Program Official

Principal Investigator

Hashem B
El-Serag
Awardee Organization

Baylor College Of Medicine
United States

Fiscal Year
2024
Activity Code
P01
Early Stage Investigator Grants (ESI)
Not Applicable
Project End Date

Multilevel factors associated with heterogeneity in risk of liver cancer within Hispanics with cirrhosis

PROGRAM SUMMARY / ABSTRACT This application is being submitted in response to the Notice of Special Interest (NOSI) identified as NOTCA-24-032. I currently serve as PI/PD for the currently active (year 2 of 5) P01 CA263025 (Prevention of Hepatocellular Carcinoma Related to Metabolic Syndrome). Hepatocellular carcinoma (HCC) is one of the fastest growing causes of cancer deaths among Americans. In the past decade, there has been an epidemic increase in metabolic (dysfunction) associated fatty liver disease (MAFLD)-related cirrhosis and HCC. MAFLD is estimated to affect 1 billion individuals globally and is projected to become the leading cause of HCC in the next 2 decades. In the U.S., Hispanics are currently most affected by both MAFLD and HCC. There is an urgent need to develop effective strategies to reduce HCC burden in the growing MAFLD population. The overall goal of the Program Project is to reduce the burden of HCC-related mortality through better understanding of contemporary risk factors (e.g., metabolic traits and biomarkers) and protective factors (e.g., chemoprevention, HCC surveillance) of HCC related to MAFLD. We have established one of the largest and most characterized multiethnic cohort of persons with MAFLD-related cirrhosis, the Texas HCC Consortium (THCCC) Cohort. This Administrative Supplement aims to increase the impact of our THCCC research by adding measurements of multilevel factors. The goal of Project 1 of the parent Program Project is to identify risk factors and biomarkers associated with HCC risk among cirrhosis patients, such that those at highest risk can be targeted for prevention and early detection. This Administrative Supplement will increase and expand the influence of Project 1 by using multilevel factors characterizing genetic ancestries and neighborhood socioeconomic disadvantage to address important gaps in our understanding of heterogeneity in HCC risk within Hispanic populations with cirrhosis. Our Specific Aims are to: (1) examine the associations between genetic ancestry and HCC risk using admixture mapping analysis among Hispanic cirrhosis patients with (cases) and without HCC (controls) in the THCCC cohort; and (2) examine how the joint associations of genetic ancestry and neighborhood socioeconomic disadvantage affects HCC risk within Hispanic cirrhosis patients. The central hypotheses of this Supplement are that greater proportion of European ancestry and Indigenous ancestry (representing genetic influences) are associated with an increased risk of developing HCC, and that HCC risk within Hispanics with cirrhosis will vary by level of neighborhood disadvantage (representing environmental influences). The work proposed is relevant to the parent grant and its original work scope, but will provide important findings that will drive subsequent investigations and preventive measures to address the heterogeneity in HCC risk within the Hispanic population in the U.S.

Publications

  • Kanwal F, Neuschwander-Tetri BA, Loomba R, Rinella ME. Metabolic dysfunction-associated steatotic liver disease: Update and impact of new nomenclature on the American Association for the Study of Liver Diseases practice guidance on nonalcoholic fatty liver disease. Hepatology (Baltimore, Md.). 2024 May 1;79(5):1212-1219. Epub 2023 Nov 9. PMID: 38445559
  • Thrift AP, Kanwal F, Liu Y, Khaderi S, Singal AG, Marrero JA, Loo N, Asrani SK, Luster M, Al-Sarraj A, Ning J, Tsavachidis S, Gu X, Amos CI, El-Serag HB. Risk stratification for hepatocellular cancer among patients with cirrhosis using a hepatic fat polygenic risk score. PloS one. 2023 Feb 28;18(2):e0282309. doi: 10.1371/journal.pone.0282309. eCollection 2023. PMID: 36854015
  • Kanwal F, Khaderi S, Singal AG, Marrero JA, Asrani SK, Amos CI, Thrift AP, Kramer JR, Yu X, Cao Y, Luster M, Al-Sarraj A, Ning J, El-Serag HB. Risk Stratification Model for Hepatocellular Cancer in Patients With Cirrhosis. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2023 Dec;21(13):3296-3304.e3. Epub 2023 Apr 30. PMID: 37390101
  • Bhatnagar A, Prakash S, Lymberopoulos P, Goff C, Shaikh A, Kim D, Ahmed A, Berg C, Naggie S, Kanwal F, Cholankeril G, Lee TH. Transplanting hepatitis B surface antigen-positive livers in the United States: Outcomes and opportunities. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2023 Aug;23(8):1221-1226. Epub 2023 Apr 26. PMID: 37116583
  • Kim HS, Xiao X, Byun J, Jun G, DeSantis SM, Chen H, Thrift AP, El-Serag HB, Kanwal F, Amos CI. Synergistic Associations of PNPLA3 I148M Variant, Alcohol Intake, and Obesity With Risk of Cirrhosis, Hepatocellular Carcinoma, and Mortality. JAMA network open. 2022 Oct 3;5(10):e2234221. PMID: 36190732
  • El-Serag H, Kanwal F, Ning J, Powell H, Khaderi S, Singal AG, Asrani S, Marrero JA, Amos CI, Thrift AP, Luster M, Alsarraj A, Olivares L, Skapura D, Deng J, Salem E, Najjar O, Yu X, Duong H, Scheurer ME, Ballantyne CM, Kaochar S. Serum biomarker signature is predictive of the risk of hepatocellular cancer in patients with cirrhosis. Gut. 2024 Feb 16. Epub 2024 Feb 16. PMID: 38365278
  • El-Serag HB, Akhdar G, Thrift AP, Luster M, Khaderi S, Alsarraj A, Duong H, Kanwal F. Bioimpedance analysis predicts the etiology of cirrhosis in a prospective cohort study. Hepatology communications. 2023 Sep 11;7. (10). doi: 10.1097/HC9.0000000000000253. eCollection 2023 Oct 1. PMID: 37695087
  • El-Serag HB, Ward JW, Asrani SK, Singal AG, Rich N, Thrift AP, Deshpande S, Turner BJ, Kaseb AO, Harrison AC, Fortune BE, Kanwal F. Prevention of Hepatocellular Carcinoma (HCC). White Paper of the Texas Collaborative Center for Hepatocellular Cancer (TeCH) Multi-stakeholder Conference. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2023 Aug;21(9):2183-2192. Epub 2023 Apr 20. PMID: 37086825
  • Kanwal F, Kramer JR, Li L, Yang YX, Cao Y, Yu X, Samuel R, Ali B, Desiderio R, Cholankeril G, Bajaj M, El-Serag HB, Asch SM. GLP-1 Receptor Agonists and Risk for Cirrhosis and Related Complications in Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease. JAMA internal medicine. 2024 Nov 1;184(11):1314-1323. PMID: 39283612