Racial/ethnic- and county-specific prevalence of chronic hepatitis B and its burden in California

Racial/ethnic- and county-specific prevalence of chronic hepatitis B and its burden in California Background: In the United States, the highest burden of chronic hepatitis B (CHB) and CHB-related liver cancer is in the state of California, primarily in the San Francisco (SF) Bay and Los Angeles (LA) areas. The aim of this study was to estimate county-specific hepatitis B surface antigen (HBsAg) prevalence and quantify CHB cases by age, race/ethnicity, nativity, and disease activity status. Methods: Twelve counties in SF Bay Area and three large counties in LA area were included for this analysis. Race/ethnicity-specific prevalence of HBsAg for each county and the state of California as a whole, was estimated by including prevalence data from the National Health and Nutrition Examination Survey and various studies that estimated HBsAg prevalence in US and foreign-born Asian Pacific Islanders, Hispanic, and Black populations. In addition, clinical data of 2000 consecutive CHB patients (collected between 2009 and 2014) from a large clinical consortium in the SF Bay area were used to calculate the age-specific disease burden. Results: Of the 15 counties analyzed, SF had the highest HBsAg prevalence (1.78%), followed by Santa Clara (1.63%) and Alameda (1.45%). The majority of CHB cases were estimated to be in LA County (83,770), followed by Santa Clara (31,273), and Alameda (23,764). Among the CHB cases, 12.7% is active HBeAg positive, 24.2% is active HBeAg negative, and 10.6% has cirrhosis. Conclusion: This study confirms and quantifies the current burden of CHB in high endemic counties in the state of California using population-level estimates combined with clinical data including those from the community. Keywords: HBV, Disease status, California, Burden of disease Background primarily in the San Francisco (SF) bay and Los Angeles As a leading cause of liver disease, liver cancer, and liver (LA) areas [3]. However, only 34.6% are diagnosed [2], transplantation, chronic hepatitis B (CHB) is an import- 33.3% of those diagnosed receive care [4], and 45% of ant public health problem globally [1]. In 2013, viral those linked to care receive treatment if eligible accord- hepatitis took the lives of about 1.45 million people and ing to treatment guidelines [5]. Without diagnosis, link- was the seventh leading cause of death in the world, sur- age to care and treatment, one in four people with CHB passing malaria and tuberculosis [1]. An estimated will die from cirrhosis, liver cancer, and/or liver failure 850,000–2.2 million people in the United States (US) live [6]. In US regions with high proportion of immigrants, with CHB and only 34.6% are aware of their infection such as the SF Bay area, the vast majority of confirmed [2]. The highest prevalence of CHB and CHB-related cases of CHB are Asian or Pacific Islander (API) [2]. A liver cancer in the U.S is in the state of California (CA), study from San Francisco found that of all hepatitis B virus (HBV) infection cases reported, 84% were API and of those 80% were foreign born [7]. In the U.S., the preva- * Correspondence: mtoy@stanford.edu lence of CHB among foreign-born people is estimated to Asian Liver Center, Department of Surgery, Stanford University School of Medicine, 780 Welch Road, CJ130D, Palo Alto, CA 94304, USA be 10 times higher than the national prevalence rate [8]. A Full list of author information is available at the end of the article © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Toy et al. Hepatology, Medicine and Policy (2018) 3:6 Page 2 of 9 seroprevalence survey study on Asian Americans in the ethnicity- and nativity- as well as age-specific prevalence SF Bay area concluded that 8.9% API were infected with rates, where reported, in the studies that we used as preva- CHB but 65.4% of the chronically infected adults were un- lence data to calculate the overall prevalence for the SF Bay aware of their infection [2]. One of the four overarching area, the LA area and for the entire state of California. goals of the Department of Health and Human Services In all race/ethnicity groups of ages 0–19 years, except Action Plan for the Prevention, Care and Treatment of for the Black foreign-born Africa and Haiti groups as Viral Hepatitis is to increase the diagnosis rate of CHB well as the API foreign-born East Asia, we used the from 33 to 66% by 2020 [9]. NHANES 2015 data. NHANES reported a prevalence of The National Health and Nutrition Examination Survey 0.03% (0.01–0.08) among 6–19 year old group, which we (NHANES) has been the primary data source for HBV used for 0–19 year olds in the White, Hispanic, Black [10] prevalence estimate in the US population. However, US-born, API US-born Korea, Japan and South Asia due to the small sample size in the survey, it is not an ap- groups, as well as the Japanese foreign-born group. We propriate source for county- and state-specific prevalence used the prevalence that was 10-fold greater than the estimates of CHB [11]. In addition, county-level and race/ general population explanation of the NHANES study ethnicity-specific data are important for setting priorities and applied it to the Black foreign-born in Jamaica and in public health and resource allocation at the local level Dominican Republic, API US-born East Asian and API and since the distribution of CHB disease burden varies foreign-born Korean groups for estimating the preva- by race/ethnicity which itself varies by counties. Thus, lence among 0–19 year olds. to fill this gap, the aim of this study was to estimate the In order to quantify the age-specific “active” disease prevalence of HBsAg and quantify CHB active disease burden in relation to CHB activity and cirrhosis, we an- burden in the state of CA and certain specific counties alyzed clinical baseline data such as HBV DNA and ala- by age, race/ethnicity, and disease activity status, using nine aminotransferase (ALT) levels of 2000 consecutive population-based data and clinical data from a large new treatment-naïve CHB patients who presented be- clinical and community consortium in the SF bay area. tween 2009 and 2014 at several hepatology and commu- nity gastroenterology and primary care clinics as of the SF Methods Bay Area Consortium (SFBAC). Following the American As a first step, we obtained age-specific population for Association for the Study of Liver Disease (AASLD) 12 counties in the SF Bay area and 3 large counties in guidelines [6], disease status was defined as “active” by the the LA area (Los Angeles, San Bernardino and Orange following criteria: presence of cirrhosis or an elevation of counties) as well as county-specific race/ethnicity distri- ALT > 2 times the upper limit of normal (ULN) or evi- butions in these populations from the US census [12]. dence of significant histological disease plus elevated HBV We then categorized the population according to the fol- DNA above 2000 IU/mL for HBeAg-negative and above lowing four major racial/ethnic groups: White, Hispanic, 20,000 IU/mL for HBeAg-positive non-cirrhotic cases. Black, and API. Nativity data for Black and API popula- tions were also obtained from the US census bureau. Results Approximately, 10.3% of Blacks in the US are foreign Estimates of HBsAg prevalence and burden born [13], of whom 36% were born in Africa, 35% in The age-specific foreign-born distribution for API for Jamaica and