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Prevalence [is higher] of chronic hepatitis B among foreign-born persons living in the United States by country of origin
 
 
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Hepatology Nov 22 2011 adv pub

Kris V. Kowdley1 , Chia C. Wang1 , Sue Welch2 , Henry Roberts3 , and Carol L. Brosgart4
Author Affiliations:
From the 1 Center for Liver Disease, Digestive Disease Institute, Virginia Mason Medical Center, Seattle,
WA; 2 Plan A, Inc., Mountain View, CA; 3 Centers for Disease Control and Prevention, Epidemiology and
Surveillance Branch, Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD,
and TB Prevention, Atlanta, GA; 4 UCSF School of Medicine and UC Berkeley Joint Medical Program,
Berkeley, CA

"This analysis suggests that the number of FB persons living with CHB in the U.S. 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 U.S. may be as high as 2.2 million......The finding that as many as 1.6 million FB in the U.S. 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% to 70% of all persons with CHB in the U.S. are undiagnosed, and only about 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 (2-24). Since 2008, 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 since maternal-neonatal transmission of HBV occurs in approximately 1000 infants born to HBsAg-positive mothers in the U.S. each year (3).....

.....The number of FB persons in the U.S. 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 U.S. via screening and follow-up to ensure they benefit from monitoring and treatment"

Abstract


Estimates of the prevalence of chronic hepatitis B (CHB) in the U.S. 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 U.S. living with CHB by their country of origin. We performed a systematic review for reports of HBsAg seroprevalence rates in 102 countries (covering PubMed 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 U.S. 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 million to 1.61 million) FB in the U.S. living with CHB in 2009; 58% migrated from Asia and 11% migrated from Africa, where hepatitis B is highly endemic. About 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 U.S. 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 U.S. may be as high as 2.2 million.

Chronic hepatitis B (CHB) is a major global health problem, with an estimated 350-400 million persons affected worldwide (1, 2). 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 U.S. is unknown because screening for CHB is not part of routine care and CHB surveillance activities are under-funded, under-developed, and poorly integrated (3). Published estimates of the total number of persons living with CHB in the U.S. range from 550,000 to 2 million (5-8), of whom 40%-70% may be foreign-born (FB) persons (5). About 2.8% of the refugees entering the U.S. from 2006 to 2008 who were tested through screening programs were HBsAg-positive (9); 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 U.S. (e.g., institutionalized, homeless, and foreign-born) are under-represented (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.

RESULTS

Search Results.
Flow of the systematic review is summarized by world region in Table 1. (Results for individual countries are in Appendix Table A3, Supporting Information.) More than 17,500 articles were identified in PubMed searches; full text of 2,859 articles was assessed; and data from 3,276 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 and Appendix Table A4, Supporting Information). 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; about 38%, between 1990 and 1999; and 28%, in 2000 or later. Overall, about 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 9 per country (range 0 to 376), and more than half 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 seen 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 is included.) Countries with the highest pooled HBsAg rates are 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 U.S. by world region of origin were calculated using the country-specific RE pooled prevalence rates and the number of FB in the U.S. from each country in the region. FB persons who migrated from Africa have 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 U.S. is 3.45% (95% CI; 2.72%-4.19%).

Confidence intervals for the country-specific RE pooled CHB rates are broad (Table 3). Cochran’s Q-test and I2 statistic performed for each country-specific meta-analysis support heterogeneity among the surveys for the majority of countries (Appendix Table A5, Supporting Information). The I2 statistic was 55% or higher (indicating significant heterogeneity) for all except 3 meta-analyses (14-15). Q-tests were significant (P <0.10) in the meta-analyses for all countries except 6, 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 U.S. is 2.52% (95% CI; 2.35%-2.69%). The FE pooled prevalence rate is 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 is 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 differ, we calculated separate RE pooled prevalence rates for emigrants and for in-country populations (Appendix Table A6, Supporting Information). No data for emigrants were available for 50 countries and none for in-county populations were available for 4 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-test (15)); 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 4 countries (i.e., Cambodia, Afghanistan, Ethiopia, and Senegal), the pooled rate in emigrants was higher.

