Abstract
Background:
Immigrants are the largest subgroup living with chronic hepatitis B (HBV) infection in the United States. It is not well understood how immigration and associated social and cultural factors impact adherence to HBV monitoring.
Methods:
We conducted a multicenter multilingual survey among foreign-born adults with chronic HBV between 7/2021–4/2023. Participants were surveyed regarding 1) immigration factors, 2) acculturation and language preferences 3) social determinants of health and 4) HBV-related clinical factors. The primary outcome was optimal adherence, defined as 100% of time with at least annual testing of HBV DNA, ALT, and ultrasound while under care. Logistic regression was used to examine survey factors associated with outcome.
Results:
274 foreign-born patients with HBV (median 57 years, 57% male) from 32 birth countries were included. 13% had immigrated within the past 10 years and 62% were US citizens. Nearly all (92%) reported seeing a specialist for HBV, with 72% currently on treatment. 44% of participants had optimal adherence to monitoring over a median of 6 years (2–7) under care. Factors associated with more optimal adherence on multivariate testing included non-English survey language (OR 2.32, 95% CI 1.15–4.66), non-US citizens (OR 2.05, 95% CI 1.01–4.15), and higher education (college vs high school or less: OR 2.39, 95% CI 1.09–5.24). Medicare insurance (vs private) was associated with less optimal adherence (OR 0.42, 95% CI 0.19–0.94).
Conclusion:
Adherence to long-term monitoring is suboptimal among a diverse cohort of immigrants with chronic HBV. More efforts to engage and retain immigrants in care are needed.
Keywords: immigrant health, social determinants of health, viral hepatitis, care cascade
Graphical Abstract
INTRODUCTION
Chronic hepatitis B virus (HBV) infection disproportionately affects foreign-born (FB) in the United States (US), particularly immigrants from Asia and sub-Saharan Africa, where seroprevalence rates may exceed 5% and perinatal/horizontal acquisition is dominant1. Estimated HBV seroprevalence among US FB is 3.9% in Asians, 1.9% in blacks, 0.6% in whites, and 0.2% in Hispanics, approximating nearly 550,000 total affected individuals2. Continued immigration has kept FB prevalence constant over the past two decades, whereas rates among US-born have declined2. Altogether, FB reflect the largest subgroup of Americans with HBV and yet have suboptimal awareness of infection3. Chronic HBV patients continue to have higher mortality compared to the general population despite highly effective therapies4. Delays in care may play a role for FB, with presentation at older ages and longer duration of disease resulting in more advanced disease and liver-related complications at diagnosis5.
Current studies on HBV care delivery are largely retrospective and administrative, leading to lack of granular and accurate data on country of birth, time of immigration, citizenship, and degree of acculturation6,7. These are important factors that may affect healthcare access and outcomes for foreign-born patients. There is a notable paucity in literature addressing the impact of both immigration-related and other social determinants of health (SDOH) on healthcare delivery for patients with HBV. The primary focus previously has been on awareness/screening, yet linkage to care after diagnosis and care retention are equally as important8,9. As chronic HBV is a lifelong diagnosis currently without cure, longitudinal follow-up and monitoring is essential to determine disease trajectory, treatment indications, and offer cancer surveillance. Limited access to language interpretation services, cultural stigma, and lack of health insurance have been identified as potential barriers in FB population, but it is unclear if such factors impact long-term care and outcomes10.
To address these knowledge gaps, this multicenter survey study aimed to characterize immigration-related factors and SDOH among a diverse cohort of FB adults with chronic HBV infection. Furthermore, we examined rates of completion of guideline-based HBV care metrics and the association between immigration and SDOH with long-term disease monitoring.
