Principal Investigator

Anna S.F.
Awardee Organization

University Of Michigan At Ann Arbor
United States

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


This proposal is submitted in response to RFA-CA-17-025. Hepatocellular carcinoma (HCC) is the most common primary liver cancer and one of the few cancers with increasing incidence in the United States. Survival of patients with HCC is poor because most patients are diagnosed at late stages when treatment options are limited. HCC surveillance can detect cancers early and improve survival but it is inconsistently implemented. Not all liver nodules detected on surveillance imaging are malignant, these indeterminate nodules require follow up imaging to determine if they are HCC. This proposal assembles a team of specialists with complementary expertise in liver diseases, liver cancer, radiology, engineering, statistics, and information technology. The goals are to: (1) Improve HCC surveillance uptake in patients with cirrhosis by leveraging electronic medical records to remind healthcare providers and patients when they are due for screening tests; (2) Leverage analytic morphomics and machine learning to increase the detectability of HCC at an early stage; and (3) Increase detectability of HCC at an early stage using tagged HCC-specific peptides. We have worked closely together for many years and have participated/led many NIH funded clinical research networks. We have expertise and experience to carry out the proposed studies and will collaborate with other centers in the Liver Center Network to validate the methods/models we develop. We will also enroll patients with cirrhosis and collect data and specimens and provide access to existing well characterized data and specimen repositories that include both prevalent and incident HCC for Trans-Network studies. We are confident we will be able to contribute to this Liver Cancer Network and to early detection of HCC in multiple ways.


