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Grant Details

Grant Number: 5R01CA212008-04 Interpret this number
Primary Investigator: Singal, Amit
Organization: Ut Southwestern Medical Center
Project Title: Harms of Hepatocellular Carcinoma Screening in Patients with Cirrhosis
Fiscal Year: 2020


PROJECT SUMMARY / ABSTRACT The incidence of hepatocellular carcinoma (HCC) is rising in the U.S and is projected to become the 3rd leading cause of cancer death by 2030. Over 90% of HCC occur in cirrhosis, and HCC is the leading cause of death for these patients. Although several professional societies recommend use of abdominal ultrasound and alpha fetoprotein (AFP), a serum biomarker, every 6 months in patients with cirrhosis, limitations in the literature have precluded consensus recommendations. Two systematic reviews concluded prior studies have notable limitations including a lack of data regarding screening harms. Potential harms of HCC screening include: 1) physical and financial harms from diagnostic evaluation in screen-positive patients (e.g., contrast injury, radiation exposure, biopsy complications); 2) overdiagnosis; and 3) psychosocial harms due to positive or indeterminate screen results. Because the survival benefit of HCC screening appears modest, a comprehensive harms assessment is needed to inform guidelines, build consensus among primary care providers and specialists, and guide patient and provider decision-making about HCC screening. Leveraging a multi-center randomized trial assessing screening benefits in a socioeconomically (~30% underinsured) and racially diverse (>50% Black or Hispanic) population of 3000 patients with cirrhosis followed in 3 healthcare settings (academic tertiary care center, safety-net health system, and Veterans Affairs system) over a 4-year period, we propose to: Aim 1: Assess the effect of HCC screening on a) physical harms due to follow-up tests, b) financial harms, and c) overdiagnosis in patients with severe liver dysfunction or comorbid illness, through electronic medical record data, manual chart review, and validated survey measures Aim 2: Assess the effect of HCC screening on screening-related psychosocial harms, e.g. cancer-specific worry, situational anxiety, mood disturbances, and decisional regret, through longitudinal validated measures and qualitative interviews Aim 3: Create and disseminate a balance sheet of benefits and harms to inform patients, nurses, providers, healthcare organizations, payers, and policymakers about the value of HCC screening in patients with cirrhosis We will use mixed-effect regression analysis to identify if screening-related harms differ by patient, provider, and healthcare system factors. These data will complement concurrently collected data about screening benefits from the randomized trial to provide the highest quality data available about benefits and harms of HCC screening at a time when policy decisions about HCC screening are being made. We will immediately translate our study findings to facilitate patient-provider discussions, inform payer decisions about reimbursement, and guide policy decisions on HCC screening in patients with cirrhosis.