MATERIALS AND METHODS
The FOCUS-HBV Cohort and Study Setting
The Foreign-Born Care Cascade in US for Hepatitis B (FOCUS-HBV) cohort is a multi-center cross-sectional survey study of FB patients with chronic HBV. We recruited from primary and specialty clinics from July 2021 to April 2023 from two diverse immigrant populations: Los Angeles County (LAC; California) and the greater Washington DMV area (District of Columbia, Virginia, Maryland). These cities ranked 3rd and 20th in the world for largest absolute number of immigrants. Recruitment occurred at the following sites: (1) Keck Medical Center at the University of Southern California (Keck USC); (2) Los Angeles General Medical Center (LAG), (3) MedStar Georgetown healthcare systems (GT); and (4) National Institutes of Health (NIH). Keck USC and GT are both tertiary care facilities with large transplant programs while LAG is the largest safety net facility in LAC. GT provides additional ambulatory services to DMV area. NIH patient population is predominantly of low-income, often uninsured, immigrant residents. Institutional review board approval was obtained from the corresponding regulatory body for each participating site.
Recruitment and Survey Design
FB patients with HBV completed a survey that was linked to retrospective data on HBV management in the electronic medical record (EMR). Inclusion criteria included (1) self-reported birth outside of the US, (2) adult (age>18 years), (3) diagnosis of HBV with positive hepatitis B surface antigen (HBsAg) test, and (4) able to provide informed consent. Informed consent was obtained and survey was administered by paper or an electronic tablet directly into REDCap. Translated surveys were available in Spanish, Traditional/Simplified Chinese, and Vietnamese. If preferred language was not available or participant was illiterate, the survey was administered over the telephone with a certified translator or in-person with a language-concordant research coordinator if available. Participants received a gift card stipend.
The 43-item survey was pilot-tested on 10 participants. The final version (see Supplemental) had four major components: (1) immigration factors, (2) acculturation, (3) self-reported healthcare utilization and history of HBV management, and (3) demographics and social determinants of health. For immigration, we captured birthplace, duration in the US, citizenship, and primary language. We measured acculturation using the Vancouver Index of Acculturation (VIA)11. VIA is a validated bi-dimensional instrument that assesses orientations of an individual towards heritage (i.e., native country) and mainstream (i.e., host country) cultural domains using their values, social relationships and preferred cultural norms. VIA has been shown to have good reliability and validity among different cultural groups12. The instrument asks participants on a Likert scale how strongly they agree or disagree with 20 statements, with one item referring to the heritage culture and a mirror item referring to the mainstream culture. High scores towards mainstream indicate greater acculturation, while high scores towards heritage indicate lower acculturation. For HBV, the survey assessed disease awareness, access to subspecialty care, treatment history, frequency of monitoring, and any liver-related complications. Lastly, participants answered demographic information and SDOH including highest education, employment, annual household income, and insurance.
Data Collection and Outcome Ascertainment
We collected clinical, laboratory, and outcomes data on survey participants from EMR, including provider type, family history of hepatocellular carcinoma (HCC), treatment history, and diagnosis of cirrhosis and/or HCC. Both current (within the past year) and historical monitoring of alanine aminotransferase (ALT), HBV DNA, imaging and alpha-fetoprotein were abstracted.
Adherence to monitoring was defined by at least annual testing of HBV DNA, ALT, and ultrasound (or other imaging) for HCC surveillance. Ultrasound was included if participant met AASLD guideline criteria of Asian or African male over the age of 40, Asian female over the age of 50, and/or history of cirrhosis13. Optimal adherence to monitoring was defined as 100% (number of years with at least annual testing divided by the total number of years under care) obtained among those who were not surveyed at their initial visit for chronic HBV.
