Assessing the impact of hepatitis B immune globulin (HBIG) on responses to hepatitis B vaccine during co-administration.

INTRODUCTION: A hepatitis B vaccination (HepB) series with an initial dose of hepatitis B immune globulin (HBIG) is the recommended prophylaxis for infants born to mothers with chronic hepatitis B virus (HBV) infection and for HBV-exposed persons without known protection. The HepB and HBIG are administered at different sites (limbs). Instances of HepB and HBIG administered at the same site are documented but the impact on immune responses to HepB remains unanswered. METHODS: Newborn and adult BALB/c mice received one dose of HepB at time zero alone or with HBIG in the same or different sites, followed by 2 additional doses of HepB at 3 and 10 weeks (newborn mice) or 4 and 16 weeks (adult mice). To study memory responses mice were given a 4th, booster, dose of HepB at 26 weeks and B cells analyzed. RESULTS: Administration of HepB with HBIG resulted in reduced responses to HepB following the first 2 doses, regardless of site, compared to mice that received HepB only. Lower levels of antibody to HBV surface antigen (anti-HBs) were observed at the end of the 3-dose series (p < 0.0001) in all groups of newborn mice that received HepB and HBIG. In adult mice, this difference was only seen when HepB and HBIG were delivered at the same site. However, following a HepB booster at 26 weeks, HBsAg-specific B-cell expansion and memory phenotype were not impacted by initial HBIG administration CONCLUSION: Administration of HBIG with HepB can delay and reduce responses to HepB in mice. Our findings suggest that the initial circulating levels of HBIG could prevent infection despite an impaired response to vaccine and support the current recommendation of assessing seroprotection after series completion for infants born to HBV carrier mothers, including in cases where vaccine and HBIG are administered incorrectly at the same site.

Estimating Annual Births to Hepatitis B Surface Antigen-Positive Women in the United States by Using Data on Maternal Country of Birth.

OBJECTIVE: A national estimate of births to hepatitis B surface antigen (HBsAg)-positive women can help public health programs plan surveillance, educational, and outreach activities to improve identification and management of at-risk women and infants. Stratifying mothers by country of birth allows for the application of region-specific HBsAg prevalence estimates, which can more precisely estimate the number of at-risk infants. The objective of our study was to estimate the number of births to HBsAg-positive women in the United States with more granularity than previous models. METHODS: We developed a model that incorporated maternal country of birth (MCOB) and updated HBsAg prevalence estimates. We assessed birth certificate data by MCOB, and we stratified US-born mothers by race/ethnicity, US territory-born mothers by territory, and non-US-born mothers by region. We multiplied and summed data in each subcategory by using HBsAg prevalence estimates calculated from the 2009-2014 National Health and Nutrition Examination Surveys or Perinatal Hepatitis B Prevention Program. We compared the findings of our MCOB model with a race/ethnicity model. RESULTS: In 2015, an estimated 20 678 infants were born to HBsAg-positive women in the United States, representing 0.5% of all births. Births to US-born and non-US-born women comprised 77.2% and 21.5% of all births, respectively, and 40.1% and 57.9% of estimated births to HBsAg-positive women, respectively. The estimated contribution of births to HBsAg-positive women varied by MCOB region, from 4 (0.03%) infants born to women from Australia/Oceania to 5795 (28.0%) infants born to women from East Asia. Our MCOB model estimated 5666 fewer births to HBsAg-positive women than did the race/ethnicity model. CONCLUSIONS: As global vaccine programs reduce HBsAg prevalence, the MCOB model can incorporate evolving HBsAg prevalence estimates for women from various regions of the world.

Recent and occult hepatitis B virus infections among blood donors in the United States.

