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1.
Liver Int ; 44(6): 1422-1434, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38456620

RESUMEN

BACKGROUND: The use of antiviral agents, specifically tenofovir disoproxil fumarate (TDF), in pregnant women to prevent mother-to-child HBV transmission is a key step towards hepatitis elimination. However, data on using tenofovir alafenamide (TAF) is insufficient. The frequent occurrence of postpartum ALT flares may impact the clinical implementation. METHODS: The maternal and infant outcomes were compared in multi-centre trials of high viral load HBsAg/HBeAg+ pregnant women receiving TAF or TDF from the third trimester until 2 weeks postpartum with intensive follow-ups. To explore the dynamic pre- and postpartum changes in ALT levels, we used a group-based trajectory model for analysing data of 332 women from three prospective studies. RESULTS: After treatment, the maternal HBV DNA levels significantly decreased from baseline to delivery: 7.87 ± 0.59 to 3.99 ± 1.07 Log10 IU/mL TAF (n = 78) and 8.30 ± 0.36 to 4.47 ± 0.86 Log10 IU/mL (TDF, n = 53), with viral load reductions of 3.87 versus 3.83 Log10 IU/mL. The HBsAg-positive rates among 12-month-old infants were 1.28% (1/78) versus 1.82% (1/55) respectively (p = 1.00). Of the TAF or TDF-treated mothers, 25.64% versus 16.98% experienced ALT > 2X ULN, and 11.54% versus 1.89% received extended antiviral treatment. Our model revealed four distinct ALT patterns: stable ALT (87.2%), moderate (8.0%) or marked (2.4%) postpartum flares, or prepartum elevations (2.4%). CONCLUSIONS: TAF effectively reduces mother-to-child HBV transmission, but prophylaxis failure still occurred in few cases. Postpartum ALT flares are common in women receiving TAF or TDF during pregnancy. Approximately 12.8% of mothers may require extended postpartum antiviral treatment. CLINICAL TRIAL NUMBER: NCT03695029 (ClinicalTrials.gov).


Asunto(s)
Alanina Transaminasa , Alanina , Antivirales , Transmisión Vertical de Enfermedad Infecciosa , Complicaciones Infecciosas del Embarazo , Tenofovir , Carga Viral , Humanos , Tenofovir/uso terapéutico , Tenofovir/análogos & derivados , Femenino , Embarazo , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Antivirales/uso terapéutico , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Complicaciones Infecciosas del Embarazo/virología , Adulto , Alanina/uso terapéutico , Alanina/análogos & derivados , Alanina Transaminasa/sangre , Estudios Prospectivos , Recién Nacido , Hepatitis B/transmisión , Hepatitis B/tratamiento farmacológico , Hepatitis B/prevención & control , Adenina/análogos & derivados , Adenina/uso terapéutico , Virus de la Hepatitis B/genética , ADN Viral/sangre , Lactante
2.
Clin Infect Dis ; 76(3): e783-e790, 2023 02 08.
Artículo en Inglés | MEDLINE | ID: mdl-35789261

RESUMEN

BACKGROUND: Maternal tenofovir disoproxil fumarate (TDF) therapy during late pregnancy can reduce mother-to-infant transmission of hepatitis B virus (HBV). We investigated HBV mutations associated with maternal TDF therapy and their role in infant immunonophylaxis failure (IPF). METHODS: Serum samples from untreated (n = 89) and TDF-treated (n = 68), highly viremic, chronically infected mothers and their infants were analyzed for HBV DNA by nested polymerase chain reaction (PCR) and direct sequencing. RESULTS: At delivery, compared with untreated mothers, TDF-treated mothers had a lower HBV DNA titer and a higher frequency of basal core promoter (BCP) gene mutations, but they had similar frequencies in pre-S/S and pre-core/core mutations. The 14 mothers harboring surface "a" determinant mutants did not transmit the mutants to their immunized infants. Such mutants were found in 3 of 13 IPF infants; the 13 mothers had wild-type hepatitis B surface antigen (HBsAg). In univariable analysis, maternal HBV DNA titer (odds ratio [OR]: 1.54; 95% confidence intervals [CI]: 1.02-2.33; P = .039), genotype C (OR: 4.18; 95% CI: 1.28-13.62; P = .018) and pre-S1 wild-type sequence (OR: 6.33; 95% CI: 1.85-21.68; P = .003) at delivery were associated with infant IPF. Multivariable analyses showed that maternal genotype C (OR: 3.71; 95% CI: 1.11-12.36; P = .033) and pre-S1 wild-type (OR: 6.34; 95% CI: 1.79-22.44; P = .004) were associated with infant IPF independently of maternal viremia. CONCLUSIONS: Along with high maternal HBV DNA titer at delivery, maternal genotype C and pre-S1 wild-type sequence were potential risk factors for infant IPF, although BCP mutations were not. The offspring of pregnant women harboring "a" determinant mutants as major strains seemed to be protected by immunoprophylaxis. CLINICAL TRIALS REGISTRATION: NCT01312012.