Statistical Analysis
Descriptive statistics were used to describe survey and clinical characteristics of the FOCUS-HBV cohort overall. Comparison testing of characteristics between those with and without optimal adherence were performed using Pearson’s Chi-square, Wilcoxon rank-sum testing and t-test when appropriate. Logistic regression models were used to examine the association between immigration, acculturation, social determinants and clinical factors with primary outcome. Univariate predictors of outcome significant at p<0.10 were included in a multivariable logistic regression model with multiple imputation performed for missingness. Both recent immigration (less than 10 years in US) and citizenship status met criteria for inclusion in the multivariable model but the two variables had high negative correlation; we chose to retain citizenship in the final model due to lower Akaike information criterion suggesting better model fit. Collinearity was checked with variance inflation factor testing. Multiple imputation using the multivariate normal distribution method was employed for variables with missingness (see Supplemental Methods for details)14. Statistical significance was set at an alpha of 0.05; analyses were performed using STATA v18 (College Station, TX).
RESULTS
Survey response rate ranged between 54–69%. A total of 274 FB chronic HBV were enrolled with 33.9% from LAG, 26.6% from Keck USC, 28.5% from GT, and 11.0% from NIH. Median cohort age was 57 years (IQR 48–75) and the majority (56.7%) were men (Table 1). 85.8% self-reported as Asian, 5.8% Hispanic, 2.6% Black, 2.6% White, 2.9% Other, and 0.4% Native Hawaiian/Pacific Islander. Nearly half of the cohort (48.9%) had some or full college degree. 54.5% were employed, followed by 18.6% retired. The median household number was 3 persons (IQR 2–4), and median household income was split evenly with 15.7% reporting less than $25K, 22.6% between $25–100K and 25.2% over $100K, with 36.5% choosing not to report their income. The highest proportion had private insurance (39.8%), followed by Medicare (24.5%), Medicaid (19.7%), and other insurance (13.9%).
Table 1.
Survey results of FOCUS-HBV participants (n=274)
| Demographics and Social Determinants of Health | |
|---|---|
|
| |
| Age, years | 57 (48–65) |
| Female sex | 119 (43.3%) |
| Married or domestic partnership | 181 (66.1%) |
| Race/Ethnicity | |
| Hispanic | 16 (5.8%) |
| Asian | 235 (85.8%) |
| Other | 15 (5.5%) |
| Missing/Prefer not to answer | 8 (2.9%) |
| Education | |
| High school or less | 66 (23.0%) |
| Some or completed college | 134 (48.9%) |
| Graduate degree | 58 (21.2%) |
| Prefer not to answer/missing | 19 (6.9%) |
| Employment status | |
| Employed | 149 (54.4%) |
| Retired | 51 (18.6%) |
| Unemployed | 26 (9.5%) |
| Homemaker | 11 (4.0%) |
| Other | 11 (4.0%) |
| Disabled | 6 (2.2%) |
| Prefer not to answer/missing | 20 (7.3%) |
| Number of people in household | 3 (2–4) |
| Annual Household Income | |
| Less than $25,000 | 43 (15.7%) |
| $25,000-$100,000 | 62 (22.6%) |
| More than $100,000 | 69 (25.2%) |
| Prefer not to answer/missing | 100 (36.5%) |
| Insurance | |
| Private | 109 (39.8%) |
| Medicare | 67 (24.5%) |
| Medicaid | 54 (19.7%) |
| Other | 38 (13.9%) |
| Prefer not to answer/missing | 6 (2.2%) |
| Immigration and Acculturation | |
|
| |
| Duration in US, years | 30 (17–41) |
| Recent immigrant (less than 10 years in US) | 36 (13.1%) |
| Citizenship status | |
| Citizen | 170 (62.0%) |
| Permanent resident | 50 (18.3%) |
| Temporary resident | 17 (6.2%) |
| None of the above | 11 (4.0%) |
| Prefer not to answer/missing | 26 (9.5%) |
| Frequency of home country visits | |
| Within last 5 years | 106 (38.7%) |
| More than 5 years ago | 77 (28.1%) |
| Never returned | 67 (25.5%) |
| Prefer not to answer/missing | 24 (8.8%) |
| Preferred Language | |
| Only or more native | 161 (58.8%) |
| Equal native or English | 55 (20.1%) |
| More or only English | 55 (20.1%) |
| Prefer not to answer/missing | 3 (1.1%) |
| Non-English survey | 66 (24.1%) |
| Acculturation (mean) | |
| Heritage score | 6.7 (±1.7) |
| Mainstream score | 6.3 (±1.7) |
Continuous data presented as median (interquartile range) or mean (±standard deviation). Categorical data presented as number and proportions.
