Mitigating Hepatitis B (HBV) Infections: Template for Eradicating the World’s Second Deadliest Cancer

Moon S. Chen, Jr., Ph.D., M.P.H.

Professor, Division of Hematology and Oncology, UC Davis School of Medicine

Associate Director, Cancer Control/Cancer Health Disparities

UC Davis Comprehensive Cancer Center

Sacramento, CA

18th Conference on Healthcare of the Chinese in North America

October 8, 2016

ACKNOWLEDGMENTS

The views expressed are those of the presenter and do

not necessarily represent the views of the NIH. However, I

am grateful for the support provided through the NCI to

AANCART (U54 CA153499) and the opportunity to be

part of the Cancer Prevention Symposium

Slides created by: Julie Dang, MPH, CHES

Presentation objectives:

1. Review the epidemiological significance of chronic Hepatitis B

(HBV) infections for foreign-born Asian Americans and its

etiological role in hepatocellular carcinoma. Why care?

2. Highlight research, policies, and practices that can be

leveraged in community and clinical settings to mitigate HBV-

linked hepatocellular carcinoma. What can be done?

3. Discuss the potential of HBV prevention and control as being

the next “smallpox”, i.e., the next disease that could be

eliminated/eradicated. What is the take-away?

Significance of chronic HBV for foreign-born and

its etiological role in hepatocellular carcinoma

Liver cancer is now the world’s second

deadliest cancer.

Globally, HBV is the primary cause of cancer after tobacco use.

“Following tobacco use,

infections as a group may

be the most important

preventable cause of

cancer in humans.”

Kuper, Adami, Trichopoulos, 2000

Global

Population,

7.4 billion

Infected in

their lifetime,

2 billion

Chronically

infected,

400 million

Global Magnitude of HBV

Asian Americans with Chronic HBV

Asian Americans 6%

US DEMOGRAPHICS

Percent Change: 2000 to 2010

9.7%5.7%

12.3%

18.4%

43.3%

35.4%

24.4%

32.0%

To

tal

po

pu

lati

on

Wh

ite

Bla

ck

AIA

N

Asia

n

NH

PI

SO

R

Tw

o o

rM

ore

Race

s

Source: Census 2000 and 2010 Census

HBsAg Prevalence

8% - High

2-7% - Intermediate

< 2% - Low

Significance

Liver cancer due to hepatitis B viral infection is a major cancer burden for people of color.

Lands of Origin:

• Southeast

Asia (Hmong)

• Vietnam

• China

• Korea

Apr 14

9 March 2016, Cancer

Prostate

-4.0

Colorectum

-3.0

Lung and Bronchus

-2.4

All Malignant

Cancers

-1.4

Pancreas

1.2

Melanoma of Skin

2.0

Liver & intrahepatic

duct 3.7

Thyroid

5.3

-6 -4 -2 0 2 4 6Average Annual Percent Change

Trends in Cancer Incidence, 1992 to 2012, Males

USA

Siegel R, Miller KD, Jemal A. Cancer Statistics 2016. CA Cancer J Clin 2016; 66: 7-30

Colorectum

-2.8

Lung and Bronchus

-1.1

Female Breast

0.0

All Malignant

Cancers

0.0

Melanoma of Skin

0.9

Pancreas

1.1

Uterine Corpus

1.5

Liver and

Intrahepatic Bile

Duct

3.0

Thyroid

5.2

-4 -2 0 2 4 6

Average Annual Percent Change

Trends in Cancer Incidence, 1992 to 2012, Females

USA

Siegel R, Miller KD, Jemal A. Cancer Statistics 2016. CA Cancer J Clin 2016; 66: 7-30

HBV HCV

Similarities• Both cause asymptomatic chronic viral infections

• Both are IARC classified carcinogens

• Both require specific serological detection

• Both etiologically related to liver cancer

Differences-Structure

-Prevalence

-Risk

--Vaccine

• Circular DNA genome

• 2.2 million Americans

• >50% Asian Americans

• Born in > 2% HBV endemic

areas

• Vaccination possible

• ssRNA genome

• 3.5 million Americans

• >75% baby boomers

• 1945-65 birth cohort

• Currently no vaccination

Trends in Cancer Mortality, 1992 to 2012, Males

USA

Siegel R, Miller KD, Jemal A. Cancer Statistics 2016. CA Cancer J Clin 2016; 66: 7-30