BACKGROUND: Characteristics of US blood donors with recent (RBI) or occult (OBI) hepatitis B virus (HBV) infection are not well defined. METHODS: Donors with RBI and OBI were identified by nucleic acid and serologic testing among 34.4 million donations during 2009-2015. Consenting donors were interviewed and their HBV S-gene sequenced. RESULTS: The overall rate of HBV-infected donors was 7.95 per 100,000; of these, 0.35 per 100,000 and 1.70 per 100,000 were RBI and OBI, respectively. RBI (n = 120) and OBI (n = 583) donors constituted 26% of all HBV-infected (n = 2735) donors. Detection of HBV DNA in 92% of OBI donors required individual donation nucleic acid testing. Donors with OBI compared to RBI were older (mean age, 48 vs 39 years; p < 0.0001) with lower median viral loads (9 vs. 529 IU/mL; p < 0.0001). A higher proportion of OBI than RBI donors were born or resided in an endemic country (39% vs. 5%; p = 0.0078). Seventy-seven percent of all RBI and OBI donors had multiple sex partners, an HBV-risk factor. Of 40 RBI and 10 OBI donors whose S gene was sequenced, 33 (83%) and 6 (60%), respectively, carried HBV subgenotype A2; 18 (55%) and 2 (33%), respectively, shared an identical sequence. Infection with 1 or more putative HBV-immune-escape mutants was identified in 5 (50%) of OBI but no RBI donors. CONCLUSION: RBI and OBI continue to be identified at low rates, confirming the importance of comprehensive HBV DNA screening of US blood donations. HBV-infected donors require referral for care and evaluation and contact tracing; their HBV strains may provide important information on emergent genotypes.

Tenofovir Exposure during Pregnancy and Postpartum in Women Receiving Tenofovir Disoproxil Fumarate for the Prevention of Mother-to-Child Transmission of Hepatitis B Virus.

We assessed tenofovir exposure during pregnancy and postpartum in hepatitis B virus (HBV)-infected HIV-uninfected women receiving tenofovir disoproxil fumarate (TDF) to prevent mother-to-child transmission of HBV. Data from 154 women who received TDF within a randomized controlled trial were included. Individual plasma tenofovir exposures (area under the concentration-time curve from 0 to 24 h [AUC0-24]) were estimated using a population pharmacokinetic approach. The estimated geometric mean tenofovir AUC0-24 was 20% (95% confidence interval [95% CI], 19 to 21%) lower during pregnancy than during postpartum; this modest reduction in the absence of HBV transmission suggests that no dose adjustment is needed.

Hepatitis B Surface Antigen Seroprevalence among Prevaccine and Vaccine Era Children in Bangladesh.

Bangladesh introduced hepatitis B vaccine in a phased manner during 2003-2005 into the routine childhood vaccination schedule. This study was designed to evaluate the impact of the introduction of hepatitis B vaccine in Bangladesh by comparing hepatitis B surface antigen (HBsAg) prevalence among children born before and after vaccine introduction and to estimate the risk of vertical transmission of chronic hepatitis B virus (HBV) infection from mother to infant. We also evaluated the field sensitivity and specificity of an HBsAg point-of-care test strip. We selected a nationally representative sample of 2,100 prevaccine era and 2,100 vaccine era children. We collected a 5-mL blood sample from each child. One drop of blood was used to perform rapid HBsAg testing. If a child had a positive HBsAg test result with the rapid test, a blood sample was collected from the mother of the HBsAg-positive child and from the mothers of two subsequently enrolled HBsAg-negative children. All samples were tested for serologic markers of HBV infection using standard enzyme-linked immunosorbent assay. One (0.05%) child in the vaccine era group and 27 (1.2%; 95% confidence interval [CI]: 0.8-1.7%) children in the prevaccine era group were HBsAg positive. Mothers of HBsAg-positive children were more likely to be HBsAg positive than mothers of HBsAg-negative children (odds ratios = 4.7; 95% CI: 1.0-21.7%). Sensitivity of the HBsAg rapid test was 91.2% (95% CI: 76.6-98.1%) and specificity was 100% (95% CI: 99.9-100%). The study results suggest that even without a birth dose, the hepatitis B vaccine program in Bangladesh was highly effective in preventing chronic HBV infection among children.

Tenofovir versus Placebo to Prevent Perinatal Transmission of Hepatitis B.

