Noele P. Nelson

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.

Epidemiology of Hepatitis B Virus Infection and Impact of Vaccination on Disease

Integration of hepatitis B vaccination into national immunization programs has resulted in substantial reductions of hepatitis B virus (HBV) transmission in previously high endemic countries. The key strategy for control of the HBV epidemic is birth dose and infant vaccination. Additional measures include use of hepatitis B immunoglobulin (HBIG) and diagnosis of mothers at high risk of transmitting HBV and use of antiviral agents during pregnancy to decrease maternal DNA concentrations to undetectable concentrations. Despite the substantial decrease in HBV cases since vaccination introduction, implementation of birth dose vaccination in low-income and middle-income countries and vaccination of high-risk adults remain challenging.

Increased Hepatitis C Virus (HCV) Detection in Women of Childbearing Age and Potential Risk for Vertical Transmission — United States and Kentucky, 2011–2014

Hepatitis C virus (HCV) infection is a leading cause of liver-related morbidity and mortality (1). Transmission of HCV is primarily via parenteral blood exposure, and HCV can be transmitted vertically from mother to child. Vertical transmission occurs in 5.8% (95% confidence interval = 4.2%-7.8%) of infants born to women who are infected only with HCV and in up to twice as many infants born to women who are also infected with human immunodeficiency virus (HIV) (2) or who have high HCV viral loads (3,4); there is currently no recommended intervention to prevent transmission of infection from mother to child (3). Increased reported incidence of HCV infection among persons aged ≤30 years (5,6) with similar increases among women and men in this age group (6), raises concern about increases in the number of pregnant women with HCV infection, and in the number of infants who could be exposed to HCV at birth. Data from one large commercial laboratory and birth certificate data were used to investigate trends in HCV detection among women of childbearing age,* HCV testing among children aged ≤2 years, and the proportions of infants born to HCV-infected women nationally and in Kentucky, the state with the highest incidence of acute HCV infection during 2011-2014 (6). During 2011-2014, commercial laboratory data indicated that national rates of HCV detection (antibody or RNA positivity(†)) among women of childbearing age increased 22%, and HCV testing (antibody or RNA) among children aged ≤2 years increased 14%; birth certificate data indicated that the proportion of infants born to HCV-infected mothers increased 68%, from 0.19% to 0.32%. During the same time in Kentucky, the HCV detection rate among women of childbearing age increased >200%, HCV testing among children aged ≤2 years increased 151%, and the proportion of infants born to HCV-infected women increased 124%, from 0.71% to 1.59%. Increases in the rate of HCV detection among women of childbearing age suggest a potential risk for vertical transmission of HCV. These findings highlight the importance of following current CDC recommendations to identify, counsel, and test persons at risk for HCV infection (1,7), including pregnant women, as well as consider developing public health policies for routine HCV testing of pregnant women, and expanding current policies for testing and monitoring children born to HCV-infected women. Expansion of HCV reporting and surveillance requirements will enhance case identification and prevention strategies.

Hepatitis B vaccine response among infants born to hepatitis B surface antigen-positive women

PURPOSE Annually, an estimated 25,000 infants are born to hepatitis B surface antigen (HBsAg)-positive women in the United States. Hepatitis B (HepB) vaccine and hepatitis B immune globulin (HBIG) are recommended at birth, followed by completion of vaccine series and post-vaccination serologic testing (PVST). In a large cohort of infants born to HBsAg-positive women, factors influencing vaccine response were evaluated. METHODS Data were from HBsAg-negative infants born to HBsAg-positive women in the Enhanced Perinatal Hepatitis B Prevention Program (EPHBPP) from 2008 to 2013. Vaccine non-responders were defined as infants with antibody to hepatitis B surface antigen (anti-HBs) <10mIU/mL at PVST after receiving ≥3 vaccine doses. Multivariable analyses modeled statistically significant predictor variables associated with non-response. RESULTS A total of 17,951 maternal-infant pairs were enrolled; 8654 HBsAg-negative infants born to HBsAg-positive mothers received ≥3 doses of vaccine with anti-HBs results. 8199 (94.7%) infants responded to a primary HepB series; 199 (94.8%) to a second series. Factors associated with anti-HBs <10mIU/mL included gestational age <37 weeks, vaccine birth dose >12h after birth, timing of final vaccine dose <6 months after birth, receipt of 3 vs. 4 vaccine doses, and PVST interval >6 months from final vaccine dose in bivariate analysis. PVST interval >6 months from final vaccine dose (OR=2.7, CI=2.0, 3.6) was significantly associated with anti-HBs <10mIU/mL; the proportion increased from 2% at 1-2 months to 21.6% at 15-16 months after the final dose. Receipt of a 4th dose improved the response rate (OR=0.5, CI=0.3, 0.8). CONCLUSIONS Ninety-five percent of a large cohort of uninfected infants born to HBsAg-positive mothers in the United States responded to primary HepB vaccine series. The proportion of infants with anti-HBs <10mIU/mL increased with longer interval between the final vaccine dose and PVST. Optimal timing of PVST is within 1-2 months of final vaccine dose to avoid unnecessary revaccination.

