RESUMEN
The aim of this study was to estimate the amount of childhood hepatitis B virus transmission in children born in the UK, a very low-prevalence country, that is preventable only by universal hepatitis B immunization of infants. Oral fluid specimens were collected from schoolchildren aged 7-11 years in four inner city multi-ethnic areas and tested for the presence of antibody to hepatitis B core antigen (anti-HBc). Those found positive or indeterminate were followed up with testing on serum to confirm their hepatitis B status. The overall prevalence of anti-HBc in children was low [0.26%, 95% confidence interval (CI) 0.14-0.44]. The estimated average annual incidence of hepatitis B was estimated to be 29.26/100 000 children (95% CI 16.00-49.08). The total incidence that is preventable only by a universal infant immunization programme in the UK was estimated to be between 5.00 and 12.49/100 000. The study demonstrates that the extent of horizontal childhood hepatitis B virus transmission is low in children born in the UK and suggests that schools in the UK are an uncommon setting for the transmission of the virus. Targeted hepatitis B testing and immunization of migrants from intermediate- and high-prevalence countries is likely to be a more effective measure to reduce childhood transmission than a universal infant immunization programme.
Asunto(s)
Etnicidad , Hepatitis B/epidemiología , Hepatitis B/transmisión , Niño , Estudios Transversales , Emigrantes e Inmigrantes , Inglaterra/epidemiología , Familia , Femenino , Hepatitis B/etnología , Hepatitis B/prevención & control , Virus de la Hepatitis B/inmunología , Humanos , Masculino , Vigilancia de la Población , Encuestas y CuestionariosRESUMEN
In spring 2009 a new strain of influenza A(H1N1) emerged and caused a worldwide pandemic. This study utilized a large collection of respiratory specimens from suspected cases of influenza A(H1N1) in the UK West Midlands during the pandemic in order to investigate which other respiratory viruses were circulating and whether they played any role in the increased hospitalization rates seen during that period. Study specimens were selected from community and hospitalized patients positive and negative for influenza A(H1N1) and tested by PCR for other respiratory viruses. A number of infections diagnosed as influenza during the summer influenza outbreak were found to be due to other virus infections (most commonly rhinovirus). No statistically significant difference was found between the rates of respiratory virus co-infection with H1N1 in patients from community or hospital locations suggesting underlying factors were likely to be more significant than viral co-infections in determining severity of influenza A(H1N1) disease.
Asunto(s)
Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Gripe Humana/epidemiología , Gripe Humana/virología , Pandemias , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/virología , Virus/aislamiento & purificación , Adolescente , Adulto , Niño , Preescolar , Coinfección , Inglaterra/epidemiología , Hospitalización , Humanos , Subtipo H1N1 del Virus de la Influenza A/clasificación , Gripe Humana/diagnóstico , Persona de Mediana Edad , Prevalencia , Infecciones del Sistema Respiratorio/diagnóstico , Estaciones del Año , Virus/genética , Adulto JovenRESUMEN
The purpose of this study was to validate through natural exposure a cut-off level of varicella zoster IgG as protective against infection with varicella zoster virus (VZV). Laboratory testing to determine VZV immune status of pregnant women exposed to varicella is recommended. Quantitative assays are now available which are sensitive and specific. More than 200 consecutive requests for screening in pregnant patients with recent varicella contacts were followed-up by questionnaire. DiaSorin LIAISON and VZV time resolved fluorescence immuno assay (VZV TRFIA) were used to measure VZV antibody level. One hundred fifty out of 209 (72%) questionnaires were returned; 14 patients developed varicella, 129 did not and seven were not known. Patients who had been given VZIG and developed varicella on follow-up had a mean antibody level before VZIG of 28 mIU/ml and 62 mIU/ml, by LIAISON and TRFIA, respectively. The mean IgG level of those that did not develop varicella was 885 and 866 mIU/ml by LIAISON and TRFIA, respectively. Those with levels <100 mIU/ml were more likely to develop chicken pox than those with levels >100 mIU/ml (relative risk of 10.4 for LIAISON and 8.8 for TRFIA). On the basis of the relatively small numbers in this study, quantitative assays, using a 100mIU/ml cut-off, can differentiate between those who are susceptible and those who are protected against exposure, however follow-up studies should include sampling for VZV DNA and IgM.