BACKGROUND: Pregnant women with an elevated viral load of hepatitis B virus (HBV) have a risk of transmitting infection to their infants, despite the infants' receiving hepatitis B immune globulin. METHODS: In this multicenter, double-blind clinical trial performed in Thailand, we randomly assigned hepatitis B e antigen (HBeAg)-positive pregnant women with an alanine aminotransferase level of 60 IU or less per liter to receive tenofovir disoproxil fumarate (TDF) or placebo from 28 weeks of gestation to 2 months post partum. Infants received hepatitis B immune globulin at birth and hepatitis B vaccine at birth and at 1, 2, 4, and 6 months. The primary end point was a hepatitis B surface antigen (HBsAg)-positive status in the infant, confirmed by the HBV DNA level at 6 months of age. We calculated that a sample of 328 women would provide the trial with 90% power to detect a difference of at least 9 percentage points in the transmission rate (expected rate, 3% in the TDF group vs. 12% in the placebo group). RESULTS: From January 2013 to August 2015, we enrolled 331 women; 168 women were randomly assigned to the TDF group and 163 to the placebo group. At enrollment, the median gestational age was 28.3 weeks, and the median HBV DNA level was 8.0 log10 IU per milliliter. Among 322 deliveries (97% of the participants), there were 319 singleton births, two twin pairs, and one stillborn infant. The median time from birth to administration of hepatitis B immune globulin was 1.3 hours, and the median time from birth to administration of hepatitis B vaccine was 1.2 hours. In the primary analysis, none of the 147 infants (0%; 95% confidence interval [CI], 0 to 2) in the TDF group were infected, as compared with 3 of 147 (2%; 95% CI, 0 to 6) in the placebo group (P=0.12). The rate of adverse events did not differ significantly between groups. The incidence of a maternal alanine aminotransferase level of more than 300 IU per liter after discontinuation of the trial regimen was 6% in the TDF group and 3% in the placebo group (P=0.29). CONCLUSIONS: In a setting in which the rate of mother-to-child HBV transmission was low with the administration of hepatitis B immune globulin and hepatitis B vaccine in infants born to HBeAg-positive mothers, the additional maternal use of TDF did not result in a significantly lower rate of transmission. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ClinicalTrials.gov number, NCT01745822 .).

Assessment of State Perinatal Hepatitis B Prevention Laws.

INTRODUCTION: Identifying pregnant women with hepatitis B virus (HBV) infection for post-exposure prophylaxis of their infants is critical to preventing mother-to-child transmission of HBV infection. HBV infection in infancy results in premature death from chronic liver disease or cancer in 25% of affected infants. Universal screening of pregnant women for HBV infection is the standard of care, and in many states is supported by laws for screening and reporting these infections to public health. No recent assessment of state screening and reporting laws for HBV infection has been published. METHODS: In 2014, the authors analyzed laws current through December 31, 2013 from U.S. jurisdictions (50 states and the District of Columbia) related to HBV infection and hepatitis B surface antigen screening and reporting requirements generally and for pregnant women specifically. RESULTS: All states require reporting of cases of HBV infection. Twenty-six states require pregnant women to be screened. Thirty-three states require public health reporting of HBV infections in pregnant women, but only 12 states require reporting pregnancy status of women with HBV infection. CONCLUSIONS: This assessment revealed significant variability in laws related to screening and reporting of HBV infection among pregnant women in the U.S. Implementing comprehensive HBV infection screening and reporting laws for pregnant women may facilitate identifying HBV-infected pregnant women and preventing HBV infection in their infants.

Prevention of mother-to-child transmission of hepatitis B virus: a phase III, placebo-controlled, double-blind, randomized clinical trial to assess the efficacy and safety of a short course of tenofovir disoproxil fumarate in women with hepatitis B virus e-antigen.

BACKGROUND: Chronic hepatitis B virus (HBV) infection is complicated by cirrhosis and liver cancer. In Thailand, 6-7 % of adults are chronically infected with HBV. The risk of mother-to-child transmission (MTCT) of HBV has been estimated to be about 12 % when mothers have a high hepatitis B viral load, even if infants receive passive-active prophylaxis with HBV immunoglobulin (HBIg) and initiate the hepatitis B vaccine series at birth. We designed a study to assess the efficacy and safety of a short course of maternal tenofovir disoproxil fumarate (TDF) among women with a marker of high viral load for the prevention of MTCT of HBV. METHODS: The study is a phase III, multicenter (17 sites in Thailand), placebo-controlled, double-blind, randomized 1:1, two-arm clinical trial of TDF 300 mg once daily versus placebo among pregnant women from 28 weeks' gestation through 2-month post-partum. All infants receive HBIg at birth, and a hepatitis B (HB) vaccination series according to Thai guidelines: birth, and age 1, 2, 4 and 6 months. Participant women at study entry must be age ≥18 years, hepatitis B surface antigen (HBsAg) and e-antigen (HBeAg) positive, have alanine aminotransferase (ALT) level < 30 IU/L at screening (confirmed < 60 IU/L pre-entry), negative hepatitis C serology, creatinine clearance >50 mL/min, and no history of anti-HBV antiviral treatment. The target sample size of 328 mother/infant pairs assumed 156 evaluable cases per arm to detect a ≥9 % difference in MTCT transmission (3 % experimental arm versus 12 % placebo arm) with 90 % power. Mothers and infants are followed until 12 months after delivery. The primary infant endpoint is detection of HBsAg, confirmed by detection of HBV DNA at six months of age. Secondary endpoints are maternal and infant adverse events, acute exacerbations of maternal hepatitis B disease (ALT >300 IU/L, defined as a "flare") following discontinuation of study treatment, infant HBV infection status and growth up to 12 months of age. DISCUSSION: The results of this randomized trial will clarify the efficacy and safety of a short course of antiviral treatment to prevent mother-to-child transmission of HBV and inform international guidelines. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01745822 .

