Principal Investigator

Fasiha
Kanwal
Awardee Organization

Baylor College Of Medicine
United States

Fiscal Year
2023
Activity Code
U01
Early Stage Investigator Grants (ESI)
Not Eligible
Project End Date

Risk Stratification for and Early Detection of Liver Cancer

The Translational Research Center (TRC) includes a diverse team of clinical and translational researchers with a strong track record of working together to reduce hepatocellular cancer (HCC). The TRC uses data from a unique group of patients with cirrhosis who are being recruited from eight different sites throughout Texas (the TRC cohort). Our TRC cohort currently includes > 3700 patients with cirrhosis (>10,000 follow up surveillance visits and >190 HCC cases) who have diverse risk factors, including cured HCV and non-alcoholic fatty liver disease. These patients are under routine HCC surveillance and their biological samples and clinical and radiological data for each visit is stored; it is a valuable resource for our research and other Consortium projects. We also launched a separate prospective cohort of patients with indeterminate liver nodules, which is a high risk and high priority group for HCC risk stratification and early detection. We are collecting surveys, clinical data, images and biospecimens from this cohort. The catalytic effects of our TRC are seen in the productivity of our junior investigators, who started innovative new initiatives and programs. Our work had a broad impact, including helping develop various society guidelines on HCC surveillance. Using data and the strong network of investigators and institutions collaborating with our TRC, we have already generated important data on risk factors and risk stratification for HCC. We also developed and demonstrated the framework for adding patientand liver disease-related factors to new blood-biomarker profiles to improve early HCC detection. Here, we propose to build a novel imaging repository, including MRI images from our cohort. We will annotate and incorporate data from abdominal ultrasound reports for our TRC cohort using novel, scalable machine learning pipelines. We will also strengthen our data by appending information from the State cancer registries. Using data from different sources available to us, we will develop and test new personalized methods to stratify risk that blends information from clinical factors, blood-based biomarkers, and imaging (radiomics) to predict future development of HCC in patients with cirrhosis across diverse risk factors (Aim 1). We showed that the HCC Early Detection Screening (HES) algorithm, when combined with HCC blood-based biomarkers (AFP‐L3, DCP) in HES version 2.0 (HES v2.0), substantially improved early detection. We will validate and compare HES v2.0 with GALAD, another early detection algorithm, and evaluate their performance versus the current standard ultrasound-based surveillance (Aim 2). In Aim 3, we will develop a new mathematical model to look at how useful current and emerging biomarkers are for detecting HCC. We will also assess the risks, costs, and benefits of HCC surveillance using different cutoffs of existing and novel blood and imaging biomarkers. We will develop and disseminate an online Simulator so that other investigators can evaluate the potential clinical utility of HCC early detection biomarkers as potential surveillance tools. Our translational approach will have both an immediate and long-lasting impact on HCC-related morbidity and mortality.