Seroprevalence Rates by Survey Date. To assess if CHB seroprevalence has 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 Appendix Table A7, Supporting Information. For 63 countries, the pooled rates in surveys done in 2000 and after are not significantly different from pooled rates in surveys done before 1990. For 36 countries rates are lower in the later decade and for 3 countries rates are 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 substantial between-survey heterogeneity is still evident in most subgroups. Results of 15 of the 17 country-specific meta-regression analyses agree 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 (Appendix Table A8, Supporting Information). Although rates are generally higher in males than in females, the data are not sufficient to use for prevalence calculations.

Study Quality. Pooled prevalence rates were not appreciably affected by weighting for study quality in the 9 countries we tested. Pooled prevalence rates weighted for study quality fell within the confidence intervals 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 calculation of pooled prevalence rates used for estimating the number of FB living with CHB.

Number of FB with CHB Living in the U.S. Based on census data and pooled CHB prevalence rates from the RE meta-analyses using all surveys for a given country combined, we estimate that the number of FB in the U.S. living with CHB in 2009 (Table 3) was 1.32 million persons (95% CI; 1.04 million to 1.61 million). About 58% of the FB persons living with CHB migrated from Asia and about 11% migrated from Africa, where CHB is hyperendemic (Figure 1). About 7% of the FB with CHB in the U.S. are from Central America, a region with lower CHB rates but many more emigrants to the United States. The 5 countries from which the largest numbers of FB with CHB originate are 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 Mexicans immigrants). Using the pooled CHB prevalence rates from the FE meta-analyses (all surveys combined), the number of FB in the U.S. living with CHB in 2009 was 967,281 persons (95% CI; 902,328 to 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) yields an estimate of 1.23 million (95% CI; 784,175-1,833,960) FB in the U.S. with CHB (Figure 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 U.S. 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 (Appendix Table A9). This calculation indicates the number of FB living with CHB in the U.S. 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 have greater uncertainty than the estimate based on all surveys combined and should be interpreted with caution.

DISCUSSION

In this study, we used an approach to estimating the prevalence of CHB in the FB that avoids a major shortcoming of CHB studies based on sampling of FB persons living in the U.S.—namely that these studies under-represent 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 U.S. originate. The results of this analysis suggest that the number of FB persons living with CHB in the U.S. is larger than previous estimates (Figure 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 U.S., of whom 317,000 (95% CI; 202,000-479,000) were FB (6). This is almost certainly an underestimate because NHANES under-represents populations at high risk for HBV, such as Asian-Pacific Islanders and institutionalized, incarcerated, and homeless persons (3, 22). A second study estimated 800,000 to 1.4 million persons in the U.S. 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, using census data and estimates of CHB rates by ethnicity, calculated a total CHB prevalence of 2 million persons, of whom 774,027 are 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 U.S. 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 1999-2006 (6) and 2.6% derived by Cohen (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 Census Bureau assumes ACS data include undocumented persons, who represented about 30% of the FB in the U.S. in 2009 (12-13). Adding our estimate of 1.04 to 1.61 million FB persons with CHB to previous estimates of 229,000 to 534,000 non-institutionalized U.S.-born persons with CHB and 74,000 institutionalized persons with CHB (5), the total prevalence of CHB in the U.S. may be as high as 2.2 million. The RE meta-analyses suggest that about 52% (682,622 [95% CI; 572,845-792,352]) of the FB persons with CHB migrated to the U.S. 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% to 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 U.S. 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 U.S. 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, 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, 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 has 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 refugees 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 (Figure 2).

Further, for some countries, the pooled CHB prevalence rates from the meta-analyses are higher than rates reported in immigrants recently arriving in the U.S. (9). These studies, however, have small samples and may not be representative of FB persons arriving earlier. Appendix Table A10 compares pooled prevalence rates from the meta-analyses with data reported for refugees from 31 countries who were screened on arrival to the U.S. during two time periods (i.e., 1979 to 1991 and 2006 to 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 to 1991 for most countries. Given that 40% of the FB living in the U.S. 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 U.S. in 2009 includes persons of different ages who migrated to the U.S. 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 U.S. 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% to 70% of all persons with CHB in the U.S. are undiagnosed, and only about 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 (2-24). Since 2008, 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 since maternal-neonatal transmission of HBV occurs in approximately 1000 infants born to HBsAg-positive mothers in the U.S. each year (3).

The number of FB persons in the U.S. 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 U.S. via screening and follow-up to ensure they benefit from monitoring and treatment.

 
 
 
 
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