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Hepatitis B in the united states: a major health disparity affecting many foreign-born populations
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"We estimate a total of 1.32 million (95% confidence interval: 1.04-1.61) FB in the United States living with CHB in 2009; 58% migrated from Asia and 11% migrated from Africa, where hepatitis B is highly endemic. Approximately 7% migrated from Central America, a region with lower CHB rates, but many more emigrants to the United States. This analysis suggests that the number of FB persons living with CHB in the United States may be significantly greater than previously reported. Assuming 300,000-600,000 U.S.-born persons with CHB, the total prevalence of CHB in the United States may be as high as 2.2 million."

Hepatology accepted article July 2012

Editorial- John W. Ward, MD
Kathy K. Byrd, MD, MPH
Division of Viral Hepatitis
National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention
Centers for Disease Control and Prevention

In this issue of Hepatology, Kowdley et al. estimate 3.45% or 1.23-1.42 million of all foreign born persons in the United States, are living with hepatitis B, a rate more than 10-fold higher than the prevalence of the general US population (0.27%) (1). High rates of chronic hepatitis B among the U.S. foreign born reflect the large global burden of hepatitis B, 370 million persons around the world, and the migration to the United States from countries where prevalence of HBV is highest. More than 60% of new immigrants to the United States come from countries of increased hepatitis B endemicity (HBsAg prevalence of >2%). Most HBV-infected persons from these countries become infected at birth or during early childhood, when the risk for chronic HBV infection is greatest; 25% of persons with chronic HBV remain at risk of premature death from hepatitis B-related liver disease (e.g., hepatocellular carcinoma [HCC]) (2). In the United States, estimates of HBV prevalence are derived from the National Health and Nutrition Examination Survey (NHANES). However, this survey under-represents some populations with high hepatitis B virus (HBV) prevalence. For example, NHANES data do not identify respondents born in most Asian or any African countries or report racial/ethnic categories that indicate origins in these countries (3,4). These limitations in data collection mask hepatitis B-related health disparities contributing to the "silent epidemic" of viral hepatitis in the United States (5,6).

Seeking to fill the void in national health surveys, Kowdley et al. reviewed the medical literature published since 1980 to gather data for general population groups (e.g., pregnant women and military recruits) and then pooled these data to obtain the prevalence of chronic hepatitis B (HBsAg+) e by country. To estimate the number of persons residing in the United States by country of origin, prevalence data were brought together with data from the U.S. Census American Community Survey (ACS), a household survey which collects various data, including country of birth (http://www.census.gov/acs/www/) (7). The authors acknowledge limitations to their approach: chronic HBV seroprevalence data were scarce for many countries (one third of countries had conducted fewer than six surveys), often varied substantially from one survey within a country to another, and most (72%) data were obtained from surveys conducted prior to 2000.

Compared with the results of another recently published study, the findings of Kowdley et al. appear to be conservative. Bringing together CDC and WHO data to estimate HBV prevalence, Mitchell et al. estimated chronic hepatitis B prevalence among persons who immigrated during 1974-2008 to be 4.6% (8), higher than the 3.45% estimate derived by Kowdley et al. The Mitchell analysis revealed that the number of imported cases of hepatitis B increased over time (30,000 in 1988 to 62,000 in 2006).

Data from these indirect approaches suggest that NHANES underestimates the number of persons with hepatitis B in the United States. However, like the Kowdley study, NHANES shows an increased burden of hepatitis B among the foreign born, albeit lower (0.03%--3.28%, depending on race/ethnicity) than the indirect estimations. Surveys of HBV infection specifically targeting foreign-born populations are needed to refine estimates of disease burden. The Kowdley study is particularly valuable in estimating HBV prevalence by country of birth drawing attention to the diverse populations experiencing hepatitis B as a health disparity. In the United States, nearly 40% (~ 515,000 persons) of all foreign-born persons living with hepatitis B come from three countries: China, Vietnam, and the Philippines. However, a sizeable number of immigrants from other countries with increased burdens of HBV, including other countries of Asia (e.g., India, ~54,000 cases), the Caribbean (e.g., Dominican Republic,47,000 cases) and countries of Africa (e.g., Ethiopia, ~ 14,500 cases). The vast differences in culture and language represented by these populations require the development of culturally appropriate HBV prevention programs.