Dominican Republic, 15% in Haiti, and 9% in age groups 0–19, 20–29, 30–39, 40–49, 50–59, 60–69, East and South America, and 5% elsewhere [14]. Within and 70+ were 22, 64, 83, 87, 89, 87, 90%, respectively. the API population, we further divided the groups into: Combining population distribution by county, race/ethnicity South Asian (23.3%), Korean (8.6%), Japanese (6.7%) and and nativity with race/ethnic specific HBsAg-prevalence, we other East Asian (61.4%) [15, 16]. Secondly, we calculated estimated that overall, all race-combined, there are 104,734 age-specific API foreign-born population distribution from (range 70,952–153,598) CHB cases or 1.18% (range the US census data [17]and used theseage-specificdistri- 0.80–1.73%) in the SF Bay area. Table 2 shows the esti- butions for the East Asia, Korea and South Asia group. For mated overall age-specific HBsAg-prevalence (all race example, the Japanese foreign born distribution was re- combined) and related number of CHB cases in the SF ported to be 27% in the US [15]. Next, we collected race/ Bay area. ethnicity- and nativity-specific HBsAg prevalence data As shown, the highest prevalence was amongst ages among White [11], Hispanic [11, 18], Black [11, 19–21]and 40–49 (2.08%) with a total of 25,627 (24.5% of all cases), APIs [2, 11, 19, 22–24] in the US from the literature. Jung followed by 1.86% for those between the ages of 30 et al. reported a 0% (353 people tested) of HBsAg preva- and 39. In the LA area, with a population of 15.5 lence among 70+ year old Hispanic population, which we million, we estimated that the overall prevalence is decided not to take and assume the same prevalence for 60 0.71% (range 0.46–1.12%), with a total of 109,442 (range +asthe 60–69 age-group (0.38%). Table 1 shows the race/ 71,363–172,482) with CHB. For California as a state with Toy et al. Hepatology, Medicine and Policy (2018) 3:6 Page 3 of 9 Table 1 Race/ethnicity- and nativity-specific HBsAg prevalence data from literature review Race/Ethnicity Ages 0–19 Prevalence (range) Reference Ages > 19 Prevalence (range) Reference White 0.03% (0.01–0.08) Roberts et al. [11] 0.10% (0.05–0.20) Roberts et al. [11] Hispanic 0.03% (0.01–0.08) Roberts et al. [11]20–29 0.16% (0.05–0.47) Jung et al. [18] 30–39 0.14% (0.04–0.42) 40–49 0.49% (0.24–1.00) 50–59 0.39% (0.21–0.72) 60–69 0.38% (0.10–1.37) 70 + 0.38% (0.10–1.37) Black US-Born 0.03% (0.01–0.08) Roberts et al. [11] 0.10% (0.05–0.20) Roberts et al. [11] Black Foreign-Born Africa 7.30% (6.50–8.00) Ugwu et al. [20]20–29 10.45% (9.50–11.30) Ugwu et al. [20] 30–39 11.20% (9.70–12.70) 40–49 6.99% (5.60–8.30) 50–59 10.86% (9.70–12.00) 60+ 10.86% (9.70–12.00) Jamaica and Dominican Rep. 0.30% (0.10–0.80) Roberts et al. [11] 2.10% (0.70–4.00) Din et al. [19] Haiti 2.50% (2.10–3.00) Tohme et al. [21] 2.50% (2.10–3.00) Tohme et al. [21] South & Central America 0.30% (0.10–0.80) Roberts et al. [11] 0.60% (0.2–2.00) Din et al. [19] API US Born East Asia 0.30% (0.10–0.80) Roberts et al. [11] 1.40% (0.65–1.90) Din et al. [19] Korea 0.03% (0.01–0.08) Roberts et al. [11] 1.40% (0.65–1.90) Din et al. [19] Japan 0.03% (0.01–0.08) Roberts et al. [11] 0.10% (0.05–0.20) Roberts et al. [11] South Asia 0.03% (0.01–0.08) Roberts et al. [11] 1.40% (0.65–1.90) Din et al. [19] API Foreign Born East Asia 1.10% (0.90–1.90) Shuler et al. [23]20–29 5.40% (3.10–8.50) Lin et al. [2] 30–39 11.50% (8.30–15.20) 40–49 12.20% (9.70–15.00) 50–59 8.80% (7.00–10.80) 60–69 8.00% (5.90–10.60) 70–79 6.70% (4.00–10.40) 80+ 3.70% (1.00–9.30) Korea 0.30% (0.10–0.80) Roberts et al. [11]20–29 1.18% (0.43–2.55) Hyun et al. [22] 30–39 2.53% (1.61–3.77) 40–49 2.76% (2.00–3.70) 50–59 2.90% (2.23–3.69) 60–69 2.06% (1.37–2.96) 70–79 1.37% (0.59–2.68) 80+ 2.17% (1.17–2.77) Japan 0.03% (0.01–0.08) Roberts et al. [11] 1.02% (1.01–1.02) Tanaka et al. [24] South Asia 0.30% (0.10–0.80) Roberts et al. [11] 2.70% (1.60–4.00) Din et al. [19] Definitions of race and ethnicity according to the US Census Bureau: White- A person having origins in any of the original peoples of Europe, the Middle East, or North Africa. Black or African American- A person having origins in any of the Black racial groups of Africa. Asian- A person having origins in any of the original peoples of the Far East, South East Asia, or the Indian subcontinent including, for example, Cambodia, China, India, Japan, Korea, Malaysia, Pakistan, the Philippine Islands, Thailand and Vietnam. Native Hawaiian or other Pacific Islander- A person having origins in any of the original peoples of Hawaii, Guam, Samoa, or other Pacific Islands. Hispanic origin can be viewed as the heritage, nationality, lineage, or country of birth of the person or the person’s parents or ancestors before arriving in the US The foreign born population includes anyone who is not a U.S citizen at birth, including those who became U.S citizens through naturalization API Asian Pacific Islander, US United States, HBsAg hepatitis B surface antigen We adapted from Jung et al. and assumed a 0.38% for 70+ We took a weighted average of Tanaka et al.’s HBV screening cohort ages 40–74 which we calculated to be 1.02% Toy et al. Hepatology, Medicine and Policy (2018) 3:6 Page 4 of 9 Table 2 Estimated HBsAg prevalence and estimated number of HBsAg-positive cases in the San Francisco Bay area Age Group (Years) Population (2015) HBsAg-positive cases (range) HBsAg-prevalence (range) 0–19 2,202,500 2607 (1474–5577) 0.12% (0.07–0.25%) 20–29 1,254,437 11,106 (6113–18,053) 0.89% (0.49–1.44%) 30–39 1,311,988 24,436(16,842–33,961) 1.86% (1.28–2.59%) 40–49 1,230,512 25,627 (19,102–33,946) 2.08% (1.55–2.76%) 50–59 1,192,159 19,120 (14,218–25,231) 1.60% (1.19–2.12%) 60–69 898,217 12,940 (8709–19,866) 1.44% (0.97–2.21%) 70–79 473,888 6117 (3455–10,572) 1.29% (0.73–2.23%) 80+ 310,260 2781 (1039–6393) 0.90% (0.34–2.06%) Total 8,873,961 104,734 (70,952–153,598) 1.18% (0.80–1.73%) Total population year 2015, counties: San Francisco, Santa Clara, Alameda, San Mateo, Contra Costa, San Joaquin, Merced, Monterey, Stanislaus, Marin, Santa Cruz and San Benito HBsAg hepatitis B surface antigen a population of 39.1 million, the prevalence was estimated Figure 2 shows the population and HBsAg distribution in to be 0.78% (0.51–1.21%), with a total estimated case the SF Bay area (Fig. 2a), Santa Clara County (Fig. 2b), and number as 305,419 (range 200,100–475,523). San Benito County (Fig. 2c). As shown, the SF Bay area has a 24.5% API population, but accounts for 88.5% of all CHB County-, race/ethnicity-, and nativity-specific HBsAg cases. Santa Clara County has the highest API population prevalence and burden (36%) and they account for 94% of the HBsAg-positive Of the 15 counties analyzed, SF County had the highest cases in the county. San Benito County has the highest His- HBsAg prevalence (1.78%), followed by Santa Clara panic population (59%), and they account for 38% of the (1.63%), Alameda (1.45%), San Mateo (1.40%) and Contra HBsAg-positive cases in the county. In contrast, although Costa (0.88%), as shown in Fig. 1. However, LA County API constitutes only 4% of the population in San Benito, (83,770), Santa Clara (31,273), Alameda (23,764) and they account for 50% of the HBsAg cases in this county. Orange County (15,091) have high number of individ- In the SF Bay area, the HBsAg prevalence in API is es- uals with HBsAg due to its large population. timated to be 4.26%. Although API comprises of 24.5% Fig. 1 HBsAg prevalence and number of chronic hepatitis B