Publications

  • Shaikh A, Goli K, Lee TH, Rich NE, Benhammou JN, Keeling S, Kim D, Ahmed A, Goss J, Rana A, Singal AG, Kanwal F, Cholankeril G. Reduction in Racial and Ethnic Disparity in Survival Following Liver Transplant for Hepatocellular Carcinoma in the Direct-acting Antiviral Era. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2023 Aug;21(9):2288-2297.e4. Epub 2022 Dec 12. PMID: 36521738
  • Kanwal F, Shubrook JH, Adams LA, Pfotenhauer K, Wai-Sun Wong V, Wright E, Abdelmalek MF, Harrison SA, Loomba R, Mantzoros CS, Bugianesi E, Eckel RH, Kaplan LM, El-Serag HB, Cusi K. Clinical Care Pathway for the Risk Stratification and Management of Patients With Nonalcoholic Fatty Liver Disease. Gastroenterology. 2021 Nov;161(5):1657-1669. Epub 2021 Sep 20. PMID: 34602251
  • 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
  • Kramer JR, Cao Y, Li L, Smith D, Chhatwal J, El-Serag HB, Kanwal F. Longitudinal Associations of Risk Factors and Hepatocellular Carcinoma in Patients With Cured Hepatitis C Virus Infection. The American journal of gastroenterology. 2022 Nov 1;117(11):1834-1844. Epub 2022 Aug 23. PMID: 36327437
  • Shaikh A, Lee TH, Rich NE, Benhammou JN, Lymberopoulos P, Agopian VG, Kim D, Ahmed A, Hernaez R, Berg CL, Goss J, Rana A, Kanwal F, Cholankeril G. Survival following liver transplantation for hepatocellular carcinoma after implementation of MMaT-3 policy. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2023 Oct 1;29(10):1138-1142. Epub 2023 May 3. PMID: 37129867
  • Kramer JR, Natarajan Y, Dai J, Yu X, Li L, El-Serag HB, Kanwal F. Effect of diabetes medications and glycemic control on risk of hepatocellular cancer in patients with nonalcoholic fatty liver disease. Hepatology (Baltimore, Md.). 2022 Jun;75(6):1420-1428. Epub 2021 Dec 19. PMID: 34779535
  • Kanwal F, Khaderi S, Singal AG, Marrero JA, Loo N, Asrani SK, Amos CI, Thrift AP, Gu X, Luster M, Al-Sarraj A, Ning J, El-Serag HB. Risk factors for HCC in contemporary cohorts of patients with cirrhosis. Hepatology (Baltimore, Md.). 2023 Mar 1;77(3):997-1005. Epub 2023 Feb 17. PMID: 35229329
  • Zhang J, Ning J, Huang X, Li R. On the time-varying predictive performance of longitudinal biomarkers: Measure and estimation. Statistics in medicine. 2021 Oct 15;40(23):5065-5077. Epub 2021 Jun 22. PMID: 34159633
  • Cholankeril G, Kramer JR, Chu J, Yu X, Balakrishnan M, Li L, El-Serag HB, Kanwal F. Longitudinal changes in fibrosis markers are associated with risk of cirrhosis and hepatocellular carcinoma in non-alcoholic fatty liver disease. Journal of hepatology. 2023 Mar;78(3):493-500. Epub 2022 Nov 17. PMID: 36402450
  • Patel AA, Tapper EB, Kanwal F, Woodrell CD, Hansen L, Lai JC, Rogal S, McDermott C, Rakoski M, Ufere NN. Targets and study design for symptom-focused trials aimed at patients with cirrhosis: An expert consensus. Hepatology communications. 2023 Jun 2;7. (6). doi: 10.1097/HC9.0000000000000135. eCollection 2023 Jun 1. PMID: 37267219
  • Kanwal F, Singal AG. Surveillance for Hepatocellular Carcinoma: Current Best Practice and Future Direction. Gastroenterology. 2019 Jul;157(1):54-64. Epub 2019 Apr 12. PMID: 30986389
  • 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
  • Zhang C, Ning J, Belle SH, Squires RH, Cai J, Li R. Assessing predictive discrimination performance of biomarkers in the presence of treatment-induced dependent censoring. Journal of the Royal Statistical Society. Series C, Applied statistics. 2022 Nov;71(5):1137-1157. Epub 2022 May 25. PMID: 36466585
  • Cholankeril G, El-Serag HB. Current Challenges and Future Direction in Surveillance for Hepatocellular Carcinoma in Patients with Nonalcoholic Fatty Liver Disease. Seminars in liver disease. 2023 Feb;43(1):89-99. Epub 2022 Oct 10. PMID: 36216350
  • 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