Progress Toward Eliminating Hepatitis A Disease in the United States.

Hepatitis A virus (HAV) disease disproportionately affects adolescents and young adults, American Indian/Alaska Native and Hispanic racial/ethnic groups, and disadvantaged populations. During 1996-2006, the Advisory Committee on Immunization Practices (ACIP) made incremental changes in hepatitis A (HepA) vaccination recommendations to increase coverage for children and persons at high risk for HAV infection. This report examines the temporal association of ACIP-recommended HepA vaccination and disparities (on the absolute scale) in cases of HAV disease and on seroprevalence of HAV-related protection (measured as antibody to HAV [anti-HAV]). ACIP-recommended childhood HepA vaccination in the United States has eliminated most absolute disparities in HAV disease by age, race/ethnicity, and geographic area with relatively modest ≥1-dose and ≥2-dose vaccine coverage. However, the increasing proportion of cases of HAV disease among adults with identified and unidentified sources of exposure underscores the importance of considering new strategies for preventing HAV infection among U.S. adults. For continued progress to be made toward elimination of HAV disease in the United States, additional strategies are needed to prevent HAV infection among an emerging population of susceptible adults. Notably, HAV infection remains endemic in much of the world, contributing to U.S. cases through international travel and the global food economy.

Characteristics of Pregnant Women With Hepatitis B Virus Infection in 5 US Public Health Jurisdictions, 2008-2012.

OBJECTIVE: We estimated the prevalence of hepatitis B surface antigen (HBsAg), a serologic marker of active hepatitis B virus (HBV) infection, among pregnant women, and estimated the proportion HBsAg-positive pregnant women who had received additional recommended testing. METHODS: From 2008 through 2012, Perinatal Hepatitis B Prevention Programs (PHBPPs) in Florida, Michigan, Minnesota, New York City, and Texas prospectively collected data on demographic characteristics of HBsAg-positive pregnant women. We estimated the prevalence of HBsAg positivity among pregnant women by demographic characteristics using natality data. PHBPPs (excluding Texas) collected additional recommended testing (for hepatitis B e antigen [HBeAg] and/or HBV deoxyribonucleic acid [DNA]) among HBsAg-positive pregnant women to measure levels of viremia. RESULTS: During the study period, 15,205 HBsAg-positive women were case-managed. The median age of HBsAg-positive women was 29 years; prenatal HBsAg screening was at a median of 27 weeks pre-delivery. Of 15,205 HBsAg-positive women, 11,293 (74.3%) were foreign-born. In four PHBPPs with 14,098 pregnancies among 12,214 HBsAg-positive women, HBeAg and/or HBV DNA testing was documented for 2,794 (19.8%) pregnancies. The estimated prevalence of HBsAg positivity among pregnant women was 0.38% (17,023 of 4,468,773). HBsAg prevalence was highest among foreign-born women from most regions in Asia (2.0% to 8.7%; with the exception of South Asia, 0.4%) and Africa (3.4%). CONCLUSION: One-fifth of HBsAg-positive pregnant women had documentation for HBeAg and/or HBV DNA, and about one-third reported receiving care for HBV infection during a case-managed pregnancy. Greater emphasis is needed on prenatal evaluation for HBV liver disease care and treatment among pregnant women with HBV infection.

Estimated Annual Perinatal Hepatitis B Virus Infections in the United States, 2000-2009.