  • 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
  • Parikh ND, Tayob N, Singal AG. Blood-based biomarkers for hepatocellular carcinoma screening: Approaching the end of the ultrasound era? Journal of hepatology. 2023 Jan;78(1):207-216. Epub 2022 Sep 8. PMID: 36089157
  • Parikh ND, Mehta AS, Singal AG, Block T, Marrero JA, Lok AS. Biomarkers for the Early Detection of Hepatocellular Carcinoma. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2020 Dec;29(12):2495-2503. Epub 2020 Apr 1. PMID: 32238405
  • Hertz DL, Chen L, Henry NL, Griggs JJ, Hayes DF, Derstine BA, Su GL, Wang SC, Pai MP. Muscle mass affects paclitaxel systemic exposure and may inform personalized paclitaxel dosing. British journal of clinical pharmacology. 2022 Jul;88(7):3222-3229. Epub 2022 Feb 14. PMID: 35083783
  • Parikh ND, Dehmlow C, Ellies T, Tapper EB, Lok ASF. Development and Implementation of a Hepatocellular Carcinoma Surveillance Quality Metric. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2023 Mar;21(3):576-580.e1. Epub 2022 Dec 16. PMID: 36535495
  • Singal AG, Zhang E, Narasimman M, Rich NE, Waljee AK, Hoshida Y, Yang JD, Reig M, Cabibbo G, Nahon P, Parikh ND, Marrero JA. HCC surveillance improves early detection, curative treatment receipt, and survival in patients with cirrhosis: A meta-analysis. Journal of hepatology. 2022 Jul;77(1):128-139. Epub 2022 Feb 6. PMID: 35139400
  • Brown AM, Kassab I, Massani M, Townsend W, Singal AG, Soydal C, Moreno-Luna L, Roberts LR, Chen VL, Parikh ND. TACE versus TARE for patients with hepatocellular carcinoma: Overall and individual patient level meta analysis. Cancer medicine. 2023 Feb;12(3):2590-2599. Epub 2022 Aug 9. PMID: 35943116
  • Parikh ND, Singal AG, Hutton DW, Tapper EB. Cost-Effectiveness of Hepatocellular Carcinoma Surveillance: An Assessment of Benefits and Harms. The American journal of gastroenterology. 2020 Oct;115(10):1642-1649. PMID: 32530829
  • Fujiwara N, Kobayashi M, Fobar AJ, Hoshida A, Marquez CA, Koneru B, Panda G, Taguri M, Qian T, Raman I, Li QZ, Hoshida H, Sezaki H, Kumada H, Tateishi R, Yokoo T, Yopp AC, Chung RT, Fuchs BC, Baumert TF, Marrero JA, Parikh ND, Zhu S, Singal AG, Hoshida Y. A blood-based prognostic liver secretome signature and long-term hepatocellular carcinoma risk in advanced liver fibrosis. Med (New York, N.Y.). 2021 Jul 9;2(7):836-850.e10. Epub 2021 Apr 21. PMID: 34318286
  • Liang KH, Zhang P, Lin CL, Wang SC, Hu TH, Yeh CT, Su GL. Morphomic Signatures Derived from Computed Tomography Predict Hepatocellular Carcinoma Occurrence in Cirrhotic Patients. Digestive diseases and sciences. 2020 Jul;65(7):2130-2139. Epub 2019 Nov 2. PMID: 31677071
  • Singal AG, Hoshida Y, Pinato DJ, Marrero J, Nault JC, Paradis V, Tayob N, Sherman M, Lim YS, Feng Z, Lok AS, Rinaudo JA, Srivastava S, Llovet JM, Villanueva A. International Liver Cancer Association (ILCA) White Paper on Biomarker Development for Hepatocellular Carcinoma. Gastroenterology. 2021 Jun;160(7):2572-2584. Epub 2021 Mar 9. PMID: 33705745
  • Mazumder NR, Enchakalody B, Zhang P, Su GL. Using Artificial Intelligence to Predict Cirrhosis From Computed Tomography Scans. Clinical and translational gastroenterology. 2023 Oct 1;14(10):e00616. PMID: 37436183
  • Feng S, Meng X, Li Z, Chang TS, Wu X, Zhou J, Joshi B, Choi EY, Zhao L, Zhu J, Wang TD. Multi-Modal Imaging Probe for Glypican-3 Overexpressed in Orthotopic Hepatocellular Carcinoma. Journal of medicinal chemistry. 2021 Nov 11;64(21):15639-15650. Epub 2021 Sep 30. PMID: 34590489
  • Zou WY, Enchakalody BE, Zhang P, Shah N, Saini SD, Wang NC, Wang SC, Su GL. Automated Measurements of Body Composition in Abdominal CT Scans Using Artificial Intelligence Can Predict Mortality in Patients With Cirrhosis. Hepatology communications. 2021 Nov;5(11):1901-1910. Epub 2021 Jul 7. PMID: 34558818
  • Rich NE, Parikh ND, Singal AG. REPLY. Hepatology (Baltimore, Md.). 2021 Sep;74(3):1715. Epub 2021 Jun 7. PMID: 33617660
