Why we should routinely screen Asian American adults for hepatitis B: A cross-sectional study of Asians in California
Hepatology Oct 2007
Steven Y. Lin 1 2 *, Ellen T. Chang 1 2 3 4, Samuel K. So 1 2 3
1School of Medicine, Stanford University, Stanford, CA
2Asian Liver Center, Stanford University, Stanford, CA
3Stanford Comprehensive Cancer Center, Stanford, CA
4Northern California Cancer Center, Fremont, CA
Chronic hepatitis B virus (HBV) infection is a serious liver disease that, if left undiagnosed or without appropriate medical management, is associated with a 25% chance of death from cirrhosis or liver cancer. To study the demographics and prevalence of chronic HBV infection and HBV vaccination in the Asian American population, we provided free HBV serological screening and administered a survey to 3163 Asian American adult volunteers in the San Francisco Bay Area between 2001 and 2006.
Of those screened, 8.9% were chronically infected with HBV. Notably, one-half to two-thirds (65.4%) of the chronically infected adults were unaware that they were infected. Of those who were not chronically infected, 44.8% lacked protective antibodies against HBV and were likely susceptible to future infection.
Men were twice as likely as women to be chronically infected (12.1% versus 6.4%).
Asian Americans born in East Asia, Southeast Asia, or the Pacific Islands were 19.4 times more likely to be chronically infected than those born in the United States.
Self-reporting of prior vaccination was unreliable to assess protection against HBV. Among the 12% who reported having been vaccinated, 5.2% were chronically infected, and 20.3% lacked protective antibodies.
Conclusion: Given the high prevalence of unrecognized chronic HBV infection in the Asian American population, we call for healthcare providers to routinely screen Asian adults for HBV, regardless of their vaccination status. Those who test positive should be provided with culturally appropriate information to prevent disease transmission and proper medical management to reduce their risk of liver disease.
Asian Americans represent a diverse community of many cultures and are the fastest growing racial group in the United States, constituting 4.3% of the total population (12.5 million people). Despite its rapidly growing population, the Asian American community is frequently overlooked by healthcare providers and public health officials, and this leaves Asian Americans to bear a 'disproportionate burden of disease and premature death'. The U.S. Census Bureau projects that the Asian American community will grow to 33.4 million people, or 8% of the total population, by 2050. If Asian Americans continue to suffer disproportionately from disease, this expected demographic change will certainly magnify the deteriorating public health conditions caused by racial health disparities in the United States.
One of the greatest health disparities between Asian Americans and their white counterparts is liver cancer. Asian Americans are 2.7 times more likely to develop and 2.4 times more likely to die from this malignant neoplasm. Among all racial groups in the United States, only Asian Americans experience cancer as the leading cause of death. Although liver cancer is relatively uncommon in the United States, it is the second most common cause of cancer mortality in Asian American men. Despite medical advances, the 5-year survival rate for liver cancer remains below 10%, thus emphasizing the need for preventive action in the high-risk Asian American community.
The disparity in liver cancer incidence and mortality is largely due to the disproportionately high prevalence of chronic hepatitis B virus (HBV) infection among Asian Americans. Over half of all liver cancer cases in the world are attributable to chronic, or persistent, HBV infection. Chronic HBV infection is endemic in East Asia, Southeast Asia, and the Pacific Islands, where the estimated prevalence ranges from 2.4%-16.0%. Because most (68.9%) Asian Americans living in the United States are foreign-born, chronic HBV infection represents a vital public health problem that must be addressed at the national level.
Most Asian Americans who are chronically infected with HBV acquire their infection at birth through mother-to-child transmission of HBV or during early childhood through horizontal transmission, which puts them at a 200-fold greater risk of developing liver disease than those who are not infected.[12-14] More than 90% of newly infected infants, 25%-50% of children infected between ages 1 and 5 years, and 6%-10% of acutely infected older children and adults develop chronic HBV infection. The remainder of the infected individuals generally develop antibody-mediated immunity to HBV. Without early detection and appropriate medical management, Asian Americans living with chronic HBV infection face a 25% risk of death from cirrhosis or liver cancer. Recent studies show that sustained suppression of HBV replication by an antiviral treatment can lower the risk of developing cirrhosis or liver cancer,[16-18] and regular liver cancer screening can lead to early detection and improved survival.
