Racial discrimination, knowledge, and health outcomes: The mediating role of hepatitis B‐related stigma among patients with chronic hepatitis B

It is well described in current literature that Hepatitis B virus (HBV) affects Asian Americans more than any other racial group in the United States and that there is a stigma attached to this condition. The effects of stigma can be lasting, penetrating physiologically and psychologically, yet few studies have focused on the consequences of this phenomenon. The purpose of this study was to examine the mediating role of stigma in the effect of racial discrimination and knowledge (of HBV sequelae) on health status of Korean Americans with chronic hepatitis B (CHB). Three hundred sixty‐five CHB patients were recruited and enrolled from two clinics in Philadelphia and Los Angeles. Depressive symptoms were measured using the Patient Health Question‐9 (PHQ‐9), physical health via self‐rated health survey and stigma via hepatitis B quality of life (HBQOL)—stigma survey. Perceived racial discrimination and knowledge of CHB sequelae were independent variables. The cohort had an average age of 60.1 years (range 19–84, SD 10.7), 56% were male and 94% were born in South Korea. Mediational analysis found that stigma was a significant mediator between both racial discrimination (indirect effect = .037, Bootstrap 95% CI = [.010–.064]) and sequelae knowledge (indirect effect = .097, Bootstrap 95% CI = [.018–.176]) and depressive symptoms. Stigma also had a direct effect on depressive symptoms (β = .136, p < .01) and self‐rated health (β = .018, p < .05). In addition, age, gender, education and employment were related to health outcomes. The findings of this study indicate that HBV‐related stigma is an important mediator of mental health outcomes in this population. Future studies should identify other psychosocial factors to develop effective intervention programs to reduce stigma and improve quality of life among CHB patients.


| INTRODUC TI ON S
Hepatitis B virus (HBV) affects millions of individuals worldwide and contributes to hundreds of thousands of deaths each year. 1 Though frequently asymptomatic, HBV can pose a threat of serious morbidity-persisting as chronic hepatitis B (CHB)-and mortality.It is wellestablished that HBV disproportionately affects Asian Americans, 2 and they are up to 11 times as likely as White Americans to develop hepatocellular carcinoma as sequela of HBV. 3 Considering the unequal burden of chronic HBV carried by Asian Americans, it is unsurprising that they have the highest liver cancer mortality rate of any racial group in the U.S. 4 HBV is further complicated by stigma that surrounds the infection.Erving Goffman defined stigma as 'an attribute that is deeply discrediting' that reduces the individual 'from a whole and usual person to a tainted, discounted one 5 '.An individual can internalize stigma surrounding their disease, but it can also manifest in social contexts as discriminatory behavior. 6Chinese law in the 1980s and 90s permitted institutions to discriminate against those with HBV infection.Despite this practice being outlawed in 2010, HBV stigma persists worldwide 7,8 and can impact diagnosis and management of the disease. 9,102][13] Existing literature on this topic has also shown that in patients with liver cirrhosis, an increased level of stigma was associated with depression and decreased quality of life. 10Other studies have shown associations between HBV-related stigma and decreased screening and health-seeking behaviors. 9,105][16] Existing literature suggests that misinformation about HBV transmission promotes stigma and discrimination, 17 and that isolating behaviors exhibited by CHB patients may be explained by a lack of knowledge about the virus.This is supported by studies showing that higher levels of education 16,18 and more knowledge about HBV 6,12,17 are associated with lower levels of stigma.There is little existing research that examines the connection between knowledge of HBV sequelae (including cirrhosis and hepatocellular carcinoma) and HBV-related stigma and, subsequently, mental and physical health outcomes.
There are proven negative consequences of HBV stigma, 3,6,11,12,[16][17][18][19] which is why it necessitates further investigation of its predictors and implications.A systematic review conducted of literature published from 2009 to 2019 found that more studies have explored stigma related to hepatitis C virus (HCV) infection than HBV. 20Studies have investigated CHB in Asian populations, but few have concentrated on the associated, stigma.
This study aims to fill a gap in current research by characterizing the social factors and mental and physical health outcomes associated with HBV-related stigma in Korean Americans.Specifically, the study explores the role of stigma as a mediator of the effects of racial discrimination and knowledge of HBV sequelae on health outcomes.The mechanisms by which stigma influences health status in patients with CHB has not been examined and needs to be explored given the poor health outcomes in this population.