  • Tayob N, Kanwal F, Alsarraj A, Hernaez R, El-Serag HB. The Performance of AFP, AFP-3, DCP as Biomarkers for Detection of Hepatocellular Carcinoma (HCC): A Phase 3 Biomarker Study in the United States. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2023 Feb;21(2):415-423.e4. Epub 2022 Feb 3. PMID: 35124267
  • Chen Q, Ayer T, Adee MG, Wang X, Kanwal F, Chhatwal J. Assessment of Incidence of and Surveillance Burden for Hepatocellular Carcinoma Among Patients With Hepatitis C in the Era of Direct-Acting Antiviral Agents. JAMA network open. 2020 Nov 2;3(11):e2021173. PMID: 33206188
  • Chhatwal J, Hajjar A, Mueller PP, Nemutlu G, Kulkarni N, Peters MLB, Kanwal F. Hepatocellular Carcinoma Incidence Threshold for Surveillance in Virologically Cured Hepatitis C Individuals. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2024 Jan;22(1):91-101.e6. Epub 2023 Jun 9. PMID: 37302445
  • Shaikh A, Goli K, Rich NE, Benhammou JN, Khaderi S, Hernaez R, Agopian VG, Vierling JM, Kim D, Ahmed A, Goss JA, Rana A, Kanwal F, Cholankeril G. Early Impact of MMaT-3 Policy on Liver Transplant Waitlist Outcomes for Hepatocellular Carcinoma. Transplantation direct. 2022 Apr 12;8(5):e1313. doi: 10.1097/TXD.0000000000001313. eCollection 2022 May. PMID: 35434283
  • Parikh ND, Tayob N, Al-Jarrah T, Kramer J, Melcher J, Smith D, Marquardt P, Liu PH, Tang R, Kanwal F, Singal AG. Barriers to Surveillance for Hepatocellular Carcinoma in a Multicenter Cohort. JAMA network open. 2022 Jul 1;5(7):e2223504. PMID: 35867057
  • Goff C, Shaikh A, Goli K, El-Serag HB, Kanwal F, Cholankeril G, Liver Cancer Investigator Working Group, Rana A, Aloor FZ, Cholankeril R, Rich NE, Benhammou JN, Kim D, Ahmed A, Goss J. Contemporary Changes in Etiology for Hepatocellular Carcinoma in Liver Transplantation. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2023 Aug;21(9):2410-2412.e1. Epub 2022 Jul 20. PMID: 35870770
  • Kanneganti M, Marrero JA, Parikh ND, Kanwal F, Yokoo T, Mendiratta-Lala M, Rich NE, Gopal P, Singal AG. Clinical outcomes of patients with Liver Imaging Reporting and Data System 3 or Liver Imaging Reporting and Data System 4 observations in patients with cirrhosis: A systematic review. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2022 Dec;28(12):1865-1875. Epub 2022 Sep 5. PMID: 35980600
  • Singal AG, Lok AS, Feng Z, Kanwal F, Parikh ND. Conceptual Model for the Hepatocellular Carcinoma Screening Continuum: Current Status and Research Agenda. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2022 Jan;20(1):9-18. Epub 2020 Sep 19. PMID: 32961340
  • Lymberopoulos P, Prakash S, Shaikh A, Bhatnagar A, Allam AK, Goli K, Goss JA, Kanwal F, Rana A, Kowdley KV, Jalal P, George Cholankeril. Long-term outcomes and trends in liver transplantation for hereditary hemochromatosis in the United States. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2023 Jan 1;29(1):15-25. Epub 2022 Jul 21. PMID: 35770428
  • Benhammou JN, Rich NE, Cholankeril G, Zhang P, Zeng W, Rao S, Tayob N, National Cancer Institute’s Translational Liver Consortium Early-Career Working Group, Li W, Wu X, Feng S, Fujiwara N, Meng X, Zhu S, Zaidi S. DETECT: Development of Technologies for Early HCC Detection. Gastroenterology. 2022 Jul;163(1):21-27. Epub 2022 Mar 23. PMID: 35339460
  • Mueller PP, Chen Q, Ayer T, Nemutlu GS, Hajjar A, Bethea ED, Peters MLB, Lee BP, Janjua NZ, Kanwal F, Chhatwal J. Duration and cost-effectiveness of hepatocellular carcinoma surveillance in hepatitis C patients after viral eradication. Journal of hepatology. 2022 Jul;77(1):55-62. Epub 2022 Feb 12. PMID: 35157959
  • Zhang J, Ning J, Li R. Evaluating Dynamic Discrimination Performance of Risk Prediction Models for Survival Outcomes. Statistics in biosciences. 2023 Jul;15(2):353-371. Epub 2023 Feb 2. PMID: 37691982
  • Wai-Sun Wong V, Kanwal F. On the Proposed Definition of Metabolic-Associated Fatty Liver Disease. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2021 May;19(5):865-870. Epub 2021 Jan 13. PMID: 33453398