Thirty-two unique birth countries were represented in the cohort (Figure 1). By country, 31.1% were from China or Hong Kong, 16.1% from Vietnam, 9.9% from South Korea, 8.0% from Philippines, 6.9% from Taiwan, 4.7% from Thailand, 4.4% from Mexico, and 3.3% from Cambodia. Remaining countries had <3% representation.
Figure 1.
Diversity of FOCUS-HBV participants
Created with mapchart.net.
The median duration of living in the US was 30 years (IQR 17–41), with only 13.1% having immigrated to the US within the past 10 years. 62% of the cohort had US citizenship, while 18.3% were permanent residents and 6.2% were temporary residents. Thirteen percent had immigrated to the US from a non-birth country. Majority (58.8%) preferred speaking their native language. Most completed their survey in English, though of the 24.1% who did not, 69.7% completed in Chinese, 16.7% in Vietnamese, and 13.6% in Spanish.
Mean acculturation scores were compared across other participant characteristics (Supplemental Table 1). Participants who preferred speaking their native language had higher heritage (6.89 ±1.61 vs 6.48 ±1.58, p=0.04) and lower mainstream scores (6.11 ±1.71 vs 6.64 ±1.42, p=0.01) than patients who reported predominantly English. Female participants had higher scores than males on the heritage subscale (6.94 ±1.66 vs 6.53 ±1.61, p=0.04), but not the mainstream subscale. Non-English survey participants had lower mainstream scores (5.73 ±1.90 vs 6.46 ±1.54, p=0.002).
The majority of participants (>90%) were aware of their HBV diagnosis and had linkage to care (Figure 2). 65.3% were diagnosed in the US compared to 28.5% in their birth country at a median age of diagnosis of 34 years (IQR 23–49). Among those diagnosed in the US, median years from immigration to diagnosis was 13 (IQR 7–23). Of those linked to specialty care, 80.2% identified their provider as a hepatologist, 26.9% gastroenterologist, 7.0% infectious disease, and 2.9% other. 71.5% were on treatment. 14.2% and 9.9% reported a diagnosis of cirrhosis and HCC, respectively.
Figure 2.
Clinical characteristics of FOCUS-HBV participants
Adherence to monitoring of labs and HCC surveillance could be ascertained in 239 (87.2%) participants who were not surveyed on their first visit for a diagnosis of HBV. The median number of years under care was 6 years (IQR 3–8). In the year prior to study enrollment, 91.2% had a HBV DNA checked, 96.4% had an ALT checked, and 80.7% had an ultrasound. 104 (43.5%) participants had optimal adherence to monitoring (100% of time under care with adherence). Among those with suboptimal monitoring (<100%), the median % of time under care with adherence was 67.0% (IQR 50–86%). Most (57.0%) were missing both labs and ultrasound, 27.4% were missing ultrasound only, and 15.6% were missing labs only. There was no correlation between % adherence and years under care (r=0.03).
Those with optimal (vs suboptimal) adherence were more likely to choose a non-English survey (30.8% vs 21.5%), have a higher household income (>$100K: 28.8% vs 21.5%), and have private insurance (47.1% vs 34.1%), though no comparison reached statistical significance (Table 2). Acculturation scores were higher for heritage than mainstream subscales for both groups. Clinical characteristics were similar, though the suboptimal adherence group was slightly more likely to report having a blood test for HBV every 6 months (51.9% vs 47.1%, p=0.02), but less likely to report an ultrasound every 6 months (72.2% vs 82.5%, p=0.28).