cases in 15 counties in the State of California Toy et al. Hepatology, Medicine and Policy (2018) 3:6 Page 5 of 9 Fig. 2 Racial and ethnic distribution among HBsAg-positive and general population in the San Francisco Bay area (a), Santa Clara County (b), and San Benito County (c) of the total population it accounts for 88.5% (92701) of the Active disease burden 104,734 HBsAg-positive cases. Of the HBsAg-positive cases Table 4 shows the patient characteristics of the 2000 among API cases, 4.93% were estimated to be US born and CHB patients in the Stanford and community clinic 84.0% foreign born (Table 3). Black cases (2886) made up consortium from the SF Bay area (SFBAC). Of these, 55.8% 2.76% of total cases, with 0.39% being US born and 2.37% were male, and the median age at diagnosis was 43. About being foreign born. 22% were positive for HBeAg, with 14% non-cirrhotic Toy et al. Hepatology, Medicine and Policy (2018) 3:6 Page 6 of 9 Table 3 HBsAg-positive cases and its distribution by age, race/ethnicity and nativity within each age group in the total 104,734 estimated cases in the San Francisco Bay area Age API Black Hispanic White Total Group Foreign-Born US-Born Foreign-Born US-Born (Years) 0–19 889 (34.1%) 781 (30.0%) 435 (16.7%) 36 (1.38%) 204 (7.83%) 262 (10.0%) 2607 20–29 8059 (72.6%) 1497 (13.5%) 394 (3.55%) 69 (0.62%) 589 (5.30%) 498 (4.48%) 11,106 30–39 22,106 (90.5%) 777 (3.18%) 437 (1.79%) 73 (0.30%) 523 (2.14%) 520 (2.13%) 24,436 40–49 22,512 (87.8%) 540 (2.11%) 289 (1.13%) 68 (0.27%) 1724 (6.73%) 494 (1.93%) 25,627 50–59 16,399 (85.8%) 450 (2.35%) 386 (2.02%) 66 (0.35%) 1336 (6.99%) 483 (2.53%) 19,120 60–69 10,878 (84.1%) 377 (2.91%) 291 (2.25%) 50 (0.39%) 976 (7.54%) 368 (2.84%) 12,940 70–79 5077 (83.0%) 154 (2.52%) 151 (2.47%) 26 (0.43%) 515 (8.42%) 194 (3.17%) 6117 80+ 2068 (74.4%) 137 (4.93%) 99 (3.56%) 17 (0.61%) 333 (12.0%) 127 (4.57%) 2781 Total 87,988 (84.0%) 4713 (4.50%) 2482 (2.37%) 405 (0.39%) 6200 (5.92%) 2946 (2.81%) 104,734 (100%) active HBeAg-positive and 26% non-cirrhotic active people with CHB in CA meet the AASLD criteria for HBeAg-negative. Approximately 9% of all cases had treatment. cirrhosis. Applying clinical data from Table 4 to the SF Bay area Discussion CHB population, in Table 5, we show the estimated data This study confirms and quantifies the current burden of on HBeAg, CHB activity, and cirrhosis. The number of CHB in high endemic counties in the state of CA using active CHB cases, who are considered to be eligible for population-level estimates combined with real-world clin- antiviral treatment by the AASLD guideline because they ical data including those from the community. We esti- have significant viremia and evidence of on-going in- mated the overall all race-combined HBsAg-prevalence of flammation or hepatic fibrosis, included 14,3149 (12.6%) the SF Bay area, LA area, and the state of CA to be 1.18, in the HBeAg-positive group, and 25,636 (24.5%) in the 0.71 and 0.78%, respectively. The national US HBsAg HBeAg-negative group, with 11,112 (10.6%) cirrhosis prevalence estimated by NHANES is only 0.3% [11]. Ac- cases at baseline. In the LA area, a total of 51,952 people cording to our estimates, SF Bay area prevalence surpasses out of the 15.5 million population and 109,442 CHB the 0.3% by about 4-fold. The prevalence is highest in the cases are estimated to need antiviral treatment. When SF (1.78%), Santa Clara (1.63%), and Alameda (1.45%) projected to the state of California as a whole, out of counties. However, the burden based number of patients an estimated 305,419 CHB cases, 38,158 are active is highest in the LA (83,770), Santa Clara (31,273) and HBeAg-positive, 73,700 are active HBeAg-negative and Alameda (23,764) counties, due to the large population, 33,091 are cirrhotic. In total, an estimated 144,949 (47.5%) especially APIs, in these counties. As expected, a signifi- cant portion of the burden is among the API population, Table 4 Characteristics of the chronic hepatitis B patients from with an estimated 4.26% HBsAg-prevalence. This rate is the hepatology and community gastroenterology and primary higher than the 3.1% reported by the NHANES 2015 care clinics of the San Francisco Bay area consortium study as the true prevalence of CHB infections for Asians Parameters Results [11], including both immigrants and naturalized citizens. Total number, N 2000 Our estimate is comparable to the 3.8% prevalence re- Male 1117 (55.8%) ported by Levy et al. among men aged 18–35 years resid- ing in low-income neighborhoods in Northern California Age 43 (18–88) [25]. Although the Centers for Disease Control and Pre- HBeAg-positive 444 (22.2%) vention (CDC) estimates that Asians account for 50% of Active HBeAg-positive (non cirrhotic)* 272 (14%) all CHB cases in the US [26], our study estimated that in Active HBeAg-negative (non cirrhotic)* 510 (26%) CA, especially in the SF Bay area, APIs make up 88.5% of ALT (U/L) 39 (3–2809) all the CHB cases. Particularly relevant is the high propor- HBV DNA (log IU/mL) 4.0 (1.3–11.3) 10 tion of total CHB cases among the API foreign-born group that account for 84.0% of all the cases in the SF Bay Cirrhosis 185 (9%) area. It is estimated that the overall burden of CHB in the *Active is defined by an elevation of ALT > 2× upper limit of normal or evidence of significant histological disease plus elevated HBV DNA above U.S. will continue to increase with ongoing immigration 2000 IU/mL for HBeAg-negative, and above 20,000 IU/mL for from countries with intermediate (2–8%) to high (> 8%) HBeAg-positive [6] HBeAg hepatitis B e antigen, ALT alanine aminotransferase HBV prevalence [8]. For the foreign born population, we Toy et al. Hepatology, Medicine and Policy (2018) 3:6 Page 7 of 9 Table 5 Prevalence of chronic hepatitis B in the San Francisco Bay area by age and disease status Age Group (Years) Population (2015) Inactive CHB Active HBeAg positive Active HBeAg negative Cirrhosis 0–19 2,202,500 1805 (69.2%) 602 (23.1%) 201 (7.69%) 0 20–29 1,254,437 5360 (48.3%) 2744 (24.7%) 2701(24.3%) 300 (2.70%) 30–39 1,311,988 12,218 (50.0%) 4680 (19.2%) 6834 (28.0%) 704 (2.88%) 40–49 1,230,512 13,111 (51.2%) 2930 (11.4%) 7450 (29.1%) 2136 (8.33%) 50–59 1,192,159 9770 (51.1%) 1199 (6.27%) 5154 (27.0%) 2997 (15.7%) 60–69 898,217 7939 (61.4%) 438 (3.38%) 1813 (14.0%) 2751 (21.3%) 70–79 473,888 3186 (52.1%) 382 (6.25%) 1020 (16.7%) 1529 (25.0%) 80+ 310,260 1448 (52.1%) 174 (6.25%) 463 (16.7%) 695 (25.0%) Total 8,873,961 54,837 (52.4%) 13,149 (12.6%) 25,636 (24.5%) 11,112 (10.6%) Inactive CHB are those who are HBsAg positive with low HBV DNA or high HBV DNA but normal alanine aminotransferase or ALT levels HBeAg hepatitis B e antigen tried to use prevalence data from the US immigrant stud- to the state of CA. As there are many immigrants in ies where available rather than the prevalence in their California from the Middle East, which historically home country. had a higher HBV prevalence than Western Europe or the It is noteworthy that although currently both preva- European settlers of North America, the NHANES study lence of HBV infection and incidence of hepatocellular we used to estimate the prevalence among whites does carcinoma (HCC) due to HBV are high in the API popu- not differentiate among the white population which is lation, data from SEER registries have shown a decline likely a limitation in our study. in HCC incidence among Asians, while rates in other ra- Given the high burden of CHB and HCC in the SF