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.

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.

Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices

Summary Hepatitis B virus (HBV) is transmitted via blood or sexual contact. Persons with chronic HBV infection are at increased risk for cirrhosis and liver cancer and require medical care. This report updates and summarizes previously published recommendations from the Advisory Committee on Immunization Practices (ACIP) and CDC regarding the prevention of HBV infection in the United States. ACIP recommends testing all pregnant women for hepatitis B surface antigen (HBsAg), and testing HBsAg-positive pregnant women for hepatitis B virus deoxyribonucleic acid (HBV DNA); administration of HepB vaccine and hepatitis B immune globulin (HBIG) for infants born to HBV-infected women within 12 hours of birth, followed by completion of the vaccine series and postvaccination serologic testing; universal hepatitis B vaccination within 24 hours of birth, followed by completion of the vaccine series; and vaccination of children and adolescents aged <19 years who have not been vaccinated previously. ACIP recommends vaccination of adults at risk for HBV infection, including universal vaccination of adults in settings in which a high proportion have risk factors for HBV infection and vaccination of adults requesting protection from HBV without acknowledgment of a specific risk factor. These recommendations also provide CDC guidance for postexposure prophylaxis following occupational and other exposures. This report also briefly summarizes previously published American Association for the Study of Liver Diseasest guidelines for maternal antiviral therapy to reduce perinatal HBV transmission

Seroprevalence and susceptibility to hepatitis A in the European Union and European Economic Area: a systematic review

Most of the European Union (EU) and European Economic Area (EEA) is considered a region of very low hepatitis A virus (HAV) endemicity; however, geographical differences exist. We did a systematic review with the aim of describing seroprevalence and susceptibility in the general population or special groups in the EU and EEA. We searched databases and public health national institutes websites for HAV seroprevalence records published between Jan 1, 1975, and June 30, 2014, with no language restrictions. An updated search was done on Aug 10, 2016. We defined seroprevalence profiles (very low, low, and intermediate) as the proportion of the population with age-specific anti-HAV antibodies at age 15 and 30 years, and susceptibility profiles (low, moderate, high, and very high) as the proportion of susceptible individuals at age 30 and 50 years. We included 228 studies from 28 of 31 EU and EEA countries. For the period 2000-14, 24 countries had a very low seroprevalence profile, compared with five in 1975-89. The susceptibility among adults ranged between low and very high and had a geographical gradient, with three countries in the low susceptibility category. Since 1975, EU and EEA countries have shown decreasing seropositivity; however, considerable regional variability exists. The main limitations of this study are that the studies retrieved for analysis might not be representative of all EU and EEA publications about HAV and might have poor national representativeness. A large proportion of EU and EEA residents are now susceptible to HAV infection. Our Review supports the need to reconsider specific prevention and control measures, to further decrease HAV circulation while providing protection against the infection in the EU and EEA, and could be used to inform susceptible travellers visiting EU and EEA countries with different HAV endemicity levels.

Hepatitis A vaccination for post-exposure prophylaxis in persons aged 40 years and older.