BACKGROUND: Ninety percent of perinatal hepatitis B virus (HBV) infections result in chronic HBV (CHBV), which carries 25% risk of premature death from progressive liver injury, cirrhosis, and liver cancer. In 1990, the Centers for Disease Control and Prevention (CDC) funded Perinatal Hepatitis B Prevention Programs (PHBPP) to ensure postexposure prophylaxis for exposed infants and accelerate elimination of perinatal CHBV in the United States. From 2000 to 2009, the annual rates of perinatal CHBV reported by PHBPP (0.8%-2.4%) were consistently lower than expected rates from CDC models (3.0%-4.1%), suggesting that rates of CHBV might be higher among infants whose outcomes were not identified by PHBPP. To better understand the factors impacting modeled expected number and rates of perinatal CHBV, we examined historic CDC models, applied updated inputs to the 2009 CDC model, and performed sensitivity analyses over a range of parameter values. METHODS: Models employed estimates of the annual number of births to hepatitis B surface antigen (HBsAg)-positive pregnant women, and data from PHBPP and National Immunization Surveys. Published literature provided prenatal HBsAg screening rates, efficacy of postexposure prophylaxis (PEP), and perinatal HBV transmission rates. RESULTS: The updated 2009 model predicted 952 perinatal CHBV infections, equivalent to a baseline rate of 3.84%, among infants of HBsAg-positive women. Sensitivity analyses yielded a possible range of perinatal CHBV rates between 0.60% and 15.41%. The proportion of infants receiving timely PEP, the efficacy of PEP, and perinatal HBV transmission rate were major "drivers" of CHBV rates. Three-way sensitivity analysis yielded possible perinatal CHBV rates between 0.79% and 13.64%. CONCLUSIONS: Modeling provided useful programmatic goals for achieving elimination of perinatal CHBV in the United States. Limitations of data inputs likely contributed to discrepancies between predicted and reported rates.

Cost-effectiveness of active-passive prophylaxis and antiviral prophylaxis during pregnancy to prevent perinatal hepatitis B virus infection.

UNLABELLED: In an era of antiviral treatment, reexamination of the cost-effectiveness of strategies to prevent perinatal hepatitis B virus (HBV) transmission in the United States is needed. We used a decision tree and Markov model to estimate the cost-effectiveness of the current U.S. strategy and two alternatives: (1) Universal hepatitis B vaccination (HepB) strategy: No pregnant women are screened for hepatitis B surface antigen (HBsAg). All infants receive HepB before hospital discharge; no infants receive hepatitis B immunoglobulin (HBIG). (2) Current strategy: All pregnant women are screened for HBsAg. Infants of HBsAg-positive women receive HepB and HBIG ≤12 hours of birth. All other infants receive HepB before hospital discharge. (3) Antiviral prophylaxis strategy: All pregnant women are screened for HBsAg. HBsAg-positive women have HBV-DNA load measured. Antiviral prophylaxis is offered for 4 months starting in the third trimester to women with DNA load ≥10(6) copies/mL. HepB and HBIG are administered at birth to infants of HBsAg-positive women, and HepB is administered before hospital discharge to infants of HBsAg-negative women. Effects were measured in quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICER). Compared to the universal HepB strategy, the current strategy prevented 1,006 chronic HBV infections and saved 13,600 QALYs (ICER: $6,957/QALY saved). Antiviral prophylaxis dominated the current strategy, preventing an additional 489 chronic infections, and saving 800 QALYs and $2.8 million. The results remained robust over a wide range of assumptions. CONCLUSION: The current U.S. strategy for preventing perinatal HBV remains cost-effective compared to the universal HepB strategy. An antiviral prophylaxis strategy was cost saving compared to the current strategy and should be considered to continue to decrease the burden of perinatal hepatitis B in the United States.

Chronic Liver Disease-Associated Hospitalizations Among Adults with Diabetes, National Inpatient Sample, 2001-2012.