cial/ethnic groups will continue to rise [27, 28]. In fact, in Bay area and California, targeted prevention and control a national forecast study using SEER national data, by efforts are needed to minimize the burden in these com- 2030, Hispanics will have the highest HCC in the country, munities. A recent CDC-funded study showed that in while Asians will have the lowest HCC rates [28]. It is im- cities with large populations of Asia- and Africa-born portant to note that Hispanic is the largest racial/ethnic immigrants, community-based and refugee clinic-based population in the state of California, accounting for 39% HBV testing initiatives can identify substantial numbers of the total CA population [29]. Relative to Asians, His- of individuals with CHB [32], and stresses the fact that panics tend to have lower CHB infection but higher HCV culturally and linguistically specific approaches were ne- infection. Although our HBsAg-prevalence estimate of the cessary in all phases of the initiatives. Our data and esti- Hispanic population in the SF Bay area is only 5% of the mates can be used for resource allocation planning to total, in counties that have large Hispanic populations target specific geographic areas and subpopulations, such as San Benito and Merced, the Hispanic population race/ethnicities for effective interventions, such as makes up to 38% of all CHB cases. During the 2006–2010 screening and linkage to care with appropriate therapies, period, among individuals aged 50–64 years, Hispanics ex- to minimize the burden of CHB and its clinical conse- perienced higher HCC incidence and mortality rates than quences, such as liver cirrhosis, and liver cancer. These Asians and Whites [30]. Few studies have investigated risk interventions are urgently needed as currently most of factors for HCC in Hispanics and the reasons for the ris- the CHB patients (70%) in the US are not aware of their ing trend in this ethnic group, although one study did HBV infection and there are also large gaps at various show that HBV infection is one of the risk factors for levels of the cascade of care for those with known CHB HCC in Hispanic [30]. [5, 33–35]. Importantly, improved linkage to care can Although we analyzed 62% of the total population of identify patients who may benefit from antiviral therapy California, it is unclear whether we can generalize the which has been shown in both randomized control studies data from SF and LA reported here to the entire state of as well as large cohort studies in the US to substantially California, as SF and LA cover counties that are more reduce HCC risk in CHB patients [36, 37]. densely populated and more diverse, and the remainder 43 counties in the state are quite different. However, our Conclusion clinical data, including HBeAg status, among CHB pa- In summary, our data suggest that there are approximately tients from the university liver and community gastro- 305,000 persons living with CHB in the State of CA, and enterology and primary care clinics were comparable to about half of these (47.5%, 150,000) have cirrhosis and/or those reported by a North American multicenter study meeting AASLD guideline criteria for antiviral therapy. [31], suggesting some utility of generalizing our estimates We also found significant variation in the racial/ethnic Toy et al. Hepatology, Medicine and Policy (2018) 3:6 Page 8 of 9 make-up of the CHB population in different regions and 2. Lin SY, Chang ET, So SK. 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Kim LH, Nguyen VG, Trinh HN, Li J, Zhang JQ, Nguyen MH. Low treatment rates in patients meeting guideline criteria in diverse practice settings. Dig Abbreviations Dis Sci. 2014;59(9):2091–9. AASLD: American association for the study of liver disease; ALT: Alanine 6. Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH, aminotransferase; API: Asian or pacific islander; CA: California; CDC: Centers American Association for the Study of Liver D. AASLD guidelines for for Disease Control and Prevention; CHB: Chronic hepatitis B; treatment of chronic hepatitis B. Hepatology. 2016;63(1):261–83. DNA: Deoxyribonucleic acid; HBsAg: Hepatitis B surface antigen; 7. CDC. Characteristics of persons with chronic hepatitis B: San Francisco, HCC: Hepatocellular carcinoma; LA: Los Angeles; NHANES: National Health California, 2006. Morb Mortal Wkly Rep. 2007;56(18):446–8. and Nutrition Examination Survey; SF: San Francisco; SFBAC: San Francisco 8. 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PewSocialTrends: The Rise of Asian Americans [http://www.pewsocialtrends. Competing interests org/files/2013/04/Asian-Americans-new-full-report-04-2013.pdf]. Accessed 18 Mehlika Toy, Bin Wei, Tejpal S Virdi, An Le, Jiayi Li, Jian Zhang, Ann W. Hsing, Aug 2017. and Samuel K So have no disclosures. 16. Total Asian alone or in any combination population 2015 American Huy Trinh: Grant/research support: Gilead Sciences, Abbvie; Advisory board: Community Survey 1-Year Estimates [https://factfinder.census.gov/faces/ Gilead Sciences; Speaker: Gilead Sciences. tableservices/jsf/pages/productview.xhtml?src=bkmk]. Accessed 21 Aug. Mindie H. Nguyen: Grant/research support: Bristol Myer Squibbs, Gilead 17. U.S. Census Bureau, P. D.“Table 13. Projections of the Population by Nativity, Sciences, Janssen Pharmaceutical; Advisory board/consultant: Dynavax Hispanic Origin, and Race for the United States: 2015 to 2060 (NP2014-T13)”. Laboratories, Gilead Sciences, Intercept Pharmaceutical, Anylam 2014. 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Hepatitis B sero-prevalence and risk behaviors among immigrant men in a population-based household survey in low-income neighborhoods of northern California. J Immigr Minor Health. 2010;12(6):828–33. 26. Asian Americans and hepatitis B [https://www.cdc.gov/features/ aapihepatitisb/]. Accessed 21 Aug 27. Ha J, Yan M, Aguilar M, Bhuket T, Tana MM, Liu B, Gish RG, Wong RJ. Race/ ethnicity-specific disparities in cancer incidence, burden of disease, and overall survival among patients with hepatocellular carcinoma in the United States. Cancer. 2016;122(16):2512–23. 28. Petrick JL, Kelly SP, Altekruse SF, McGlynn KA, Rosenberg PS. Future of hepatocellular carcinoma incidence in the United States forecast through 2030. J Clin Oncol. 2016;34(15):1787–94. 29. In 2014, Latinos will surpass whites as racial/ethnic group in California [http://www.pewresearch.org/fact-tank/2014/01/24/in-2014-latinos-will- surpass-whites-as-largest-racialethnic-group-in-california/]. Accessed 21 Aug. 30. 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Editorial commentary: sliding down the Cascade of Care for Chronic Hepatitis B Virus Infection. Clin Infect Dis. 2016;63(9):1209–11. 35. Spradling PR, Xing J, Rupp LB, Moorman AC, Gordon SC, Teshale ET, Lu M, Boscarino JA, Trinacty CM, Schmidt MA, et al. Infrequent clinical assessment of chronic hepatitis B patients in United States general healthcare settings. Clin Infect Dis. 2016;63(9):1205–8. 36. Liaw YF, Sung JJ, Chow WC, Farrell G, Lee CZ, Yuen H, Tanwandee T, Tao QM, Shue K, Keene ON, et al. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med. 2004;351(15):1521–31. 37. Lin D, Yang HI, Nguyen N, Hoang J, Kim Y, Vu V, Le A, Chaung K, Nguyen V, Trinh H, et al. Reduction of chronic hepatitis B-related hepatocellular carcinoma with anti-viral therapy, including low risk patients. Aliment Pharmacol Ther. 2016;44(8):846–55. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Hepatology, Medicine and Policy Springer Journals