Hepatitis B is a vaccine-preventable disease, and immunization can virtually eliminate HBV transmission among vaccinated cohorts (5,9). Global and U.S. vaccination programs for newborn and infant hepatitis B immunization have resulted in increased hepatitis B vaccination coverage among children and adolescents. However, many countries have only recently implemented hepatitis B immunization; many foreign-born persons, who did not benefit from childhood vaccination programs at home, will be infected prior to arrival in the United States. Interventions are needed in this country to identify and reach these populations.

Since 2008, CDC has recommended HBsAg testing for all persons born in countries with HBsAg prevalence of ≥2%, referral of infected persons to care, and referral of close contacts for testing and vaccination (10). This strategy is cost-effective, and given prevalence estimates by Kowdley et al, capable of capturing 89% of foreign-born persons living with chronic hepatitis B. However, the IOM estimates up to 65% of persons living with hepatitis B infection are unaware they are infected (5).

To improve viral hepatitis prevention services, the U.S. Department of Health and Human Services (HHS) released a comprehensive plan outlining a set of actions for reducing health disparities among populations disproportionately affected by viral hepatitis, such as foreign-born persons (6). In accordance with this plan, several actions are being undertaken to improve availability of viral hepatitis data representative of foreign-born populations. For instance, CDC's REACH survey is targeting racial/ethnic minority communities to gather hepatitis B related health information (11). Public health surveillance for acute and chronic hepatitis B also

is providing valuable data; with support from CDC, health departments in San Francisco and New York City are conducting follow-up for hepatitis B case reports to collect country-of-birth and other data, which are used to evaluate recommendations for testing and direct persons to appropriate prevention and care services (12,13). Also being undertaken by CDC is an effort to use U.S. Census data and GIS programs to map populations for targeted interventions. Finally, NHANES is revising the 2011--2012 survey design to include an oversample of Asian populations (of whom two-thirds are foreign born) that should increase the precision of estimates for hepatitis B among persons born in Asian countries (14). Although these initiatives will help reveal the prevalence of hepatitis B among communities of foreign-born persons, additional public health capacity is needed to better characterize HBV prevalence among these diverse populations at risk for hepatitis B and to direct prevention resources where they are most needed. Community-based organizations (CBOs) have a unique ability to perform culturally appropriate outreach and, in partnership with health-care organizations and public health agencies, provide needed prevention services. In San Francisco, CBOs, healthcare organizations, and community leaders have united as part of the HEPB Free campaign to provide free or low cost hepatitis B screening and vaccination to Asian communities throughout the city (15). Unfortunately, examples of strong hepatitis-related CBO partnerships from other cities are few; a national search identified only 55 CBOs providing HBV prevention services and almost all function without federal support (16). Community health centers and health-care systems serving foreign-born populations also can play a vital role in ensuring that these persons are educated about their risk for HBV and provided with preventive services, including testing and linkage to care.

The study by Kowdley et al. provides convincing data that numerous and diverse foreign-born populations in the United States are at risk for chronic hepatitis B. These data, together with those from hepatitis B surveillance and community-based surveys, can help public health officials identify at-risk populations and direct prevention to communities in need of culturally appropriate services. HBV testing, followed by linkage to care and treatment, can prevent new cases of HBV infection among the foreign born and improve health outcomes for persons living with hepatitis B.