| Data collection procedure and study sample
Participant Recruitment to the Cohort After medical chart review from two clinical sites, Thomas Jefferson University Hospital (TJUH) and Asian Pacific Liver Center (APLC), 552 Korean American CHB patients aged 18 years and older were identified as potentially eligible and were contacted for recruitment.CHB patients who visited the clinics for regular follow-up visits were deemed eligible if they: (1) had medical record data from 2016 or before, (2) had not received a diagnosis of hepatocellular carcinoma (HCC), (3) had not been diagnosed with another viral infection (e.g.HCV, HIV, etc.; to eliminate confounding in disease etiology) and (4) were cognitively capable of informed consent.
Once they were deemed eligible and willing to participate in the study, they were enrolled.In addition, patients who received care at each site but did not have scheduled visits were approached via text message and telephone call to participate.Baseline data collection occurred over an 18-month period from August 2022 to January 2023.This study was approved by the Thomas Jefferson University Institutional Review Board.
Figure 1 summarizes the participant recruitment.After medical chart review, 552 CHB patients were contacted.In part due to changes in medical care use patterns during the COVID pandemic, some patients reduced their frequency of face-to-face specialty care for CHB and 140 potentially eligible patients did not return for care and did not respond to outreach via text or call.Among those who responded (n = 412), four did not keep their appointments or participate in screening for the study, and 16 were found to be study-ineligible after screening.Among those patients who were screened and study-eligible (n = 392), 27 (7%) refused to participate.The most common reason cited for refusal to participate was time constraints.365 (93%) consented and completed baseline activities.
Baseline Survey In total, 365 CHB patients were recruited and enrolled and completed baseline activities including hair sampling after signing the written consent form.When given the option to choose their preferred language, 82% (n = 299) of participants chose to complete materials in Korean and 18% (n = 66) chose to do so in English.Most respondents (83%) used a self-administered modality (63% used an iPad on site; 26% used a link remotely; and 11% completed a paper copy).17% of participants requested to have the interviewer administer the questionnaire to them, primarily due to difficulties with reading or discomfort using an iPad.It took approximately 40 min to complete the baseline survey.
Respondents generally provided complete and logically consistent responses to all elements of the survey without skipping or refusing to answer any sections.Since the survey software used, Qualtrics, automatically captures all responses, no data loss occurred.
The data reported in this study are the analysis of baseline assessments.The baseline survey included measures of sociodemographic factors, acculturation, mental and physical health status, access to health care, medication adherence, racial discrimination, HBV diagnosis and treatment.