Racial/ethnic- and county-specific prevalence of chronic hepatitis B and its burden in California

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Abstract

Background: In the United States, the highest burden of chronic hepatitis B (CHB) and CHB-related liver cancer is in the state of California, primarily in the San Francisco (SF) Bay and Los Angeles (LA) areas. The aim of this study was to estimate county-specific hepatitis B surface antigen (HBsAg) prevalence and quantify CHB cases by age, race/ethnicity, nativity, and disease activity status. Methods: Twelve counties in SF Bay Area and three large counties in LA area were included for this analysis. Race/ethnicity-specific prevalence of HBsAg for each county and the state of California as a whole, was estimated by including prevalence data from the National Health and Nutrition Examination Survey and various studies that estimated HBsAg prevalence in US and foreign-born Asian Pacific Islanders, Hispanic, and Black populations. In addition, clinical data of 2000 consecutive CHB patients (collected between 2009 and 2014) from a large clinical consortium in the SF Bay area were used to calculate the age-specific disease burden. Results: Of the 15 counties analyzed, SF had the highest HBsAg prevalence (1.78%), followed by Santa Clara (1.63%) and Alameda (1.45%). The majority of CHB cases were estimated to be in LA County (83,770), followed by Santa Clara (31,273), and Alameda (23,764). Among the CHB cases, 12.7% is active HBeAg positive, 24.2% is active HBeAg negative, and 10.6% has cirrhosis. Conclusion: This study confirms and quantifies the current burden of CHB in high endemic counties in the state of California using population-level estimates combined with clinical data including those from the community. Keywords: HBV, Disease status, California, Burden of disease Background primarily in the San Francisco (SF) bay and Los Angeles As a leading cause of liver disease, liver cancer, and liver (LA) areas [3]. However, only 34.6% are diagnosed [2], transplantation, chronic hepatitis B (CHB) is an import- 33.3% of those diagnosed receive care [4], and 45% of ant public health problem globally [1]. In 2013, viral those linked to care receive treatment if eligible accord- hepatitis took the lives of about 1.45 million people and ing to treatment guidelines [5]. Without diagnosis, link- was the seventh leading cause of death in the world, sur- age to care and treatment, one in four people with CHB passing malaria and tuberculosis [1]. An estimated will die from cirrhosis, liver cancer, and/or liver failure 850,000–2.2 million people in the United States (US) live [6]. In US regions with high proportion of immigrants, with CHB and only 34.6% are aware of their infection such as the SF Bay area, the vast majority of confirmed [2]. The highest prevalence of CHB and CHB-related cases of CHB are Asian or Pacific Islander (API) [2]. A liver cancer in the U.S is in the state of California (CA), study from San Francisco found that of all hepatitis B virus (HBV) infection cases reported, 84% were API and of those 80% were foreign born [7]. In the U.S., the preva- * Correspondence: mtoy@stanford.edu lence of CHB among foreign-born people is estimated to Asian Liver Center, Department of Surgery, Stanford University School of Medicine, 780 Welch Road, CJ130D, Palo Alto, CA 94304, USA be 10 times higher than the national prevalence rate [8]. A Full list of author information is available at the end of the article © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Toy et al. Hepatology, Medicine and Policy (2018) 3:6 Page 2 of 9 seroprevalence survey study on Asian Americans in the ethnicity- and nativity- as well as age-specific prevalence SF Bay area concluded that 8.9% API were infected with rates, where reported, in the studies that we used as preva- CHB but 65.4% of the chronically infected adults were un- lence data to calculate the overall prevalence for the SF Bay aware of their infection [2]. One of the four overarching area, the LA area and for the entire state of California. goals of the Department of Health and Human Services In all race/ethnicity groups of ages 0–19 years, except Action Plan for the Prevention, Care and Treatment of for the Black foreign-born Africa and Haiti groups as Viral Hepatitis is to increase the diagnosis rate of CHB well as the API foreign-born East Asia, we used the from 33 to 66% by 2020 [9]. NHANES 2015 data. NHANES reported a prevalence of The National Health and Nutrition Examination Survey 0.03% (0.01–0.08) among 6–19 year old group, which we (NHANES) has been the primary data source for HBV used for 0–19 year olds in the White, Hispanic, Black [10] prevalence estimate in the US population. However, US-born, API US-born Korea, Japan and South Asia due to the small sample size in the survey, it is not an ap- groups, as well as the Japanese foreign-born group. We propriate source for county- and state-specific prevalence used the prevalence that was 10-fold greater than the estimates of CHB [11]. In addition, county-level and race/ general population explanation of the NHANES study ethnicity-specific data are important for setting priorities and applied it to the Black foreign-born in Jamaica and in public health and resource allocation at the local level Dominican Republic, API US-born East Asian and API and since the distribution of CHB disease burden varies foreign-born Korean groups for estimating the preva- by race/ethnicity which itself varies by counties. Thus, lence among 0–19 year olds. to fill this gap, the aim of this study was to estimate the In order to quantify the age-specific “active” disease prevalence of HBsAg and quantify CHB active disease burden in relation to CHB activity and cirrhosis, we an- burden in the state of CA and certain specific counties alyzed clinical baseline data such as HBV DNA and ala- by age, race/ethnicity, and disease activity status, using nine aminotransferase (ALT) levels of 2000 consecutive population-based data and clinical data from a large new treatment-naïve CHB patients who presented be- clinical and community consortium in the SF bay area. tween 2009 and 2014 at several hepatology and commu- nity gastroenterology and primary care clinics as of the SF Methods Bay Area Consortium (SFBAC). Following the American As a first step, we obtained age-specific population for Association for the Study of Liver Disease (AASLD) 12 counties in the SF Bay area and 3 large counties in guidelines [6], disease status was defined as “active” by the the LA area (Los Angeles, San Bernardino and Orange following criteria: presence of cirrhosis or an elevation of counties) as well as county-specific race/ethnicity distri- ALT > 2 times the upper limit of normal (ULN) or evi- butions in these populations from the US census [12]. dence of significant histological disease plus elevated HBV We then categorized the population according to the fol- DNA above 2000 IU/mL for HBeAg-negative and above lowing four major racial/ethnic groups: White, Hispanic, 20,000 IU/mL for HBeAg-positive non-cirrhotic cases. Black, and API. Nativity data for Black and API popula- tions were also obtained from the US census bureau. Results Approximately, 10.3% of Blacks in the US are foreign Estimates of HBsAg prevalence and burden born [13], of whom 36% were born in Africa, 35% in The age-specific foreign-born distribution