May 31, 2012

Prevalence of Chronic Hepatitis B May Exceed Two Million, Higher in U.S. than Previously Reported - press announcement from Hepatology

The prevalence of chronic hepatitis B virus (HBV) infection in the U.S. may be as high as 2.2 million cases according to a new study now available in Hepatology, a journal published by Wiley-Blackwell on behalf of the American Association for the Study of Liver Diseases. Findings suggest the higher prevalence of chronic HBV can be attributed to foreign-born persons who were infected in their country of origin prior to arrival in the U.S. Emigrants from Asia and Africa, where infection with hepatitis B is highly endemic, represent close to 70% of the 1.32 million foreign-born persons living with chronic HBV in the U.S. in 2009.

Chronic HBV is a major health burden that experts say affects up to 400 million individuals worldwide, with up to 25% at risk of premature mortality due to primary liver cancer and end-stage liver disease if the infection is left untreated. In the U.S., the Centers for Disease Control and Prevention (CDC) estimate that in 2006 there were 800,000 to 1.4 million persons living with chronic HBV. However, previous reports may underestimate the true burden of chronic hepatitis B as individuals in the U.S. who are institutionalized, homeless, and foreign-born "at risk" populations are underrepresented on national health surveys.

"There is a wide discrepancy in the current estimates of the chronic HBV burden in the U.S.," explains lead author Dr. Kris Kowdley, Director of the Liver Center of Excellence at Virginia Mason Medical Center in Seattle, Washington. "Understanding the ethnic and cultural populations affected by chronic hepatitis B will provide more accurate estimates and help to develop programs for prevention, earlier diagnosis, and access to care for those at greatest risk."

For the present study researchers systematically reviewed the world's medical literature for HBV seroprevalence rates from 1980 to 2010. The team identified 256 disease prevalence surveys for emigrants from 52 countries and 1,797 surveys for the general populations of 98 countries for use in the meta-analysis. Individuals with lower or higher risk of chronic HBV than the general population and groups not likely to emigrate were excluded. These surveys provided data for populations from the 102 countries of origin for migrants to the U.S. as determined in the U.S. Census 2009 American Community Survey.

Analysis determined between 1.04 million and 1.61 million (1.32 million estimate) foreign-born persons were living with chronic hepatitis B in the U.S. in 2009. Chronically infected emigrants were mainly from Asia, Africa, and Central America, accounting for 58%, 11% and 7% of the foreign burden of disease in the U.S., respectively. "Our analysis suggests the total prevalence of chronic HBV is significantly higher, exceeding two million cases or twice the number previously reported," said Dr. Kowdley.

Senior author, Dr. Carol Brosgart, a member of the faculty at the Division of Global Health, UCSF and Senior Advisor on Science and Policy to the Viral Hepatitis Action Coalition at the CDC Foundation added, "This study highlights an important health concern for the U.S. and the need for broader hepatitis B screening of foreign-born individuals. Given our ability to treat chronic HBV and to monitor for emergence of liver cancer when it is treatable, physicians should screen the foreign-born, their children and close contacts. If these individuals do not have chronic infection and are not immune, then they are good candidates for HBV immunization. Hepatitis B is a serious infection with the risk of long-term consequences of cirrhosis, end-stage liver disease, liver cancer and premature death. Today this is a disease that we can prevent and we can treat."

In a related editorial also published in Hepatology, Drs. John Ward, the Director of the Division of Viral Hepatitis (DVH) at the CDC and Kathy Byrd, a medical epidemiologist in the DVH, note, "The study by Kowdley and colleagues provides evidence that numerous and diverse foreign-born populations in the U.S. are at risk for chronic hepatitis B. Nearly 3.5% of all foreign-born persons in the U.S. are living with this disease-a rate more than 10-fold higher than the prevalence of the general U.S. population." The editorial authors further emphasize the need for culturally specific services along with expanded HBV testing and linkage to care and treatment to prevent new infections, liver disease and cancer.

Hepatitis sickens millions around the world and kills one million people each year according to the World Hepatitis Alliance. The World Hepatitis Alliance in collaboration with the World Health Organization (WHO) have designated July 28, 2012 as World Hepatitis Day to raise awareness of viral hepatitis.


