This document summarizes a study comparing demographic and lab differences between US-born and foreign-born Asia Pacific Islanders (APIs) with hepatitis B infection at Kaiser Permanente Hawaii. The study found that foreign-born APIs were younger on average than US-born. While most patients had HMO insurance, US-born APIs were more likely to have Medicare. US-born APIs also had significantly longer enrollment durations and higher rates of undetectable viral loads, possibly due to better access to healthcare and treatment. Foreign-born APIs had higher rates of HBeAg testing likely due to higher viral loads.

1. Demographic and Lab Differences between
US-Born and Foreign-Born
Asia Pacific Islanders among the
Hepatitis B Patients of Kaiser Permanente, Hawaii
Vinutha Vijayadeva1, Cynthia Nakasato1, Stuart C Gordon2,
Loralee B Rupp2, Mei Lu2, Emily Henkle3, Joseph A Boscarino4
Kaiser Permanente Center for Health Research Hawai′i1, Henry Ford Health System 2,
The Center for Health Research Northwest3, Geisinger Health System 4
HMO Research Network Conference
Seattle 2012
© 2011, KAISER PERMANENTE CENTER FOR HEALTH RESEARCH 1

2. Background
 Globally two billion people are infected with hepatitis B virus
(HBV) and about 350 million live with chronic infection.1
 Approximately 550,000–2 million people in U.S. live with chronic
HBV2-5 with 2,000-4,000 deaths attributed to HBV annually.3,4
 40% to 70% of U.S. residents chronically infected with HBV are
foreign-born immigrants, mainly Asian and the Pacific Islanders.2
© 2011, KAISER PERMANENTE CENTER FOR HEALTH RESEARCH 2

3. Background (continued)
 HBV related liver cancer incidence is highest among APIs and is
a leading cause of cancer deaths in this population.
 Due to continuous improvements in mortality and increased life
expectancy, it is important to investigate the relationships
between different sociodemographic factors and health.
© 2011, KAISER PERMANENTE CENTER FOR HEALTH RESEARCH 3

4. Objective
 Investigate the demographic and lab differences between the
foreign-born and US-born APIs infected with HBV at Kaiser
Permanente, Hawai'i (KPHI).
– This study is a part of a larger ongoing study called Chronic Hepatitis
Cohort Study (CHeCS).
– The study protocol was reviewed by an Institutional Review Board and
the federal Office for Human Research Protections.
© 2011, KAISER PERMANENTE CENTER FOR HEALTH RESEARCH 4

5. CHeCS
 CHeCS is a dynamic multicenter cohort study designed to
assess the impact of chronic infection with HBV and HCV.
 Four HMO Research Network (HMORN) sites:
– Henry Ford Health System, Detroit MI (coordinating center)
– Geisinger Health System, Danville, PA
– Kaiser Permanente- Northwest, Portland, OR
– Kaiser Permanente- Honolulu, Hawaii
 Funded by CDC Foundation.
© 2011, KAISER PERMANENTE CENTER FOR HEALTH RESEARCH 5

6. CHeCS Hepatitis B Inception Cohort Year 1 Selection
1) Patients with any utilization between 1/1/06 and 12/31/08, AND
2) At least 18yo as of last date of utilization in period 1/1/06-12/31/08 1Qualifying
Hep B diagnoses:
• Hep B chronic dx list – 070.22, 070.23,
070.32, 070.33
• Hep B acute/unspec dx list – 070.2,
070.20, 070.21, 070.3, 070.30, 070.31
Retain patients with at least 1 encounter between Retain patients with at least 1 qualifying Hep B lab
1/1/06-12/31/08 with qualifying Hep B diagnosis1 test3 between 1/1/06-12/31/08 with positive/ 2Qualifying
CLD* diagnoses:
(primary or secondary) detectable result (*CLD = Chronic Liver Disease)
571.5, 456.0, 456.1, 789.59, 155.0, V42.7,
V49.83
3Qualifying Hep B lab tests:
Distinct MRNs - Candidate patients • HBsAG
Pull full history of all encounters with qualifying Hep diagnoses & • HBeAG
• HBVQL
all Hep lab results for all NC candidate patients • HBVQT
Inclusion Category 1 Inclusion Category 2 Inclusion Category 6
Inclusion Category 3 Inclusion Category 4 Inclusion Category 5
Throughout full patient hx: Throughout full patient hx: Throughout full patient hx:
Throughout full patient hx: Throughout full patient hx: Throughout full patient
Two or more encounters Qualifying Hep B dx1 or HBsAG + AND an elevated
Any two of the following tests HBcABM neg prior to or hx:
with qualifying Hep B CLD dx2 at any time AND ALT/SGPT (above normal
positive/detectable at least 6 at the same time as any HBcABT pos at any
diagnoses1 (primary or HBsAG + or HBVQL upper limit) -- at least 6
mos apart (any two tests or of the following results : time AND HBsAG pos
secondary) -- occurring at +/detectable or HBVQT mos apart (either first)
same test): HBsAG, HBeAG, HBsAG + or HBVQL at any time
least 6 mos. apart +/detectable at any time NI6 = 156
HBVQL, or HBVQT +/detectable or HBVQT
+/detectable
EXCLUDE
Distinct MRNs INCLUDE in cohort YES Patient qualifies NO
(but eligible to be reviewed for inclusion next year)
TIME ZERO=Earliest date of qualifying Hep under any inclusion
category above? Distinct MRNs
B dx or pos. test result in full patient hx
© 2011, KAISER PERMANENTE CENTER FOR HEALTH RESEARCH 6