Asunto(s)
Hepatitis B , Complicaciones Infecciosas del Embarazo , Femenino , Humanos , Lactante , Embarazo , Antivirales , ADN Viral , Hepatitis B/tratamiento farmacológico , Hepatitis B/prevención & control , Antígenos de Superficie de la Hepatitis B/genética , Virus de la Hepatitis B/genética , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Madres , Tenofovir/uso terapéutico , Viremia/tratamiento farmacológico
3.
J Viral Hepat ; 29(2): 107-114, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34724288

RESUMEN

Tenofovir disoproxil fumarate (TDF) is the preferred treatment to prevent mother-to-infant transmission in highly viremic HBV-infected women. Data on hepatitis B surface antigen (HBsAg) levels in pregnant women are lacking. We aimed to investigate prepartum and postpartum HBsAg kinetics and its correlation with HBV DNA in pregnant women. HBV-infected mothers with HBV DNA ≥7.5 log10  IU/ml were tested for HBsAg and HBV DNA from baseline to 6 months postpartum. Of the 186 pregnant women with comparable baseline HBsAg and HBV DNA, 101 received TDF from the third trimester until 1 month postpartum. At delivery, TDF group had mildly lower HBsAg (4.32 ± 0.47 vs. 4.54 ± 0.35 log10  IU/ml, p = .0004) and markedly lower HBV DNA (4.26 ± 0.97 vs. 8.11 ± 0.70 log10  IU/ml, p < .0001) than the control group. In the TDF group, mean reduction of HBsAg and HBV DNA from baseline to delivery were 0.22 ± 0.38 and 3.96 ± 0.93 log10  IU/ml. HBsAg reduction had a positive correlation (r = .309; p = .0017) with HBV DNA reduction, and was predictive of HBV DNA reduction ≥3 log10  IU/ml (area under the receiver operating characteristic curve, 0.67; 95% confidence interval, 0.50-0.82). At 6 months postpartum, TDF and control group had comparable HBsAg and HBV DNA. In conclusion, HBsAg decreased slightly at delivery in pregnant women receiving TDF. For monitoring the effect of antiviral therapy during pregnancy, HBV DNA is a better marker than HBsAg. Our data provided valuable information regarding monitoring HBV-infected pregnant women using antiviral therapy.


Asunto(s)
Hepatitis B Crónica , Hepatitis B , Complicaciones Infecciosas del Embarazo , Antivirales/uso terapéutico , ADN Viral , Femenino , Hepatitis B/tratamiento farmacológico , Hepatitis B/prevención & control , Antígenos de Superficie de la Hepatitis B , Virus de la Hepatitis B/genética , Hepatitis B Crónica/tratamiento farmacológico , Humanos , Lactante , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Cinética , Embarazo , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Mujeres Embarazadas , Tenofovir/uso terapéutico , Carga Viral
4.
Clin Gastroenterol Hepatol ; 19(7): 1494-1496, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-32712392

RESUMEN

Tenofovir disoproxil fumurate (TDF) therapy during late pregnancy in highly viremic mothers can reduce residual overt hepatitis B virus (HBV) infections of their infants that occur despite immunoprophylaxis.1,2 Occult HBV infection (OBI) has been defined as the presence of HBV DNA in liver or sera in subjects seronegative for hepatitis B surface antigen (HBsAg).3 OBI has been found in varying proportions of immunized infants born to HBsAg-positive mothers.4-6 We aimed to investigate the impact of maternal TDF therapy during pregnancy on vertically acquired OBI.


Asunto(s)
Virus de la Hepatitis B , Hepatitis B , ADN Viral , Femenino , Hepatitis B/prevención & control , Antígenos de Superficie de la Hepatitis B , Virus de la Hepatitis B/genética , Humanos , Lactante , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Madres , Embarazo , Tenofovir/uso terapéutico
5.
J Hepatol ; 72(6): 1082-1087, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32044401