Asunto(s)
Anticuerpos Antivirales/sangre , Varicela/diagnóstico , Varicela/patología , Herpesvirus Humano 3/aislamiento & purificación , Complicaciones Infecciosas del Embarazo/diagnóstico , Complicaciones Infecciosas del Embarazo/patología , Varicela/inmunología , Varicela/virología , Femenino , Estudios de Seguimiento , Herpesvirus Humano 3/inmunología , Humanos , Inmunoensayo/métodos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Inmunoglobulinas Intravenosas/administración & dosificación , Factores Inmunológicos/administración & dosificación , Embarazo , Complicaciones Infecciosas del Embarazo/inmunología , Complicaciones Infecciosas del Embarazo/virología , Encuestas y CuestionariosRESUMEN
BACKGROUND: Determination of Varicella Zoster virus (VZV) immune status in pregnant women without history of chickenpox is important in identifying those who genuinely need VZV immune globulin prophylaxis following significant exposure to chickenpox or shingles. Immune status testing requires highly sensitive and specific immunoassays for timely and accurate results. OBJECTIVES: To compare the performance of DiaSorin LIAISON and Biomerieux VIDAS VZV-IgG assays with reference to a VZV-IgG time-resolved fluorescence immunoassay (TRFIA). STUDY DESIGN: A panel of sera collected from 65 pregnant contacts of VZV and 62 individuals tested for VZV immunity was tested in all three assays. Dose-response curves were generated using International Standards W1044 and 90/690. RESULTS: Sensitivity and specificity of VIDAS compared to VZV-TRFIA was 54.5% and 97.9% respectively and for LIAISON compared to VZV-TRFIA was 67% and 100% respectively. Both assays correlated well with TRFIA with R2 correlation coefficients of 0.79 and 0.76 respectively. Dose-response curves showed both Standards behaved in a similar manner in each assay. For VIDAS, the test cut-off value of 0.9 correlated with 275-280mIU/ml and for LIAISON a cut-off value of 150mIU/ml correlated with 208-219mIU/ml. CONCLUSIONS: By dose-response data and in comparison with TRFIA, LIAISON is more sensitive and specific than VIDAS.
Asunto(s)
Anticuerpos Antivirales/sangre , Varicela/prevención & control , Herpes Zóster/prevención & control , Herpesvirus Humano 3/inmunología , Inmunoglobulina G/sangre , Varicela/diagnóstico , Femenino , Fluorescencia , Herpes Zóster/diagnóstico , Herpesvirus Humano 3/aislamiento & purificación , Humanos , Inmunoensayo/métodos , Embarazo , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Hepatitis B vaccine and hepatitis B immunoglobulin are considered for newborn infants of HBsAg-positive mothers to prevent hepatitis B infection. OBJECTIVES: To assess the beneficial and harmful effects of hepatitis B vaccines and hepatitis B immunoglobulin in newborn infants of HBsAg-positive mothers. SEARCH STRATEGY: Trials were identified through The Cochrane Neonatal Group Controlled Trials Register, The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials in The Cochrane Library, MEDLINE, and EMBASE (until February 2004), authors of trials, and pharmaceutical companies. SELECTION CRITERIA: Randomised clinical trials comparing: plasma-derived vaccine (PDV) or recombinant vaccine (RV) versus no intervention, placebo, or other active vaccines; hepatitis B immunoglobulin versus no intervention, placebo, or other control immunoglobulin; as well as PDV or RV plus hepatitis B immunoglobulin versus no intervention, placebo, or other control vaccines or immunoglobulin. DATA COLLECTION AND ANALYSIS: Outcomes are assessed at maximal follow-up. The primary outcome measure was hepatitis B occurrence, based on a blood specimen positive for HBsAg, HBeAg, or antibody to hepatitis B core antigen (anti-HBc). Binary outcomes are reported as relative risks (RR) with 95% confidence interval (CI). Subgroup analyses were performed with regard to methodological quality of the trial, mother's HBe-Ag status, and time of immunisation after birth. MAIN RESULTS: We identified 29 randomised clinical trials, five of which were considered high quality. Only three trials reported inclusion of hepatitis B e-antigen negative mothers. Compared with placebo/no intervention, vaccine reduced hepatitis B occurrence (RR 0.28, 95% confidence interval (CI) 0.20 to 0.40, 4 trials). No significant differences of hepatitis B occurrence were found comparing recombinant vaccine (RV) versus plasma-derived vaccine (PDV) (RR 1.00, 95% CI 0.71 to 1.42, 4 trials) and high-dose versus low-dose vaccine (PDV: RR 0.97, 95% CI 0.55 to 1.68, 3 trials; RV: RR 0.78, 95% CI 0.31 to 1.94, 1 trial). Compared with placebo/no intervention, hepatitis B immunoglobulin or the combination of vaccine plus hepatitis B immunoglobulin reduced hepatitis B occurrence (hepatitis B immunoglobulin: RR 0.50, 95% CI 0.41 to 0.60, 1 trial; PDV plus hepatitis B immunoglobulin: RR 0.08, 95% CI 0.03 to 0.17, 3 trials). Compared with vaccine, vaccine plus hepatitis B immunoglobulin reduced hepatitis B occurrence (RR 0.54, 95% CI 0.41 to 0.73, 10 trials). Hepatitis B vaccine and hepatitis B immunoglobulin seem safe, but few trials reported on adverse events. AUTHORS' CONCLUSIONS: Vaccine, hepatitis B immunoglobulin, and vaccine plus hepatitis B immunoglobulin prevent hepatitis B occurrence in newborn infants of HBsAg positive mothers.
Asunto(s)
Anticuerpos contra la Hepatitis B/uso terapéutico , Vacunas contra Hepatitis B/uso terapéutico , Antígenos e de la Hepatitis B/sangre , Hepatitis B/prevención & control , Femenino , Hepatitis B/inmunología , Humanos , Recién Nacido , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
OBJECTIVES: To establish natural seroconversion rates and incidence of hepatic pathology in perinatally infected hepatitis B carriers. METHODS: Seventy three perinatally infected hepatitis B carriers identified through maternal screening were evaluated. Fifty three were born to parents from the Indian subcontinent, nine were Oriental, six were Afro-Caribbean, and five were white. Median follow up was 10.24 (range 2.02-20.16) years. RESULTS: Only three of the children followed up had cleared hepatitis B surface antigen during this period, and 30% of the children had seroconverted to anti-HBe. Seroconversions to anti-HBe were observed in Asian (18/50) and white (4/5) children, but not in Oriental or Afro-Caribbean children. More girls (40%) than boys (23%) had seroconverted, but the difference was not significant. All children were asymptomatic with normal physical examination, growth, and development. Almost half (48%) of the hepatitis B e antigen (HBeAg) positive children had normal hepatic transaminases and liver function. Thirty five liver biopsies were performed in children with active virus replication (HBeAg or hepatitis B virus DNA positive) who were being considered for antiviral treatment as part of a clinical trial and were scored using the Ishak method. Two thirds (62%) of the children had mild hepatitis, 60% had mild fibrosis, and 18% had moderate to severe fibrosis. There was a weak correlation between histological evidence of hepatitis and hepatic transaminase activity, implying that biochemical monitoring of hepatic disease activity may be ineffective. CONCLUSIONS: These asymptomatic hepatitis B virus carrier children remain infectious in the medium to long term with notable liver pathology. They should receive antiviral treatment to reduce infectivity and to prevent further progression of liver disease. Hepatic transaminases alone are not a reliable marker of liver pathology, and liver histology is essential before consideration for antiviral treatment.