| Measures
Outcome measures Depressive symptoms were measured using the Patient Health Questionnaire (PHQ-9), Korean version. 21The PHQ-9 is a self-administered questionnaire for depression screening and diagnosis in primary care. 22In a systematic review, the PHQ-9 had strong psychometric properties including strong reliability and validity measuring depression. 23The validity and reliability of PHQ-9 has been reported for the Korean population previously, 24 and the Cronbach's alpha for the current study was 0.87.Each of the nine questions had four answer categories: 'not at all' (=0); 'several days' (=1); 'more than half the days' (=2); and 'nearly every day' (=3).Higher scores on the PHQ-9 indicate higher depressive symptoms.
Self-rated health was measured by asking 'in general, would you say your health is?' The subjects rated their physical health on a fivepoint scale from 1 (excellent) to 5 (poor), with higher scores indicating worse self-rated health.
Mediator Perceived HBV stigma was measured by the Hepatitis B Quality of Life Instrument (HBQOL)-stigma subscale, 25 a valid and reliable instrument characterized by six questions that prompt the subject to respond on a five-point Likert scale (never [=0] to all the time [=4]).Consistent with previous studies, the scores of the six questions were summed to create a 'stigma score', with higher scores indicating a higher level of perceived HBV-related stigma. 25,26The sum of stigma ranged from 0 to 24 (mean ± SD).Cronbach's alpha for the current study was 0.93.
Independent variables Psychosocial factors were measured by perceived racial discrimination and sequelae of CHB.Discrimination is defined as the 'differential treatment of members of groups by both individuals and social institutions'. 27Perceived racial discrimination was measured using the 9-item Everyday Discrimination Scale (EDS). 28The questions in this measure were preceded by the words 'In your day-to-day life how often have any of the following things happened to you' followed by the statement such as, 'You are treated with less courtesy than other people are?' Each item is scored on a scale of 0 (never) to 5 (almost every day).Exploratory factor analysis showed two factor solutions (n = 6, α = .86for factor1; n = 3, α = .85for factor2).In this study, we used the six questions of factor1.The items were summed to create a total score with a mean of 3.93 (SD = 5.16) and range of 0 to 30.Sequelae of CHB was measured by asking seven questions about perceived consequences of CHB (e.g. HBV can cause liver cancer; people with HBV are infected for life).

| Statistical analysis
Descriptive statistics including frequency, mean, standard deviation and range were used to present sociodemographic characteristics.
Cross-tabulation using Chi-square analysis for categorical variables and Student's t-test for continuous variables were conducted.
Preliminary analyses were conducted to check the assumptions of normality, linearity, homoscedasticity and multicollinearity.Bivariate associations among the study variables were tested using Pearson correlation.For mediation analyses, we used structural equation modeling with the full information maximum likelihood estimation method.Two separate models for physical health and depressive symptoms were analysed.Sociodemographic characteristics that showed significant association in bivariate analyses with the outcome variables were included in the multiple mediation analysis to control for confounding variables.We also conducted the biascorrected bootstrap confidence interval (CI) method for inferential tests of the indirect effects in mediation analysis. 30Five thousand bootstrap iterations created the bootstrap sample for estimating the indirect effect of mediation analysis.If a bootstrap 95% CI includes 0, then the indirect effect is considered non-significant.Missing data were minimal (ranging from 0 to 7 out of 365) for all study variables.A p value <.05 (two-sided) was considered statistically significant.
Table 1 presents the cohort characteristics.The average age of participants was 60.1 years (range 19-84, SD 10.7).The cohort was 56% male, and 97% were born in South Korea.Most (81%) were currently married or living with a partner.Approximately 56% had completed college.One-third reported poor or no proficiency in English.Most (92%) had any type of health insurance.The average time since HBV diagnosis was 26.9 years (range 5-52, SD 10.3), and 58% had a family history of HBV infection.Based on medical chart review, one third had non-alcoholic fatty liver disease (NAFLD) and about 14% had diagnosed liver cirrhosis.About 15% had diabetes mellitus.
Table 2 presents zero-order correlations between variables.
In addition, age, gender, education, marital status and employment were associated with outcome variables and were all included in the model as covariates.Moreover, gender was associated with stigma (r = .166,p < .01),having higher stigma for females.None of the variables were highly correlated (r > .40),reducing the problems of multicollinearity.
To explore the mediation effects of stigma on the associations between perceived racial discrimination and knowledge of sequelae and self-rated health and depressive symptoms, mediation analyses were conducted (see Figure 2).The results on the mediating effects of stigma are presented in Table 3. Sociodemographic variables including age, gender, education, marital status and employment were all included in the model as covariates.First, perceived racial discrimination and sequelae were related to stigma.Second, perceived racial discrimination had a direct effect on depressive symptoms (β = 236, p < .01).Third, stigma had a significant mediating effect on the relationships between perceived racial discrimination (indirect effect = .037,Bootstrap 95% CI: .010-.064) and knowledge of sequelae (indirect effect = .097,Bootstrap 95% CI: .018-.176) and depressive symptoms.Fourth, there was no mediating effect of stigma on the relationships between perceived racial discrimination/ sequelae and self-rated health (p < .10).Finally, patients who were older and female had poorer self-rated health and higher depressive symptoms.Those who were employed and completed an education level higher than college had better physical health and lower depressive symptoms.

