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Texas Collaborative Center for Hepatocellular Cancer
(TeCH)FUNDED BY CANCER PREVENTION AND RESEARCH INSTITUTE OF TEXAS (CPRIT)
RP190641AUGUST 31ST, 2019 – AUGUST 30TH, 2024
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The goal of TeCH is to reduce HCC mortality in Texas by reducing the number of people who develop cancer or
detecting it early when it is curable.
To support and enhance research collaborations among CAP researchers by providing multiple levels of connectivity and necessary research support
To setup the framework to educate healthcare providers, researchers, and the public on best practices and to engage private and public entities in policy considerations
To engage all stakeholders and solicit strategies to improve HCC-related prevention and care and to best disseminate those improvements
To begin disseminating results on best practices and new opportunities that will impact HCC in Texas
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Organizational Structure of TeCH
Oversight, Evaluation, and Coordination Research Support and Synergy Dissemination and Implementation
Steering Committee Scientific Committee Clinical Network Committee
Administrative Core Data and Biospecimen Core Community Outreach Committee
External Advisory Committee Annual Symposium Committee
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Changing HCC Epidemiology in the United States and Texas
HASHEM B EL-SERAG, M.D. , M.P.H.
PROFESSOR AND CHAIR OF MEDICINE
BAYLOR COLLEGE OF MEDICINE
HOUSTON TEXAS
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Gastroenterology 2017 152, 812-820
Age-adjusted HCC Incidence Rates in the United States between 2000 and 2012
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White et al, 2017.
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HCC Incidence Rates in Texas
0
5
10
15
20
25
2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015
Age
-adj
uste
d in
cide
nce
rate
Hispanic, Texas
NH black, Texas
Hispanic, Nationwide
NH black, Nationwide
NH white, Texas
NH white, Nationwide
El-Serag et al 2019
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HCV was the Dominant Risk Factor for HCC in the United States (1999)
(N=691)
Chart1
HCV
Both
HBV
Neither
Sales
0.47
0.05
0.15
0.33
Sheet1
Sales
HCV0.47
Both0.05
HBV0.15
Neither0.33
To update the chart, enter data into this table. The data is automatically saved in the chart.
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Factors Associated With Increased HCC Risk in Patients with Active HCV Infection
Modifiable◦ Alcohol consumption◦ Nonalcoholic fatty liver disease◦ Obesity◦ Diabetes
Viral◦ Genotype 3◦ Coinfection with HBV or HIV
AASLD, IDSA, IAS–USA. Recommendations for testing, managing, and treating hepatitis C. http://www.hcvguidelines.org. Accessed July 15, 2015.
Non-modifiable• Older age at time of
infection• Male sex• Hispanic ethnicity
Antiviral Treatment with SVR
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0.0%
2.0%
4.0%
6.0%
8.0%
10.0%
Cum
ulat
ive
inci
denc
e of
HCC
2982 2453(35) 1617(36) 636(14) 5(3) 0(0)No SVR19518 19372(85) 14364(68) 6128(29) 0(1) 0(0)SVR
N at risk (N HCC)
0 5 10 15 20 25Months after end of treatment
No SVR
SVR
Cumulative HCC incidence rates by DAA-related SVR
Kanwal F et al., Gastroenterology 2017
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0.1 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 2.2 2.4 2.6 2.8
OverallAgeYounger than 6565 year and olderRaceWhiteAfrican AmericanHispanicsDiabetes NoYes Alcohol useNoYes Drug useNoYes FIB-43.25
Incidence rate (per 100 person year)
Annual Incidence of HCC after SVR Stratified by Cirrhosis
Without cirrhosis With cirrhosis1.82%
(95% CI, 1.66-2.0%)
Kanwal F, Gastroenterology 2017
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HCV-related HCC Has Started to Decline
HCV
0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
1.8
2009 2010 2011 2012 2013 2014 2015 2016 2017 2018
HCV
ALD
HBV
NAFLD
Kim D et al. Gastroenterology 2020
National Vital Statistics System
2009-2018
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HCC is Declining in Young Men
Females Males
Zhang X, El-Serag HB, Thrift AP. Cancer Epidemiol Biomarkers Prev. 2020 J
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Viral factors Host Factors External Factors
HBV: Risk Factors for Progression to HCC
Persistently high HBV DNA levels
HBV CP variant
HBV genotype (C > B)
• Older age• Male gender• Asians??• Advanced fibrosis • Persistent ALT elevation• Recurrent hepatitis
flares• HDV, HCV coinfections• HIV coinfection • Family history of HCC
• Alcohol• Aflatoxin• Smoking
Antiviral Treatment
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HBV Vaccination and HCC: Taiwan Experience
• HCC prevention extended from childhood to early adulthood• Failures: incomplete vaccination, maternal HBsAg or HBeAg
J Natl Cancer Inst 2009; 101:1348-1355
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Globesity
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Obesity and Risk of HCCMost—but not all—studies suggest a modest increase in the relative risk of HCC in obese persons
Saunders D, et al. APT 2010.Gupta A et al. Am J Clin Oncol. 2018
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DiabetesN=173,643
No Diabetes N=650,620
P
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Obesity/Diabetes and HCCDistal vs. Proximal Associations
Obesity/Diabetes
Distal associations
HCC
Proximal associations• Abdominal obesity• Humoral Mechanisms• Medications• NAFLD/NASH• Genetic Factors
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Natural History of NAFLD
NAFLD
Isolated Fatty Liver
NASH
NASH Cirrhosis
HCC
Decompensation
~70-75%
~11% over 15 years, but significant variability
1. ↑ risk of death compared with general population1. Cardiovascular2. Malignancy3. Liver-related
2. NASH with fibrosis portends worse prognosis 1. Fibrosis progression a/w DM, severe IR, weight
gain >5kg, rising ALT, AST
~7.2% over 6.5 years
19-45% over 7-10 years
1. None to very minimal progression to fibrosis
2. No ↑ risk of death compared with the general population
Fatty Liver with Mild Inflammation
Possible sampling variability withsome risk of progression
~20-25%
Modified from Torres DM et el. Features, diagnosis, and treatment of NAFLD. Clin Gastro Hepatol 2012;10:837-858.