OBJECTIVE: Many people with diabetes have a variety of diabetes-related complications. Among the variety of conditions associated with diabetes, however, liver diseases are less well recognized. As such, we aimed to describe chronic liver disease (CLD)-associated hospitalization rates among U.S. adults with diabetes from 2001-2012. METHODS: We used a nationally representative database of hospitalizations, the National Inpatient Sample, to determine CLD-associated hospitalization rates among U.S. adults aged ≥ 18 years with and without diabetes, from 2001-2012. Hospitalizations listing an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code for CLD on the discharge record were selected for analysis and were further classified by diabetes status based on concurrent presence of a diabetes ICD-9-CM code. We calculated average annual age-adjusted hospitalization rates and 95% confidence intervals (CIs), and conducted a test for trend. RESULTS: For 2001-2012, the total age-adjusted CLD-associated hospitalization rate among adults with diabetes (1,680.9 per 100,000 population; 95% CI 1,577.2, 1,784.6) was approximately four times the rate of adults without diabetes (424.2 per 100,000 population; 95% CI 413.4, 435.1). Total age-adjusted hospitalization rates of adults with and without diabetes increased 59% and 48%, respectively, from 2001-2002 to 2011-2012 (p<0.001). Hepatitis C- and chronic hepatitis and cirrhosis-associated hospitalizations comprised the largest proportion of total CLD-associated hospitalizations among adults with and without diabetes. CONCLUSION: Providers should be aware of the potential existence of CLD among adults with diabetes and counsel patients on preventive methods to avoid progressive liver damage.

Decreasing immunity to hepatitis A virus infection among US adults: Findings from the National Health and Nutrition Examination Survey (NHANES), 1999-2012.

BACKGROUND: The clinical course of hepatitis A virus (HAV) infection is more severe with increased age. In the United States, surveillance data reported to CDC since 2011 indicate increases in both the absolute number of cases and the mean age of cases. Total antibody to HAV (anti-HAV) is a marker of immunity. METHODS: We analyzed National Health and Nutrition Examination Survey (NHANES) data for anti-HAV from respondents aged ≥ 2 years collected from 2007 to 2012 and compared with data collected 10 years earlier (1999-2006). For US-born adults aged ≥ 20 years, we estimated age-adjusted anti-HAV prevalence by demographic and other characteristics, evaluated factors associated with anti-HAV positivity and examined anti-HAV prevalence by decade of birth. RESULTS: The prevalence of anti-HAV among adults aged ≥ 20 years was 24.2% (95% CI 22.5-25.9) during 2007-2012, a significant decline from 29.5% (95% CI 28.0-31.1) during 1999-2006. Prevalence of anti-HAV was consistently lower in 2007-2012 compared to 1999-2006 by all characteristics examined. In 2007-2012, the lowest age-specific prevalence was among adults aged 30-49 years (16.1-17.6%). Factors significantly associated with anti-HAV positivity among adults were older age, Mexican American ethnicity, living below poverty, less education, and not having insurance. By decade of birth, the prevalence of anti-HAV was slightly lower in 2009-2012 than in 1999-2002, except among persons born from 1980 to 1989. CONCLUSIONS: NHANES data document very low prevalence of hepatitis A immunity among U.S. adults aged 30-49 years; waning of anti-HAV over time may be minimal. Improving vaccination coverage among susceptible adults should be considered.

Update: Shortened Interval for Postvaccination Serologic Testing of Infants Born to Hepatitis B-Infected Mothers.

Infants born to hepatitis B-infected mothers receive postexposure prophylaxis to reduce their risk for perinatal hepatitis B virus (HBV) infection. Postexposure prophylaxis consists of hepatitis B (HepB) vaccine and hepatitis B immune globulin administered within 12 hours of birth, followed by completion of the 3-dose or 4-dose HepB vaccine series. Postvaccination serologic testing (PVST) assesses an infant's response to HepB vaccination and has typically occurred at age 9-18 months. This report provides a CDC update recommending shortening the interval for PVST from age 9-18 months to age 9-12 months. Providers should order PVST (consisting of hepatitis B surface antigen [HBsAg] and antibody to HBsAg [anti-HBs]) for infants born to HBsAg-positive mothers at age 9-12 months (or 1-2 months after the final dose of the vaccine series, if the series is delayed). This recommendation was prompted by the discontinuation of production of Hib/HepB vaccine (Comvax) and new data from the Enhanced Perinatal Hepatitis B Prevention Program supporting PVST 1・2 months after receipt of the last HepB vaccine dose, and at age ≥9 months.

Self-reported hepatitis A vaccination as a predictor of hepatitis A virus antibody protection in U.S. adults: National Health and Nutrition Examination Survey 2007-2012.