Because the majority of liver cancer cases in Asian Americans are caused by chronic HBV infection, any preventive action against liver cancer must include a comprehensive screening strategy to identify individuals who are chronically infected with HBV. Screening for HBV is especially critical because patients with chronic HBV infection are usually asymptomatic until advanced liver disease has already developed. To set the stage for future population-based interventions, we conducted a cross-sectional study in one of the largest Asian communities in the United States: the San Francisco Bay Area of California. In this report, we describe the prevalence of chronic HBV infection and hepatitis B vaccination among 3163 Asian American adults.
Patients and Methods
The Asian Liver Center at Stanford University is a nonprofit organization that spearheads educational outreach and advocacy efforts in the areas of hepatitis B and liver cancer prevention. At regularly spaced intervals between August 2001 and August 2006, we provided free HBV serological screening to 3279 Asian American adults (aged 18 years and above) in the San Francisco Bay Area. Participants learned about our free screening program through Chinese-language and English-language advertisements in newspapers and on radio and television. Participants were screened at community-based events, including street fairs, cultural festivals, and clinics held at community-based organizations and churches, in San Francisco, San Jose, Cupertino, Millbrae, Milpitas, and Sunnyvale (where Asians constitute over 30% of the population) and at a screening clinic at Stanford Hospital.
Serological Screening and Survey.
Blood samples were collected by venipuncture and tested at the Stanford Hospital Clinical Laboratories for both hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HBs), or for HBsAg alone, with test kits manufactured by Abbott Laboratories (Abbott Park, IL). Testing for anti-HBs was initiated approximately halfway through the study period and was performed on all individuals who participated afterward. Because most Asians are infected with HBV either during birth or early childhood, participants who tested positive for HBsAg were considered to have chronic HBV infection. HBsAg positivity was confirmed by the retesting of all samples that initially tested positive. Unprotected participants were defined as those who tested negative for both HBsAg and anti-HBs (defined as <10 mIU/mL). Of the 3279 individuals screened, 116 (3.5%) were excluded because of inconclusive blood tests (i.e., insufficient blood or equivocal values), and this left 3163 participants for this study. At the time of the screening, the participants completed a survey, written in both Chinese and English, assessing their age, sex, country of birth, personal or family history of hepatitis B diagnosis, and previous hepatitis B vaccination. All participants provided written informed consent. All study procedures were approved by the Stanford University Institutional Review Board.
Of the 3163 participants screened, the age range was 18-101 years (median = 52.9 years; 58.7% were 50 years or older). Among those with known demographic information, 60.3% (1833) were female, and 39.7% (1205) were male. The majority of the participants (93.4%) were born in East Asia, Southeast Asia, or the Pacific Islands (Table 1). In comparison, the general Asian adult population of the San Francisco Bay Area was younger (median age = 39 years; 30.0% were 50 years or older), more likely to be male (48.0%), and less likely to have been born in Asia or the Pacific Islands (82.0%).
Chi-square tests were used for crude comparisons of the prevalence of HBsAg positivity (that is, chronic HBV infection) or HBsAg and anti-HBs negativity (that is, susceptibility to HBV) across participant characteristics. Exact binomial 95% confidence intervals (CIs) were calculated for each prevalence. A multivariable logistic regression analysis was performed to estimate the relative risk (RR; approximated by the odds ratio), with 95% CI, of being chronically infected or being unprotected against HBV. Participants who tested positive for HBsAg or were not tested for anti-HBs were excluded from the analysis of associations with risk of HBV susceptibility.
All RR estimates were adjusted for the participants' 10-year age group, sex, and country of birth (China, East Asia other than China, Southeast Asia/Pacific Islands, United States, other, or unknown/missing). Likelihood ratio tests for heterogeneity were computed with a cross-product term between a covariate and age group (for example, <50 or 50 years) or sex. Missing values were included in statistical models as indicator variables. Some individuals had missing data because they were not required to complete the entire survey to be screened. However, they were included in the analysis to avoid the selective exclusion of certain participants. All statistical tests were 2-sided. The results were not appreciably affected when the analysis was restricted to participants born in China (32.1%) or those with complete demographic data (77.8%).