Prevalence of chronic hepatitis B among foreign-born persons living in the United States by country of origin


Estimates of the prevalence of chronic hepatitis B (CHB) in the United States differ significantly, and the contribution of foreign-born (FB) persons has not been adequately described. The aim of this study was to estimate the number of FB persons in the United States living with CHB by their country of origin. We performed a systematic review for reports of HBsAg seroprevalence rates in 102 countries (covering PubMed from 1980 to July 2010). Data from 1,373 articles meeting inclusion criteria were extracted into country-specific databases. We identified 256 seroprevalence surveys in emigrants from 52 countries (including 689,078 persons) and 1,797 surveys in the general populations of 98 countries (including 17,861,035 persons). Surveys including individuals with lower or higher risk of CHB than the general population were excluded. Data were combined using meta-analytic methods to determine country-specific pooled CHB prevalence rates. Rates were multiplied by the number of FB living in the United States in 2009 by country of birth from the U.S. Census Bureau to yield the number of FB with CHB from each country. We estimate a total of 1.32 million (95% confidence interval: 1.04-1.61) FB in the United States living with CHB in 2009; 58% migrated from Asia and 11% migrated from Africa, where hepatitis B is highly endemic. Approximately 7% migrated from Central America, a region with lower CHB rates, but many more emigrants to the United States. This analysis suggests that the number of FB persons living with CHB in the United States may be significantly greater than previously reported. Assuming 300,000-600,000 U.S.-born persons with CHB, the total prevalence of CHB in the United States may be as high as 2.2 million. (Hepatology 2012)

Chronic hepatitis B (CHB) is a major global health problem, with an estimated 350-400 million persons affected worldwide.1, 2 The prevalence of CHB varies greatly among countries, with the highest rates in Asia, Africa, and the Pacific Islands.1 Approximately 15%-25% of persons with CHB are at risk for premature death from CHB-related complications, primarily hepatocellular carcinoma and end-stage liver disease.3, 4

The true burden of CHB in the United States is unknown, because screening for CHB is not part of routine care and CHB surveillance activities are underfunded, underdeveloped, and poorly integrated.3 Published estimates of the total number of persons living with CHB in the United States range from 550,000 to 2 million,5-8 of whom 40%-70% may be foreign-born (FB) persons.5 Approximately 2.8% of the refugees entering the United States from 2006 to 2008 who were tested through screening programs were hepatitis B surface antigen (HBsAg) positive9; even higher rates were reported in refugees arriving between 1979 and 1991.10 In contrast, only 0.1%-0.2% of U.S.-born persons are chronically infected with hepatitis B virus (HBV).5-8

The Institute of Medicine concluded that estimates of CHB prevalence rates based on National Health and Nutrition Examination Surveys (NHANES) are underestimates, because the persons at greatest risk for CHB in the United States (e.g., institutionalized, homeless, and FB) are underrepresented.3 In this study, we present an alternative approach to estimating the burden of CHB that uses U.S. Census data for the number of FB from 102 different countries of origin and estimates of the CHB rates in these persons derived from systematic review and meta-analysis of HBsAg seroprevalence reported in immigrants and in-country populations of these countries.

Better estimates of the true burden of CHB and the ethnic and cultural characteristics of the affected population will help develop programs for prevention, earlier diagnosis, and linkage to care. The extensive database of country-specific HBsAg survey data created for this study may also be a resource for additional studies of CHB epidemiology.


In this study, we used an approach to estimating the prevalence of CHB in the FB that avoided a major shortcoming of CHB studies based on sampling of FB persons living in the United States-namely, that these studies underrepresent FB persons and others at high risk for CHB.3, 22 Our approach focused on the FB, and we systematically reviewed, on a county-by-country basis, the majority of available data on HBsAg seroprevalence rates in emigrants and in-country populations of 102 countries from which FB in the United States originate. The results of this analysis suggest that the number of FB persons living with CHB in the United States is larger than previous estimates (Fig. 2).