7. Data sources
Demography table: Encounter
Date of birth, Race, Gender, table:
Country of Origin (COO) Diagnoses, date
Lab Virtual Data Warehouse Medications
(VDW) Source
Procedures Census table:
Enrollment
Household income &
Education
Survey
Non VDW Source
Chart abstractions
© 2011, KAISER PERMANENTE CENTER FOR HEALTH RESEARCH 7

8. Country of origin (COO)
 VDW (n=349) supplemented with
– Survey (n=55)
– Chart abstractions (n=109)
 Computed variable based on COO
– Foreign-born
– US-born
© 2011, KAISER PERMANENTE CENTER FOR HEALTH RESEARCH 8

9. Hawaii Sample CHeCS HBV Cohort
N = 739
Excluded Non-Cases &
insufficient evidence
n = 86
HBV / HBV+HCV
n = 653
Excluded Non APIs
n = 132
HBV / HBV+HCV
and APIs
n = 521 Excluded subjects with no
country of origin (COO)
n=8
HBV /
HBV+HCV, APIs and
COO
n = 513
Foreign-born US-born
n = 388 n = 125
© 2011, KAISER PERMANENTE CENTER FOR HEALTH RESEARCH 9

10. Statistical analysis
 Analysis performed using SAS, version 9.2 (SAS Institute Inc, Cary, NC)
 T-test for continuous variables
 Chi-square or Fischer's Exact for the categorical variables
 Wilcoxan Rank Sum test for the categorical values that were clearly ordinal
except for viral loads because of the varying upper & lower levels of
quantitation for these tests
© 2011, KAISER PERMANENTE CENTER FOR HEALTH RESEARCH 10

11. Hawaii VDW race
15.80% 19.17%
0.77%
Hawaiian, Pacific Islanders
3.53%
Asians
White
Black & AI/AN
Unknown
60.74%
Before non API exclusion n = 653, 1 missing for race
© 2011, KAISER PERMANENTE CENTER FOR HEALTH RESEARCH 11

12. Variables of interest
Chronic hepatitis B tests
Socio-demographic
(between 2001-2008)
– Age (yr): most recent visit prior – Alanine Aminotransferase
to 2008 (ALT, IU/L): maximum
– Gender (F/M) – HBV viral load (QUANT, IU/ml):
– Income (estimated by census most recent
tract geocode) – HBeAg
– Insurance type – Liver biopsy
– Enrollment length (months):
from 01/01/1998
© 2011, KAISER PERMANENTE CENTER FOR HEALTH RESEARCH 12

13. Age group
30
25 Foreign-born
US-born
20
% 15
10
5
0
<20 20-<30 30-<40 40-<50 50-<60 60-<70 70-<80 >=80
Age groups
Mean SD - Foreign-born: 49.0 13.8 & US-born: 53.8 17.4
© 2011, KAISER PERMANENTE CENTER FOR HEALTH RESEARCH 13

14. Gender
60
Foreign-born
US-born
55
% 50
45
40
Female Male
Fisher’s Exact test 0.41
© 2011, KAISER PERMANENTE CENTER FOR HEALTH RESEARCH 14

15. Income level
60
Foreign-born
50
US-born
40
% 30
20
10
0
<15,000 15,000 - 29,000 30,000 - 49,000 50,000 - 75,000 >75,000
Income levels
(estimated by census tract geocode)
Status known: Foreign-born 382 & US-born 124
Wilcoxon Rank Sum test 0.06
© 2011, KAISER PERMANENTE CENTER FOR HEALTH RESEARCH 15

16. Insurance
100
Foreign-born
80
US-born
60
%
40
20
0
Medicaid Medicare Plus HMO
Status known: Foreign-born 366 & US-born 127
Fisher’s Exact test <0.01
© 2011, KAISER PERMANENTE CENTER FOR HEALTH RESEARCH 16