  • Woolen SA, Singal AG, Davenport MS, Troost JP, Khalatbari S, Mittal S, Siddiqui S, Fobar A, Morris J, Odewole M, Tapper EB, Pillai A, Parikh ND. Patient Preferences for Hepatocellular Carcinoma Surveillance Parameters. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2022 Jan;20(1):204-215.e6. Epub 2021 Feb 19. PMID: 33618022
  • Wolf E, Rich NE, Marrero JA, Parikh ND, Singal AG. Use of Hepatocellular Carcinoma Surveillance in Patients With Cirrhosis: A Systematic Review and Meta-Analysis. Hepatology (Baltimore, Md.). 2021 Feb;73(2):713-725. Epub 2020 Nov 20. PMID: 32383272
  • Wang M, Singal AG, Parikh N, Kono Y, Marrero J, Mehta A. A Biomarker Panel Based upon AFP, Fucosylated Kininogen and PEG-Precipitated IgG Is Highly Accurate for the Early Detection Hepatocellular Carcinoma in Patients with Cirrhosis in Phase II and Phase III Biomarker Evaluation. Cancers. 2022 Dec 2;14. (23). PMID: 36497452
  • 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
  • Yokoo T, Masaki N, Parikh ND, Lane BF, Feng Z, Mendiratta-Lala M, Lee CH, Khatri G, Marsh TL, Shetty K, Dunn CT, Al-Jarrah T, Aslam A, Davenport MS, Gopal P, Rich NE, Lok AS, Singal AG. Multicenter Validation of Abbreviated MRI for Detecting Early-Stage Hepatocellular Carcinoma. Radiology. 2023 Apr;307(2):e220917. Epub 2023 Jan 24. PMID: 36692401
  • Toyoda H, Hiraoka A, Olivares J, Al-Jarrah T, Devlin P, Kaneoka Y, Maeda A, Yopp AC, Parikh ND, Singal AG. Outcome of Hepatocellular Carcinoma Detected During Surveillance: Comparing USA and Japan. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2021 Nov;19(11):2379-2388.e6. Epub 2020 Oct 22. PMID: 33295281
  • Singal AG, Tayob N, Mehta A, Marrero JA, El-Serag H, Jin Q, Saenz de Viteri C, Fobar A, Parikh ND. GALAD demonstrates high sensitivity for HCC surveillance in a cohort of patients with cirrhosis. Hepatology (Baltimore, Md.). 2022 Mar;75(3):541-549. Epub 2021 Dec 17. PMID: 34618932
  • Serper M, Parikh ND, Thiele G, Ovchinsky N, Mehta S, Kuo A, Ho C, Kanwal F, Volk M, Asrani SK, Ghabril MS, Lake JR, Merriman RB, Morgan TR, Tapper EB. Patient-reported outcomes in HCC: A scoping review by the Practice Metrics Committee of the American Association for the Study of Liver Diseases. Hepatology (Baltimore, Md.). 2022 Jul;76(1):251-274. Epub 2022 Jan 22. PMID: 34990516
  • Parikh ND, Mehta N, Hoteit MA, Yang JD, John BV, Moon AM, Salgia RJ, Pillai A, Kassab I, Saeed N, Thyssen E, Nathani P, McKinney J, Chan W, Durkin C, Connor M, Alsudaney M, Konjeti R, Durand B, Nissen NN, Kim HP, Paknikar R, Rich NE, Schipper MJ, Singal AG. Association between sustained virological response and clinical outcomes in patients with hepatitis C infection and hepatocellular carcinoma. Cancer. 2022 Oct 1;128(19):3470-3478. Epub 2022 Jul 7. PMID: 35796530
  • Tayob N, Lok ASF, Feng Z. A multivariate parametric empirical Bayes screening approach for early detection of hepatocellular carcinoma using multiple longitudinal biomarkers. Statistics in medicine. 2022 Jun 15;41(13):2338-2353. Epub 2022 Feb 23. PMID: 35199349
  • Singal AG, Parikh ND. Reply. Hepatology (Baltimore, Md.). 2022 Aug;76(2):E40-E41. Epub 2022 Apr 24. PMID: 35302647
  • 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
  • Chen VL, Xu D, Wicha MS, Lok AS, Parikh ND. Utility of Liquid Biopsy Analysis in Detection of Hepatocellular Carcinoma, Determination of Prognosis, and Disease Monitoring: A Systematic Review. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2020 Dec;18(13):2879-2902.e9. Epub 2020 Apr 11. PMID: 32289533
  • Harding-Theobald E, Louissaint J, Maraj B, Cuaresma E, Townsend W, Mendiratta-Lala M, Singal AG, Su GL, Lok AS, Parikh ND. Systematic review: radiomics for the diagnosis and prognosis of hepatocellular carcinoma. Alimentary pharmacology & therapeutics. 2021 Oct;54(7):890-901. Epub 2021 Aug 12. PMID: 34390014
  • Su GL, Zhang P, Belancourt PX, Youles B, Enchakalody B, Perumalswami P, Waljee A, Saini S. Incorporation of quantitative imaging data using artificial intelligence improves risk prediction in veterans with liver disease. Hepatology (Baltimore, Md.). 2023 Dec 29. Epub 2023 Dec 29. PMID: 38156985