RESUMEN
OBJECTIVE: To evaluate the efficacy and safety of telbivudine use during the second and third trimester of pregnancy for reducing hepatitis B virus (HBV) transmission from highly viremic hepatitis B e antigen-positive (HBeAg+) mothers to their fetuses. METHODS: Pregnant women, between weeks 20 to 32 of gestation, who were HBeAg+ and had HBV DNA more than 1.0*10(7) copies/mL were enrolled in our study. The women were offered inclusion into one of two treatment arms, based upon their personal preference: telbivudine or no telbivudine. The patients in the telbivudine treatment arm were administered 600 mg/d telbivudine at least until postpartum week 4. All delivered infants in both treatment arms were administered hepatitis B immune globulin (HBIG; 200 IU) within 12 hours of delivery and recombinant HBV vaccine (20 mug) at 0, 1 and 6 months. The HBV perinatal transmission rate was determined by measuring HBsAg and HBV DNA in infants at postpartum week 28. RESULTS: A total of 220 pregnant women were enrolled in our study, 120 chose the telbivudine arm and 100 chose the control arm. All telbivudine treated subjects were registered in the Antiretroviral Pregnancy Registry. Telbivudine treatment was associated with a marked reduction in the mothers' serum HBV DNA, HBeAg and ALT levels before delivery. A striking decline of HBV DNA levels in treated mothers was observed at week 2 of treatment, which was followed by a gradual and steady decrease that continued until delivery. Thirty-seven (31%) of the telbivudine-treated mothers and none (0%) of the untreated controls had polymerase chain reaction-undetectable viremia at delivery. At week 28, 0% of the infants delivered from telbivudine-treated mothers were HBsAg+ or HBV DNA+, as compared to 8% HBsAg+ or HBV DNA+ in the untreated control arm (P = 0.002). No telbivudine discontinuations occurred from adverse events, and no congenital deformities were observed in the infants delivered to telbivudine-treated mothers. Eighty mothers discontinued telbivudine at week 4 postpartum, and there were no cases of severe hepatitis. There were no significant differences between the two treatment arms for postpartum hemorrhage, adverse events during pregnancy, cesarean section, gestational age, or infants' height/weight or Apgar scores. CONCLUSIONS: Telbivudine use during the second and third trimester of pregnancy in HBeAg+ highly viremic mothers can safely reduce perinatal HBV transmission rates. Telbivudine was well-tolerated by our patient group. Furthermore, no safety concerns were observed in either the telbivudine-treated mothers or their delivered infants in short term follow-up.
Asunto(s)
Hepatitis B/transmisión , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Nucleósidos/uso terapéutico , Complicaciones Infecciosas del Embarazo/prevención & control , Pirimidinonas/uso terapéutico , Adulto , ADN Viral , Femenino , Hepatitis B/virología , Virus de la Hepatitis B , Humanos , Nucleósidos/efectos adversos , Embarazo , Complicaciones Infecciosas del Embarazo/virología , Segundo Trimestre del Embarazo , Tercer Trimestre del Embarazo , Pirimidinonas/efectos adversos , Telbivudina , Timidina/análogos & derivados , Carga Viral , Adulto JovenRESUMEN
BACKGROUND & AIMS: Telbivudine reduces hepatitis B virus (HBV) DNA and normalizes levels of alanine aminotransferase (ALT) in patients with chronic hepatitis B (CHB). We investigated its use in preventing vertical transmission. METHODS: We performed an open-label, prospective study of 88 hepatitis B (HB) e antigen (HBeAg)-positive pregnant women with CHB, levels of HBV DNA >6 log(10) copies/mL, and increased levels of ALT. Women were given telbivudine (n = 53) starting in the 2nd or 3rd trimester, or no treatment (controls, n = 35) and followed until postpartum week (PPW) 28. All infants received standard immunoprophylaxis after birth. RESULTS: At 28 weeks, none of the infants whose mothers received telbivudine had immunoprophylaxis failure, whereas 8.6% of the infants of control mothers did (P = .029). There were no differences between groups in mothers' adverse events or infants' congenital deformities, gestational age, height, and weight, or Apgar scores. At postpartum week 28, significantly more telbivudine-treated mothers had levels of HBV DNA <500 copies/mL, normalized levels of ALT, and hepatitis B e antigen seroconversion compared with controls (58% vs none, P < .001; 92% vs 71%; P = .008; and 15% vs none; P < .001, respectively) but none had loss of hepatitis B surface antigen. Telbivudine-treated mothers had no virologic breakthrough (HBV DNA >1 log(10) increase from <500 copies/mL) or discontinuations from adverse events. After delivery, 13/52 patients discontinued telbivudine due to preference. There were no episodes of severe hepatitis (levels of ALT >10 times the upper limit of normal) in either group during 28 weeks of postpartum observation. CONCLUSIONS: Women with CHB given telbivudine during the second or third trimester of pregnancy have reduced rates of perinatal transmission. Telbivudine produced no adverse events in mothers or infants by 28 weeks.