Prostate

-3.6

Colorectum

-2.9

Lung and

Bronchus

-2.7

All Malignant

Cancers

-1.8

Melanoma of Skin

0.3

Pancreas

0.3

Thyroid

1.5

Liver and

Intrahepatic Bile

Duct

2.8

-4 -3 -2 -1 0 1 2 3 4

Average Change

7.6

12.8

12.9

13.9

14.5

0 2 4 6 8 10 12 14 16

Non-Hispanic White

Non-Hispanic Black

Hispanic

American Indian/Alaska Native

Asian/Pacific Islander

Liver & Intrahepatic bile duct cancer mortality

rates for males, USA, 2008-2012 per 100,000

Siegel RL et al. Cancer Statistics, 2016; CA Cancer J Cln 2016; 66:7-30

Trends in Cancer Mortality, 1992 to 2012, Females

USA

Siegel R, Miller KD, Jemal A. Cancer Statistics 2016. CA Cancer J Clin 2016; 66: 7-30

Colorectum

-2.9

Female Breast

-1.9

All Malignant

Cancers

-1.4

Lung and Bronchus

-1.4

Melanoma of Skin

-0.5

Thyroid

-0.5

Pancreas

0.4

Uterine Corpus

1.1

Liver and

Intrahepatic Bile

Duct

2.1

-4 -3 -2 -1 0 1 2 3Average Annual Percent Change

3.1

4.4

5.6

6.1

6.3

0 1 2 3 4 5 6 7

Non-Hispanic White

Non-Hispanic Black

Hispanic

Asian/Pacific Islander

American Indian/Alaska Native

Liver & Intrahepatic bile duct cancer mortality

rates for females, USA, 2008-2012 per 100,000

Siegel RL et al. Cancer Statistics, 2016; CA Cancer J Cln 2016; 66:7-30

Asian American Cancer Mortality Trends Reported By Race/ Ethnicity

Table 1. Top 5 sites of cancer-related mortality, ranked as a proportion of all cancer deaths, by race/ethnicity

(2003–2011)

Thompson, C. A., Gomez, S. L., Hastings, K. G., Kapphahn, K., Yu, P., Shariff-Marco, S., … Palaniappan, L. P. (2016). The Burden of Cancer in Asian Americans: A

Report of National Mortality Trends by Asian Ethnicity. Cancer Epidemiology, Biomarkers & Prevention: A Publication of the American Association for Cancer

Research, Cosponsored by the American Society of Preventive Oncology, 25(10), 1371–1382. https://doi.org/10.1158/1055-9965.EPI-16-0167

Is chronic hepatitis B being undertreated?

Journal of Viral Hepatitis

Volume 18, Issue 6, pages 377-383, 8 DEC 2010 DOI: 10.1111/j.1365-2893.2010.01401.x

http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2893.2010.01401.x/full#f1

54.4% 31.1%14.5%

HBV

Diabetes, Obesity,

Aflatoxins, Metabolic Syndrome,

Other??

HCV

Hepatocellular

Carcinoma

De Flora, S., & La Maestra, S. (2015). Epidemiology of cancers of infectious origin and prevention strategies. Journal

of preventive medicine and hygiene, 56(1), 15-20.

85.5%

Impact & limitations of community &

clinically-based interventions

Community-Based Interventions to

Promote Hepatitis B Testing

Liver Cancer Control for Asian AmericansNCI P01CA109091-04A1

Lay Health Worker Visiting Home

Conducting Survey

Impact of Lay Health Workers

6-year randomized controlled trial (2006-

2011)

LHW intervention

HBV vs general nutrition

260 Hmong adults through in-home

education and patient navigation

Chen, MS, et al. Cancer Epidemiol Biomarkers Prev 2013;22:782-91.