RESUMEN

BACKGROUND & AIMS: Tenofovir disoproxil fumarate (TDF) is the preferred treatment to prevent maternal transmission of HBV, owing to its efficacy and safety. However, data are lacking on the long-term safety outcomes in children following fetal exposure to TDF. METHODS: Children participating in a prospective, multisite trial of maternal TDF treatment during late pregnancy were recruited for follow-up visits once a year. Growth parameters, serum biochemistry, HBV serology, and bone mineral density (BMD) by dual-energy x-ray absorptiometery scan were measured. RESULTS: One hundred and twenty-eight children, 71 in the TDF and 57 in the control group, completed 255 follow-up visits at the age of 2 to 7 (median, 4.08) years. No differences in z-scores for weight-for-age (0.26 ± 0.90 vs. 0.22 ± 0.99, p = 0.481), z-scores for height-for-age (0.20 ± 1.02 vs. 0.25 ± 0.98, p = 0.812), and estimated glomerular filtration rate (169.12 ± 50.48 vs. 169.06 ± 34.46 ml/min/1.73m2, p = 0.479) were detected. After adjustment for age, sex and HBV status by multiple linear regression, children in the TDF and control group had comparable levels of serum calcium, phosphorus, bone-specific alkaline phosphatase, calcidiol and BMD of lumbar spines (0.55 ± 0.01 vs. 0.57 ± 0.01 g/cm2, p = 0.159) and left hip (0.56 ± 0.01 vs. 0.56 ± 0.01 g/cm2, p = 0.926). CONCLUSIONS: Children of HBV-infected mothers who did or did not receive tenofovir disoproxil fumarate treatment during late pregnancy had comparable long-term growth, renal function, and bone development up to 6-7 years after delivery. CLINICAL TRIAL NUMBER: NCT01312012 (ClinicalTrials.gov) LAY SUMMARY: Currently there are insufficient long-term safety data in children born to mothers who took antiviral agents during pregnancy to prevent mother-to-infant transmission of hepatitis B virus (HBV). In this study, we found that children of HBV-infected mothers who did or did not receive tenofovir disoproxil fumarate treatment during late pregnancy had comparable long-term growth, renal function, and bone development up to 6-7 years after delivery.


Asunto(s)
Antivirales/efectos adversos , Desarrollo Óseo/efectos de los fármacos , Virus de la Hepatitis B/genética , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/transmisión , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Tenofovir/efectos adversos , Adulto , Niño , Preescolar , ADN Viral/sangre , ADN Viral/genética , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Hepatitis B Crónica/sangre , Humanos , Riñón/fisiología , Masculino , Embarazo , Complicaciones Infecciosas del Embarazo/sangre , Estudios Prospectivos , Adulto Joven
6.
J Infect Dis ; 216(suppl_8): S785-S791, 2017 11 16.
Artículo en Inglés | MEDLINE | ID: mdl-29156049

RESUMEN

Hepatitis B virus (HBV) immunization has been effectively preventing chronic HBV infection with >90% efficacy in countries with universal neonatal immunization. Perinatal mother-to-infant transmission of HBV remains the major cause of chronic HBV infection despite immunization. Maternal hepatitis B e-antigen (HBeAg) and high viral load have been noted to be the most important risk factors for transmission. In recent years, short-term antiviral therapy for pregnant women in the third trimester has been shown to be highly effective in reducing 90% of vaccine failure in children. It is important to monitor maternal aminotransferase elevations postpartum. Long-term outcome of mothers and children is needed and awaits further investigations. Despite the above-mentioned preventive measures, it is also important to monitor high-risk children at 1 year of age with hepatitis B surface antigen and anti-hepatitis B to identify those with chronic HBV infection. Most of the children with chronic HBV infection were in the immune-tolerant phase. The goals for antiviral treatment in children are to reduce severity of liver injury, achieve HBeAg seroconversion, and prevent development of liver fibrosis and cancer. Studies on antiviral therapy are undergoing to elucidate the optimal indication and drug treatment for children. The ideal future goal of treatment is to eradicate chronic HBV infection globally.


Asunto(s)
Vacunas contra Hepatitis B/uso terapéutico , Hepatitis B Crónica/tratamiento farmacológico , Inmunización , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Complicaciones Infecciosas del Embarazo/prevención & control , Atención Prenatal , Adulto , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Embarazo , Complicaciones Infecciosas del Embarazo/virología , Tercer Trimestre del Embarazo , Mujeres Embarazadas
7.
Hepatology ; 64(5): 1451-1461, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-27044007