for API for Jamaica and Dominican Republic, 15% in Haiti, and 9% in age groups 0–19, 20–29, 30–39, 40–49, 50–59, 60–69, East and South America, and 5% elsewhere [14]. Within and 70+ were 22, 64, 83, 87, 89, 87, 90%, respectively. the API population, we further divided the groups into: Combining population distribution by county, race/ethnicity South Asian (23.3%), Korean (8.6%), Japanese (6.7%) and and nativity with race/ethnic specific HBsAg-prevalence, we other East Asian (61.4%) [15, 16]. Secondly, we calculated estimated that overall, all race-combined, there are 104,734 age-specific API foreign-born population distribution from (range 70,952–153,598) CHB cases or 1.18% (range the US census data [17]and used theseage-specificdistri- 0.80–1.73%) in the SF Bay area. Table 2 shows the esti- butions for the East Asia, Korea and South Asia group. For mated overall age-specific HBsAg-prevalence (all race example, the Japanese foreign born distribution was re- combined) and related number of CHB cases in the SF ported to be 27% in the US [15]. Next, we collected race/ Bay area. ethnicity- and nativity-specific HBsAg prevalence data As shown, the highest prevalence was amongst ages among White [11], Hispanic [11, 18], Black [11, 19–21]and 40–49 (2.08%) with a total of 25,627 (24.5% of all cases), APIs [2, 11, 19, 22–24] in the US from the literature. Jung followed by 1.86% for those between the ages of 30 et al. reported a 0% (353 people tested) of HBsAg preva- and 39. In the LA area, with a population of 15.5 lence among 70+ year old Hispanic population, which we million, we estimated that the overall prevalence is decided not to take and assume the same prevalence for 60 0.71% (range 0.46–1.12%), with a total of 109,442 (range +asthe 60–69 age-group (0.38%). Table 1 shows the race/ 71,363–172,482) with CHB. For California as a state with Toy et al. Hepatology, Medicine and Policy (2018) 3:6 Page 3 of 9 Table 1 Race/ethnicity- and nativity-specific HBsAg prevalence data from literature review Race/Ethnicity Ages 0–19 Prevalence (range) Reference Ages > 19 Prevalence (range) Reference White 0.03% (0.01–0.08) Roberts et al. [11] 0.10% (0.05–0.20) Roberts et al. [11] Hispanic 0.03% (0.01–0.08) Roberts et al. [11]20–29 0.16% (0.05–0.47) Jung et al. [18] 30–39 0.14% (0.04–0.42) 40–49 0.49% (0.24–1.00) 50–59 0.39% (0.21–0.72) 60–69 0.38% (0.10–1.37) 70 + 0.38% (0.10–1.37) Black US-Born 0.03% (0.01–0.08) Roberts et al. [11] 0.10% (0.05–0.20) Roberts et al. [11] Black Foreign-Born Africa 7.30% (6.50–8.00) Ugwu et al. [20]20–29 10.45% (9.50–11.30) Ugwu et al. [20] 30–39 11.20% (9.70–12.70) 40–49 6.99% (5.60–8.30) 50–59 10.86% (9.70–12.00) 60+ 10.86% (9.70–12.00) Jamaica and Dominican Rep. 0.30% (0.10–0.80) Roberts et al. [11] 2.10% (0.70–4.00) Din et al. [19] Haiti 2.50% (2.10–3.00) Tohme et al. [21] 2.50% (2.10–3.00) Tohme et al. [21] South & Central America 0.30% (0.10–0.80) Roberts et al. [11] 0.60% (0.2–2.00) Din et al. [19] API US Born East Asia 0.30% (0.10–0.80) Roberts et al. [11] 1.40% (0.65–1.90) Din et al. [19] Korea 0.03% (0.01–0.08) Roberts et al. [11] 1.40% (0.65–1.90) Din et al. [19] Japan 0.03% (0.01–0.08) Roberts et al. [11] 0.10% (0.05–0.20) Roberts et al. [11] South Asia 0.03% (0.01–0.08) Roberts et al. [11] 1.40% (0.65–1.90) Din et al. [19] API Foreign Born East Asia 1.10% (0.90–1.90) Shuler et al. [23]20–29 5.40% (3.10–8.50) Lin et al. [2] 30–39 11.50% (8.30–15.20) 40–49 12.20% (9.70–15.00) 50–59 8.80% (7.00–10.80) 60–69 8.00% (5.90–10.60) 70–79 6.70% (4.00–10.40) 80+ 3.70% (1.00–9.30) Korea 0.30% (0.10–0.80) Roberts et al. [11]20–29 1.18% (0.43–2.55) Hyun et al. [22] 30–39 2.53% (1.61–3.77) 40–49 2.76% (2.00–3.70) 50–59 2.90% (2.23–3.69) 60–69 2.06% (1.37–2.96) 70–79 1.37% (0.59–2.68) 80+ 2.17% (1.17–2.77) Japan 0.03% (0.01–0.08) Roberts et al. [11] 1.02% (1.01–1.02) Tanaka et al. [24] South Asia 0.30% (0.10–0.80) Roberts et al. [11] 2.70% (1.60–4.00) Din et al. [19] Definitions of race and ethnicity according to the US Census Bureau: White- A person having origins in any of the original peoples of Europe, the Middle East, or North Africa. Black or African American- A person having origins in any of the Black racial groups of Africa. Asian- A person having origins in any of the original peoples of the Far East, South East Asia, or the Indian subcontinent including, for example, Cambodia, China, India, Japan, Korea, Malaysia, Pakistan, the Philippine Islands, Thailand and Vietnam. Native Hawaiian or other Pacific Islander- A person having origins in any of the original peoples of Hawaii, Guam, Samoa, or other Pacific Islands. Hispanic origin can be viewed as the heritage, nationality, lineage, or country of birth of the person or the person’s parents or ancestors before arriving in the US The foreign born population includes anyone who is not a U.S citizen at birth, including those who became U.S citizens through naturalization API Asian Pacific Islander, US United States, HBsAg hepatitis B surface antigen We adapted from Jung et al. and assumed a 0.38% for 70+ We took a weighted average of Tanaka et al.’s HBV screening cohort ages 40–74 which we calculated to be 1.02% Toy et al. Hepatology, Medicine and Policy (2018) 3:6 Page 4 of 9 Table 2 Estimated HBsAg prevalence and estimated number of HBsAg-positive cases in the San Francisco Bay area Age Group (Years) Population (2015) HBsAg-positive cases (range) HBsAg-prevalence (range) 0–19 2,202,500 2607 (1474–5577) 0.12% (0.07–0.25%) 20–29 1,254,437 11,106 (6113–18,053) 0.89% (0.49–1.44%) 30–39 1,311,988 24,436(16,842–33,961) 1.86% (1.28–2.59%) 40–49 1,230,512 25,627 (19,102–33,946) 2.08% (1.55–2.76%) 50–59 1,192,159 19,120 (14,218–25,231) 1.60% (1.19–2.12%) 60–69 898,217 12,940 (8709–19,866) 1.44% (0.97–2.21%) 70–79 473,888 6117 (3455–10,572) 1.29% (0.73–2.23%) 80+ 310,260 2781 (1039–6393) 0.90% (0.34–2.06%) Total 8,873,961 104,734 (70,952–153,598) 1.18% (0.80–1.73%) Total population year 2015, counties: San Francisco, Santa Clara, Alameda, San Mateo, Contra Costa, San Joaquin, Merced, Monterey, Stanislaus, Marin, Santa Cruz and San Benito HBsAg hepatitis B surface antigen a population of 39.1 million, the prevalence was estimated Figure 2 shows the population and HBsAg distribution in to be 0.78% (0.51–1.21%), with a total estimated case the SF Bay area (Fig. 2a), Santa Clara County (Fig. 2b), and number as 305,419 (range 200,100–475,523). San Benito County (Fig. 2c). As shown, the SF Bay area has a 24.5% API population, but accounts for 88.5% of all CHB County-, race/ethnicity-, and nativity-specific HBsAg cases. Santa Clara County has the highest API population prevalence and burden (36%) and they account for 94% of the HBsAg-positive Of the 15 counties analyzed, SF County had the highest cases in the county. San Benito County has the highest His- HBsAg prevalence (1.78%), followed by Santa Clara panic population (59%), and they account for 38% of the (1.63%), Alameda (1.45%), San Mateo (1.40%) and Contra HBsAg-positive cases in the county. In contrast, although Costa (0.88%), as shown in Fig. 1. However, LA County API constitutes only 4% of the population in San Benito, (83,770), Santa Clara (31,273), Alameda (23,764) and they account for 50% of the HBsAg cases in this county. Orange County (15,091) have high number of individ- In the SF Bay area, the HBsAg prevalence in API is es- uals with HBsAg due to its large population. timated to be 4.26%. Although API comprises of 24.5% Fig. 1 HBsAg prevalence and