17. Enrollment length
120
Foreign-born
100
US-born SD 38
80
SD 45
Months
60
40
20
T-test <0.01
0
Enrollment length
© 2011, KAISER PERMANENTE CENTER FOR HEALTH RESEARCH 17

18. Alanine Aminotransferase (ALT)
80
70
Foreign-born
60
US-born
50
% 40
30
20
10
0
<LLN &/or Normal >ULN to ≤ 2xULN >2xULN to ≤4xULN >4xULN to ≤8xULN > 8xULN
Status known: Foreign-born 385 & US-born 124
Wilcoxon Rank Sums test 0.79
© 2011, KAISER PERMANENTE CENTER FOR HEALTH RESEARCH 18

19. HBV Viral load (QUANT)
80
US-born have significantly higher
Foreign-born
70
proportion of undetectable US-born
60 viral load compared to foreign-born.
50
% 40
30
20
10
0
Undetectable >300 to ≤2,000 >2,000 to ≤20,000 >20,000 to >200,000
(detectable) ≤200,000 (ULD=200,000)
Status known: Foreign-born 278 & US-born 76
Wilcoxon Rank Sums test 0.13
© 2011, KAISER PERMANENTE CENTER FOR HEALTH RESEARCH 19

20. HBeAg ever tested & Liver biopsy
80
70 Foreign-born
60 US-born
50
% 40
30
20
10
0
HBeAg Liver biopsy
Fisher’s Exact test: HBeAG 0.01 & biopsy >0.99
© 2011, KAISER PERMANENTE CENTER FOR HEALTH RESEARCH 20

21. Summary & Discussion
 Foreign-born APIs are much younger compared to US-born.
 US-born APIs have higher income level compared to foreign-
born but the difference was not significant.
 While most of the patients had HMO insurance, US-born APIs are
more likely to have Medicare Plus.
 US-born APIs have significantly higher duration of enrollment
compared to foreign-born
© 2011, KAISER PERMANENTE CENTER FOR HEALTH RESEARCH 21

22. Summary & Discussion
 US-born have significantly higher undetectable viral load (most
recent) compared to foreign-born
– Increased number of HBV infected US-born APIs are in inactive
state, probably due to:
 Spontaneous resolution or treatment
 Access to the health care
– Higher enrollment length
– Higher income level
– Older age group with additional insurance like Medicare Plus
– Language
 Foreign-born have significantly higher HBeAg testing compared
to US-born likely because of higher viral load.
© 2011, KAISER PERMANENTE CENTER FOR HEALTH RESEARCH 22

23. Next steps
 Test the treatment difference between the foreign-born and US-
born APIs
 Compare the foreign-born APIs from high to low HBV prevalent
countries
 To incorporate the survey data for information on transmission
of HBV
© 2011, KAISER PERMANENTE CENTER FOR HEALTH RESEARCH 23

24. Acknowledgments
 Philip Spradling, MD
 Anne Moorman, BSN MPH
 Scott D Holmberg, MD MPH
 Nancy Oja-Tebbe, BS
© 2011, KAISER PERMANENTE CENTER FOR HEALTH RESEARCH 24

25. References
1. Hepatitis B Fact sheet No. 204. 2008. [Accessed August 31, 2012]. http://www.who.int/mediacentre/factsheets/fs204/en/.
2. Weinbaum CM, Williams I, Mast EE, Wang SA, Finelli L, Wasley A, et al. Centers for Disease Control and Prevention. Recommendations
for identification and public health management of persons with chronic hepatitis B virus infection. MMWR Recommend Rep
2008;57(RR-8):1-20.
3. Wasley A, Kruszon-Moran D, Kuhnert W, Simard EP, Finelli L, McQuillen G, Bell B. The prevalence of hepatitis B infection in the United
States in the era of vaccination. J Infect Dis 2010;202:192-201.7.
4. Cohen C, Evans AA, London WT, Block J, Conti M, Block T. Underestimation of chronic hepatitis B infection in the United States of
America. J Viral Hepat 2008;15:12-13.
5. Ioannou GN. Hepatitis B virus in the United States: infection, exposure, and immunity rates in a nationally representative study. Ann Int
Med 2011;154:391-398.
6. Paisano EL. We the Americans: Asians. Washington,DC: US Dept of Commerce, Bureau of the Census;September, 1993.
7. Vogt T, Wise ME, Shih H, Williams IT. Hepatitis B mortality in the United States, 1990--2004 [Abstract]. 45th Annual Meeting of Infectious
Diseases Society of America, San Diego, California; October 4--7, 2007.
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26. MahaloQuestions
© 2011, KAISER PERMANENTE CENTER FOR HEALTH RESEARCH 26