OBJECTIVES: To estimate the predictive value of self-reported hepatitis A vaccine (HepA) receipt for the presence of hepatitis A virus (HAV) antibody (anti-HAV) from either past infection or vaccination, as an indicator of HAV protection. METHODS: Using 2007-2012 National Health and Nutrition Examination Survey data, we assigned participants to 4 groups based on self-reported HepA receipt and anti-HAV results. We compared characteristics across groups and calculated three measures of agreement between self-report and serologic status (anti-HAV): percentage concordance, and positive (PPV) and negative (NPV) predictive values. Using logistic regression we investigated factors associated with agreement between self-reported vaccination status and serological results. RESULTS: Demographic and other characteristics varied significantly across the 4 groups. Overall agreement between self-reported HepA receipt and serological results was 63.6% (95% confidence interval [CI] 61.9-65.2); PPV and NPV of self-reported vaccination status for serological result were 47.0% (95% CI 44.2-49.8) and 69.4% (95% CI 67.0-71.8), respectively. Mexican American and foreign-born adults had the highest PPVs (71.5% [95% CI 65.9-76.5], and 75.8% [95% CI 71.4-79.7]) and the lowest NPVs (21.8% [95% CI 18.5-25.4], and 20.0% [95% CI 17.2-23.1]), respectively. Young (ages 20-29 years), US-born, and non-Hispanic White adults had the lowest PPVs (37.9% [95% CI 34.5-41.5], 39.1% [95% CI, 36.0-42.3], and 39.8% [36.1-43.7]), and the highest NPVs (76.9% [95% CI 72.2-81.0, 78.5% [95% CI 76.5-80.4)], and 80.6% [95% CI 78.2-82.8), respectively. Multivariate logistic analyses found age, race/ethnicity, education, place of birth and income to be significantly associated with agreement between self-reported vaccination status and serological results. CONCLUSIONS: When assessing hepatitis A protection, self-report of not having received HepA was most likely to identify persons at risk for hepatitis A infection (no anti-HAV) among young, US-born and non-Hispanic White adults, and self-report of HepA receipt was least likely to be reliable among adults with the same characteristics.

Outcomes of infants born to women infected with hepatitis B.

BACKGROUND AND OBJECTIVES: Perinatal exposure is an important mode of hepatitis B virus (HBV) transmission, resulting in chronic disease in ∼ 90% of infected infants. Immunoprophylaxis recommended for infants born to hepatitis B surface antigen-positive mothers reduces up to 95% of perinatal HBV infections. We sought to identify factors associated with perinatal HBV transmission. METHODS: We analyzed prospectively collected data from 5 of 64 US-funded Perinatal Hepatitis B Prevention Programs during 2007-2013. We examined effects of maternal demographic and laboratory results, infant gestational age and birth weight, and immunoprophylactic management on perinatal HBV infection. RESULTS: Data from 17,951 mother-infant pairs were analyzed. Among 9252 (51.5%) infants for whom hepatitis B surface antigen testing results were available, 100 (1.1%) acquired perinatal HBV infection. Both hepatitis B (HepB) vaccine and hepatitis B immune globulin were administered within 12 hours of birth for 10,760 (94.9%) of 11,335 infants with information. Perinatal HBV infection was associated with younger maternal age (P = .01), Asian/Pacific Islander race (P < .01), maternal hepatitis B e-antigen positivity (P < .01), maternal antibody to hepatitis B e-antigen negativity (P < .01), maternal viral load ≥ 2000 IU/mL (P = .04), and infant receipt of <3 HepB vaccine doses (P = .01). Four infants born to 429 mothers with viral load testing were infected; all 4 were born to mothers with viral loads in the ninth or tenth decile. CONCLUSIONS: Perinatal HBV infection occurred among 1% of infants, most of whom received recommended immunoprophylaxis. Infants at greatest risk of infection were those born to women who were younger, hepatitis B e-antigen positive, or who had a high viral load or those infants who received <3 HepB vaccine doses.

Hepatitis B vaccination among adolescents 13-17 years, United States, 2006-2012.