Table 2.
FOCUS-HBV cohort characteristics stratified by adherence (n=239)
| Suboptimal adherence N=135 | Optimal adherence N=104 | p-value | |
|---|---|---|---|
|
| |||
| Age, years | 58.0 (50.0–65.0) | 57.0 (45.0–66.0) | 0.31 |
| Female sex | 64 (47.4%) | 39 (37.9%) | 0.19 |
| Survey language | |||
| English | 106 (78.5%) | 72 (69.2%) | 0.10 |
| Non-English | 29 (21.5%) | 32 (30.8%) | |
| Race/ethnicity | |||
| Asian | 122 (90.4%) | 83 (79.8%) | 0.14 |
| Hispanic | 5 (3.7%) | 9 (8.7%) | |
| Other | 5 (3.7%) | 7 (6.7%) | |
| Missing/Prefer not to answer | 3 (2.2%) | 5 (4.8%) | |
| Region of origin | |||
| East Asian | 66 (51.6%) | 49 (48.5%) | 0.75 |
| Southeast Asian | 45 (35.2%) | 35 (34.7%) | |
| Other | 17 (13.3%) | 17 (16.8%) | |
| Years in US | |||
| Less than 10 | 10 (7.6%) | 15 (15.2%) | 0.07 |
| 10 or more | 122 (92.4%) | 84 (84.8%) | |
| Citizenship Status | |||
| Citizen | 93 (68.9%) | 61 (58.7%) | 0.25 |
| Non-citizen | 30 (22.2%) | 32 (30.8%) | |
| Prefer not to answer/missing | 12 (8.9%) | 11 (10.6%) | |
| Frequency of home country visits | |||
| Within last 5 years | 57 (42.2%) | 38 (36.5%) | 0.80 |
| More than 5 years ago | 38 (28.1%) | 30 (28.8%) | |
| Never returned | 29 (21.5%) | 27 (26.0%) | |
| Prefer not to answer/missing | 11 (8.1%) | 9 (8.7%) | |
| Preferred Language | |||
| Only or more native | 79 (58.5%) | 62 (59.6%) | 0.29 |
| Equal native or English | 23 (17.0%) | 24 (23.1%) | |
| More or only English | 32 (23.7%) | 16 (15.4%) | |
| Prefer not to answer/missing | 1 (0.7%) | 2 (1.9%) | |
| Acculturation (mean) | |||
| Heritage score | 6.9 (5.4–8.0) | 6.8 (5.4–7.9) | 0.70 |
| Mainstream score | 6.2 (5.3–7.4) | 6.2 (5.0–7.5) | 0.44 |
| Marital Status | |||
| Married or Domestic Partnership | 89 (65.9%) | 67 (64.4%) | 0.97 |
| Single, Divorced, Separated, Widower | 41 (30.4%) | 33 (31.7%) | |
| Prefer not to answer/missing | 5 (3.7%) | 4 (3.8%) | |
| Education | |||
| High school or less | 41 (30.4%) | 20 (19.2%) | 0.20 |
| Some or completed college | 58 (43.0%) | 56 (53.8%) | |
| Graduate degree | 26 (19.3%) | 22 (21.2%) | |
| Prefer not to answer/missing | 10 (7.4%) | 6 (5.8%) | |
| Employment status | |||
| Employed | 73 (54.1%) | 59 (56.7%) | 0.91 |
| Not employed | 53 (39.3%) | 39 (37.5%) | |
| Prefer not to answer/missing | 9 (6.7%) | 6 (5.8%) | |
| Number of people in household | 3.0 (2.0–4.0) | 2.0 (2.0–4.0) | 0.65 |
| Annual Household Income | |||
| Less than $25,000 | 26 (19.3%) | 16 (15.4%) | 0.08 |
| $25,000-$100,000 | 25 (18.5%) | 29 (27.9%) | |
| More than $100,000 | 29 (21.5%) | 30 (28.8%) | |
| Prefer not to answer/missing | 55 (40.7%) | 29 (27.9%) | |
| Insurance | 0.18 | ||
| Private | 46 (34.1%) | 49 (47.1%) | |
| Medicare | 40 (29.6%) | 19 (18.3%) | |
| Medicaid | 27 (20.0%) | 23 (22.1%) | |
| Other | 19 (14.1%) | 11 (10.6%) | |
| Prefer not to answer/missing | 3 (2.2%) | 2 (1.9%) | |
| HBV treatment | 0.16 | ||
| Currently on treatment | 97 (72.9%) | 85 (83.3%) | |
| Previously treated | 11 (8.3%) | 6 (5.9%) | |
| Never treated | 25 (18.8%) | 11 (10.8%) | |
| HBV provider type | |||
| Hepatologist | 97 (76.4%) | 79 (78.2%) | 0.74 |