A report based on data from NHANES for 1999-2006 estimated 730,000 (95% CI: 550,000-940,000) persons with CHB living in the United States, of whom 317,000 (95% CI: 202,000-479,000) were FB.6 This is almost certainly an underestimate, because NHANES underrepresents populations at high risk for HBV, such as Asian-Pacific Islanders and institutionalized, incarcerated, and homeless persons.3, 22 A second study estimated that 800,000-1.4 million persons in the United States were living with CHB in 2006, of whom 229,000-534,000 were U.S.-born and 375,000-975,000 were FB.5 These estimates are based on multiple data sources, including (1) NHANES, (2) estimates of the number and CHB prevalence of persons in institutions and group quarters, (3) country-specific CHB prevalence rates reported in the literature, and (4) estimates of the U.S. population by country of birth. Cohen et al., using census data and estimates of CHB rates by ethnicity, calculated a total CHB prevalence of 2 million persons, of whom 774,027 were FB Asians and Pacific Islanders.7 Because the FB population grew by less than 3% from 2006 to 2009,12 the difference between our estimate of 1.32 million FB with CHB and earlier estimates is explained by higher CHB rates derived from the meta-analyses. The RE meta-analyses based on all surveys for a given country combined yielded an average CHB prevalence rate among the FB in the United States of 3.45% (95% CI: 2.72-4.19). The average rates from the meta-analyses in which surveys and FB populations were stratified by decade are 4.45% (95% CI: 2.85-6.09), 3.40% (95% CI: 2.33-4.53), and 2.95% (95% CI: 2.13-3.82), for the decades "before 1990," "1990-1999," and "2000 and later," respectively. These rates are significantly higher than 0.89% (95% CI: 0.55-1.35) found for FB in NHANES 1999-20066 and 2.6% derived by Weinbaum et al.5 The rate from this meta-analysis is also higher than the prevalence of 0.59% found in NHANES 1999-2008 for white, black, or Hispanic FB persons, but similar to the prevalence of 3.28% for FB of other race or ethnicity.8

This estimate of 1.32 million FB with CHB includes undocumented persons. The U.S. Census Bureau assumes ACS data include undocumented persons, who represented approximately 30% of the FB in the United States in 2009.12, 13 Adding our estimate of 1.04-1.61 million FB persons with CHB to previous estimates of 229,000-534,000 noninstitutionalized U.S.-born persons with CHB and 74,000 institutionalized persons with CHB,5 the total prevalence of CHB in the United States may be as high as 2.2 million.

The RE meta-analyses suggest that approximately 52% (682,622; 95% CI: 572,845-792,352) of the FB persons with CHB migrated to the United States from countries classified as having high HBV endemicity (i.e., with CHB rates 8% or higher); another 37% (495,001; 95% CI: 375,867-614,369) migrated from countries with intermediate endemicity (i.e., CHB rates 2-7.9%); the remaining 11% (147,070; 95% CI: 95,576-202,194) migrated from countries where CHB rates are less than 2%.5 The contribution of persons from Central America to the FB population with CHB was larger than expected. However, because of the large number of FB in the United States from this region (i.e., 14.4 million), small differences in CHB rates result in large differences in the number with CHB. Few studies were found documenting HBsAg seroprevalence in Central America outside Mexico, and rates in blood donors were used for El Salvador, Honduras, Panama, and Belize. Additional seroprevalence data for these countries are needed.

These prevalence estimates have limitations and should be viewed as a systematic attempt to make the best use of available data. First, literature searches were limited to PubMed, and additional potentially relevant articles may have been found had we also searched EMBASE and CINAHL databases. In addition, potentially relevant surveys reported in languages other than English were omitted because not all non-English papers were acquired and translated.