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HCC in Patients with (Biochemical) NAFLD452,767 with NAFLD and 450,627 w/o NAFLD
0.35
0.30
0.25
0.2
0.15
0.1
0.05
0Ann
ual H
CC in
cide
nce/
1000
PY
NAFLD Controls
Hazard ratio7.5 (95% CI=6.05-9.23 )
Mean 9.1 (SD 2.9) year follow-up
NAFLD: 727 HCC = 0.20/1000 PYNon-NALFD: 87 HCC = 0.02/1000 PY
Kanwal F et. al. Gastroenterology 2018
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HCC Incidence in Subgroups Of Patients with NAFLD
0.2 0.4 0.6 0.8 1.0 8.0 10.0 12.0 20.0Incidence rate per 1000 person-years
DiabetesNo
Yes
Age (year)65
Race BlackWhite
Hispanic
Cirrhosis Diagnosis, high FIB-4Diagnosis, low FIB-4
High FIB-4No diagnosis, low FIB-4
Kanwal F, et. al. Gastroenterology 2018.
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Dyslipidemiaalone
10.0
8.0
6.0
5.0
4.0
3.0
2.0
1.0
0
Dyslipidemia & hypertension
Adju
sted
haz
ard
ratio
Dyslipidemia & diabetes
Dyslipidemia, hypertension &
diabetes
BMI 30
Stratified Analyses in 208,403 Patients with Dyslipidemia
Factors Associated with Risk of NAFLD Progression to Cirrhosis or HCC
Multivariate Analyses (Joint Effects)
Kanwal F, et al. Hepatology 2019
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1500 VA patients & HCC (2005- 2010) Patients without cirrhosis 13%Risk of HCC in absence of cirrhosis NAFLD:
OR: 5.4; 95% CI (3.4–8.5) Metabolic Syndrome:
OR: 5.0; 95% CI (3.1–7.8)
HCC in the Absence of Cirrhosis
Mittal A et al Clinical Gastroenterology and Hepatology 2015
• NAFLD and Metabolic Syndrome are main risk factors for HCC in the absence of cirrhosis
Chart1
NAFLDNAFLD
HCVHCV
HBVHBV
Alcohol abuseAlcohol abuse
IdiopathicIdiopathic
Cirrhosis
No cirrhosis
65.4
34.6
91.1
8.9
92.3
7.7
88.9
11.1
66.2
33.8
Sheet1
NAFLDHCVHBVAlcohol abuseIdiopathic
Cirrhosis65.491.192.388.966.2
No cirrhosis34.68.97.711.133.8
Sheet1
Cirrhosis
No cirrhosis
Sheet2
Sheet3
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Metabolic Associated Fatty Liver Disease (MAFLD)
Eslam M, et al. Gastroenterology 2020
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Prevalence of Risk Factors vs Risk of HCC
Previous State Present/Future State
Prevalence of Risk Factor
HCC
Risk
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Disease typePrevalence in
general population
Risk estimate of HCC
Population attributable
fraction
HBV 0.5-1% 20-25 5-10%HCV 1-2% 20-25 20-25%Alcoholic liver disease 10-15% 2-3 20-30%
Metabolic syndrome 30-40% 1.5-2.5 30-40%
MAFLD 70-80% 1.5 70-80%
HCC Risk FactorsPrevalence, Relative Risk Estimates, and
Population Attributable Fraction
Drop Decline Drop
El-Serag HB, et al. Gastroenterology 2018.