RESUMEN

Despite immunoprophylaxis, hepatitis B virus (HBV) transmission in highly viremic mothers remains a global health issue. Using quantitative maternal surface antigen (HBsAg) to predict HBV infection in infants has not been investigated. We enrolled 526 mother-infant pairs with positive maternal HBsAg under current immunoprophylaxis. Maternal viral load and quantitative HBsAg were measured in the peripartum period. Infant HBsAg seropositivity for more than 6 months was defined as chronic infection. Rates of chronic infection in infants at various maternal HBsAg levels were estimated using a multivariate logistic regression model. Results showed that maternal HBsAg was positively correlated with maternal viral load (r = 0.69; P < 0.001) and accurately predicted maternal viral load above 6, 7, and 8 log10 IU/mL with an area under the receiver operating characteristic curve (AUC) of 0.97, 0.98, and 0.95. Nineteen infants were chronically infected. After adjustment for the other risk factor, maternal HBsAg level was significantly associated with risk of infection (adjusted odds ratio for each log10 IU/mL increase, 15.02; 95% confidence interval [CI], 3.89-57.94; P < 0.001). The AUC for predicting infection by quantitative maternal HBsAg was comparable to that by maternal viral load (0.89 vs. 0.87; P = 0.459). Estimated rates of infection at maternal HBsAg levels of 4, 4.5, and 5 log10 IU/mL were 2.4% (95% CI, 0.1-4.6; P = 0.04), 8.6% (95% CI, 4.5-12.7; P < 0.001), and 26.4% (95% CI, 12.6-40.2; P < 0.001). CONCLUSION: Quantitative maternal HBsAg predicts infection in infants as well as maternal viral load does. Antiviral therapy may be considered in pregnant women with an HBsAg level above 4-4.5 log10 IU/mL to interrupt mother-to-infant transmission. (Hepatology 2016;64:1451-1461).


Asunto(s)
Antígenos de Superficie de la Hepatitis B/sangre , Hepatitis B Crónica/transmisión , Transmisión Vertical de Enfermedad Infecciosa , Adulto , Femenino , Hepatitis B Crónica/epidemiología , Humanos , Lactante , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa/estadística & datos numéricos , Masculino , Valor Predictivo de las Pruebas , Embarazo , Carga Viral
8.
J Hepatol ; 59(1): 24-30, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23485519

RESUMEN

BACKGROUND & AIMS: Immunoprophylaxis reduces but does not completely eradicate hepatitis B virus (HBV) transmission. This prospective study aims at assessing the rate and risk factors of maternally transmitted HBV infection. METHODS: We enrolled 303 mother-infant pairs with positive maternal hepatitis B surface antigen (HBsAg) under current immunization program. Maternal viral load was determined by a real-time PCR-based assay. The children were tested for HBsAg at 4-8 months and/or 1-3 years of age. Rates of HBV infection were estimated using a multivariate logistic regression model. RESULTS: HBeAg-positive mothers (81/303, 26.7%) had higher viral loads than HBeAg-negative mothers (7.4 ± 1.9 vs. 2.7 ± 1.4 log10 copies/ml, p<0.0001). Ten children, born to HBeAg-positive mothers with high viral load (median, 8.4; range, 6.5-9.5 log10 copies/ml), were chronically infected. After adjustment for maternal age, birth type, factors related to maternal-fetal hemorrhage, gestational age, infant gender, birth weight, timeliness of vaccination, and feeding practice, maternal viral load was significantly associated with risk of infection (adjusted odds ratio for each log10 copy/ml increase, 3.49; 95% confidence interval (CI), 1.63-7.48; p=0.001). The predictive rates of infection at maternal viral load levels of 7, 8, and 9 log10 copies/ml were 6.6% (95% CI, 0.5-12.6%; p=0.033), 14.6% (95% CI, 5.6-23.6%; p=0.001), and 27.7% (95% CI, 13.1-42.4%; p<0.001), respectively. CONCLUSIONS: Additional strategies to further reduce transmission should be considered in mothers with a viral load above 7-8 log10 copies/ml.


Asunto(s)
Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/transmisión , Transmisión Vertical de Enfermedad Infecciosa , Complicaciones Infecciosas del Embarazo/virología , Adulto , Preescolar , Femenino , Antígenos e de la Hepatitis B/sangre , Hepatitis B Crónica/virología , Humanos , Inmunización Pasiva , Inmunoglobulinas/uso terapéutico , Lactante , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Masculino , Embarazo , Estudios Prospectivos , Factores de Riesgo , Carga Viral , Adulto Joven
9.
Gastroenterology ; 142(4): 773-781.e2, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22198276

