TLC and THCCC Hashem B ElSerag MD MPH Chair and Professor Department of Medicine Baylor College of Medicine Houston Texas Translational Liver Cancer TLC Consortium TLC is addressing these challenges in HCC research ID: 1009240
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1. Translational Liver Consortia:TLC and THCCCHashem B. El-Serag, MD, MPHChair and ProfessorDepartment of MedicineBaylor College of MedicineHouston, Texas
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3. Translational Liver Cancer (TLC) Consortium TLC is addressing these challenges in HCC research. Main goals:Stratification of patients with cirrhosis, who are at risk for developing liver cancerSurveillance for liver cancers in patients with cirrhosisEarly detection of liver cancerRFA-CA-17-025/028 establish a Liver Cancer Consortium to advance translational research focused on early detection of liver cancer.
4. Translational Research Center InvestigatorsPrincipal InvestigatorsInstitutionsTitleFasiha Kanwal, MDBaylor College of MedicineRisk Stratification for and Early Detection of Liver CancerAnna Lok, MD, Grace Su, MD; Thomas Wang, MD, PhDUniversity of MichiganNovel Strategies to Improve Liver Cancer Surveillance Uptake and Early DetectionLopa Mishra, MD; Kirti Shetty, MD; Shulin Li, PhD; Herbert Yu, MD, PhDGeorge Washington University (LM); University of Maryland (KS); MD Anderson Cancer Center (SL); University of Hawaii (HY)Pathway Specific Functional Biomarkers for the Early Detection of Liver CancerAmit Singal, MD, MScUT Southwestern Medical CenterPrecision Risk Stratification and Screening for HCC among Patients with Cirrhosis in the United StatesXianghong (Jasmine) Zhou, PhD; Samuel French, MD, PhD; Steven-Huy HanUniversity of California Los AngelesUCLA Center in Early Detection of Liver Cancer
5. Aim 1. Develop and test novel personalized risk stratification indices for predicting future HCC development in cirrhosis from diverse etiologies Aim 2. Develop and evaluate an algorithm combining existing HCC blood-based biomarkers (AFP, AFPL3, DCP), their longitudinal changes and host features (e.g., cirrhosis etiology) to improve early HCC detection Aim 3. Evaluate novel plasma-based methylation markers for cell-free DNA (MDMs) as an independent surveillance biomarker for early HCC detection Baylor TRC: Specific Aims
6. Prospective cohort of cirrhosis patients (CPRIT) Baylor TRCVA Surveillance Cohort (VASC)Patients with cirrhosis from outpatient clinics at the Houston VAProspectively followed under active HCC surveillance in Houston between 08/2014 and 12/2016. Follow up 12/2018Study Cohorts
7. HCC Incidence Rates in TexasEl-Serag et al 2019
8. Texas Hepatocellular Carcinoma Consortium (THCCC) Risk Assessment PrimaryPrevention Detection Diagnosis CancerTreatment Quality of Cancer Cancer Contiuum
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10. Inclusion CriteriaAble and willing to provide written informed consent and HIPAA authorization.Candidates must be > 18 years of ageDiagnosis of cirrhosis Histopathology US, CT, or MRI showing a cirrhotic/nodular/irregular liver and any of these criteria:SplenomegalyPresence of intraabdominal varicesPresence of collateralsRecanalized umbilical veinAscitesElastography done by ultrasound or MRI showing advanced fibrosisA serum marker of hepatic fibrosis (FIB4, APRI, or Fibrotest/Fibrosure) showing cirrhosis or stage 4 fibrosis in the setting of chronic liver disease.Presence of varices on endoscopy or imaging.Clinical history of cirrhosis complications such as ascites and variceal bleedingFeng et al. Am J Gastroenterol. 2019;114(3):530-532.Inclusion Criteria for THCCC Exclusion criteria: HCC or uncontrolled ascites or hepatic encephalopathy, metastatic cancer
11. Primary EndpointMain clinical outcome: incident HCC Detected at least 1 month after an HCC-free baseline assessmentDefined by:Histopathological diagnosis Radiological diagnosis using CT or MRI with arterial, portal venous and venous delayed phaseOne year after HCC diagnosis, sites will ascertain patient’s vital status as well as any treatments that they have received for HCC
12. Total Accrual (New Subjects) as of March 2021Institution NameStart DateTotal Accrual% of Total RegisteredMichael E DeBakey VAMC12/21/201663324.2%Parkland Health and Hospital System01/10/201749719.0%UT Southwestern Medical Center at Dallas01/09/201745217.2%Baylor College of Medicine02/09/201754420.8%The Texas Liver Institute04/20/20171405.3%Baylor Scott & White Research Institute06/14/20191867.1%Doctor’s Hospital at Renaissance10/8/20191305.0%Baylor All Saints Medical Center06/04/2020391.5%Total-2621100%*Start date is defined as the date that the first subject was enrolled.
