine whether HCC-related HBV mutations including 1762T/1764A double mutation and pre-S deletions occur more frequently in HBV/HIV co-infected individuals compared to HBV mono-infected individuals. In this study, the basic core promoter (BCP) and the preS/S regions of HBV isolated from 61 pairs of HBV/HIV co-infected and HBV mono-infected participants were analyzed. We found that the prevalence of HBV isolates with 1762T/1764A and/or preS deletion mutations was 37.7% (95% CI: 29.1-46.3). The prevalence of these mutations in HBV/HIV co-infected group (52.5%, 95% CI: 40.0-65.0) was significantly higher than in the HBV mono-infected group (23.0%, 95% CI: 12.4-33.6) (X2=11.307, P<0.05). HBV/HIV co-infection was associated with higher viral loads but these higher viral loads were not associated with the higher prevalence of HCC-related HBV mutations. Individually 1762T1764A (44.3%) or preS deletions (23%) occurred more frequently in isolates from co-infected compared to mono-infected individuals (21.3%, 4.9%, respectively) (X2=7.290, P<0.05; X2=8.270, P<0.05). Moreover, 1762T/1764A and preS deletions occurred more frequently in genotypes C and I compared to genotype B (p<0.05). Multivariate analysis revealed that co-infection with HIV was associated with the development of both 1762T/1764A ((RR: 2.932(1.325-6.488)) and preS deletions ((RR: 5.759(1.562-21.235)). These results demonstrate that co-infection with HIV was associated with increased prevalence of HCC-related mutations in HBV isolates from Chinese patients.
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Coinfecção , Infecções por HIV , Antígenos de Superfície da Hepatite B/genética , Vírus da Hepatite B/genética , Hepatite B/epidemiologia , Hepatite B/virologia , Mutação , Adulto , Idoso , Povo Asiático , Contagem de Linfócito CD4 , China/epidemiologia , DNA Viral , Feminino , Genótipo , Vírus da Hepatite B/classificação , Vírus da Hepatite B/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Filogenia , Prevalência , Deleção de Sequência , Carga ViralRESUMO
OBJECTIVES: The aim of this study was to identify serum proteins with differential concentrations between hepatocellular carcinoma (HCC) patients and HBsAg asymptomatic carriers among individuals infected with hepatitis B virus (HBV) with basal core promoter (BCP) double mutations (A1762T, G1764A). METHODS: iTRAQ and liquid chromatography-tandem mass spectrometry were used to identify differentially expressed protein, and an ELISA test was used for the validation test. RESULTS: The total number of proteins identified was 1,125, of which 239 showed statistically significant differences in their expression. The relative concentrations of serum dihydrolipoyl dehydrogenase (DLD), which showed the most significant correlation with liver diseases and infection, were significantly lower in HCC patients than asymptomatic HBsAg carriers and individuals negative for HBsAg. However, only the difference between HCC patients with BCP double mutations and HBsAg-negative individuals could be confirmed by ELISA. Meanwhile, we found that the concentrations of serum DLD in those infected with HBV with BCP double mutations were significantly lower than in individuals with the wild-type BCP. However, the difference in the concentrations of serum DLD between individuals with wild-type BCP and those negative for HBsAg was not significant. CONCLUSIONS: HBV with BCP double mutations are associated with lower concentrations of serum DLD.
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Carcinoma Hepatocelular/virologia , Di-Hidrolipoamida Desidrogenase/sangue , Vírus da Hepatite B/genética , Hepatite B Crônica/virologia , Neoplasias Hepáticas/virologia , Regiões Promotoras Genéticas , Proteínas do Core Viral/genética , Adulto , Infecções Assintomáticas , Carcinoma Hepatocelular/enzimologia , Hepatite B/virologia , Antígenos de Superfície da Hepatite B/sangue , Hepatite B Crônica/enzimologia , Humanos , Neoplasias Hepáticas/enzimologia , Masculino , Pessoa de Meia-Idade , Mutação , Reação em Cadeia da Polimerase , Proteômica , Análise de Sequência de DNA , Espectrometria de Massas em TandemRESUMO
The importance of transmission of occult HBV infection (OBI) via transfusion, organ transplantation and hemodialysis has been widely recognized. However, data regarding the transmission of OBI through close contact remain limited. In this study, serum samples were obtained from a child and his parents. The child had received the standard vaccination regimen at birth and produced protective antibody. Sera were tested for HBV serological markers. Nested PCR assays were used to detect HBV DNA and the amplicons were cloned and their sequences subjected to phylogenetic analysis. The results showed that both parents had occult infections while the child had an overt infection. Twelve, eleven and nine clones, from the father, mother and son, respectively, were sequenced. Serotypes adrq+, ayw1, ayw and ayr were found in the father and ayw1, adw2 and adwq+ in the mother; adrq+ was the only serotype in son. Genotype B, subgenotype C2 and a recombinant were identified in the father and genotype B, subgenotype C5 and three recombinants were found in the mother. Subgenotype C2 was the only genotype identified in the child. A phylogenetic tree showed that all of the child's sequences and most of the father's sequences clustered together. However, none of mother's sequences clustered with those of the child. The surface gene from the child and his father had the same amino acid substitution pattern (T118K, T123N and G145A). We concluded that the father was the source of the son's HBV infection, suggesting that occult HBV infection may be transmitted through close contact and manifest as an overt infection.