RESUMEN

BACKGROUND & AIMS: Mother-to-infant transmission is the major cause of hepatitis B virus (HBV) infection among immunized children. There has been much debate about screening pregnant women and administering hepatitis B immunoglobulin (HBIG) to newborns. We analyzed the rate of HBV infection among children born to hepatitis B surface antigen (HBsAg)-positive mothers and whether HBIG administration reduces transmission. METHODS: We analyzed data from 2356 children born to HBsAg-positive mothers, identified through prenatal maternal screens. In addition to HBV vaccines, HBIG was given to all 583 children with hepatitis B e antigen (HBeAg)-positive mothers and to 723 of 1773 children with HBeAg-negative mothers. Serology tests for HBV were performed from 2007 to 2009, when children were 0.5-10 years old. RESULTS: A significantly greater percentage of children with HBeAg-positive mothers tested positive for antibodies against the hepatitis B core protein (16.76%) and HBsAg (9.26%) than children with HBeAg-negative mothers (1.58% and 0.29%, respectively; P < .0001 and <.001). Among the HBV-infected children, the rate of chronicity also was higher among children with HBeAg-positive mothers than children with HBeAg-negative mothers (54% vs 17%; P = .002). Similar rates of antibodies against the hepatitis B core protein (0.99% and 1.88%; P = .19) and HBsAg (0.14% and 0.29%; P = .65) were noted in children born to HBeAg-negative mothers who were or were not given HBIG. Infantile fulminant hepatitis developed in 1 of 1050 children who did not receive HBIG (.095%). CONCLUSIONS: Children born to HBeAg-positive mothers are at greatest risk for chronic HBV infection (9.26%), despite immunization. Administration of HBIG to infants born to HBeAg-negative mothers did not appear to reduce the rate of chronic HBV infection, but might prevent infantile fulminant hepatitis. Screening pregnant women for HBsAg and HBeAg might control mother-to-infant transmission of HBV.


Asunto(s)
Vacunas contra Hepatitis B/administración & dosificación , Hepatitis B Crónica/diagnóstico , Hepatitis B Crónica/prevención & control , Hepatitis B Crónica/transmisión , Inmunoglobulinas/administración & dosificación , Transmisión Vertical de Enfermedad Infecciosa , Tamizaje Masivo , Atención Prenatal , Biomarcadores/análisis , Distribución de Chi-Cuadrado , Niño , Preescolar , Femenino , Anticuerpos contra la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/sangre , Humanos , Inmunidad Humoral , Esquemas de Inmunización , Lactante , Recién Nacido , Fallo Hepático Agudo/prevención & control , Fallo Hepático Agudo/virología , Valor Predictivo de las Pruebas , Embarazo , Taiwán , Factores de Tiempo , Resultado del Tratamiento , Carga Viral
10.
Hepatology ; 53(2): 429-36, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21274864

RESUMEN

UNLABELLED: Genotypes B and C are the major hepatitis B virus (HBV) genotypes in Taiwan, and genotype C is associated with more severe liver disease than genotype B. Whether the implementation of the hepatitis B immunization program has affected the secular trend of the HBV genotype distribution remains unknown. We thus investigated the HBV genotypes in hepatitis B surface antigen (HBsAg)-carrier children born before the implementation of the universal infant immunization program and in those born afterward. One hundred seven children who were infected with HBV despite appropriate immunization were enrolled as immunized cases with HBV breakthrough infection. Each case was matched with two unimmunized HBsAg carriers according to the age at enrollment. HBV genotypes were determined with molecular methods. Compared with unimmunized HBsAg carriers, more immunized children had HBsAg-positive mothers (65.9% versus 100%, P < 0.001) and were infected with genotype C (16.4% versus 42.1%, P < 0.001). Among the children born to HBsAg-positive mothers, the mothers' and children's HBV genotypes were highly concordant in both unimmunized [κ = 0.97, 95% confidence interval (CI) = 0.90-1.00] and immunized children (κ = 0.97, 95% CI = 0.92-1.00). After adjustments for gender, maternal age, and delivery mode, immunized HBsAg-carrier children born to HBsAg-positive mothers had a higher likelihood of genotype C infection than unimmunized children (odds ratio = 3.03, 95% CI = 1.62-5.65, P = 0.001). However, the increased genotype C to genotype B ratio was not seen in the HBsAg-carrier mother pool in the postimmunization era. CONCLUSION: In the postimmunization era, most HBV breakthrough infections are due to maternal transmission, and immunized children born to genotype C mothers may have a higher rate of breakthrough infection than those born to genotype B mothers.