Asunto(s)
Portador Sano/patología , Hepatitis B/patología , Transmisión Vertical de Enfermedad Infecciosa , Adolescente , Adulto , Biomarcadores/análisis , Niño , Preescolar , ADN Viral/análisis , Femenino , Estudios de Seguimiento , Hepatitis B/transmisión , Hepatitis B/virología , Anticuerpos contra la Hepatitis B/sangre , Antígenos e de la Hepatitis B/sangre , Virus de la Hepatitis B/aislamiento & purificación , Virus de la Hepatitis B/fisiología , Hepatitis B Crónica/inmunología , Hepatitis B Crónica/patología , Hepatitis B Crónica/virología , Humanos , Recién Nacido , Embarazo , Complicaciones Infecciosas del Embarazo , Pronóstico , Índice de Severidad de la Enfermedad , Transaminasas/metabolismo , Replicación ViralRESUMEN
BACKGROUND: Laboratory-based study funded by the Research and Development Division of the Department of Health to inform the decision making on guidelines for the conduct of exposure prone procedures (EPPs) by health care workers who are hepatitis B carriers. OBJECTIVES: Define the quantity and nature of hepatitis B virus (HBV) DNA in hepatitis carriers whose serum does not contain hepatitis B e antigen (HBeAg) and in surgeons previously cleared to conduct EPPs who have transmitted HBV to their patients. STUDY DESIGN: Cross-sectional survey using HBV DNA quantification, genotyping and sequencing comparing transmitting surgeons and asymptomatic carriers. RESULTS: HBV DNA could be detected and quantified in 64.5% (136 of 211) of carriers whose serum did not contain HBeAg with a median level 3.6 log(10) copies/ml (range of 5.7 log(10) copies). Pre-core mutation appeared not to affect the HBV DNA level, however, all surgeons carried codon 28 variants and transmitted these variants to their patients. The lowest HBV DNA level in a transmitting surgeon was 4 x 10(4) copies/ml. CONCLUSIONS: Pre-core mutations are common in carriers whose serum does not contain HBeAg and do not specifically identify carriers whose HBV DNA levels are high. It was possible to define a level of virus above which transmission of hepatitis B during conduct of EPPs could not be excluded.
Asunto(s)
ADN Viral/sangre , Cirugía General , Personal de Salud , Virus de la Hepatitis B/aislamiento & purificación , Hepatitis B/transmisión , Transmisión de Enfermedad Infecciosa de Profesional a Paciente , Portador Sano/transmisión , Portador Sano/virología , Hepatitis B/virología , Antígenos e de la Hepatitis B/sangre , Virus de la Hepatitis B/clasificación , Virus de la Hepatitis B/genética , HumanosRESUMEN
Until recently, carriers of hepatitis B virus (HBV) were allowed to undertake exposure prone procedures providing their serum did not contain HBeAg. However, the recent description of hepatitis B transmission events occurring from HBV-infected health care workers who conduct exposure prone procedures demonstrated that the then current Department of Health guidelines needed to be revised. As part of a series of studies carried out to determine if viral load measurements are a more secure means of assessing the conduct of exposure prone procedures, the suitability of commercially available assays for HBV DNA detection and quantification were investigated. This study describes a comparative analysis on the performances of three assays each based on a different methodology. The assays included the QUANTIPLEX HBV DNA Assay (bDNA), (Chiron Diagnostics Ltd.), the AMPLICOR HBV Monitor Test, (Roche Diagnostics Systems) and the Digene Hybrid Capture System HBV DNA Assay (Digene Corporation). Calibration curves from experiments using the Eurohep ad and ay HBV DNA standard controls indicated a close correlation between the three assays over the dynamic ranges claimed by the manufacturers, although the Quantiplex assay did appear to be over-reporting. This became more apparent when testing patients undergoing anti-viral therapy where the Quantiplex assay consistently over-reported by 0.5 log(10) when compared with the Amplicor assay. The results of this study indicate that based on its dynamic range, the Amplicor HBV Monitor test is the most appropriate assay for the routine investigation of anti-HBe carriers, which will have lower levels of HBV DNA. The investigation also highlights the need for using accepted standard HBV DNA control sera. This will be essential when using an assay to establish whether health care workers who are hepatitis B carriers can be allowed to perform exposure prone procedures under the new guidelines of the UK Department of Health.