number of chronic hepatitis B cases in 15 counties in the State of California Toy et al. Hepatology, Medicine and Policy (2018) 3:6 Page 5 of 9 Fig. 2 Racial and ethnic distribution among HBsAg-positive and general population in the San Francisco Bay area (a), Santa Clara County (b), and San Benito County (c) of the total population it accounts for 88.5% (92701) of the Active disease burden 104,734 HBsAg-positive cases. Of the HBsAg-positive cases Table 4 shows the patient characteristics of the 2000 among API cases, 4.93% were estimated to be US born and CHB patients in the Stanford and community clinic 84.0% foreign born (Table 3). Black cases (2886) made up consortium from the SF Bay area (SFBAC). Of these, 55.8% 2.76% of total cases, with 0.39% being US born and 2.37% were male, and the median age at diagnosis was 43. About being foreign born. 22% were positive for HBeAg, with 14% non-cirrhotic Toy et al. Hepatology, Medicine and Policy (2018) 3:6 Page 6 of 9 Table 3 HBsAg-positive cases and its distribution by age, race/ethnicity and nativity within each age group in the total 104,734 estimated cases in the San Francisco Bay area Age API Black Hispanic White Total Group Foreign-Born US-Born Foreign-Born US-Born (Years) 0–19 889 (34.1%) 781 (30.0%) 435 (16.7%) 36 (1.38%) 204 (7.83%) 262 (10.0%) 2607 20–29 8059 (72.6%) 1497 (13.5%) 394 (3.55%) 69 (0.62%) 589 (5.30%) 498 (4.48%) 11,106 30–39 22,106 (90.5%) 777 (3.18%) 437 (1.79%) 73 (0.30%) 523 (2.14%) 520 (2.13%) 24,436 40–49 22,512 (87.8%) 540 (2.11%) 289 (1.13%) 68 (0.27%) 1724 (6.73%) 494 (1.93%) 25,627 50–59 16,399 (85.8%) 450 (2.35%) 386 (2.02%) 66 (0.35%) 1336 (6.99%) 483 (2.53%) 19,120 60–69 10,878 (84.1%) 377 (2.91%) 291 (2.25%) 50 (0.39%) 976 (7.54%) 368 (2.84%) 12,940 70–79 5077 (83.0%) 154 (2.52%) 151 (2.47%) 26 (0.43%) 515 (8.42%) 194 (3.17%) 6117 80+ 2068 (74.4%) 137 (4.93%) 99 (3.56%) 17 (0.61%) 333 (12.0%) 127 (4.57%) 2781 Total 87,988 (84.0%) 4713 (4.50%) 2482 (2.37%) 405 (0.39%) 6200 (5.92%) 2946 (2.81%) 104,734 (100%) active HBeAg-positive and 26% non-cirrhotic active people with CHB in CA meet the AASLD criteria for HBeAg-negative. Approximately 9% of all cases had treatment. cirrhosis. Applying clinical data from Table 4 to the SF Bay area Discussion CHB population, in Table 5, we show the estimated data This study confirms and quantifies the current burden of on HBeAg, CHB activity, and cirrhosis. The number of CHB in high endemic counties in the state of CA using active CHB cases, who are considered to be eligible for population-level estimates combined with real-world clin- antiviral treatment by the AASLD guideline because they ical data including those from the community. We esti- have significant viremia and evidence of on-going in- mated the overall all race-combined HBsAg-prevalence of flammation or hepatic fibrosis, included 14,3149 (12.6%) the SF Bay area, LA area, and the state of CA to be 1.18, in the HBeAg-positive group, and 25,636 (24.5%) in the 0.71 and 0.78%, respectively. The national US HBsAg HBeAg-negative group, with 11,112 (10.6%) cirrhosis prevalence estimated by NHANES is only 0.3% [11]. Ac- cases at baseline. In the LA area, a total of 51,952 people cording to our estimates, SF Bay area prevalence surpasses out of the 15.5 million population and 109,442 CHB the 0.3% by about 4-fold. The prevalence is highest in the cases are estimated to need antiviral treatment. When SF (1.78%), Santa Clara (1.63%), and Alameda (1.45%) projected to the state of California as a whole, out of counties. However, the burden based number of patients an estimated 305,419 CHB cases, 38,158 are active is highest in the LA (83,770), Santa Clara (31,273) and HBeAg-positive, 73,700 are active HBeAg-negative and Alameda (23,764) counties, due to the large population, 33,091 are cirrhotic. In total, an estimated 144,949 (47.5%) especially APIs, in these counties. As expected, a signifi- cant portion of the burden is among the API population, Table 4 Characteristics of the chronic hepatitis B patients from with an estimated 4.26% HBsAg-prevalence. This rate is the hepatology and community gastroenterology and primary higher than the 3.1% reported by the NHANES 2015 care clinics of the San Francisco Bay area consortium study as the true prevalence of CHB infections for Asians Parameters Results [11], including both immigrants and naturalized citizens. Total number, N 2000 Our estimate is comparable to the 3.8% prevalence re- Male 1117 (55.8%) ported by Levy et al. among men aged 18–35 years resid- ing in low-income neighborhoods in Northern California Age 43 (18–88) [25]. Although the Centers for Disease Control and Pre- HBeAg-positive 444 (22.2%) vention (CDC) estimates that Asians account for 50% of Active HBeAg-positive (non cirrhotic)* 272 (14%) all CHB cases in the US [26], our study estimated that in Active HBeAg-negative (non cirrhotic)* 510 (26%) CA, especially in the SF Bay area, APIs make up 88.5% of ALT (U/L) 39 (3–2809) all the CHB cases. Particularly relevant is the high propor- HBV DNA (log IU/mL) 4.0 (1.3–11.3) 10 tion of total CHB cases among the API foreign-born group that account for 84.0% of all the cases in the SF Bay Cirrhosis 185 (9%) area. It is estimated that the overall burden of CHB in the *Active is defined by an elevation of ALT > 2× upper limit of normal or evidence of significant histological disease plus elevated HBV DNA above U.S. will continue to increase with ongoing immigration 2000 IU/mL for HBeAg-negative, and above 20,000 IU/mL for from countries with intermediate (2–8%) to high (> 8%) HBeAg-positive [6] HBeAg hepatitis B e antigen, ALT alanine aminotransferase HBV prevalence [8]. For the foreign born population, we Toy et al. Hepatology, Medicine and Policy (2018) 3:6 Page 7 of 9 Table 5 Prevalence of chronic hepatitis B in the San Francisco Bay area by age and disease status Age Group (Years) Population (2015) Inactive CHB Active HBeAg positive Active HBeAg negative Cirrhosis 0–19 2,202,500 1805 (69.2%) 602 (23.1%) 201 (7.69%) 0 20–29 1,254,437 5360 (48.3%) 2744 (24.7%) 2701(24.3%) 300 (2.70%) 30–39 1,311,988 12,218 (50.0%) 4680 (19.2%) 6834 (28.0%) 704 (2.88%) 40–49 1,230,512 13,111 (51.2%) 2930 (11.4%) 7450 (29.1%) 2136 (8.33%) 50–59 1,192,159 9770 (51.1%) 1199 (6.27%) 5154 (27.0%) 2997 (15.7%) 60–69 898,217 7939 (61.4%) 438 (3.38%) 1813 (14.0%) 2751 (21.3%) 70–79 473,888 3186 (52.1%) 382 (6.25%) 1020 (16.7%) 1529 (25.0%) 80+ 310,260 1448 (52.1%) 174 (6.25%) 463 (16.7%) 695 (25.0%) Total 8,873,961 54,837 (52.4%) 13,149 (12.6%) 25,636 (24.5%) 11,112 (10.6%) Inactive CHB are those who are HBsAg positive with low HBV DNA or high HBV DNA but normal alanine aminotransferase or ALT levels HBeAg hepatitis B e antigen tried to use prevalence data from the US immigrant stud- to the state of CA. As there are many immigrants in ies where available rather than the prevalence in their California from the Middle East, which historically home country. had a higher HBV prevalence than Western Europe or the It is noteworthy that although currently both preva- European settlers of North America, the NHANES study lence of HBV infection and incidence of hepatocellular we used to estimate the prevalence among whites does carcinoma (HCC) due to HBV are high in the API popu- not differentiate among the white population which is lation, data from SEER registries have shown a decline likely a limitation in our study. in HCC incidence among Asians, while rates in other ra- Given the high