Another concern is whether the country-specific CHB rates from the meta-analyses are representative of the FB who migrated to the United States and were living there in 2009. Because no seroprevalence data in emigrants were available for more than half the countries, we combined prevalence data from emigrants with data from populations still living in the countries of origin. Nationally representative surveys were included, but were available for only a few countries. Most in-country surveys were done in population subgroups at "average risk" for HBV infection (e.g., pregnant women, school children, clerical and factory workers, and military recruits). Biases introduced by using data from these subgroups likely vary from country to country and depend on factors such as dominant routes of HBV transmission, attendance rates at antenatal clinics and schools, whether military service is mandatory, and the particular array of surveys available for each country. We excluded surveys in persons at higher risk for HBV (e.g., sex workers, injection drug users, and homeless) because these persons are less representative of emigrants.

Comparison of RE pooled prevalence rates in emigrants with those in in-country populations did not reveal a systematic bias toward higher rates in either group, although this analysis had large uncertainty. It is likely that emigrants from some countries have lower CHB rates (e.g., because they have higher socioeconomic status and resources to emigrate) or higher rates (e.g., because they lived in refugee camps) than in-country populations. If only data from surveys in emigrants are used for the 52 countries for which data are available, the estimate of the number of FB living with CHB is still significantly higher than estimates from NHANES-based studies (Fig. 2).

Furthermore, for some countries, the pooled CHB prevalence rates from the meta-analyses are higher than rates reported in immigrants recently arriving in the United States.9 These studies, however, have small samples and may not be representative of FB persons arriving earlier. Supporting Table 10 compares pooled prevalence rates from the meta-analyses with data reported for refugees from 31 countries who were screened on arrival to the United States during two time periods (i.e., 1979-1991 and 2006-2008).9, 10 For most countries, rates from the meta-analyses are higher than rates reported for refugees arriving between 2006 and 2008; in contrast, rates from the meta-analyses are similar to rates reported for migrants arriving in 1979-1991 for most countries. Given that 40% of the FB living in the United States arrived before 1990, the earlier rates are probably more representative.12

Finally, data were not sufficient to assess other factors likely to contribute to the observed heterogeneity, such as differences by race, ethnicity, age, socioeconomics, or geographic location within the country of origin. The FB population living in the United States in 2009 included persons of different ages who migrated to the United States in different decades through different routes (e.g., as economic migrants, family reunification participants, adoptees, or refugees). Given the limitations of the available data, we opted to pool surveys from different dates, locations, and populations within the country, and the results must be viewed with this caveat in mind.

The finding that as many as 1.6 million FB in the United States may be living with CHB-nearly twice the number previously estimated-highlights the need for HBV screening in all FB persons. As many as 60%-70% of all persons with CHB in the United States are undiagnosed, and only approximately half of those diagnosed receive appropriate care.23 Numerous personal, cultural, economic, and environmental factors create barriers that may result in a high proportion of FB persons remaining unaware of their infection.23, 24 Since 2008, Centers for Disease Control and Prevention (CDC) guidelines have recommended routine serologic HBsAg screening for all FB persons from countries with HBsAg prevalence rates of 2% or higher, regardless of their vaccination history, and for unvaccinated U.S.-born children of FB parents from countries with high HBsAg endemicity.5 Routine screening of pregnant women is especially important, because maternal-neonatal transmission of HBV occurs in approximately 1,000 infants born to HBsAg-positive mothers in the United States each year.3

The number of FB persons in the United States increased from 19.8 million in 1990 to 38.4 million in 2009,12, 25 and between 1980 and 2009, more than 25 million FB persons became legal U.S. permanent residents.26 The number of FB living with CHB will continue to increase with ongoing immigration from countries with intermediate and high HBV endemicity. Primary care physicians and general internists have an opportunity to identify FB persons living with CHB in the United States via screening and follow-up to ensure they benefit from monitoring and treatment.


Search Results.