Asunto(s)
ADN Viral/sangre , Personal de Salud , Hepatitis B/virología , Reacción en Cadena de la Polimerasa/métodos , Juego de Reactivos para Diagnóstico , Carga Viral , Calibración , Hepatitis B/sangre , Virus de la Hepatitis B/genética , HumanosRESUMEN
A point mutation assay was used to study the codon 28 and codon 1 precore mutant status of 310 chronic hepatitis B carriers (82 HBeAg positive and 228 HBeAg negative). Fourteen of 228 (6%) of HBeAg negative carriers had high levels of serum HBV DNA. Nine of these were explained by precore variants, three by core promoter variants, and two were not explained by recognised precore changes. Nested PCR detected serum HBV DNA in 36% (82/228) of HBeAg negative carriers and 63% (52/82) of these had precore variants. Four of 82 (4%) of the HBeAg positive carriers had precore variants, all as mixed mutant/wild type populations and evidence indicated that these carriers were seroconverting. Overall 23% (52/228) of HBeAg negative carriers had both serum HBV DNA and codon 1 or 28 precore mutations. A sexual transmission event from an HBeAg negative carrier with a relatively low serum HBV DNA level (10(4)-10(6) genome copies/ml) and only core promoter mutations was observed. Despite high rates of variant carriage in the antenatal sub-group perinatal transmission was not observed. The results of direct sequencing on 45 carriers validated the point mutation assay and also showed that codon 28 mutations were only seen in carriers with the genotype CCT at codon 15. For the Caucasian population a higher prevalence of codon 28 mutations (13/25 or 52%) than expected was seen. Liver biopsy data indicated that there was no link between the presence or absence of precore mutants and the severity of liver disease.
Asunto(s)
Antígenos del Núcleo de la Hepatitis B/genética , Virus de la Hepatitis B/genética , Hepatitis B Crónica/virología , Mutación Puntual , Adolescente , Adulto , Portador Sano , ADN Viral/sangre , Femenino , Antígenos e de la Hepatitis B/inmunología , Hepatitis B Crónica/sangre , Hepatitis B Crónica/epidemiología , Hepatitis B Crónica/inmunología , Humanos , Masculino , Regiones Promotoras Genéticas , Precursores de Proteínas/genética , Análisis de Secuencia de ADN/métodos , Reino Unido/epidemiologíaRESUMEN
The infectivity of 310 hepatitis B carriers (among antenatal and genitourinary medicine clinic attendees, blood donors, and patients of a liver disease unit) was assessed using three different assays: chemiluminescent molecular hybridisation assay (Murex Digene), column-based solution hybridisation assay (Abbott Genostics) and in-house polymerase chain reaction (PCR). PCR was found to be at least 100 times more sensitive (1 x 10(4) copies/mL) than Murex Digene (3.2 x 10(6) copies/mL) and Abbott Genostics (3.7 x 10(7) copies/mL). Comparison of the hepatitis B e antigen (HBeAg)/anti-HBe status and hepatitis B virus (HBV) DNA level confirmed an association between these two variables. The overall detection rate of HBV DNA by Murex Digene was 28% (87/310): 89% (73/82) in the HBeAg positive group, 10% (4/40) in the HBeAg/anti HBe negative group, and 5% (10/188) in the anti-HBe positive group. The detection rate by PCR increased to 53% (163/310): 98% (80/82) in the HBeAg positive group, 38% (15/40) in the HBeAg/anti-HBe negative group, and 36% (67/188) in the anti-HBe positive group. HBV DNA detection rates by all three assays in 97 liver disease unit patients were higher, particularly in anti-HBe positive patients, than in the cohort overall, probably reflecting a higher rate of active liver disease in these patients. HBV DNA was detected at the lowest rate in the antenatal clinic group. We suggest that HBeAg negative patients who are positive by PCR but negative by either Murex Digene or Abbott Genostics are still infectious. A cut-off serum HBV DNA level of 10(4) copies/mL is proposed, below which transmission is unlikely to occur, but further studies using quantitative PCR are needed to refine the cut-off level.