Asunto(s)
Vacunas contra Hepatitis B/uso terapéutico , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/inmunología , Hepatitis B/genética , Hepatitis B/prevención & control , Programas de Inmunización , Adolescente , Adulto , Niño , Preescolar , Femenino , Genotipo , Hepatitis B/epidemiología , Antígenos de Superficie de la Hepatitis B/sangre , Humanos , Incidencia , Transmisión Vertical de Enfermedad Infecciosa/estadística & datos numéricos , Masculino , Análisis de Regresión , Estudios Retrospectivos , Taiwán/epidemiología , Adulto Joven
11.
Hepatol Int ; 16(4): 789-798, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35635688

RESUMEN

BACKGROUND AND AIMS: Hepatitis B virus (HBV) vaccine failure remains a hurdle to the global elimination of HBV infections in the vaccination era. We aimed to elucidate the relationships between HBV entry receptor sodium taurocholate co-transporting polypeptide (NTCP) and vaccine failure in children born to highly infectious mothers. METHODS: The genetic variants rs7154439, rs4646285, rs4646287, and rs2296651 were genotyped in 170 children with chronic HBV infections and 138 control children of mothers positive for hepatitis B e antigen (HBeAg). All children received hepatitis B immunoglobulin and complete HBV vaccination. Total RNAs from 82 adult non-tumor liver tissues were quantified for NTCP, type I interferons and interferon-induced transmembrane protein 3 (IFITM3) levels. RESULTS: A higher rate of the GA/AA genotype (28.3% vs. 15.3%, p = 0.006) of the genetic variant rs4646287 in intron 1 of the NTCP gene was detected in control children compared to the carrier children. The rs4646287 G > A genotype was associated with younger ages at which spontaneous HBeAg seroconversion occurred (10.8 ± 8.4 vs. 14.6 ± 8.7 years, p = 0.003) in chronic HBV-infected children. Unique correlation patterns of NTCP and innate immunity-related genes (type I interferons and IFITM3) were found in HBV-infected liver tissues with the rs4646287 G > A genotype. CONCLUSION: The rs4646287 G > A genotype of the NTCP gene may be associated with lower risk for HBV vaccine failure in children born to highly infectious mothers. The protective effect of rs4646287 G > A was also present in carrier children, evidenced by earlier spontaneous HBeAg seroconversion.


Asunto(s)
Vacunas contra Hepatitis B , Hepatitis B Crónica , Transportadores de Anión Orgánico Sodio-Dependiente , Simportadores , Adulto , Niño , Antígenos de Superficie de la Hepatitis B , Vacunas contra Hepatitis B/administración & dosificación , Antígenos e de la Hepatitis B , Hepatitis B Crónica/prevención & control , Humanos , Interferón Tipo I/metabolismo , Transportadores de Anión Orgánico Sodio-Dependiente/genética , Proteínas de Unión al ARN , Simportadores/genética
12.
Liver Int ; 31(9): 1373-80, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21745315

RESUMEN

BACKGROUND AND AIMS: This cohort study investigated the long-term effect of maternal hepatitis B virus (HBV) sero-status on the spontaneous HBeAg seroconversion in offspring with chronic HBV infection. METHODS: A total of 185 HBeAg-positive chronic HBV-infected children, with maternal HBV seromarkers checked, were enrolled. The median age at enrolment and follow-up duration was 5.7 years (range, neonate to 16.5 years) and 20.2 years (range, 4.2-31.0 years) respectively. These children were grouped according to the initial maternal HBsAg and HBeAg status: (i) children of non-carrier mothers (n=48); (ii) children of HBeAg-negative chronic HBV-infected mothers (n=57); (iii) children of HBeAg-positive chronic HBV-infected mothers (n=80). HBV seromarkers and liver function profiles of these children were performed at 6-month intervals. RESULTS: One hundred and twenty-one (65.4%) subjects had achieved spontaneous HBeAg seroconversion at the end of this follow-up study. Spontaneous HBeAg seroconversion was achieved in 83.3% of children with non-carrier mothers, 73.7% of children with HBeAg-negative chronic HBV-infected mothers and 48.8% of children with HBeAg-positive mothers during similar duration (P<0.001). Positive maternal HBeAg and genotype C were associated with delayed spontaneous HBeAg seroconversion in multivariate analysis (P=0.01 and P=0.002 respectively). In children of HBeAg-positive chronic HBV-infected mothers, persistent presence of maternal HBeAg showed a trend of association with delayed HBeAg seroconversion in their offspring (P=0.06). Children of late maternal HBeAg seroconversion (>40 years old) had delayed HBeAg seroconversion compared with those of early HBeAg seroconversion mothers (P=0.06). CONCLUSIONS: Persistence of maternal HBeAg is an important risk factor for delayed spontaneous HBeAg seroconversion in children with chronic HBV infection.


