Baylor College Of Medicine
United States
Prevention of Hepatocellular Carcinoma Related to Metabolic Syndrome
Hepatocelluar carcinoma (HCC) is the fastest growing cause 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. 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 (PP) is to reduce the burden of HCCrelated 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 propose three highly integrated studies. Central to this PP is leveraging and expanding our multicity, prospective cohort of persons with MAFLD-related cirrhosis, the Texas HCCC Consortium (THCCC) Cohort, which will serve as a resource for the proposed studies. The goal of Project 1 is to develop HCC risk stratification models based on phenotypic, metabolic, radiomic and genetic markers of metabolic dysfunction among patients with cirrhosis. We propose the analysis of data and biospecimens from the prospective THCCC cohort of >5000 patients with cirrhosis (and 350-400 incident HCC) to develop a suite of risk score algorithms) for predicting the risk of HCC among patients with cirrhosis. The goal of Project 2 is to evaluate the chemopreventive effects and potential harms of metformin, statins or glitazones in reducing the risk of HCC in individuals with MAFLD. We propose a retrospective cohort study using national VA datasets of >580,000 patients with MAFLD. We will also examine the effect of genetic markers on the chemopreventive effects of these medications in patients with MAFLD cirrhosis in THCCC. The goal of Project 3 is to examine comparative cost-effectiveness of prevention strategies in MAFLD. We will develop a mathematical simulation model and perform comparative analyses of benefits vs. harms of chemoprevention and HCC surveillance in individuals with MAFLD, and of using precision surveillance/chemoprevention using HCC risk stratification We propose a Data & Analysis Core to support data management, data harmonization, statistical analyses and web-based tools; a Biospecimen and Biomarker Development Core to support collection, processing, transport and storage of serum and DNA samples from THCCC cohort; and conduct biomarker assays for the projects, and an Administrative Core to provide management, communication and coordination among projects, Cores, investigators and staff.
Publications
- Cholankeril G, Thrift AP, Khaderi S, Kanwal F, El-Serag HB, THCCC Working Group, Duong H, Singal AG, Asrani SK, Kourkompetis T, Zamir A, Marrero JA, Hernaez R, Luster M, Al-Sarraj A, Salem E. Temporal Changes in Risk Factors of Hepatocellular Carcinoma in a Prospective Cirrhosis Cohort. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2025 Jun;23(7):1268-1270.e2. Epub 2024 Dec 16. PMID: 39694208
- Lim H, El-Serag HB, Luster M, Grove ML, Byun J, Jung Y, Han Y, Boerwinkle E, Amos CI, Thrift AP. DNA Methylation Profile in Buffy Coat Identifies Methylation Differences Between Cirrhosis with and Without Hepatocellular Carcinoma. Cancers. 2025 Jan 15;17. (2). PMID: 39858049
- 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
- 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
- Fujiwara N, Lopez C, Marsh TL, Raman I, Marquez CA, Paul S, Mishra SK, Kubota N, Katz C, Kanzaki H, Gonzalez M, Quirk L, Deodhar S, Selvakumar P, Raj P, Parikh ND, Roberts LR, Schwartz ME, Nguyen MH, Befeler AS, Page-Lester S, Srivastava S, Feng Z, Reddy KR, Khaderi S, Asrani SK, Kanwal F, El-Serag HB, Marrero JA, Singal AG, Hoshida Y. Phase 3 Validation of PAaM for Hepatocellular Carcinoma Risk Stratification in Cirrhosis. Gastroenterology. 2025 Mar;168(3):556-567.e7. Epub 2024 Nov 8. PMID: 39521255
- 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
- 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
- Sokale IO, Rosales O, Thrift AP, El-Serag HB, Burgess E, Oluyomi AO. Differences in Hepatocellular Carcinoma Incidence Trends Across US Census Divisions, 2001 to 2021. Cancers. 2025 Apr 24;17. (9). PMID: 40361358
- 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
- Thrift AP, Kanwal F, Lim H, Duong H, Liu Y, Singal AG, Khaderi S, Asrani SK, Amos CI, El-Serag HB. PNPLA3, Obesity, and Heavy Alcohol Use in Cirrhosis Patients May Exert a Synergistic Increase Hepatocellular Carcinoma Risk. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2024 Sep;22(9):1858-1866.e4. Epub 2024 May 9. PMID: 38729396
- 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
- 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
- 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
- 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, Jin Q, Tayob N, Salem E, Luster M, Alsarraj A, Khaderi S, Singal AG, Marrero JA, Asrani SK, Kanwal F. HES V2.0 outperforms GALAD for detection of HCC: A phase 3 biomarker study in the United States. Hepatology (Baltimore, Md.). 2025 Feb 1;81(2):465-475. Epub 2024 Jun 19. PMID: 38899967