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Current Hepatology Reports

, Volume 18, Issue 4, pp 383–389 | Cite as

Harms of Hepatocellular Carcinoma Surveillance

  • Jan Petrasek
  • Amit G. Singal
  • Nicole E. RichEmail author
Hepatic Cancer (N Parikh, Section Editor)
  • 26 Downloads
Part of the following topical collections:
  1. Topical Collection on Hepatic Cancer

Abstract

Purpose of Review

Hepatocellular carcinoma (HCC) surveillance in patients with cirrhosis is associated with decreased mortality by enabling early tumor detection. However, the benefits of any cancer screening program must be considered in light of potential physical, financial, and psychological harms, as well as the risk of overdiagnosis. Herein, we summarize the potential harms of HCC surveillance.

Recent Findings

To date, two retrospective studies have addressed physical harms of HCC surveillance. Based on these data, 15% to 28% of patients undergoing HCC surveillance experience physical harm including additional cross-sectional imaging or liver biopsy. Although psychological and financial harms have been reported for other cancers, there are currently limited data specific to HCC. An ongoing multi-center prospective study assessing all four types of harms should provide data in the near future.

Summary

HCC screening may improve survival by diagnosing tumors at an early stage, but limited sensitivity and specificity of screening tests can result in unintended harms. There is a need for further quality data evaluating both the benefits and harms of HCC surveillance.

Keywords

Hepatocellular cancer Screening Risks Overdiagnosis 

Abbreviations

AASLD

American Association for the Study of Liver Diseases

AFP

Alpha-fetoprotein

CT

Computed tomography

HCC

Hepatocellular carcinoma

EASL

European Association for the Study of the Liver

MRI

Magnetic resonance imaging

NASH

Nonalcoholic steatohepatitis

NCCN

National Comprehensive Cancer Network

Notes

Authors’ Contributions

Jan Petrasek: Concept and design, drafting of the manuscript

Amit G. Singal: Concept and design, drafting of the manuscript

Nicole E. Rich: Concept and design, drafting of the manuscript

All authors approved the final version of this manuscript.

Funding Information

Amit Singal’s research is supported by the National Cancer Institute R01 CA212008 and R01 CA222900.

Compliance with Ethical Standards

Conflict of Interest

Amit Singal has been on advisory boards and served as a consultant for Wako Diagnostics, Roche, Exact Sciences, Glycotest, Bayer, Eisai, BMS, and Exelixis.

Jan Petrasek and Nicole E. Rich each declare no potential conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