Asunto(s)
Antígenos e de la Hepatitis B/sangre , Virus de la Hepatitis B/inmunología , Hepatitis B Crónica/inmunología , Adolescente , Adulto , Alanina Transaminasa/sangre , Biomarcadores/sangre , Portador Sano , Distribución de Chi-Cuadrado , Niño , Preescolar , Femenino , Genotipo , Antígenos de Superficie de la Hepatitis B/sangre , Virus de la Hepatitis B/genética , Hepatitis B Crónica/sangre , Hepatitis B Crónica/diagnóstico , Hepatitis B Crónica/transmisión , Humanos , Lactante , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa , Estimación de Kaplan-Meier , Masculino , Intercambio Materno-Fetal , Persona de Mediana Edad , Embarazo , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , Factores Sexuales , Taiwán , Factores de Tiempo , Adulto Joven
13.
Artículo en Inglés | MEDLINE | ID: mdl-32340799

RESUMEN

Women at childbearing age and pregnant ladies living in the areas of high or intermediate prevalence of hepatitis B virus (HBV) remain at risk of getting the infection and passing the infections to their offspring via mother-to-child transmission (MTCT) of HBV. HBV infection may affect the mothers by active hepatitis, very occasionally liver cirrhosis and rarely fulminant hepatitis and liver failure. The virus may be transmitted to the babies despite immunoprophylaxis in the setting of very high maternal viral load. Tenofovir disoproxil fumarate (TDF) has been shown to be efficacious to reduce MTCT of HBV, which contributes to the elimination of chronic HBV infection by 2030, the goal set by World Health Organization.


Asunto(s)
Antivirales/uso terapéutico , Gastroenterólogos/psicología , Hepatitis B/tratamiento farmacológico , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Telbivudina/uso terapéutico , Tenofovir/uso terapéutico , Adulto , Niño , ADN Viral , Femenino , Hepatitis B/transmisión , Antígenos e de la Hepatitis B/sangre , Antígenos e de la Hepatitis B/uso terapéutico , Virus de la Hepatitis B , Humanos , Lactante , Inflamación/tratamiento farmacológico , Inflamación/etiología , Masculino , Persona de Mediana Edad , Embarazo , Complicaciones Infecciosas del Embarazo/prevención & control , Complicaciones Infecciosas del Embarazo/virología
15.
Aliment Pharmacol Ther ; 50(3): 306-316, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31271463

RESUMEN

BACKGROUND: Maternal anti-viral treatment prevents mother-to-infant transmission of hepatitis B virus (HBV), but the role of neonatal viremia on subsequent HBV infection is not clear. AIMS: To investigate the effect of maternal anti-viral treatment on neonatal serum HBV DNA and hepatitis B surface antigen (HBsAg) in infants born to highly viremic mothers and the roles of neonatal markers in predicting chronic HBV infection in children. METHODS: Serum HBV DNA and HBsAg were tested in children. Of the 201 pregnant mothers, 110 received tenofovir during the third trimester. Chronic infection in children was defined by HBsAg seropositivity at 6 or 12 months lasting more than 6 months. RESULTS: The maternal HBV viral loads from baseline to delivery were 8.25 ± 0.48 to 4.29 ± 0.98 log10  IU/mL; and 8.29 ± 0.49 to 8.12 ± 0.68 log10  IU/mL in the tenofovir and control group respectively. Of the 208 children, those in the tenofovir group had a lower rate of neonatal HBV DNA seropositivity at birth (5.22% vs 30.11%, P < 0.0001) and HBsAg seropositivity at 6 months (1.74% vs 11.83%, P = 0.003) and 12 months (1.74% vs 10.75%, P = 0.007). In a first multivariate analysis, maternal HBV DNA level at delivery (odds ratio = 1.70, P = 0.0172) and neonatal HBsAg positivity (odds ratio = 19.37, P < 0.0001) were significantly associated with children's chronic HBV infection. In a second model, neonatal HBV DNA positivity was a strong independent influence variable (odds ratio = 61.89, P = 0.0002). CONCLUSIONS: Maternal tenofovir therapy decreased maternal viral load and neonatal viremia. Positive neonatal HBV DNA was highly correlated with chronic HBV infection in children. Clinical Trial Identifier: NCT01312012.


Asunto(s)
Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/prevención & control , Hepatitis B Crónica/transmisión , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Tenofovir/uso terapéutico , Adulto , Antivirales/uso terapéutico , Niño , ADN Viral/sangre , Femenino , Hepatitis B/tratamiento farmacológico , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos e de la Hepatitis B/sangre , Virus de la Hepatitis B/genética , Hepatitis B Crónica/diagnóstico , Herpesvirus Cercopitecino 1/genética , Humanos , Lactante , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa/estadística & datos numéricos , Masculino , Madres , Embarazo , Complicaciones Infecciosas del Embarazo/diagnóstico , Pronóstico , Carga Viral/efectos de los fármacos , Viremia/congénito , Viremia/diagnóstico , Viremia/tratamiento farmacológico , Viremia/transmisión , Adulto Joven
17.
Expert Rev Gastroenterol Hepatol ; 10(3): 317-30, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26566769