Asunto(s)
Portador Sano/diagnóstico , Virus de la Hepatitis B/aislamiento & purificación , Hepatitis B/prevención & control , Adulto , Estudios de Cohortes , Inglaterra/epidemiología , Femenino , Hepatitis B/inmunología , Anticuerpos contra la Hepatitis B/sangre , Anticuerpos contra la Hepatitis B/aislamiento & purificación , Antígenos e de la Hepatitis B/sangre , Antígenos e de la Hepatitis B/aislamiento & purificación , Hepatitis B Crónica/epidemiología , Hepatitis B Crónica/inmunología , Humanos , Masculino , Embarazo , Sensibilidad y EspecificidadAsunto(s)
Vacunas contra Hepatitis B , Hepatitis B/prevención & control , Complicaciones Infecciosas del Embarazo/prevención & control , Femenino , Humanos , Lactante , Recién Nacido , Auditoría Médica , Aceptación de la Atención de Salud , Cooperación del Paciente , Embarazo , Estudios Retrospectivos , Factores de RiesgoRESUMEN
AIMS: To validate the sensitivity of universal antenatal screening for hepatitis B surface antigen (HBsAg) by testing pools of 10 sera, and to review 10 years' experience using this method. METHODS: 66,945 antenatal patients were tested between 1986 and 1996 using the pooled method. All sera from 1996 (n = 6050) were retrieved and retrospectively tested individually. An in vitro determination of the effect of pooling on sensitivity was performed by checkerboard neutralisation assay. RESULTS: 26 HBsAg positive women were detected by universal screening over 10 years; 12 had non-European surnames and five had known risk factors for hepatitis B infection. High titre anti-HBs sera in the pool reduced the sensitivity of the HBsAg assay, though the effect was only significant at low levels of HBsAg carriage. CONCLUSIONS: The prevalence of hepatitis B is extremely low in the antenatal population served by Plymouth PHL. Pooling is unlikely to reduce sensitivity enough to lead to significant preventable vertical transmission, and is a cost-effective and valid strategy in areas of low seroprevalence.
Asunto(s)
Recolección de Muestras de Sangre/métodos , Hepatitis B/prevención & control , Tamizaje Masivo/métodos , Complicaciones Infecciosas del Embarazo/prevención & control , Atención Prenatal/métodos , Portador Sano/prevención & control , Inglaterra , Femenino , Antígenos de Superficie de la Hepatitis B/sangre , Humanos , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Embarazo , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
A colourimetric assay for the analysis of point mutations in PCR amplified DNA fragments from hepatitis B virus (HBV) is described. The method was applied for analysis of the single point mutation in codon 28 of the precore gene of HBV, which inhibits expression of HBe antigen. The assay, which uses a microtitre plate formate, incorporates fluorescein-labelled dideoxynucleotides as opposed to radioactively-labelled deoxynucleotides used in methods described previously. Synthetic control wild type and mutant oligonucleotides were tested to optimise the reaction conditions. The assay was thus shown to yield both qualitative and quantitative data on the relative proportions of wild type and mutant sequences within a given sample. Amplicons from clinical specimens of known sequence were analysed to validate the assay. Sixteen chronic carriers of HBV were tested using the codon 28 point mutation assay, and the results were confirmed by direct sequencing. The method described is suitable for applications where point mutations are of interest.