  1. 1.
    Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014;74:2913–21.Google Scholar
  2. 2.
    Moon AM, Singal AG, Tapper EB. Contemporary epidemiology of chronic liver disease and cirrhosis. Clin Gastroenterol Hepatol. 2019.Google Scholar
  3. 3.
    Llovet JM, Bru C, Bruix J. Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis. 1999;19:329–38.PubMedGoogle Scholar
  4. 4.
    Yang B, Zhang B, Xu Y, Wang W, Shen Y, Zhang A, et al. Prospective study of early detection for primary liver cancer. J Cancer Res Clin Oncol. 1997;123:357–60.PubMedGoogle Scholar
  5. 5.
    Zhang BH, Yang BH, Tang ZY. Randomized controlled trial of screening for hepatocellular carcinoma. J Cancer Res Clin Oncol. 2004;130:417–22.PubMedGoogle Scholar
  6. 6.
    Singal AG, Pillai A, Tiro J. Early detection, curative treatment, and survival rates for hepatocellular carcinoma surveillance in patients with cirrhosis: a meta-analysis. PLoS Med. 2014;11:e1001624.PubMedPubMedCentralGoogle Scholar
  7. 7.
    EASL clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 2018;69:182–236.Google Scholar
  8. 8.
    Marrero JA, Kulik LM, Sirlin CB, Zhu AX, Finn RS, Abecassis MM, et al. Diagnosis, staging, and management of hepatocellular carcinoma: 2018 Practice guidance by the American Association for the Study of Liver Diseases. Hepatology. 2018;68:723–50.PubMedPubMedCentralGoogle Scholar
  9. 9.
    National Comprehensive Cancer Network. Hepatobiliary cancers (version 3.2019). In.Google Scholar
  10. 10.
    Singal AG, Yopp A, Skinner SC, Packer M, Lee WM, Tiro JA. Utilization of hepatocellular carcinoma surveillance among American patients: a systematic review. J Gen Intern Med. 2012;27:861–7.PubMedPubMedCentralGoogle Scholar
  11. 11.
    Choi DT, Kum HC, Park S, Ohsfeldt RL, Shen Y, Parikh ND, et al. Hepatocellular carcinoma screening is associated with increased survival of patients with cirrhosis. Clin Gastroenterol Hepatol. 2019;17:976–987.e974.PubMedGoogle Scholar
  12. 12.
    Rich NE, Parikh ND, Singal AG. Overdiagnosis: an understudied issue in hepatocellular carcinoma surveillance. Semin Liver Dis. 2017;37:296–304.PubMedGoogle Scholar
  13. 13.
    Kanwal F, Singal AG. Surveillance for hepatocellular carcinoma: current best practice and future direction. Gastroenterology. 2019;157:54–64.PubMedGoogle Scholar
  14. 14.
    Heleno B, Thomsen MF, Rodrigues DS, Jorgensen KJ, Brodersen J. Quantification of harms in cancer screening trials: literature review. Bmj. 2013;347:f5334.PubMedPubMedCentralGoogle Scholar
  15. 15.
    Korenstein D, Chimonas S, Barrow B, Keyhani S, Troy A, Lipitz-Snyderman A. Development of a conceptual map of negative consequences for patients of overuse of medical tests and treatments. JAMA Intern Med. 2018;178:1401–7.PubMedGoogle Scholar
  16. 16.
    Tzartzeva K, Obi J, Rich NE, Parikh ND, Marrero JA, Yopp A, et al. Surveillance imaging and alpha fetoprotein for early detection of hepatocellular carcinoma in patients with cirrhosis: a meta-analysis. Gastroenterology. 2018;154:1706–1718.e1701.PubMedPubMedCentralGoogle Scholar
  17. 17.
    Lodhia N, Kader M, Mayes T, Mantry P, Maliakkal B. Risk of contrast-induced nephropathy in hospitalized patients with cirrhosis. World J Gastroenterol. 2009;15:1459–64.PubMedPubMedCentralGoogle Scholar
  18. 18.
    Ergun I, Keven K, Uruc I, Ekmekci Y, Canbakan B, Erden I, et al. The safety of gadolinium in patients with stage 3 and 4 renal failure. Nephrol Dial Transplant. 2006;21:697–700.PubMedGoogle Scholar
  19. 19.
    Heshmatzadeh Behzadi A, Farooq Z, Newhouse JH, Prince MR. MRI and CT contrast media extravasation: a systematic review. Medicine (Baltimore). 2018;97:e0055.Google Scholar
  20. 20.
    Dewey M, Schink T, Dewey CF. Claustrophobia during magnetic resonance imaging: cohort study in over 55,000 patients. J Magn Reson Imaging. 2007;26:1322–7.PubMedGoogle Scholar
  21. 21.
    Khawaja AZ, Cassidy DB, Al Shakarchi J, McGrogan DG, Inston NG, Jones RG. Revisiting the risks of MRI with gadolinium based contrast agents-review of literature and guidelines. Insights Imaging. 2015;6:553–8.PubMedPubMedCentralGoogle Scholar
  22. 22.