  • Jacob JS, Shaikh A, Goli K, Rich NE, Benhammou JN, Ahmed A, Kim D, Rana A, Goss JA, Naggie S, Lee TH, Kanwal F, Cholankeril G. Improved Survival After Liver Transplantation for Patients With Human Immunodeficiency Virus (HIV) and HIV/Hepatitis C Virus Coinfection in the Integrase Strand Transfer Inhibitor and Direct-Acting Antiviral Eras. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2023 Feb 18;76(4):592-599. PMID: 36221143
  • Hernaez R, Karvellas CJ, Liu Y, Sacleux SC, Khemichian S, Stein LL, Shetty K, Lindenmeyer CC, Boike JR, Simonetto DA, Rahimi RS, Jalal PK, Izzy M, Kriss MS, Im GY, Lin MV, Jou JH, Fortune BE, Cholankeril G, Kuo A, Mahmud N, Kanwal F, Saliba F, Sundaram V, Artzner T, Jalan R, Multi-Organ Dysfunction and Evaluation for Liver Transplantation (MODEL) Consortium, Al Attar A, Kosari K, Garcia R, Salmastyan G, Cranford W, Patel P, Xue P, Mishra S, Parks M, Flocco G, Gao J, Wu T, Thanneeru P, Reddy V, Gao J, Hurtado M, Mohamed I, Vyhmeister R, Lopez CR, Campbell B, Winters AC, Simpson MA, Ying X. The novel SALT-M score predicts 1-year post-transplant mortality in patients with severe acute-on-chronic liver failure. Journal of hepatology. 2023 Sep;79(3):717-727. Epub 2023 Jun 12. PMID: 37315809
  • Cholankeril G, Kanwal F. NAFLD and HCC: Time to Bridge the Gap. Hepatology (Baltimore, Md.). 2021 Nov;74(5):2336-2338. Epub 2021 Aug 30. PMID: 34164841
  • 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
  • Jones PD, Lai JC, Bajaj JS, Kanwal F. Actionable Solutions to Achieve Health Equity in Chronic Liver Disease. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2023 Jul;21(8):1992-2000. Epub 2023 Apr 13. PMID: 37061105
  • Singal AG, El-Serag HB. Rational HCC screening approaches for patients with NAFLD. Journal of hepatology. 2022 Jan;76(1):195-201. Epub 2021 Sep 9. PMID: 34508791
  • Kim HS, Yu X, Kramer J, Thrift AP, Richardson P, Hsu YC, Flores A, El-Serag HB, Kanwal F. Comparative performance of risk prediction models for hepatitis B-related hepatocellular carcinoma in the United States. Journal of hepatology. 2022 Feb;76(2):294-301. Epub 2021 Sep 23. PMID: 34563579
  • 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
  • Natarajan Y, Kramer JR, Yu X, Li L, Thrift AP, El-Serag HB, Kanwal F. Risk of Cirrhosis and Hepatocellular Cancer in Patients With NAFLD and Normal Liver Enzymes. Hepatology (Baltimore, Md.). 2020 Oct;72(4):1242-1252. PMID: 32022277
  • Keeling SS, McDonald MF, Anand A, Handing GE, Prather LL, Christmann CR, Jalal PK, Kanwal F, Cholankeril G, Goss JA, Rana A. Significant improvements, but consistent disparities in survival for African Americans after liver transplantation. Clinical transplantation. 2022 Jun;36(6):e14646. Epub 2022 Mar 25. PMID: 35304775
  • Lymberopoulos P, Shaikh A, Rich NE, Benhammou JN, Kanwal F, Cholankeril G. Comparable Survival for Hepatitis C-Related Hepatocellular Carcinoma After Liver Transplantation Irrespective of Viremic Status. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2023 May;21(5):1362-1364.e1. Epub 2022 Mar 26. PMID: 35346850
  • Chu J, Cholankeril G, Yu X, Rana A, Natarajan Y, El-Serag HB, Kramer J, Kanwal F. Clinical Course and Outcomes of Patients with Nonalcoholic Fatty Liver Disease-Related Hepatocellular Cancer (NAFLD-HCC). Digestive diseases and sciences. 2023 Mar;68(3):1060-1070. Epub 2022 Jun 27. PMID: 35759159
  • El-Serag HB, Kanwal F, Feng Z, Marrero JA, Khaderi S, Singal AG, Texas Hepatocellular Carcinoma Consortium. Risk Factors for Cirrhosis in Contemporary Hepatology Practices-Findings From the Texas Hepatocellular Carcinoma Consortium Cohort. Gastroenterology. 2020 Jul;159(1):376-377. Epub 2020 Mar 29. PMID: 32234536
  • Zhang X, Daniel CR, Soltero V, Vargas X, Jain S, Kanwal F, Thrift AP, Balakrishnan M. A Study of Dietary Patterns Derived by Cluster Analysis and Their Association With Metabolic Dysfunction-Associated Steatotic Liver Disease Severity Among Hispanic Patients. The American journal of gastroenterology. 2023 Oct 9. Epub 2023 Oct 9. PMID: 37737674