Hepatocellular carcinoma tumour volume doubling time: a systematic review and meta-analysis.
Authors: Nathani P. , Gopal P. , Rich N. , Yopp A. , Yokoo T. , John B. , Marrero J. , Parikh N. , Singal A.G. .
Source: Gut, 2021 Feb; 70(2), p. 401-407.
EPub date: 2020-05-12.
PMID: 32398224
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Cost-Effectiveness of Hepatocellular Carcinoma Surveillance: An Assessment of Benefits and Harms.
Authors: Parikh N.D. , Singal A.G. , Hutton D.W. , Tapper E.B. .
Source: The American journal of gastroenterology, 2020 10; 115(10), p. 1642-1649.
PMID: 32530829
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Thrombocytosis is associated with worse survival in patients with hepatocellular carcinoma.
Authors: Liu P.H. , Hsu C.Y. , Su C.W. , Huang Y.H. , Hou M.C. , Rich N.E. , Fujiwara N. , Hoshida Y. , Singal A.G. , Huo T.I. .
Source: Liver international : official journal of the International Association for the Study of the Liver, 2020 10; 40(10), p. 2522-2534.
EPub date: 2020-06-28.
PMID: 32511831
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Patient-Reported Barriers are Associated With Receipt of Hepatocellular Carcinoma Surveillance in a Multicenter Cohort of Patients With Cirrhosis.
Authors: Singal A.G. , Tiro J.A. , Murphy C.C. , Blackwell J.M. , Kramer J.R. , Khan A. , Liu Y. , Zhang S. , Phillips J.L. , Hernaez R. .
Source: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, 2020-07-03; , .
EPub date: 2020-07-03.
PMID: 32629122
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Epidemiology and surveillance for hepatocellular carcinoma: New trends.
Authors: Singal A.G. , Lampertico P. , Nahon P. .
Source: Journal of hepatology, 2020 02; 72(2), p. 250-261.
PMID: 31954490
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Role of imaging in management of hepatocellular carcinoma: surveillance, diagnosis, and treatment response.
Authors: Osho A. , Rich N.E. , Singal A.G. .
Source: Hepatoma research, 2020; 6, .
EPub date: 2020-08-27.
PMID: 32944652
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Harms of hepatocellular carcinoma surveillance.
Authors: Petrasek J. , Singal A.G. , Rich N.E. .
Source: Current hepatology reports, 2019 Dec; 18(4), p. 383-389.
EPub date: 2019-10-15.
PMID: 33214987
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Hepatocellular carcinoma surveillance in the 21st century: Saving lives or causing harm?
Authors: Hanouneh I.A. , Alkhouri N. , Singal A.G. .
Source: Clinical and molecular hepatology, 2019 09; 25(3), p. 264-269.
EPub date: 2019-03-04.
PMID: 30827081
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Surveillance for Hepatocellular Carcinoma: Current Best Practice and Future Direction.
Authors: Kanwal F. , Singal A.G. .
Source: Gastroenterology, 2019 07; 157(1), p. 54-64.
EPub date: 2019-04-12.
PMID: 30986389
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AGA Clinical Practice Update on Interaction Between Oral Direct-Acting Antivirals for Chronic Hepatitis C Infection and Hepatocellular Carcinoma: Expert Review.
Authors: Singal A.G. , Lim J.K. , Kanwal F. .
Source: Gastroenterology, 2019 06; 156(8), p. 2149-2157.
EPub date: 2019-03-13.
PMID: 30878469
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Hepatocellular Carcinoma Screening Is Associated With Increased Survival of Patients With Cirrhosis.
Authors: Choi D.T. , Kum H.C. , Park S. , Ohsfeldt R.L. , Shen Y. , Parikh N.D. , Singal A.G. .
Source: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, 2019 04; 17(5), p. 976-987.e4.
EPub date: 2018-10-26.
PMID: 30616961
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Frequency and Outcomes of Abnormal Imaging in Patients With Cirrhosis Enrolled in a Hepatocellular Carcinoma Surveillance Program.
Authors: Konerman M.A. , Verma A. , Zhao B. , Singal A.G. , Lok A.S. , Parikh N.D. .
Source: Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 2019 03; 25(3), p. 369-379.
PMID: 30582779
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Primary Care Provider Practice Patterns and Barriers to Hepatocellular Carcinoma Surveillance.
Authors: Simmons O.L. , Feng Y. , Parikh N.D. , Singal A.G. .
Source: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, 2019 03; 17(4), p. 766-773.
EPub date: 2018-07-26.
PMID: 30056183
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Mailed Outreach Invitations Significantly Improve HCC Surveillance Rates in Patients With Cirrhosis: A Randomized Clinical Trial.
Authors: Singal A.G. , Tiro J.A. , Murphy C.C. , Marrero J.A. , McCallister K. , Fullington H. , Mejias C. , Waljee A.K. , Pechero Bishop W. , Santini N.O. , et al. .
Source: Hepatology (Baltimore, Md.), 2019 01; 69(1), p. 121-130.
EPub date: 2018-12-14.
PMID: 30070379
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Systematic review with meta-analysis: recurrence of hepatocellular carcinoma following direct-acting antiviral therapy.
Authors: Saraiya N. , Yopp A.C. , Rich N.E. , Odewole M. , Parikh N.D. , Singal A.G. .
Source: Alimentary pharmacology & therapeutics, 2018 07; 48(2), p. 127-137.
EPub date: 2018-05-30.
PMID: 29851093
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Surveillance Imaging and Alpha Fetoprotein for Early Detection of Hepatocellular Carcinoma in Patients With Cirrhosis: A Meta-analysis.
Authors: Tzartzeva K. , Obi J. , Rich N.E. , Parikh N.D. , Marrero J.A. , Yopp A. , Waljee A.K. , Singal A.G. .
Source: Gastroenterology, 2018 05; 154(6), p. 1706-1718.e1.
EPub date: 2018-02-06.
PMID: 29425931
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Overdiagnosis: An Understudied Issue in Hepatocellular Carcinoma Surveillance.
Authors: Rich N.E. , Parikh N.D. , Singal A.G. .
Source: Seminars in liver disease, 2017 11; 37(4), p. 296-304.
EPub date: 2017-12-22.
PMID: 29272892
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