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Vírus da Hepatite B/fisiologia , Hepatite B/transmissão , Adulto , Sequência de Aminoácidos , Substituição de Aminoácidos , Feminino , Hepatite B/prevenção & controle , Antígenos de Superfície da Hepatite B/química , Antígenos de Superfície da Hepatite B/genética , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Habitação , Humanos , Imunização , Lactente , Recém-Nascido , Masculino , Dados de Sequência Molecular , Mutação , SorogrupoRESUMO
Assays used for HIV cross-sectional incidence testing can misclassify some individuals with nonrecent HIV infection as recently infected, overestimating HIV incidence. We analyzed the frequency and factors associated with false-recent misclassification on subjects from Quangxi, China known to have long-term infection using the limited antigen-avidity assay (LAg-Avidity). Stored samples from treatment-naive individuals from Guangxi, China were tested using the LAg-Avidity. A total of 362 samples from individuals known to be infected 2 to 13.5 years were tested and the false-recent rate (FRR), the frequency of samples with a positive result, was determined at different cutoff values of the assay. Additionally, factors associated with misclassification were determined. The FRR of the LAg-Avidity was 1.1% (4/362) using a cutoff of 1.5 normalized optical density units (OD-n). All four samples had viral loads >1,000 copies/ml. Using a cutoff of 3.0 OD-n the FRR was 5.5% (20/362), with four samples having viral loads <1,000 copies/ml. Factors associated with a higher odds of misclassification were female gender (OR 7.7, 95% CI 1.0-56.4) and being a female sex worker (OR 31.3, 95% CI 4.0-242). At the higher cutoff, being of Zhuang decent, relative to Han, had higher odds of misclassification (OR 6.2, 95% CI 1.99-19.0). The LAg-Avidity assay had a low FRR in this Chinese population. Further investigations of the higher frequency of low LAg-Avidity results seen in female sex workers and individuals of Zhuang descent should be explored in a larger study.
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Afinidade de Anticorpos , Anticorpos Anti-HIV/sangue , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , Sobreviventes , Adulto , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Adulto JovemRESUMO
Cross-sectional analyses showed that the prevalence of basal core promoter (BCP) double mutations (nt 1762T, 1764A) of hepatitis B virus (HBV) gradually increases with age. We aimed to determine the incidence rate of the mutations over 10 years. Study subjects were selected from the Long An cohort established in 2004, including 59 with HBV with single mutations at nt 1762 or 1764 in the BCP and 342 with wild type BCP sequences at baseline. Their serum samples for analysis were obtained at the 3rd and 10th annual visits, respectively. The results showed that the annual incidence rate of BCP double mutations is 3.8% (95% confidence interval [CI]: 1.4-6.2) and tends to decrease with age. The peak incidence is in the 30-34 years age-group. The incidence rate in HBeAg positive individuals (5.5%) is significantly higher than in those without HBeAg (3.4%) (P<0.05). The incidence rate is significantly higher in genotype C (4.8%) than in genotype B (2.8%) or I (3.1%). The incidence rate of the mutations (6.8%) developing from a single mutation at nt 1762 or 1764 is significantly higher than that (3.8%) from the wild type sequence (P<0.005). The difference in incidence of single mutations between nt 1762 (0.7%) and 1764 (0.03%) is significant (P<0.05). In conclusion, the incidence rate of BCP double mutations tends to decrease with age after the age of 35 years. Viruses with a single mutation at nt 1762 or 1764 are more prone to develop double mutations. Nt 1762 is the more common site of the first mutation.