Increasing Screening in the Hmong

Community by Lay Health Workers

0

5

10

15

20

25

30

HBV Testing HBV

Knowledge

Pe

rce

nta

ge

HBV Nutrition

P = 0.01

P = 0.0003

LHW had a significant

impact on HBV testing

but rates remained low

90% reported having

medical insurance

80% reported having a

regular physician

Chen MS, et al. Cancer Epidemiol Biomarkers Prev.2013 22:782-91.

Using EMR to Increase HBV Testing

76 PCP randomized during 175

outpatient visits

Intervention (n = 88) Control (n = 87)

HBsAg Ordered 36 (40.9%) 1 (1.1%)

HBsAg Tested 30 (34.1%) 0

HBsAg POS 4 (4.5%) 0

Hsu L, et al. Dig Dis Sc. 2013;58:807-14

Thousand Asian American Study (TAAS)

Sacramento Collaborative to Advance Testing &

Care of Hepatitis B (SCrATCH B)

• Health System “Inreach”

*Identification of “untested”

*Recruitment to testing

*Identification of HBsAg positive patients

*Case management of HBsAg positive patients

Mitigating Liver Cancer Health Disparities Among

Asian Americans

Funding Publications Collaborations Shared Resources

U54 CA153499 PCD, 2012 UCSF, UCLA, University of Hawaii, Biostatistics

P01 CA1090901 DDS, 2013 Hmong Women’s Heritage Association Biorepository

R21 CA179722 CEBP, 2013, 2014, 2015 Office of Clinical ResearchU54 MD

006970 JCG, 2014

CDC PS0039441 CA: A CA J Clin, 2016

U51 PS004633

UC Davis Team

Thao Moua Lo

Community: Statistically significant impact by bilingual/bicultural lay health worker intervention to increase HBV testing

Clinical: EMR-based messaging significantly increases HBV screening by primary care providers

Genomics: Only NCI-funded R21 to examine biologic determinants of differential liver cancer survival rates among Asian Americans

Back to the Community: Completing initial 1000 Asian American Study for HBV screening and funded to screen 2000 more Asian Americans and link them to care

Chen Stewart Tong Bowlus Dang

Increasing Hepatitis B (HBV) testing to reduce liver cancer risk

NGS-based identification of an HCC-specific blood genomic signature and its association with specific

immune inflammatory cell subsets

HBV-linked HCC as the next

“smallpox”

Propose:

December 1979

WHO Announces Global Eradication of

Smallpox!

14

Parallels: Comparing Smallpoxwith HBV

Reservoir: only in humans

Etiology: both viral

Transmission: communicable

Prevention: both vaccine-preventable

Major CDC Initiatives to prevent and manage Hepatitis B

1991: Hepatitis B virus: A Comprehensive Strategy for Eliminating

Transmission in the U.S. through universal childhood vaccination

2005-6: Comprehensive immunization strategy to eliminate

hepatitis B in the United States.

2008: Recommendations for the Identification and Public Health

management of persons with chronic Hepatitis B virus infections

2011: Use of Hepatitis B vaccination for adults with diabetes

mellitus

2015: Action Plan for the Prevention, Care, and Treatment of Viral

Hepatitis

Preventing perinatal transmission

Evidence for the Effectiveness of Universal HBV Vaccination

on HBV Infection and HCC in Taiwanese Children

Incidence of

HCC

0.7

0.57

0.36

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

1981-86 1988-90 1990-94

Pe

r 1

00

,00

0 /

yr

Source: Beasley RP, et al., Lancet 1981 Lok ASF, Gastroenterology 2004

Presentation objectives:

1. Review the epidemiological significance of chronic Hepatitis B

(HBV) infections for foreign-born Asian Americans and its

etiological role in hepatocellular carcinoma. Why care?

2. Highlight research, policies, and practices that can be

leveraged in community and clinical settings to mitigate HBV-

linked hepatocellular carcinoma. What can be done?

3. Discuss the potential of HBV prevention and control as being

the next “smallpox”, i.e., the next disease that could be

eliminated/eradicated. What is the take-away?

Apr 29 Draft as of Apr 14

“Longest journey begins with a single step.”