| Gastroenterologist | 32 (25.2%) | 26 (25.7%) | 0.93 |
| Infectious disease | 7 (5.5%) | 7 (6.9%) | 0.66 |
| Primary care or other | 2 (1.6%) | 4 (4.0%) | 0.26 |
| Clinic visit for HBV in past 6 months | 120 (88.9%) | 91 (88.3%) | 0.99 |
| Blood test for HBV every 6 months | 69 (51.9%) | 48 (47.1%) | 0.02 |
| Ultrasound every 6 months | 96 (72.2%) | 85 (82.5%) | 0.28 |
| Cirrhosis | 15 (11.1%) | 18 (17.3%) | 0.17 |
| Hepatocellular carcinoma | 8 (5.9%) | 13 (12.5%) | 0.08 |
Continuous data presented as median (interquartile range) or mean (±standard deviation). Categorical data presented as number and proportions.
We examined the association between survey responses and adherence to monitoring (univariate in Supplemental Table 2; final model in Table 3). In our multivariable model, participants who completed the survey in a language other than English (OR 2.32, 95% CI 1.15–4.66) and those who were not US citizens (OR 2.05, 95% CI 1.01–4.15) had more optimal adherence. Compared to those with high school education or less, those who had some or completed college (OR 2.39, 95% CI 1.09–5.24) and those with a graduate degree (OR 2.15, 95% CI 0.83–5.56) had more optimal adherence, though the latter was not statistically significant. Lastly, less optimal adherence was observed among those with Medicare compared to private insurance (OR 0.42, 95% CI 0.19–0.94). There was no statistical difference in adherence by study site.
Table 3.
Multivariate model for optimal adherence to HBV monitoring
| Variable | OR | 95% CI | p-value |
|---|---|---|---|
| Survey language | |||
| English | ref | -- | -- |
| Non-English | 2.32 | 1.15–4.66 | 0.02 |
| Immigration status | |||
| Citizen | ref | -- | -- |
| Non-citizen | 2.05 | 1.01–4.15 | 0.05 |
| Age, per year ↑ | 1.00 | 0.97–1.02 | 0.80 |
| Education | |||
| High school or less | ref | -- | -- |
| Some or completed college | 2.39 | 1.09–5.24 | 0.03 |
| Graduate degree | 2.15 | 0.83–5.56 | 0.11 |
| Insurance | |||
| Private | ref | ||
| Medicare | 0.42 | 0.19–0.94 | 0.04 |
| Medicaid | 0.74 | 0.33–1.67 | 0.48 |
| Other | 0.50 | 0.20–1.28 | 0.15 |
| Current HBV treatment | |||
| No | ref | ||
| Yes | 1.84 | 0.93–3.66 | 0.08 |
DISCUSSION
The FOCUS-HBV cohort captured the ethnic diversity of chronic HBV immigrants living in the US. Although 84% of patients immigrated from Asia, 14 distinct Asian countries were represented. In addition, there was broad socioeconomic diversity, with representation from all strata of education, income, and access to healthcare. Despite these differences, self-reported awareness, linkage to care, treatment uptake, and routine visits and monitoring for chronic HBV was high. However, less than half had optimal (100%) adherence to long-term monitoring, defined as annual monitoring of liver panel, HBV DNA, and HCC surveillance (if eligible). The frequency of monitoring we required is the higher end of the 6–12 month interval recommended by AASLD guidelines13. This suggests efforts to retain and continually engage patients in care for this dynamic disease condition are still needed.