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Texas HCC Consortium (THCCC) Accrual as of October 12, 2020
Institution Name Start Date* Total Accrual % of Total Registered
Michael E DeBakey VAMC Dec. 21, 2016 630 25.1%
UT Southwestern Medical Center at Dallas Jan. 9, 2017 435 17.4%
Parkland Health and Hospital System Jan. 10, 2017 493 19.7%
Baylor College of Medicine Feb. 9, 2017 525 20.9%
The Texas Liver Institute Apr. 20, 2017 140 5.6%
Baylor Scott & White Research Institute Jun. 14, 2019 172 6.9%
Doctor’s Hospital at Renaissance Oct. 8, 2019 93 3.7%
Baylor All Saints Medical Center Jun. 4, 2020 18 0.7%
Total 2506 100%
*Start date is defined as the date that the first subject was enrolled.
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THCCC: Cirrhosis Risk Factors in the Main Racial/Ethnic Groups
(El-Serag HB et al. Gastroenterology; 2020 accepted)
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HCC Incidence Rate as of February 19, 2020
Abbreviations:OSD: Off-study dateDD: Death dateHCC: HCC date
†Whichever occurs first
𝐻𝐻𝐻𝐻𝐻𝐻 𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴 𝐼𝐼𝐴𝐴𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐴𝐴𝐼𝐼𝐼𝐼 𝑅𝑅𝐴𝐴𝑅𝑅𝐼𝐼 =75
𝑂𝑂𝑂𝑂𝑂𝑂,𝑂𝑂𝑂𝑂,𝐻𝐻𝐻𝐻𝐻𝐻, 𝑜𝑜𝑜𝑜 𝐻𝐻𝐴𝐴𝑜𝑜𝑜𝑜𝐼𝐼𝐴𝐴𝑅𝑅 𝑂𝑂𝐴𝐴𝑅𝑅𝐼𝐼† − 𝑅𝑅𝐼𝐼𝑅𝑅𝐼𝐼𝑅𝑅𝑅𝑅𝑜𝑜𝐴𝐴𝑅𝑅𝐼𝐼𝑜𝑜𝐴𝐴 𝑂𝑂𝐴𝐴𝑅𝑅𝐼𝐼365.24
= 𝟏𝟏.𝟗𝟗𝟗𝟗%
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SummaryChanging HCC Risk Factors◦ Less active HCV and HBV◦ More Metabolic Syndrome
Changing in HCC Risk◦ Lower individual risk but more individuals at risk
Metabolic Syndrome and HCC Risk◦ Relative risk of HCC is modestly elevated but absolute risk is low◦ Factors influencing HCC risk: abdominal obesity, diabetes, NAFLD, PNPLA3
Knowledge Needed◦ Risk stratification◦ Mechanisms◦ Treating metabolic syndrome
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AcknowledgmentsCollaborators:
• David Davila, PhD
• Jennifer Kramer, PhD
• Donna White, PhD
• Fasiha Kanwal, MD
• Aaron Thrift, PhD
Funders:• NIH NCI• NIH NIDDK• VA HSRD• CPRIT
����Texas Collaborative Center for Hepatocellular Cancer� (TeCH)�The goal of TeCH is to reduce HCC mortality in Texas by reducing the number of people who develop cancer or detecting it early when it is curable.�Organizational Structure of TeCHChanging HCC Epidemiology in the United States and TexasSlide Number 5Slide Number 6HCC Incidence Rates in TexasHCV was the Dominant Risk Factor for HCC in the United States (1999)Factors Associated With Increased HCC �Risk in Patients with Active HCV InfectionSlide Number 10Annual Incidence of HCC after SVR Stratified by CirrhosisHCV-related HCC Has Started to DeclineHCC is Declining in Young MenHBV: Risk Factors for Progression to HCCHBV Vaccination and HCC: �Taiwan ExperienceGlobesityObesity and Risk of HCCDiabetes Is Associated with a Two-fold Increase in Risk of HCCObesity/Diabetes and HCC�Distal vs. Proximal AssociationsNatural History of NAFLDHCC in Patients with (Biochemical) NAFLD�452,767 with NAFLD and 450,627 w/o NAFLDSlide Number 23�Factors Associated with Risk of NAFLD Progression to Cirrhosis or HCC �Multivariate Analyses (Joint Effects) Metabolic Associated Fatty Liver Disease (MAFLD)Prevalence of Risk Factors vs Risk of HCCHCC Risk Factors�Prevalence, Relative Risk Estimates, and Population Attributable Fraction�Texas HCC Consortium (THCCC) �Accrual as of October 12, 2020THCCC: Cirrhosis Risk Factors in the Main Racial/Ethnic Groups �(El-Serag HB et al. Gastroenterology; 2020 accepted)HCC Incidence Rate as of February 19, 2020SummaryAcknowledgments