Assuntos
Carcinoma Hepatocelular/virologia , Antígenos de Superfície da Hepatite B/genética , Vírus da Hepatite B/genética , Hepatite B Crônica/virologia , Neoplasias Hepáticas/virologia , Adulto , Idoso , Carcinoma Hepatocelular/epidemiologia , Estudos Transversais , Feminino , Hepatite B Crônica/complicações , Hepatite B Crônica/epidemiologia , Humanos , Incidência , Neoplasias Hepáticas/epidemiologia , Masculino , Pessoa de Meia-Idade , Mutação , Carga ViralRESUMO
Despite several studies regarding the correlation between serum HBsAg titers and viral loads, the association remains uncertain. Eighty-nine individuals were selected randomly from a Chinese cohort of 2,258 subjects infected persistently with hepatitis B virus (HBV) for cross-sectional and longitudinal analysis. Viral loads of mutant HBV are lower than those of wild type HBV. The serum HBsAg titers correlate positively with viral loads in both HBeAg positive and negative subjects (r = 0.449, P = 0.013; r = 0.300, P = 0.018, respectively). No correlation between serum HBsAg titer and viral loads was found in any of the four phases of chronic HBV infection. The serum HBsAg titers correlate positively with viral loads in the group with wild type sequences of the PreS/S, basal core promoter (BCP), and preC regions of HBV(r = 0.502, P = 0.040). However, the correlation was not seen in the group with mutations in these regions (r = 0.165, P = 0.257). The correlation between HBsAg titers and viral loads was seen in individuals with wild type PreS/S sequences but not in the subgroup with BCP double mutations or PreC stop mutation, although their sequences in the preS/S regions were wild type. All these findings were confirmed by the longitudinal analysis. In conclusion, the correlation between serum HBsAg levels and viral loads may not differ between HBeAg positive and negative individuals but may depend on wild-type or mutated genomic sequences. Therefore, HBsAg quantitation may be used as a surrogate for viral loads in only wild-type HBV infections.
Assuntos
Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/genética , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/virologia , Soro/virologia , Carga Viral , Adulto , China , Estudos Transversais , DNA Viral/genética , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Mutação , Análise de Sequência de DNARESUMO
During May-August 2013, a malaria outbreak comprising 874 persons in Shanglin County, China, was detected among 4,052 persons returning from overseas. Ghana was the predominant destination country, and 92.3% of malarial infections occurred in gold miners. Preventive measures should be enhanced for persons in high-risk occupations traveling to malaria-endemic countries.
Assuntos
Ouro , Malária/epidemiologia , Malária/transmissão , Mineradores , Viagem , Adolescente , Adulto , Animais , Anopheles/parasitologia , Criança , China/epidemiologia , Surtos de Doenças , Feminino , Geografia , Gana/epidemiologia , Humanos , Malária/diagnóstico , Malária/parasitologia , Masculino , Pessoa de Meia-Idade , Plasmodium malariae , Adulto JovemRESUMO
OBJECTIVES: Highly-active antiretroviral therapy (HAART) was scaled up in Guangxi, China in 2005. The number of individuals receiving free HAART increased dramatically from June 2010 under the Guangxi Government's anti-HIV programme. We aimed to determine the prevalence of HIV-transmitted drug resistance (TDR) of Guangxi. METHODS: HIV-positive, antiretroviral-naive individuals were recruited from the east (Hezhou), south (Qinzhou), west (Baise), north (Guilin) and centre (Laibin) of Guangxi. The pol gene of the virus from the individuals was analysed. RESULTS: The overall prevalence of HIV TDR was 3.2% (7/216, 95% CI 0.9-5.5). The prevalence rates in Baise, Guilin, Hezhou, Qinzhou and Laibin are 4.9% (2/41, 95% CI -1.7 to 11.5), 2.3% (1/44, 95% CI -2.1 to 5.7), 4.7% (2/43, 95% CI -1.6 to 11.0), 2.6% (1/38, 95% CI -2.5 to 7.7) and 2.0% (1/50, 95% CI -1.9 to 5.9), respectively. No significant difference in the prevalence was found among them. No factors were found to be associated with TDR, including CD4 cell counts, viral loads and genotypes. The subtypes CRF01_AE, CRF07_BC, CRF08_BC and B were found. Subtype CRF08_BC is the predominant subtype in Baise while CRF01_AE is the predominant subtype elsewhere in Guangxi. CONCLUSIONS: The prevalence of TDR in antiretroviral-naive patients in Guangxi remains low 8 years after scale-up of HAART.