Asunto(s)
Antivirales/administración & dosificación , Antígenos e de la Hepatitis B/sangre , Hepatitis B Crónica/prevención & control , Hepatitis B Crónica/transmisión , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Nucleósidos/administración & dosificación , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Pirimidinonas/administración & dosificación , Adulto , Estudios de Casos y Controles , ADN Viral/sangre , Femenino , Hepatitis B Crónica/tratamiento farmacológico , Humanos , Incidencia , Recién Nacido , Masculino , Embarazo , Estudios Prospectivos , Telbivudina , Timidina/análogos & derivadosRESUMEN
OBJECTIVE: To evaluate the therapeutic efficacy and safety of lamivudine treatment in late pregnancy by analyzing the maternal-fetal outcomes of chronic hepatitis B (CHB) mothers featuring hepatitis B e antigen (HBeAg)-positivity and highly viremic status. METHODS: A total of 256 pregnant women in the second or third trimester with monoinfected CHB, HBeAg-positivity, and HBV DNA more than 6 log10 copies/mL were divided into two groups: lamivudine (lam) treatment (n=164) or no treatment (controls; n=92). All infants were treated with hepatitis B immune globin (HBIg; 200 IU) within 12 hrs of birth and 15 days later, and were given the recombinant HBV vaccine (20 mug) at 0, 1 and 6 months. All infants were followed-up to at least seven months and hepatitis B surface antigen (HBsAg) and HBV DNA levels were used to determine perinatal transmission (PT) rates. The mothers' data from routine blood analysis, tests of hepatic and renal function, detection of HBV markers and HBV DNA were retrospectively analyzed to determine changes associated with the lam treatment. Correlations of lam treatment with HBV PT rate, alanine aminotransferase (ALT) normalization, adverse reactions, pregnancy complications, congenital deformities, and infants' growth/development were determined by statistical analyses. RESULTS: Prior to delivery, the lam-treated mothers had significantly lower HBV DNA levels (3.72+/-1.78 vs. controls: 7.83+/-0.67 log10 c/ml; t=-22.359, P less than 0.001). The rate of virological response in the lam-treated group was 97.56% (160/164). The lam-treated group had significantly higher ALT normalization rate (90.20% vs. controls: 55.88%; X2=13.349, P less than 0.001) and significantly lower HBeAg titer (957.73+/-458.42 vs. controls: 1296.35+/-383.14 S/CO; t=-5.410, P less than 0.001). At birth, the infants from lam-treated mothers had significantly lower HBsAg-positivity (15.24% (25/164) vs. controls: 30.43% (28/92); X2=8.284, P=0.004). By 7-12 months after birth, none of the infants born to lam-treated mothers tested positive for HBsAg, compared to 8.70% (8/92) of the infants born to mothers in the control group (X2=14.721, P less than 0.001). None of the lam-treated mothers required treatment discontinuation due to adverse events or lam-resistance. No congenital deformities were observed during the study and follow-up periods. There were no differences between the lam-treated and control groups for postpartum hemorrhage, gestational age, infants' height/weight or Apgar scores. CONCLUSION: In highly viremic HBsAg+ mothers with CHB, lam treatment in the second or third trimester of pregnancy is safe and effective for reducing HBV maternal-neonatal transmission.