Of the 3163 Asian American adults screened, 8.9% were chronically infected with HBV (Table 1). Notably, up to 2 in 3 (65.4%, 185 of 283) of those chronically infected were unaware that they were infected; nearly half (44.9%, 127 of 283) stated that they had never been diagnosed with HBV infection, whereas the remainder did not know or did not report whether they had been previously diagnosed. When we excluded the 190 individuals who reported having been previously diagnosed with HBV infection, 6.2% (185 of 2973) of the previously undiagnosed adults were found to be chronically infected with HBV. Participants born in East Asia (including China), Southeast Asia, or the Pacific Islands (10.7% HBsAg-positive) were approximately 20 times more likely to be chronically infected than those born in the United States (0.7% HBsAg-positive; RR = 19.4, 95% CI: 2.6, 141.8). Only 1 of 153 participants born in the United States was chronically infected.
Of participants who were not chronically infected, 44.8% (682 of 1523) lacked protective antibodies against HBV and were therefore likely susceptible to future infection (Table 1). Only 12.0% (381 of 3163) of the participants reported having been vaccinated against HBV. Of these individuals, 20.3% (45 of 222) lacked protective antibodies, and 5.2% (20 of 381) were found to be chronically infected with HBV. Participants born in China (41.6% anti-HBs-negative), elsewhere in East Asia (41.2% anti-HBs-negative), and in Southeast Asia or the Pacific Islands (46.9% anti-HBs-negative) did not differ in the risk of being unprotected against HBV (Tables 1 and 2). After adjustments for age and sex, participants born in the United States (47.2% anti-HBs-negative) had a higher risk of being unprotected against HBV than those born in China (RR = 16.8, 95% CI: 3.8, 73.5).
Males (12.1% HBsAg-positive) were about twice as likely to be chronically infected with HBV as females (6.4% HBsAg-positive; RR = 2.1, 95% CI: 1.6, 2.7; Tables 1 and 2). However, males (43.6% anti-HBs-negative) and females (45.8% anti-HBs-negative) did not differ in the risk of being unprotected against HBV. Participants 30 years old or older (46.5% anti-HBs-negative) were about 3 times more likely to be unprotected against HBV than those under 30 years of age (32.0% anti-HBs-negative; RR = 2.9, 95% CI: 1.9, 4.2). The prevalence of chronic HBV infection did not increase with age.
Participants who reported a family history of hepatitis B were about twice as likely to be chronically infected with HBV (RR = 1.9, 95% CI: 1.4, 2.6) and about half as likely to be unprotected against HBV (RR = 0.6, 95% CI: 0.4, 1.0) as those who reported no such history (Table 2). These relationships did not vary significantly by age group or sex (data not shown).
Our study shows for the first time that one-half to as many as two-thirds of Asian Americans who are chronically infected with HBV are unaware that they are infected. This carries life-threatening implications for all Asian Americans because undetected and unmanaged chronic HBV infection is associated with a 25% risk of death from cirrhosis or liver cancer. People who are chronically infected with HBV are usually asymptomatic until advanced liver disease has already developed, and screening for HBV is the only way to identify these patients early for clinical management.
Our large cross-sectional study, showing HBV seroprevalence of 8.9% among Asian American adults and 10.7% for those born in East Asia, Southeast Asia, or the Pacific Islands, is consistent with previous reports.[26-28] We also found that 6.2% of individuals not previously diagnosed with HBV infection were chronically infected. Our results add to the growing body of knowledge showing that approximately 1 in 10 foreign-born Asian adults living in the United States is chronically infected with HBV. These striking findings emphasize the need for routine HBV screening among all Asian adults, especially those who are foreign-born or have foreign-born parents, and for improved public health efforts to educate physicians and medical students about the importance of HBV screening in Asian Americans. Screening is particularly important in certain high-risk subgroups, such as patients undergoing chemotherapy, because the reactivation of undiagnosed chronic HBV infection in these patients can lead to death from acute liver failure.
Our finding that the prevalence of chronic HBV infection was highest in adults 30-49 years old and lower among older adults is consistent with previous observations of Asian and Asian American populations. The higher prevalence in younger adults could be due to several causes, including deaths from liver cancer and other liver-related diseases among chronically infected adults over 50 years of age, a higher frequency of high-risk behaviors for HBV transmission (for example, multiple sex partners or injection drug use) in this age group, delayed spontaneous seroclearance of HBsAg among some chronically infected individuals, and possibly lower participation among older adults who already knew that they were chronically infected.