Asunto(s)
Virus de la Hepatitis B/química , Virus de la Hepatitis B/genética , Mutación Puntual , Colorimetría/métodos , Análisis Mutacional de ADN , Hepatitis B/genética , Hepatitis B/virología , Humanos , Reacción en Cadena de la Polimerasa , Sensibilidad y EspecificidadRESUMEN
The evaluation of a novel assay that allows simultaneous testing for hepatitis B e antigen and its antibody in a single well is described. The results of routine application and sequential studies on patients with acute hepatitis B and chronic hepatitis B treated with interferon are presented. The specificity and sensitivity of the assay and its ability to be used to follow the response of a patient during the whole seroconversion episode has been evaluated. The assay proved to give useful information about the reactivity of the sample, especially in those patients who were changing their "e" status.
Asunto(s)
Anticuerpos contra la Hepatitis B/sangre , Antígenos e de la Hepatitis B/sangre , Hepatitis B/inmunología , Inmunoensayo/métodos , Biomarcadores , Estudios de Evaluación como Asunto , Hepatitis B/sangre , Hepatitis B/terapia , Anticuerpos contra la Hepatitis B/inmunología , Antígenos e de la Hepatitis B/inmunología , Humanos , Interferones/uso terapéutico , Juego de Reactivos para Diagnóstico , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
We describe mutations in the hepatitis B virus (HBV) polymerase gene in viruses which reactivated in two patients during therapy with -2'-deoxy-3'-thiacytidine, or lamivudine (3TC), and following orthotopic liver transplantation for chronic hepatitis B. Virus resistance to 3TC is associated with mutations which lead to amino acid substitutions in the highly conserved tyr-met-asp-asp (YMDD) motif, part of the active site of the polymerase, and which parallel those seen in resistant human immunodeficiency virus (HIV). Substitutions of valine and isoleucine for methionine were found in the two cases. The significance of single secondary mutations, which differ between viruses from the two patients, remains to be determined. Thus, viral resistance to lamivudine of hepatitis B virus mimics that of HIV and can occur in the setting of immunosuppression after liver transplantations.
Asunto(s)
Virus de la Hepatitis B/enzimología , Lamivudine/uso terapéutico , Trasplante de Hígado , Mutación , Adulto , Secuencia de Aminoácidos , Antivirales/uso terapéutico , Secuencia de Bases , ADN Polimerasa Dirigida por ADN/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Sondas de Oligonucleótidos/genéticaAsunto(s)
Hepatitis B/prevención & control , Diagnóstico Prenatal , Portador Sano , Femenino , Humanos , Países Bajos , Embarazo , Reino UnidoRESUMEN
Mutations of the precore region of hepatitis B virus (HBV) genome have been associated with fulminant and severe chronic hepatitis. However uncertainty remains about the clinical significance and transmissibility of these mutant strains. A point mutation assay (PMA) was developed to identify qualitatively and quantitatively mutations affecting precore amino acids 1 and 28. We have analysed serum samples from six mother-infant pairs where perinatal transmission of HBV has occurred and where the mothers were HBV carriers without detectable serum HBeAg. In three cases fulminant hepatitis developed in the infant, in two cases acute hepatitis resolved, and in one case the infant was immunised and did not become infected. We also examined serum from a healthcare worker, an anti-HBe-seropositive HBV carrier, believed to have transmitted HBV infection to a patient. The PMA results were confirmed in all cases by direct sequencing of polymerase chain reaction (PCR) products using nested and double-nested PCR with primers to the precore and X region. Precore aa28 mutant-type virus was detected in the serum of one mother at the time of delivery of three of her children, two of whom developed fulminant hepatitis. Another mother of an infant with fulminant hepatitis had no precore mutations. In one mother-infant pair a mixed viral population was found; the acute hepatitis B in the infant resolved. The HBV sequence from the healthcare worker was also of aa28 mutant type. No mutations of aa1 were detected in any of the specimens. The study supports the association of precore mutations with some cases of transmission of HBV infection from HBeAg-negative mothers to their infants.(ABSTRACT TRUNCATED AT 250 WORDS)