RESUMEN

Hepatitis B virus (HBV) infection causes long-term, life-threatening liver diseases worldwide. HBV is transmitted through either the horizontal or mother-to-infant route, which is the major route of transmission in endemic areas. Administration of hepatitis B immunoglobulin and hepatitis B vaccine to newborns of infected mothers prevents mother-to-infant transmission. Implementation of a universal hepatitis B vaccination program has proven successful in eliminating the infection and related complications. Nevertheless, efforts are still needed to improve global coverage of the hepatitis B vaccine. Infants born to highly viremic mothers are still at risk of infection despite current immunoprophylaxis. An increasing number of reports have shown promising efficacy and safety profiles with the use of nucleoside/nucleotide analogues in highly viremic pregnant women to prevent mother-to-infant transmission.


Asunto(s)
Antivirales/uso terapéutico , Vacunas contra Hepatitis B/uso terapéutico , Virus de la Hepatitis B/patogenicidad , Hepatitis B/tratamiento farmacológico , Hepatitis B/transmisión , Inmunoglobulinas/uso terapéutico , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Antivirales/efectos adversos , Femenino , Genotipo , Hepatitis B/diagnóstico , Vacunas contra Hepatitis B/efectos adversos , Virus de la Hepatitis B/genética , Humanos , Inmunoglobulinas/efectos adversos , Recién Nacido , Fenotipo , Embarazo , Factores de Riesgo , Resultado del Tratamiento
18.
Arch Dis Child ; 104(9): 879, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-29858271
19.
Pancreatology ; 5(4-5): 432-7, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-15985768

RESUMEN

BACKGROUND/AIM: The pancreatic functions of children with cholestatic liver diseases were unclear. Due to anatomic vicinity and common ontogenic origin, hepatobiliary disorders of infancy may also affect pancreatic function. The aim of the study was to evaluate the exocrine pancreatic function and common pancreatic function tests in children with cholestatic disorders. METHODS: In 40 children with cholestasis, fecal elastase 1 (FE1) concentrations were measured. Serum amylase and lipase values were tested. The diagnoses included 32 patients with extrahepatic cholestasis (biliary atresia (BA) and choledochal cyst), and 8 patients with intrahepatic cholestasis (progressive familial intrahepatic cholestasis and Alagille syndrome). None had renal insufficiency or clinical symptoms/signs of acute pancreatitis. RESULTS: All the patients had normal FE1 (>200 microg/g). Nineteen percent (7/37) had elevated serum amylase levels (>100 U/l). Thirty-two percent (12/37) had elevated serum lipase levels above the normal (>120 U/l). Seventy-three percent (8/11) of BA patients with bilirubin >2 mg/dl had elevated serum lipase levels compared to 18% (3/17) with bilirubin < or = 2 mg/dl (p = 0.0036). None had detectable pancreatic abnormality on ultrasonography and magnetic resonance images. CONCLUSIONS: None of the cholestatic children in this study had exocrine pancreatic insufficiency as detected by FE1. Hyperamylasemia and/or hyperlipasemia were frequently found. In children with BA, those with impaired biliary excretion tended to have elevated serum pancreatic enzymes as compared with those who had no jaundice. A decreased hepatic metabolism may be the cause.


Asunto(s)
Amilasas/sangre , Atresia Biliar/enzimología , Colestasis Intrahepática/enzimología , Heces/enzimología , Lipasa/sangre , Elastasa Pancreática/metabolismo , Síndrome de Alagille/complicaciones , Síndrome de Alagille/enzimología , Síndrome de Alagille/patología , Atresia Biliar/etiología , Atresia Biliar/patología , Niño , Preescolar , Quiste del Colédoco/complicaciones , Quiste del Colédoco/enzimología , Quiste del Colédoco/patología , Colestasis Intrahepática/genética , Colestasis Intrahepática/patología , Femenino , Humanos , Lactante , Masculino
20.
J Pediatr ; 144(3): 397-9, 2004 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-15001956

RESUMEN

We prospectively followed 426 children with chronic hepatitis B virus infection. During 6250 person-years, 2 boys developed hepatocellular carcinoma, with an incidence of 32 per 100,000 person-years. Both had e antigen seroconversion in early childhood and cirrhosis. Early e antigen seroconversion and/or cirrhosis may be risk factors for hepatocellular carcinoma.


Asunto(s)
Carcinoma Hepatocelular/epidemiología , Hepatitis B Crónica/complicaciones , Neoplasias Hepáticas/epidemiología , Adolescente , Alanina Transaminasa/sangre , Niño , Preescolar , Femenino , Antígenos e de la Hepatitis B/inmunología , Humanos , Lactante , Masculino , Estudios Prospectivos , Factores de Riesgo
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