Asunto(s)
Antivirales/uso terapéutico , Hepatitis B Crónica/tratamiento farmacológico , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Lamivudine/uso terapéutico , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Adulto , ADN Viral/sangre , Femenino , Hepatitis B Crónica/transmisión , Humanos , Lactante , Madres , Embarazo , Complicaciones Infecciosas del Embarazo/virología , Resultado del Embarazo , Tercer Trimestre del Embarazo , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND & AIMS: In the Asia-Pacific region, perinatal transmission of the hepatitis B virus (HBV) is the primary cause of chronic hepatitis B infection. Despite the use of HBIG and HBV vaccination, HBV perinatal transmission (PT) occurs in 10-30% of infants born to highly viremic mothers. We evaluated the efficacy and safety of LTD use during late pregnancy in reducing HBV transmission in highly viremic HBeAg+mothers. METHODS: Two hundred and twenty-nine HBeAg+HBV DNA levels>1.0×10(7) copies/ml mothers received telbivudine 600 mg/day from week 20 to 32 of gestation (n=135) or served as untreated controls (n=94). All infants in both arms received 200 IU of HBIg within 12 h postpartum and recombinant HBV vaccine of 20 µg at 0, 1, and 6 months. HBsAg and HBV DNA results of infants at week 28 were used to determine perinatal transmission rate. All telbivudine treated subjects were registered in the Antiretroviral Pregnancy Registry. RESULTS: Telbivudine treatment was associated with a marked reduction in serum HBV DNA and hepatitis B e antigen (HBeAg) levels and normalization of elevated ALT levels before delivery. A striking decline of HBV DNA levels started from treatment onset to week 4, and sustained in a low level since week 12. Forty-four (33%) of the 135 telbivudine-treated mothers and none (0%) of the untreated controls had polymerase chain reaction-undetectable viremia (DNA<500 copies/ml) at delivery. Seven months after delivery, the incidence of perinatal transmission was lower in the infants that completed follow-up born to the telbivudine-treated mothers than to the controls (0% vs. 8%; p=0.002). HBV DNA levels were only detectable in HBsAg+infants. No significant differences in anti-HBs levels were observed during postnatal follow-up. No serious adverse events were noted in the telbivudine-treated mothers or their infants. CONCLUSIONS: Telbivudine used during pregnancy in CHB HBeAg+highly viremic mothers can safely reduce perinatal HBV transmission. Telbivudine was well-tolerated with no safety concerns in the telbivudine-treated mothers or their infants on short term follow up. These data support the use of telbivudine in this special population.
Asunto(s)
Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/tratamiento farmacológico , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Nucleósidos/uso terapéutico , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Pirimidinonas/uso terapéutico , Adulto , Antivirales/efectos adversos , Antivirales/uso terapéutico , ADN Viral/sangre , Femenino , Anticuerpos contra la Hepatitis B/administración & dosificación , Antígenos de Superficie de la Hepatitis B/sangre , Vacunas contra Hepatitis B/administración & dosificación , Antígenos e de la Hepatitis B/sangre , Hepatitis B Crónica/prevención & control , Hepatitis B Crónica/transmisión , Humanos , Lactante , Recién Nacido , Masculino , Nucleósidos/efectos adversos , Embarazo , Complicaciones Infecciosas del Embarazo/virología , Estudios Prospectivos , Pirimidinonas/efectos adversos , Telbivudina , Timidina/análogos & derivados , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: To evaluate the efficacy of combined vaccination with 200IU dose of HBIG and 20 µg of anti-HBV vaccine for the prevention of HBV vertical transmission in babies delivered by HBeAg + and highly viremic mothers and the HBV markers' dynamic changes in babies during follow-up. METHODS: HBeAg + mothers with HBV DNA ≥ to 1.0 × 6 log(10) copies/ml were enrolled and their babies were followed up until 12 months old. The infants received HBIG 200 IU IM in 24 hrs and on day 15, and 20 µg recombinant anti-HBV vaccine at 0, 1 and 6 months. The HBV markers and HBV DNA were tested at birth day, and 1, 7, 12 months after birth respectively. The vertical transmission rate at birth and intrauterine infection rate, the HBsAb positive rate and the HBV markers' dynamic changes during follow up were evaluated. RESULTS: (1) 29 out of 127 infants with HBsAg (+) at birth, 11 of which were HBV DNA (+), HBV perinatal transmission rate was 22.83%. 2 infants' HBsAg were positive at month 1 and became negative at month 7 and 10 infants were still HBsAg (+) and HBV DNA (+). HBV intrauterine infection rate was 7.87%. (2) The positive rate of HBeAg and HBcAb in uninfected infants were 96.58% and 98.29% respectively, which declined gradually to undetectable level after immunization. No infants were HBeAb (+). (3) Infants uninfected produced effective HBsAb after vaccination. The level of HBsAb elevated gradually, and the level of HBeAg decreased quickly even to undetectable. CONCLUSION: The combination vaccination of 200 IU HBIG with 20 µg recombinant anti-HBV vaccine in the Infants delivered by HBeAg (+) and highly viremic mothers reduced obviously the rate of perinatal transmission of HBV, enhanced largely the production of antibody against HBV surface antigen and dropped the maternal HBeAg and HBcAb in infants or even to negative.