    Guo BJ, Yang ZL, Zhang LJ. Gadolinium deposition in brain: current scientific evidence and future perspectives. Front Mol Neurosci. 2018;11:335.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Eisenberg E, Konopniki M, Veitsman E, Kramskay R, Gaitini D, Baruch Y. Prevalence and characteristics of pain induced by percutaneous liver biopsy. Anesth Analg. 2003;96:1392–6 table of contents.PubMedGoogle Scholar
  24. 24.
    Seeff LB, Everson GT, Morgan TR, Curto TM, Lee WM, Ghany MG, et al. Complication rate of percutaneous liver biopsies among persons with advanced chronic liver disease in the HALT-C trial. Clin Gastroenterol Hepatol. 2010;8:877–83.PubMedPubMedCentralGoogle Scholar
  25. 25.
    Rockey DC, Caldwell SH, Goodman ZD, Nelson RC, Smith AD. Liver biopsy. Hepatology. 2009;49:1017–44.PubMedGoogle Scholar
  26. 26.
    Szpakowski J-L, Drasin TE, Lyon LL. Rate of seeding with biopsies and ablations of hepatocellular carcinoma: a retrospective cohort study. Hepatol Commun. 2017;1:841–51.PubMedPubMedCentralGoogle Scholar
  27. 27.
    Terjung B, Lemnitzer I, Dumoulin FL, Effenberger W, Brackmann HH, Sauerbruch T, et al. Bleeding complications after percutaneous liver biopsy. Digestion. 2003;67:138–45.PubMedGoogle Scholar
  28. 28.
    Gopal P, Yopp AC, Waljee AK, Chiang J, Nehra M, Kandunoori P, et al. Factors that affect accuracy of alpha-fetoprotein test in detection of hepatocellular carcinoma in patients with cirrhosis. Clin Gastroenterol Hepatol. 2014;12:870–7.PubMedGoogle Scholar
  29. 29.
    Di Bisceglie AM, Sterling RK, Chung RT, Everhart JE, Dienstag JL, Bonkovsky HL, et al. Serum alpha-fetoprotein levels in patients with advanced hepatitis C: results from the HALT-C trial. J Hepatol. 2005;43:434–41.PubMedGoogle Scholar
  30. 30.
    Atiq O, Tiro J, Yopp AC, Muffler A, Marrero JA, Parikh ND, et al. An assessment of benefits and harms of hepatocellular carcinoma surveillance in patients with cirrhosis. Hepatology. 2017;65:1196–205.PubMedGoogle Scholar
  31. 31.
    Konerman MA, Verma A, Zhao B, Singal AG, Lok AS, Parikh ND. Frequency and outcomes of abnormal imaging in patients with cirrhosis enrolled in a hepatocellular carcinoma surveillance program. Liver Transpl. 2019;25:369–79.PubMedGoogle Scholar
  32. 32.
    Taylor EJ, Jones RL, Guthrie JA, Rowe IA. Modeling the benefits and harms of surveillance for hepatocellular carcinoma: information to support informed choices. Hepatology. 2017;66:1546–55.PubMedGoogle Scholar
  33. 33.
    European Association for the Study of the L, European Organisation for R, Treatment of C. EASL–EORTC clinical practice guidelines: Management of hepatocellular carcinoma. J Hepatol. 2012;56:908–43.Google Scholar
  34. 34.
    Patibandla S OJ, Fullington H, McCallister K, Rich NE, Parikh ND, Gopal P, et al. Prospective evaluation of benefits and harms of HCC surveillance in a cirrhosis patient population. In: American Association for the Study of Liver Diseases Annual Meeting. Boston, MA; 2019.Google Scholar
  35. 35.
    Geh D, Rana FA, Reeves HL. Weighing the benefits of hepatocellular carcinoma surveillance against potential harms. J Hepatocell Carcinoma. 2019;6:23–30.PubMedPubMedCentralGoogle Scholar
  36. 36.
    Samoylova ML, Mehta N, Roberts JP, Yao FY. Predictors of ultrasound failure to detect hepatocellular carcinoma. Liver Transpl. 2018;24:1171–7.PubMedGoogle Scholar
  37. 37.
    Simmons O, Fetzer DT, Yokoo T, Marrero JA, Yopp A, Kono Y, et al. Predictors of adequate ultrasound quality for hepatocellular carcinoma surveillance in patients with cirrhosis. Aliment Pharmacol Ther. 2017;45:169–77.PubMedGoogle Scholar
  38. 38.
    Expert Panel on Gastrointestinal I, Horowitz JM, Kamel IR, Arif-Tiwari H, Asrani SK, Hindman NM, et al. ACR appropriateness criteria((R)) chronic liver disease. J Am Coll Radiol. 2017;14:S391–405.Google Scholar
  39. 39.
    Patel D. Editorial: ultrasound surveillance of hepatocellular carcinoma in the 21st century. Aliment Pharmacol Ther. 2017;45:561–2.PubMedGoogle Scholar
  40. 40.
    McGovern PM, Gross CR, Krueger RA, Engelhard DA, Cordes JE, Church TR. False-positive cancer screens and health-related quality of life. Cancer Nurs. 2004;27:347–52.PubMedGoogle Scholar
  41. 41.
    DeFrank JT, Barclay C, Sheridan S, Brewer NT, Gilliam M, Moon AM, et al. The psychological harms of screening: the evidence we have versus the evidence we need. J Gen Intern Med. 2015;30:242–8.PubMedGoogle Scholar