13. Accrual as of March 2021673726218406
14. HCC Cases as of March 2021InstitutionNumber of CasesMethod of DiagnosisMichael E DeBakey VAMC28Imaging, biopsyBaylor College of Medicine 21ImagingParkland Health and Hospital System17Imaging, biopsyThe Texas Liver Institute 3ImagingUT Southwestern Medical Center at Dallas13Imaging, biopsyBaylor Scott & White Research Institute 1ImagingDoctor’s Hospital at Renaissance1ImagingTotal84-
15. HCC Incidence Rate as of December 2020Abbreviations:OSD: Off-study dateDD: Death dateHCC: HCC date†Whichever occurs first
16. Collected Information/SamplesBaselineGermline DNASerumSurvey QuestionnaireAnthropometric MeasuresHER AbstractionLiver ImagingFollow up (6-12 months)SerumLiver ImagingLiver Decompensation/TreatmentHER Abstraction
17. Contemporary risk factors for cirrhosis in the U.SData from Trans-Texas HCC Consortium (THCCC)First 1500Etiology of cirrhosis 33.1% cured hepatitis C virus infection (HCV) 30.0% alcohol 23.3% nonalcoholic fatty liver disease 16.1% active HCV 2.5% hepatitis B virus (HBV) infection75% has metabolic dysfunction without other active risk factors HCVAlcoholMAFLDEl-Serag H, Kanwal F, et al. Gastroenterology. 2020;159:376-377
18. THCCC: Cirrhosis Risk Factors in the Main Racial/Ethnic Groups (El-Serag HB et al. Gastroenterology)
19. Associations with Risk of Incident HCC(preliminary data stratified by NAFLD)0.1 0.2 0.4 0.6 0.8 1.0 1.4 1.8 2.2 2.6 3.0 ….5.0 Overall Age Younger than 65 65 year and older Gender Male Race White African American Hispanics Diabetes No Yes Obesity No Yes (BMI>30) NAFLDOther etiologies0.1 0.2 0.4 0.6 0.8 1.0 1.4 1.8 2.2 2.6 3.0. 3.4. 3.8Unadjusted hazard ratios (95% CI)Unadjusted hazard ratios (95% CI)
20. Feng Z, Marrero JA, Khaderi S, Singal AG, Kanwal F, Loo N, Beretta L, Ning J, El-Serag HB. Design of the Texas Hepatocellular Carcinoma Consortium Cohort Study. Am J Gastroenterol 2019.Kanwal F, Kramer JR, Mapakshi S, Natarajan Y, Chayanupatkul M, Richardson PA, Li L, Desiderio R, Thrift AP, Asch SM, Chu J, El-Serag HB. Risk of Hepatocellular Cancer in Patients With Non-Alcoholic Fatty Liver Disease. Gastroenterology 2018.Dec;155(6):1828-1837. El-Serag HB, Sardell R, Thrift AP, Kanwal F, Miller P. Texas Has the Highest Hepatocellular Carcinoma Incidence Rates in the USA. Dig Dis Sci 2020.Risk Factors for Cirrhosis in Contemporary Hepatology Practices-Findings From the Texas Hepatocellular Carcinoma Consortium Cohort. El-Serag HB, Kanwal F, Feng Z, Marrero JA, Khaderi S, Singal AG; Texas Hepatocellular Carcinoma Consortium. Gastroenterology 2020. Hernaez R, Kramer JR, Khan A, Phillips J, McCallister K, Chaffin K, Hernandez AP, Fullington H, Ortiz C, Blackwell JM, Loewen A, Liu Y, Tiro JA, Lee SC, Singal AG. Depression and Anxiety Are Common Among Patients With Cirrhosis. Clin Gastroenterol Hepatol 2020. Singal AG, Tiro JA, Murphy CC, Blackwell JM, Kramer JR, Khan A, Liu Y, Zhang S, Phillips JL, Hernaez R. Patient-Reported Barriers Are Associated With Receipt of Hepatocellular Carcinoma Surveillance in a Multicenter Cohort of Patients With Cirrhosis. Clin Gastroenterol Hepatol 2020. Papers from THCCC