Even though chronic HBV infection is endemic in the countries in which 93.4% of our study participants were born, we found that only 12% of Asian American adults reported having been vaccinated against HBV. Furthermore, among participants who said they were vaccinated, about 1 of 5 (20.3%) lacked protective antibodies, and 1 of 20 (5.2%) was chronically infected. This suggests that HBV vaccine coverage among Asian American adults is likely overestimated when it is based on self-report alone. It is also possible that some individuals who tested positive for anti-HBs had been immunized but mistakenly reported that they had not received the vaccine, although we could not verify this. The substantial false-positive rate of self-reported vaccination status is most likely due to participants erroneously reporting that they have been vaccinated against HBV when they were, in fact, vaccinated against some other infection. It is also probable that some participants were vaccinated after having been chronically infected because no prevaccination HBV testing was performed. Waning immunity may also have resulted in the lack of anti-HBs among some who reported having been vaccinated. It is unlikely that participants were infected after having received the vaccine, which is highly effective. Previous studies in Seattle, WA, have found that, on average, only 1 of 3 Asian American adults reports having been vaccinated against HBV.[36-38] Our study suggests that the actual prevalence of vaccination may be even lower, thus stressing the need for expanded vaccination efforts at the national level to protect the high-risk Asian American community.
The strengths of our study include its large size, its setting in the densest population of Asians in the continental United States, and its broad representation of the Asian American community through the recruitment of participants from diverse locations. One limitation of our study is its nonrandom recruitment of participants, so our findings may not be generalizable to the entire Asian American population. In comparison with our study population, the general adult Asian population of the San Francisco Bay Area is younger and less likely to be female or foreign-born. The overrepresentation of women (who were less likely to be chronically infected) in our study may have led to an underestimation of the overall prevalence of chronic HBV infection, although such a bias would have been offset by the overrepresentation of foreign-born participants (who were more likely to be chronically infected). Likewise, any bias due to the higher proportion of older adults (who were more likely to be unprotected against HBV) in our study was balanced in part by the higher proportion of foreign-born individuals (who were less likely to be unprotected). Nevertheless, because risk factors for chronic HBV infection are not widely known in the Asian American population, it is unlikely that certain demographic subgroups were more likely to participate because they knew that they were at elevated risk.
On the other hand, the percentage of chronically infected individuals who were unaware of their infection status may have been overestimated if those who already knew they were infected were less likely to participate. However, unlike a recent study in New York City, ours did not offer free treatment to those found to be chronically infected with HBV and may thus have been less likely to attract individuals known to be chronically infected. This difference may partially account for the higher prevalence of chronic HBV infection (14.8%) reported in that study. Another limitation of our study was that participant recruitment was conducted in English and Chinese only, and this may have caused non-Chinese Asian subgroups to be underrepresented. However, because Chinese Americans constitute the largest proportion of Asian Americans in the United States, our study was designed to specifically target this subgroup.
Our study found that the prevalence of chronic HBV infection in United States-born Asian adults was significantly lower than that in those born in Asia. Interpretations of this finding are limited by the small sample size of this group and the lack of information about the parents' birthplace, which precludes us from estimating the prevalence of chronic HBV infection in the offspring of foreign-born parents. However, it is reasonable to suggest that routine screening for HBV should be extended to United States-born Asian adults whose parents were born in HBV-endemic areas in Asia because such individuals may not have received complete or timely perinatal HBV vaccination. Although the screening of all pregnant women for HBsAg has been recommended since 1988, and universal newborn vaccination against HBV has been recommended since 1991 by the Centers for Disease Control and Prevention and the Advisory Committee on Immunization Practices, a 2004 report showed that only about 50% of the expected births to HBsAg-positive women were identified for timely delivery of immunoprophylaxis, and the estimated birth dose vaccine coverage was only 46%. Using cost-effectiveness modeling, we have found that providing HBV screening to all Asian Americans is a highly cost-effective public health strategy (unpublished data, 2007).
Given the serious medical implications of this study, a strong public health response is needed. On December 8, 2006, the Centers for Disease Control and Prevention and Advisory Committee on Immunization Practices published a national recommendation that all 'foreign-born persons from regions with high endemicity of HBV infection be tested for HBV, regardless of vaccination status'. Given the high prevalence of chronic HBV infection among Asian adults, coupled with the high percentage of chronically infected Asian adults who are unaware of their infections, we believe that the screening of all Asian adults living in the United States, especially those who are foreign-born or have foreign-born parents, should become a routine practice for healthcare providers that serve this population.