Other studies have shown suboptimal rates of HBV treatment and monitoring after linkage to care6,15,16, including one that estimated treatment uptake of ~56% in specialty settings16. A second examined “care retention” defined as at least two additional visits for HBV after an initial visit, and estimated 70%6. A community-based cohort in Sacramento showed second visit attendance of 43% and treatment initiation at 16%15. Treatment uptake and monitoring in the year prior to survey were both high in our cohort, though not surprising as most patients were surveyed at a subspecialty clinic visit. However, long-term 100% adherence was only 44% and efforts to augment adherence to testing and HCC surveillance even in specialty care settings are still needed.
Non-US citizens and participants who completed the survey in non-English language had higher rates of optimal monitoring. Similarly, recent immigrants (within the past 10 years) also had proportionally better adherence to monitoring. While our initial hypothesis was lower compliance among recent immigrants due to the complexities of navigating a new healthcare system and language barriers, the alternative finding is in line with health advantages observed among recent immigrants, a paradox termed the “healthy immigrant effect”17. There is a self-selection of immigrants who are more physically fit or have healthier behavioral patterns, including heightened engagement towards their healthcare. As immigrants reside in the US for longer, these behaviors may change18. The other potential explanation is shifting socioeconomic backgrounds of immigrant waves; recent immigrants from Asia tend to be more educated, wealthier, and have more resources to healthcare access19. However, our data was mixed with both recent immigrants and non-citizens reporting lower income, but more recent citizens with a graduate degree. Interestingly, survey language but not preferred language was associated with primary outcome. Availability of preferred language, presence of English speaking caretaker who could assist, and literacy can all affect choice of survey language. Given that the non-English survey participants showed the lowest mainstream VIA scores, survey language may also be a proxy for stronger cultural mores and the healthy immigrant effect.
We found lower long-term optimal adherence among less educated and Medicare participants, highlighting education and insurance as important SDOH targets. A recent systematic review demonstrated that SDOH-focused interventions were largely effective in addressing HBV-relevant health outcomes; though heterogeneous in population and intervention structure20. Only one intervention targeted retention in care: this one-time in-person language-concordant patient educational intervention performed at a safety-net clinic successfully increased clinic follow-up, laboratory monitoring and uptake of treatment21. This simple culturally tailored patient-facing educational intervention appears feasible though validating in other community-based settings would add value. The importance of insurance coverage and access to high-quality HBV care for immigrants also cannot be understated, as testing and treatment-related costs can be substantial22. National and state policies that enhance stability of insurance coverage irregardless of citizenship or socioeconomic status is a key aspect to improving HBV care for immigrants.
In this study, acculturation did not differ by adherence status. While multiple measures to evaluate acculturation exist, the VIA score was specifically selected due to its bidimensional nature (both heritage and mainstream can be independent to each other), internal reliability, external validity among different cultural groups, and brevity12,23. The association of acculturation with health outcomes in the literature has been quite inconsistent, though higher acculturation appears connected to poorer diet, less exercise, and more metabolic conditions24,25. Similar to our study, one study of the US Vietnamese population did not show acculturation to be associated with hepatitis B testing26. It is feasible that level of acculturation impacts lifestyle choices more than medical compliance. The lack of an association of adherence with acculturation in this cohort could reflect a true absence of a relationship, though it must be interpreted cautiously considering the ethnic, linguistic, and educational heterogeneity of those surveyed, and validation in other studies coupled with a closer examination through qualitative work is needed.