BACKGROUND: Hepatitis B (HepB) vaccination is the most effective measure to prevent HBV infection. Routine HepB vaccination was recommended for infants in 1991 and catch-up vaccination has been recommended for adolescents since in 1995. The purpose of this study is to assess HepB vaccination among adolescents 13-17 years. METHODS: The 2006-2012 NIS-Teen were analyzed. Vaccination trends and coverage by birth cohort among adolescents were evaluated. Multivariable logistic regression and predictive marginal models are used to identify factors independently associated with HepB vaccination. RESULTS: HepB vaccination coverage increased from 81.3% in 2006 to 92.8% in 2012. Coverage varied by birth cohort and 79-83% received vaccination before 2 years of age for those who were born during 1995 and 1999. Among those who had not received vaccination by 11 years of age, for the 1993-1995 birth cohorts, 9-15% were vaccinated during ages 11-12 years, and 27-37% had been vaccinated through age 16 years. Coverage among adolescents 13-17 years in 2012 ranged by state from 84.4% in West Virginia to 98.7% in Florida (median 93.3%). Characteristics independently associated with a higher likelihood of HepB vaccination included living more than 5 times above poverty level, living in Northeastern or Southern region of the United States, and having a mixed facility as their vaccination provider. Those with a hospital listed as their vaccination provider and those who did not have a well-child visit at age 11-12 years were independently associated with a lower likelihood of HepB vaccination. CONCLUSIONS: Efforts focused on groups with lower coverage may reduce disparities in coverage and prevent hepatitis B infection. Parents and providers should routinely review adolescent immunizations. Routine reminder/recall, expanded access in health care settings, and standing order programs should be incorporated into routine clinical care of adolescents.

Antiviral treatment among pregnant women with chronic hepatitis B.

OBJECTIVE: To describe the antiviral treatment patterns for chronic hepatitis B (CHB) among pregnant and nonpregnant women. METHODS: Using 2011 MarketScan claims, we calculated the rates of antiviral treatment among women (aged 10-50 years) with CHB. We described the pattern of antiviral treatment during pregnancy and ≥1 month after delivery. RESULTS: We identified 6274 women with CHB during 2011. Among these, 64 of 507 (12.6%) pregnant women and 1151 of 5767 (20.0%) nonpregnant women received antiviral treatment (P < 0.01). Pregnant women were most commonly prescribed tenofovir (73.4%) and lamivudine (21.9%); nonpregnant women were most commonly prescribed tenofovir (50.2%) and entecavir (41.3%) (P < 0.01). Among 48 treated pregnant women with an identifiable delivery date, 16 (33.3%) were prescribed an antiviral before pregnancy and continued treatment for at least one month after delivery; 14 (29.2%) started treatment during the third trimester and continued at least one month after delivery. CONCLUSION: Among this insured population, pregnant women with CHB received an antiviral significantly less often than nonpregnant women. The most common antiviral prescribed for pregnant women was tenofovir. These data provide a baseline for assessing changes in treatment patterns with anticipated increased use of antivirals to prevent breakthrough perinatal hepatitis B virus infection.

Prevention of Perinatal Hepatitis B Virus Transmission.

Hepatitis B virus (HBV) infection, the most common form of chronic hepatitis worldwide, is a major public health problem affecting an estimated 360 million people globally. Mother-to-child transmission (MTCT) is responsible for more than one third of chronic HBV infections worldwide. An estimated 15%-40% of persons chronically infected develop HBV-related complications, such as cirrhosis and hepatic carcinoma, and 25% die from these complications. MTCT can occur during pregnancy or during delivery. Screening pregnant women for HBV infection, providing infant postexposure prophylaxis, and maternal treatment with antiviral medications are strategies for reducing MTCT transmission rates and the global burden of new chronic HBV infections. Administration of hepatitis B immune globulin (HBIG) and hepatitis B (HepB) vaccine within 24 hours of birth, followed by completion of the vaccine series, is 85%-95% efficacious for prevention of MTCT. Despite timely post-exposure prophylaxis, MTCT occurs in 5%-15% of infants. Hepatitis B surface antigen (HBsAg) positive, hepatitis e antigen (HBeAg) positive mothers with HBV DNA level ≥10(6) copies/mL (>200 000 IU/mL) are at greatest risk of transmitting HBV to their infants. Consensus recommendations and evidence-based guidelines for management of chronic HBV infection and screening of pregnant women have been developed. The safety and efficacy of antiviral drug use during pregnancy are areas of ongoing research. Substantial advances have been achieved globally in reducing MTCT, but MTCT remains an ongoing health problem. Attaining a better understanding of the mechanisms of MTCT, implementing existing policies on maternal screening and infant follow-up, and addressing research gaps are critical for further reductions in MTCT transmission.