The Centers for Disease Control and Prevention collaborated with state public health officials and the Food and Drug Administration to control a multistate outbreak of hepatitis A virus (HAV) in the United States during May–July 2013 (http://www.cdc.gov/hepatitis/Outbreaks/2013/A1b-03-31/index.html). Pomegranate seeds from Turkey were determined to be the most likely vehicle. As of August 1, 158 outbreak related cases were confirmed. The age range of cases was 1–84 years. Older adults are more likely to have severe disease. Importantly, 108 (68% of cases) were 40 years of age and older. All hospitalizations, 69 (44% of cases), were in persons older than 18 years of age, and 72% of hospitalized cases were older than 40 years of age. This is the largest hepatitis A outbreak since 2003 when greater than 500 cases in Pennsylvania were associated with contaminated green onions [1]. Based on the results of a study comparing the efficacy of hepatitis A vaccine and immunoglobulin G (IG) in persons 2–40 years of age [2], the Advisory Committee on Immunization Practices recommends hepatitis A vaccine for post-exposure prophylaxis (PEP) of healthy persons aged 12 months–40 years [3]. Administration of vaccine or IG is recommended within two weeks of exposure since efficacy beyond two weeks is not known. For persons aged greater than 40 years, IG is preferred; vaccine can be used if IG cannot be obtained. During the recent multi-state hepatitis A outbreak, some states opted for hepatitis A vaccine instead of IG for adults aged greater than 40 years. Hepatitis A can be more severe in older adults, and vaccine response might be less robust. However, limited data exist on the immunogenicity and efficacy of hepatitis A vaccine among older adults. In a previous hepatitis A vaccine randomized clinical trial, published results included people 18 years of age or older, but were not delineated by age groups [4]. Seroconversion to anti-HAV positive, defined as ≥20 mIU anti-HAV, served as a surrogate of protection. Unpublished data from this study indicated that at 15 and 30 days, 74% (n = 125) and 90% (n = 128) of adults ages 40–49 years seroconverted (HAV-specific IgG) after a single dose of vaccine; 54% (n = 37) and 81% (n = 42) of adults ages 50–59 years seroconverted; and 30% (n = 10) and 50% (n = 10) of adults ages ≥60 years seroconverted. The geometric mean titers (expressed in mIU/ml) at 15 and 30 days were 26.09 (n = 125) and 87.97 (n = 121) for adults ages 40–49 years; 12.80 (n = 37) and 39.70 (n = 41) for adults ages 50–59 years; and 1.62 (n = 10) and 4.49 (n = 9) for adults ages ≥60 years, respectively. The sample sizes were small for age groups 50 and older, and the data included antibody titers from two methods of vaccine administration (needle and jet-injector) [4]. However, 15 day titers for adults 40–49 years of age suggest that hepatitis A vaccine is likely to provide rapid acquisition of protection. Among adults ages 50–59 years, data suggest substantial protection by 30 days post-vaccination. Additional U.S. studies are needed to determine optimal hepatitis A vaccine use for post-exposure prophylaxis among adults older than 40 years of age, but until such studies are available, the administration of IG to this age group is preferred [3].

Hepatitis C: Review of the Epidemiology, Clinical Care, and Continued Challenges in the Direct-Acting Antiviral Era

Purpose of ReviewThis review highlights key studies and recently published data, policies, and recommendations related to hepatitis C virus (HCV) epidemiology, transmission, and treatment.Recent FindingsHCV is a leading cause of liver-related deaths, cirrhosis, and hepatocellular carcinoma. Since 2011 and accelerating since 2013, new, safe, tolerable, and curative therapies have considerably altered clinical and public health frameworks related to the prevention, control, and clinical management of HCV. Nevertheless, there are several populations in the USA that are important to consider because of disparities in HCV prevalence and transmission risk. Adults born during 1945–1965 have an estimated anti-HCV antibody prevalence of ∼3%, which is six times higher than among other adults, are often unaware of their infections, and are at increased risk of having HCV-associated morbidity and mortality from decades of chronic infection. Since the early 2000s, increasing incidence of acute HCV infections among young, white, non-urban people who inject drugs has been reported. Despite promising therapeutic advances, significant challenges remain for reducing HCV-associated morbidity and mortality.SummaryThe high burden of HCV and significant health consequences associated with chronic infection make HCV a critical public health priority. Advances in HCV treatment have created new opportunities for reducing HCV-associated morbidity and mortality. These treatments are safe, well tolerated, and highly effective; however, benefits cannot be realized without a significant increase in the number of persons tested for HCV so that all chronically infected individuals can be aware of their diagnosis and linked to appropriate clinical care.