Flow of the systematic review is summarized by world region in Table 1. Results for individual countries are in Supporting Table 3. More than 17,500 articles were identified in PubMed searches; full text of 2,859 articles was assessed and data from 3,276 articles were entered into country-specific databases. In all, we found 1,373 articles reporting data meeting criteria for use in the meta-analyses. Many articles report data for more than one survey (e.g., pregnant women and military recruits) and these were entered separately. A total of 2,053 HBsAg seroprevalence surveys involving 18.6 million subjects were used in the meta-analyses (Table 2; Supporting Table 4). Of these, 256 were surveys of emigrants (involving 689,078 subjects from 52 countries); 1,797 were surveys done in the general populations still living in the country (involving 17,861,035 subjects in 98 countries). Approximately 34% of the surveys were conducted before 1990; approximately 38% were between 1990 and 1999, and 28% were in 2000 or later. Overall, approximately 32% of the survey population was male and 44% was female; sex was not reported for 24% of the total sample.

The results of this systematic review reveal the limited availability of HBsAg seroprevalence data around the globe. Although at least one usable survey was found for all countries except Guyana and Macedonia, five or fewer surveys meeting inclusion criteria were found for one third of the countries. The median number of surveys was nine per country (range, 0-376), and more than half of the total surveys were from 11 countries. For 50 countries, no surveys in emigrants were found. Availability of data differed substantially by region; 1,066 usable surveys were found for Asia, but only 58 for Central America.

Seroprevalence Rates by Country.

Surveys used in each country-specific meta-analysis are available at http://www.plan-a.com. HBsAg seroprevalence rates reported for most countries varied significantly from survey to survey. This variation was observed in surveys among emigrants and among in-country populations and was expected, given that surveys were carried out in different populations at different times. For example, rates in India ranged from 0.25% among pregnant women attending antenatal clinics in Calcutta during 2002-2004 to 11.4% among rural adults in Western Maharashta in 1992.17, 18 Rates in China ranged from 0.7% in a 1999 survey of young children in Taipei City to 39% in adult males in Massago, Taiwan, in 1996.19, 20

Pooled Seroprevalence Rates.

Country-specific RE pooled prevalence rates calculated by combining all available studies for each of the 102 countries are shown in Table 3(no weighting by study quality was included). Countries with the highest pooled HBsAg rates were Sudan (18.6%), Liberia (16.5%), Guinea (16.3%), Eritrea (15.5%), and Zimbabwe (13.9%). Weighted average CHB rates for the FB in the United States by world region of origin were calculated by using the country-specific RE pooled prevalence rates and the number of FB in the United States from each country in the region. FB persons who migrated from Africa had the highest average CHB rate (10.3%), followed by FB from Asia (7.27%), Oceania (4.78%), and the Caribbean (4.52%). The weighted average CHB prevalence rate from the RE meta-analyses for all FB living in the United States was 3.45% (95% confidence interval [CI]: 2.72-4.19).

CIs for the country-specific RE pooled CHB rates were broad (Table 3). Cochran's Q test and I2 statistic performed for each country-specific meta-analysis supported heterogeneity among the surveys for the majority of countries (Supporting Table 5). The I2 statistic was 55% or higher (indicating significant heterogeneity) for all except three meta-analyses.14, 15 Q tests were significant (P <0.10) in the meta-analyses for all countries except six, although this test lacks statistical power in meta-analyses involving small numbers of studies.14, 15 Using FE meta-analyses, the weighted average CHB pooled prevalence rate for all FB living in the United States was 2.52% (95% CI: 2.35-2.69). The FE pooled prevalence rate was slightly higher than the RE pooled prevalence rate (13.3%, compared to 12.3%) for China, the country contributing the largest number of FB with CHB. For most other countries, the FE rate was similar to or lower than the RE rate (data not shown).

Seroprevalence Rates in Emigrants and In-Country Populations.

To assess whether CHB rates in these groups would differ, we calculated separate RE pooled prevalence rates for emigrants and for in-country populations (Supporting Table 6). No data for emigrants were available for 50 countries and none for in-county populations were available for four countries. In 35 (71%) of the 49 countries for which comparison was possible, the pooled seroprevalence rate in emigrants did not differ from the rate in in-country populations (i.e., P > 0.05 in a Z test15); in 10 countries (i.e., Philippines, Thailand, India, Iran, Pakistan, Fiji, Somalia, Zimbabwe, Egypt, and Morocco), the pooled rate in the in-country populations was higher, and in four countries (i.e., Cambodia, Afghanistan, Ethiopia, and Senegal), the pooled rate in emigrants was higher.