21. Funded Grants Leveraging THCCCU24: Consortium on Translational Research in Early Detection of Liver Cancer: Data Management and Coordinating Center (HCC-DMCC)Ziding FengU01: Precision Risk Stratification and Screening for HCC among Patients with Cirrhosis in the United States.Amit SingalU01: Risk Stratification for and Early Detection of Liver Cancer. Fasiha KanwalBCM Cancer Center: The Gut Microbiome in Cirrhosis and Hepatocellular CarcinomaAaron ThriftCPRIT: The Texas Collaborative Center for Hepatocellular Cancer Hashem El-SeragR01: Multi-Level Evaluation of Racial/Ethnic and Socioeconomic Disparities in Liver Disease Outcomes Fasiha Kanwal R01: Translation of a biomarker panel for the early detection of hepatocellular carcinoma Jorge Marrero
22. Texas Collaborative Center for Hepatocellular Cancer (TeCH)Funded by Cancer Prevention and Research Institute of Texas (CPRIT) Collaborative Action Program (CAP)RP190641August 31st, 2019 – August 30th, 2024
23. The goal of TeCH is to reduce HCC mortality in Texas (and the world) by reducing the number of people who develop cancer or detecting it early when it is curableSupport and enhance research collaborations among CAP researchers by providing multiple levels of connectivity and necessary research supportSetup the framework to educate healthcare providers, researchers, and the public on best practices and to engage private and public entities in policy considerationsEngage all stakeholders and solicit strategies to improve HCC-related prevention and care and to best disseminate those improvements Disseminate results on best practices and new opportunities that will impact HCC in Texas
24. Organizational Structure of TeCHOversight, Evaluation, and CoordinationResearch Support and SynergyDissemination and ImplementationSteering CommitteeFacilitates communication and interaction across committees and CAP research projects.Scientific CommitteeFocuses on identifying cutting-edge research questions and techniques.Clinical Network CommitteeAims to translate and implement innovations into clinical practice to identify best practices related to HCC prevention, early detection and management, and identify gaps in care. Administrative CoreData and Biospecimen CoreCommunity Outreach CommitteeGenerates culturally sensitive educational material on HCC risk factors, prevention, diagnosis, and treatment targeted at patients and at-risk communities.External Advisory CommitteeAnnual Symposium Committee
25. Newly Funded CPRIT HCC Grants through the CAPReducing Disparities in the risk of Hepatocellular CancerFasiha Kanwal, CPRITGlycotest Panel analysis in THCCC cohortAmit Singal, CPRITGenome-wide association study of HCC and cirrhosis progression in HispanicsAaron Thrift, CPRIT