| DISCUSS ION
This study examined the mediating role of stigma in the relationships between perceived racial discrimination/knowledge of sequelae and physical and mental health outcomes after controlling for sociodemographic variables among Korean Americans living with CHB.Specifically, we tested whether perceived discrimination and knowledge of HBV sequelae were associated with poorer health outcomes and whether these could be partly explained by higher levels of perceived HBV-related stigma.The results reinforced that HBV-related stigma remains relevant in this population and can have tangible effects on health outcomes, not to mention the complex social and familial implications of this phenomenon.
In this cohort, the stigma variable was also associated with knowledge of HBV sequelae.Existing literature has shown that a higher level of knowledge about HBV transmission 6,12,17 is associated with lower levels of HBV-related stigma among Asian populations.In contrast, we found that knowledge of HBV sequelae was positively associated with HBV-related stigma; those with high knowledge of HBV sequelae were more concerned about their liver disease progressing, which may lead to higher stigma.However, there is sparse information about knowledge of HBV sequelae and how this is related to stigma.Our study is novel in that it demonstrates that increased knowledge of the possibility of CHB sequelae, such as cirrhosis and liver cancer, is associated with higher levels of HBV-related stigma.More than one third (36%) of study participants demonstrated a strong knowledge of sequelae of CHB (≥6, range 0 to 7).We also found stigma to be a partial mediator in the association between knowledge of HBV sequelae and depressive symptoms.To our knowledge, ours is the first study to demonstrate the mediating role of stigma in the association between knowledge of HBV and mental health.
Stigma was also a mediator in the relationship between racial discrimination and depressive symptoms in this population.While little research exists on the effects of perceived racial discrimination on HBV-related stigma and outcomes, substantial evidence suggests that experiencing physical or emotional stress from discrimination leads to overall poorer mental health. 31Few studies have examined the associations of racial discrimination, stigma and mental health among CHB patients.Our study also found that perceived racial discrimination has a direct effect on depressive symptoms.Hence, racial discrimination is a targetable area for intervention in this population, with 45% of Asian Americans attesting that they have been a victim of racial discrimination since March 2020. 31Interestingly, stigma was a partial mediator in the relationship between discrimination and self-rated health, which was marginally significant at p-value <.10.One possible interpretation is that association between stigma and depressive symptoms was much stronger than the association between stigma and self-rated health.
Previous studies have found HBV-related stigma to be associated with isolating behaviors, such as separation from friends and family and avoidance of sharing utensils. 6,11,17,19However, the current study focused on the associations of stigma with health outcomes-both mental and physical-rather than the manifestations of stigma in patients' behaviors. Additionally

SƟgma Health outcomes
MediaƟng effect sources, possibly resulting in recall bias and incorrect answering of survey questions.
Despite these limitations, the findings of this study have important implications for health outcomes related to HBV stigma.
There is a need to develop and implement intervention programs tailored to Korean American CHB patients to improve mental health and quality of life.Thus, a culturally appropriate psychological intervention is warranted that focuses on addressing psychosocial factors (e.g.knowledge of CHB sequelae and perceived discrimination) related to stigma among Korean Americans living with CHB in the U.S.
Demographic and clinical characteristics of Korean American CHB patients (n = 365), 2021 to 2022.
temporal order.Second, our study population was recruited from two clinical sites in Philadelphia and Los Angeles.Therefore, our results cannot be generalized to all Korean American CHB patients in the United States.Future studies should include CHB patients from diverse racial and ethnic backgrounds.In addition, our data were self-reported by participants and were not verified through outside TA B L E 2