Those not diagnosed with CHB in their birth country had a prolonged time (13 years) from immigration to diagnosis. There is increasing data suggesting benefits of early treatment, including impeding oncogenesis27. Currently only tuberculous and syphilis testing are required during US entry health exams for immigrants, which represents a missed opportunity for early HBV diagnosis and linkage to care28. Paradoxically HBV vaccination is also required without initial HBV testing. A recent modelling study suggested that if we screened all new incoming US immigrants since 2022, we would increase total HBV diagnosed by over 300,000 patients29. The simple incorporation of an HBV blood test to immigration policies and entry exams would be a positive step.
Strengths of the FOCUS-HBV cohort include diversity in study sites, countries of origin, and socioeconomic backgrounds and our study is novel in linking immigration and acculturation factors to outcomes in healthcare compliance. However, there are a few key limitations. Recruitment occurred mostly in specialty care clinics in academic centers and results cannot be extrapolated to community-based or primary care settings. Our findings in a predominantly treated cohort likely skews towards better adherence to care. Patients were recruited during point of contact with healthcare system and thus self-selecting those who are more likely to be more compliant. Our study did not examine physician or system-level factors that could impact non-adherence, though differences in adherence by study site were not observed. We did not have adequate sample size for most non-Asian racial and ethnic groups and thereform unable to perform stratified analyses on race. To maintain parsimony in our survey, we did not assess other factors that might contribute to non-compliance such as health literacy, medical mistrust, stigma and discrimination, but these are important dimensions to consider in future studies. Though response rates were reasonable across all sites (lowest from the safety net clinic), non-response bias is always a possibility: we expect that responders would be biased towards better adherence. Lastly, the time period of outcome assessment overlapped with the COVID-19 pandemic, which could have interrupted care, though the high adherence to testing in the year prior to enrollment (>80% for labs and imaging) suggests marginal impact.
Engagement of immigrants, the largest subgroup with HBV in the US, is critical to meeting the World Health Organization absolute targets of an annual mortality rate from HBV infection of ≤4 per 100,000 persons, achieved through ≥90% diagnosed and ≥80% treated among eligible30. Diagnosing, linking, and retaining immigrants in care is a priority. Resources and programs to amplify adherence to monitoring for FB with HBV, with greater emphasis on established immigrants and less educated, are needed to optimize long-term outcomes.
Supplementary Material
Acknowledgements
We would like to thank all the research coordinators, providers and patients who contributed to the FOCUS-HBV study, which could not have been successful without their dedication and time.
Grant support:
This study was funded by Gilead Sciences Inc under the HBV CARE Program. KZ is supported by an NIH/NIMHD 5K23MD016963. This research was also supported in part by the Intramural Research Program of the NIH, The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).
Statement of Interests
Dr. Zhou and Dr. Hsu report institutional grant support from Gilead Sciences. NT discloses Institutional grant support from Gilead Sciences, GSK, Helio Health, Eiger Pharmaceuticals, and Durect Corp. The other authors have nothing to disclose.
Abbreviations:
- ALT:
alanine aminotransferase
- DC:
District of Columbia
- HBV:
Hepatitis B virus
- FB:
foreign-born
- HCC:
hepatocellular carcinoma
- LAC:
Los Angeles County
- SDOH:
social determinants of health
- US:
United States
- VIA:
Vancouver Index of Acculturation
Footnotes
Authorship Statement
Kali Zhou is the guarantor of the article and all authors approved the final version of the manuscript. The authors made the following contributions:
Concept and design: KZ, CH, NT
Acquisition, analysis, or interpretation of data: All authors.
Statistical analysis: CW, JD, KZ
Drafting of the manuscript: KZ, AL, CH
Critical revision of the manuscript for important intellectual content: All authors.
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