Seroprevalence Rates by Survey Date.

To assess whether CHB seroprevalence had changed over time (e.g., as a result of immunization), subgroup analyses were conducted for surveys carried out during three different decades (i.e., before 1990, 1990-1999, and 2000 and later). RE pooled prevalence rates by decade of survey for each country are shown in Supporting Table 7. For 63 countries, the pooled rates in surveys done in 2000 and after were not significantly different from pooled rates in surveys done before 1990. For 36 countries, rates were lower in the later decade, and for three countries, rates were higher. Because of the small numbers of surveys in each subgroup (median, 2-3; mean, 6-8; range, 0-142), the pooled rates from these subgroup analyses must be interpreted with caution. I2 estimates indicated that substantial between-survey heterogeneity was still evident in most subgroups. Results of 15 of the 17 country-specific metaregression analyses agreed with the subgroup analyses.

HBsAg Rates by Sex.

Because higher HBsAg seroprevalence has been reported in males than in females for some populations,21 RE pooled prevalence rates were calculated for males and for females using sex-specific data, which were available for 60 countries (Supporting Table 8). Although rates were generally higher in males than in females, the data were not sufficient to use for prevalence calculations.

Study Quality.

Pooled prevalence rates were not appreciably affected by weighting for study quality in the nine countries we tested. Pooled prevalence rates weighted for study quality fell within the CIs of the pooled rates not weighted for quality (data not shown). We did not assess study quality for the remaining 93 countries and did not use quality weighting in the calculation of pooled prevalence rates used for estimating the number of FB living with CHB.

Number of FB With CHB Living in the United States.

Based on census data and pooled CHB prevalence rates from the RE meta-analyses using all surveys for a given country combined, we estimated that the number of FB in the United States living with CHB in 2009 (Table 3) was 1.32 million persons (95% CI: 1.04-1.61). Approximately 58% of the FB persons living with CHB migrated from Asia and approximately 11% migrated from Africa, where CHB is hyperendemic (Fig. 1). Approximately 7% of the FB with CHB in the United States were from Central America, a region with lower CHB rates, but many more emigrants to the United States. The five countries from which the largest numbers of FB with CHB originate were China (243,484; 12.3% of 1.99 million Chinese immigrants), Vietnam (143,440; 12.5% of 1.15 million Vietnamese immigrants), Philippines (127,612; 7.4% of 1.73 million Filipino immigrants), Dominican Republic (84,542; 10.7% of 791,593 Dominican immigrants), and Mexico (56,243; 0.49% of 11.5 million Mexican immigrants). Using the pooled CHB prevalence rates from the FE meta-analyses (all surveys combined), the number of FB in the United States living with CHB in 2009 was 967,281 persons (95% CI: 902,328-1.03 million).

FB With CHB from Subgroup Analyses.

RE pooled prevalence rates were calculated from surveys in emigrants for 52 countries for which data were available. Substituting these rates for the rates from all studies combined (for a given country) yielded an estimate of 1.23 million (95% CI: 784,175-1,833,960) FB in the United States with CHB (Fig. 2). Subgroup analysis also suggests that CHB rates in some countries declined over time. To account for this, an alternative calculation was done using the number of FB living in the United States in 2009 that arrived from each country in each of three decades (i.e., before 1990, 1990-1999, and 2000-2009), combined with the country-specific RE pooled CHB rate based on surveys done in the corresponding decade (Supporting Table 9). This calculation indicates the number of FB living with CHB in the United States in 2009 was 1.42 million (95% CI: 952,011-1,898,658). Because of the small number of surveys in the subgroups, both estimates based on subgroup analyses had greater uncertainty than the estimate based on all surveys combined and should be interpreted with caution.

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