burden of CHB and HCC in the SF cial/ethnic groups will continue to rise [27, 28]. In fact, in Bay area and California, targeted prevention and control a national forecast study using SEER national data, by efforts are needed to minimize the burden in these com- 2030, Hispanics will have the highest HCC in the country, munities. A recent CDC-funded study showed that in while Asians will have the lowest HCC rates [28]. It is im- cities with large populations of Asia- and Africa-born portant to note that Hispanic is the largest racial/ethnic immigrants, community-based and refugee clinic-based population in the state of California, accounting for 39% HBV testing initiatives can identify substantial numbers of the total CA population [29]. Relative to Asians, His- of individuals with CHB [32], and stresses the fact that panics tend to have lower CHB infection but higher HCV culturally and linguistically specific approaches were ne- infection. Although our HBsAg-prevalence estimate of the cessary in all phases of the initiatives. Our data and esti- Hispanic population in the SF Bay area is only 5% of the mates can be used for resource allocation planning to total, in counties that have large Hispanic populations target specific geographic areas and subpopulations, such as San Benito and Merced, the Hispanic population race/ethnicities for effective interventions, such as makes up to 38% of all CHB cases. During the 2006–2010 screening and linkage to care with appropriate therapies, period, among individuals aged 50–64 years, Hispanics ex- to minimize the burden of CHB and its clinical conse- perienced higher HCC incidence and mortality rates than quences, such as liver cirrhosis, and liver cancer. These Asians and Whites [30]. Few studies have investigated risk interventions are urgently needed as currently most of factors for HCC in Hispanics and the reasons for the ris- the CHB patients (70%) in the US are not aware of their ing trend in this ethnic group, although one study did HBV infection and there are also large gaps at various show that HBV infection is one of the risk factors for levels of the cascade of care for those with known CHB HCC in Hispanic [30]. [5, 33–35]. Importantly, improved linkage to care can Although we analyzed 62% of the total population of identify patients who may benefit from antiviral therapy California, it is unclear whether we can generalize the which has been shown in both randomized control studies data from SF and LA reported here to the entire state of as well as large cohort studies in the US to substantially California, as SF and LA cover counties that are more reduce HCC risk in CHB patients [36, 37]. densely populated and more diverse, and the remainder 43 counties in the state are quite different. However, our Conclusion clinical data, including HBeAg status, among CHB pa- In summary, our data suggest that there are approximately tients from the university liver and community gastro- 305,000 persons living with CHB in the State of CA, and enterology and primary care clinics were comparable to about half of these (47.5%, 150,000) have cirrhosis and/or those reported by a North American multicenter study meeting AASLD guideline criteria for antiviral therapy. [31], suggesting some utility of generalizing our estimates We also found significant variation in the racial/ethnic Toy et al. Hepatology, Medicine and Policy (2018) 3:6 Page 8 of 9 make-up of the CHB population in different regions and 2. Lin SY, Chang ET, So SK. Why we should routinely screen Asian American adults for hepatitis B: a cross-sectional study of Asians in California. counties of the State, highlighting the need for region/ Hepatology. 2007;46(4):1034–40. county-specific approach for public health efforts target- 3. Gish RG, Cooper SL. Hepatitis B in the greater San Francisco Bay Area: an ing CHB patients. Our methodology can be applied in integrated programme to respond to a diverse local epidemic. J Viral Hepat. 2011;18(4):e40–51. other states or regions to estimate specific county, age, 4. Hu DJ, Xing J, Tohme RA, Liao Y, Pollack H, Ward JW, Holmberg SD. racial/ethnic prevalence and the overall and distribution Hepatitis B testing and access to care among racial and ethnic minorities in active/advanced disease burden that would be crucial in selected communities across the United States, 2009-2010. Hepatology. 2013;58(3):856–62. the planning of local public health efforts in those areas. 5. Kim LH, Nguyen VG, Trinh HN, Li J, Zhang JQ, Nguyen MH. Low treatment rates in patients meeting guideline criteria in diverse practice settings. Dig Abbreviations Dis Sci. 2014;59(9):2091–9. AASLD: American association for the study of liver disease; ALT: Alanine 6. Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH, aminotransferase; API: Asian or pacific islander; CA: California; CDC: Centers American Association for the Study of Liver D. AASLD guidelines for for Disease Control and Prevention; CHB: Chronic hepatitis B; treatment of chronic hepatitis B. Hepatology. 2016;63(1):261–83. DNA: Deoxyribonucleic acid; HBsAg: Hepatitis B surface antigen; 7. CDC. Characteristics of persons with chronic hepatitis B: San Francisco, HCC: Hepatocellular carcinoma; LA: Los Angeles; NHANES: National Health California, 2006. Morb Mortal Wkly Rep. 2007;56(18):446–8. and Nutrition Examination Survey; SF: San Francisco; SFBAC: San Francisco 8. Kowdley KV, Wang CC, Welch S, Roberts H, Brosgart CL. Prevalence of Bay Area Consortium; ULN: Upper limit of normal; US: United States chronic hepatitis B among foreign-born persons living in the United States by country of origin. Hepatology. 2012;56(2):422–33. Funding 9. Services HaH. In: Services DoHaH, editor. Action plan for the prevention, Funding for this study was provided by the Stanford Cancer Institute Award care, & treatment of viral hepatitis. Washington, DC; 2017. Program. 10. Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, Huang GT, Iloeje UH, Group R-HS. Risk of hepatocellular carcinoma across a biological gradient of serum Availability of data and materials hepatitis B virus DNA level. JAMA. 2006;295(1):65–73. The datasets used and/or analysed during the current study are available 11. Roberts H, Kruszon-Moran D, Ly KN, Hughes E, Iqbal K, Jiles RB, Holmberg from the corresponding author on reasonable request. SD. Prevalence of chronic hepatitis B virus (HBV) infection in U.S. households: National Health and nutrition examination survey (NHANES), Authors’ contributions 1988-2012. Hepatology. 2016;63(2):388–97. MT, MHN, SKS: Designed the study, analyzed the data, and wrote the 12. United States Census Bureau [http://www.census.gov/]. Accessed 15 Aug manuscript. BW, TSV, AL, HT, JL, JZ, AWH: Gathered the data, analyzed the data, and wrote the manuscript. All authors read and approved the final 13. Current Population Survey, Annual Social and Economic Supplement. 2013. manuscript. https://www.census.gov/programs-surveys/saipe/guidance/model-input- data/cpsasec.html. Retrieved February 17, 2017. Ethics approval and consent to participate 14. Pewsocialtrends: A rising share of the US black population is foreign born Not applicable. [http://www.pewsocialtrends.org/2015/04/09/a-rising-share-of-the-u-s-black- population-is-foreign-born/]. Accessed 18 Aug 2017. 15. 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Hepatology, Medicine and PolicySpringer Journals

Published: Jun 5, 2018

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