  42. 42.
    Brett J, Bankhead C, Henderson B, Watson E, Austoker J. The psychological impact of mammographic screening. A systematic review. Psychooncology. 2005;14:917–38.PubMedGoogle Scholar
  43. 43.
    Dale W, Bilir P, Han M, Meltzer D. The role of anxiety in prostate carcinoma: a structured review of the literature. Cancer. 2005;104:467–78.PubMedPubMedCentralGoogle Scholar
  44. 44.
    Brodersen J, Siersma VD. Long-term psychosocial consequences of false-positive screening mammography. Ann Fam Med. 2013;11:106–15.PubMedPubMedCentralGoogle Scholar
  45. 45.
    Cotter AR, Vuong K, Mustelin L, Yang Y, Rakhmankulova M, Barclay CJ, et al. Do psychological harms result from being labelled with an unexpected diagnosis of abdominal aortic aneurysm or prostate cancer through screening? A systematic review. BMJ Open. 2017;7:e017565.PubMedPubMedCentralGoogle Scholar
  46. 46.
    Fang F, Keating NL, Mucci LA, Adami HO, Stampfer MJ, Valdimarsdottir U, et al. Immediate risk of suicide and cardiovascular death after a prostate cancer diagnosis: cohort study in the United States. J Natl Cancer Inst. 2010;102:307–14.PubMedGoogle Scholar
  47. 47.
    Álamo-Junquera D, Murta-Nascimento C, Macià F, Baré M, Galcerán J, Ascunce N, et al. Effect of false-positive results on reattendance at breast cancer screening programmes in Spain. Eur J Pub Health. 2011;22:404–8.Google Scholar
  48. 48.
    Lafata JE, Simpkins J, Lamerato L, Poisson L, Divine G, Johnson CC. The economic impact of false-positive cancer screens. Cancer Epidemiol Biomark Prev. 2004;13:2126–32.Google Scholar
  49. 49.
    Treskova M, Aumann I, Golpon H, Vogel-Claussen J, Welte T, Kuhlmann A. Trade-off between benefits, harms and economic efficiency of low-dose CT lung cancer screening: a microsimulation analysis of nodule management strategies in a population-based setting. BMC Med. 2017;15:162.PubMedPubMedCentralGoogle Scholar
  50. 50.
    Singal AG MK, Ortiz C, Kramer J, Zhang S, Khan A, Liu Y, et al. Financial burden is common in U.S. patients with cirrhosis and associated with lower HCC surveillance receipt. In: American Association for the Study of Liver Diseases Annual Meeting. Boston, MA; 2019.Google Scholar
  51. 51.
    Roberts LR, Sirlin CB, Zaiem F, Almasri J, Prokop LJ, Heimbach JK, et al. Imaging for the diagnosis of hepatocellular carcinoma: a systematic review and meta-analysis. Hepatology. 2018;67:401–21.PubMedPubMedCentralGoogle Scholar
  52. 52.
    Trinchet JC, Chaffaut C, Bourcier V, Degos F, Henrion J, Fontaine H, et al. Ultrasonographic surveillance of hepatocellular carcinoma in cirrhosis: a randomized trial comparing 3- and 6-month periodicities. Hepatology. 2011;54:1987–97.PubMedGoogle Scholar
  53. 53.
    Vernuccio F, Rosenberg MD, Meyer M, Choudhury KR, Nelson RC, Marin D. Negative biopsy of focal hepatic lesions: decision tree model for patient management. Am J Roentgenol. 2019;212:677–85.Google Scholar
  54. 54.
    Caturelli E, Solmi L, Anti M, Fusilli S, Roselli P, Andriulli A, et al. Ultrasound guided fine needle biopsy of early hepatocellular carcinoma complicating liver cirrhosis: a multicentre study. Gut. 2004;53:1356–62.PubMedPubMedCentralGoogle Scholar
  55. 55.
    Rich NE JB, Parikh ND, Rowe I, Mehta N, Khatri G, Thomas S, et al. Growth rates of untreated hepatocellular carcinoma in patients with cirrhosis: a multicenter cohort study. In: American Association for the Study of Liver Diseases Annual Meeting. Boston, MA; 2019.Google Scholar
  56. 56.
    Singal AG, Marrero JA, Yopp A. Screening process failures for hepatocellular carcinoma. J Natl Compr Cancer Netw. 2014;12:375–82.Google Scholar
  57. 57.
    Ahmed Mohammed HA, Yang JD, Giama NH, Choi J, Ali HM, Mara KC, et al. Factors influencing surveillance for hepatocellular carcinoma in patients with liver cirrhosis. Liver Cancer. 2017;6:126–36.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Jan Petrasek
    • 1
  • Amit G. Singal
    • 1
  • Nicole E. Rich
    • 1
    Email author
  1. 1.Division of Digestive and Liver Diseases, Department of Internal MedicineUT Southwestern Medical CenterDallasUSA

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