Advertisement

Ultrasound Screening and Surveillance in Hepatocellular Carcinoma

  • Emily H. T. PangEmail author
  • Alison C. Harris
Ultrasound (M Hahn and M Shiemorteza, Section Editors)
Part of the following topical collections:
  1. Ultrasound

Abstract

Purpose

To review the current state of the use of ultrasound in hepatocellular carcinoma (HCC) surveillance.

Findings

Despite limitations in the evidence supporting the use of ultrasound in HCC surveillance, it has been formally recommended by a number of guidelines based on the best available evidence showing that it improves survival and is cost effective. However, ultrasound surveillance is inconsistently adopted and is prone to a number of practical and technical challenges. The recent introduction of ultrasound LI-RADS aims to standardize performance and reporting of these surveillance studies.

Summary

Despite remaining a controversial topic, semi-annual ultrasound screening for HCC is still supported by multiple hepatology societies. Ongoing evaluation of its performance and cost-effectiveness is required as new standards such as US LI-RADS, as well as evolving therapies and technologies emerge.

Keywords

Hepatocellular carcinoma Surveillance Screening Ultrasound Liver cancer Cost-effectiveness LI-RADS 

Notes

Compliance with Ethical Guidelines

Conflict of interest

Emily H. T. Pang reports honorarium received from Bayer for consulting. Alison C. Harris declares 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

Recently published papers of particular interest have been highlighted as: • Of importance

  1. 1.
    Wilson JMG, Jungner G. Principles and practice of screening for disease. Geneva: World Health Organization; 1968.Google Scholar
  2. 2.
    World Health Organization IAfRoC. Liver Cancer Fact Sheet; 2018.Google Scholar
  3. 3.
    El-Serag HB. Hepatocellular carcinoma. N Engl J Med. 2011;365(12):1118–27.CrossRefGoogle Scholar
  4. 4.
    Colombo M. Natural history of hepatocellular carcinoma. Cancer Imaging. 2005;5:85–8.CrossRefGoogle Scholar
  5. 5.
    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(4):e1001624.CrossRefGoogle Scholar
  6. 6.
    • 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(2):723–50. The most recent guidelines regarding HCC screening by major hepatology societies around the world. Google Scholar
  7. 7.
    • easloffice@easloffice.eu EAftSotLEa, Liver EAftSot. EASL clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2018;69(1):182–236. The most recent guidelines regarding HCC screening by major hepatology societies around the world. Google Scholar
  8. 8.
    • Omata M, Cheng AL, Kokudo N, Kudo M, Lee JM, Jia J, et al. Asia-Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update. Hepatol Int. 2017;11(4):317–70. The most recent guidelines regarding HCC screening by major hepatology societies around the world. Google Scholar
  9. 9.
    Collier J, Sherman M. Screening for hepatocellular carcinoma. Hepatology. 1998;27(1):273–8.CrossRefGoogle Scholar
  10. 10.
    Cottone M, Turri M, Caltagirone M, Parisi P, Orlando A, Fiorentino G, et al. Screening for hepatocellular carcinoma in patients with Child’s A cirrhosis: an 8-year prospective study by ultrasound and alphafetoprotein. J Hepatol. 1994;21(6):1029–34.CrossRefGoogle Scholar
  11. 11.
    Zhang BH, Yang BH, Tang ZY. Randomized controlled trial of screening for hepatocellular carcinoma. J Cancer Res Clin Oncol. 2004;130(7):417–22.CrossRefGoogle Scholar
  12. 12.
    Bruix J, Sherman M. Practice guidelines committee AeAftSoLD. Management of hepatocellular carcinoma. Hepatology. 2005;42(5):1208–36.CrossRefGoogle Scholar
  13. 13.
    Omata M, Lesmana LA, Tateishi R, Chen PJ, Lin SM, Yoshida H, et al. Asian Pacific association for the study of the liver consensus recommendations on hepatocellular carcinoma. Hepatol Int. 2010;4(2):439–74.CrossRefGoogle Scholar
  14. 14.
    Liver EAFTSOT, Cancer EOFRATO. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012;56(4):908–43.CrossRefGoogle Scholar
  15. 15.
    Goodman ZD. Grading and staging systems for inflammation and fibrosis in chronic liver diseases. J Hepatol. 2007;47(4):598–607.CrossRefGoogle Scholar
  16. 16.
    Kubota K, Ina H, Okada Y, Irie T. Growth rate of primary single hepatocellular carcinoma: determining optimal screening interval with contrast enhanced computed tomography. Dig Dis Sci. 2003;48(3):581–6.CrossRefGoogle Scholar
  17. 17.
    Barbara L, Benzi G, Gaiani S, Fusconi F, Zironi G, Siringo S, et al. Natural history of small untreated hepatocellular carcinoma in cirrhosis: a multivariate analysis of prognostic factors of tumor growth rate and patient survival. Hepatology. 1992;16(1):132–7.CrossRefGoogle Scholar
  18. 18.
    Sheu JC, Sung JL, Chen DS, Yang PM, Lai MY, Lee CS, et al. Growth rate of asymptomatic hepatocellular carcinoma and its clinical implications. Gastroenterology. 1985;89(2):259–66.CrossRefGoogle Scholar
  19. 19.
    Santi V, Trevisani F, Gramenzi A, Grignaschi A, Mirici-Cappa F, Del Poggio P, et al. Semiannual surveillance is superior to annual surveillance for the detection of early hepatocellular carcinoma and patient survival. J Hepatol. 2010;53(2):291–7.CrossRefGoogle Scholar
  20. 20.
    Singal A, Volk ML, Waljee A, Salgia R, Higgins P, Rogers MA, et al. Meta-analysis: surveillance with ultrasound for early-stage hepatocellular carcinoma in patients with cirrhosis. Aliment Pharmacol Ther. 2009;30(1):37–47.CrossRefGoogle Scholar
  21. 21.
    Han KH, Kim DY, Park JY, Ahn SH, Kim J, Kim SU, et al. Survival of hepatocellular carcinoma patients may be improved in surveillance interval not more than 6 months compared with more than 6 months: a 15-year prospective study. J Clin Gastroenterol. 2013;47(6):538–44.CrossRefGoogle Scholar
  22. 22.
    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(6):1987–97.CrossRefGoogle Scholar
  23. 23.
    Hanna RF, Miloushev VZ, Tang A, Finklestone LA, Brejt SZ, Sandhu RS, et al. Comparative 13-year meta-analysis of the sensitivity and positive predictive value of ultrasound, CT, and MRI for detecting hepatocellular carcinoma. Abdom Radiol. 2016;41(1):71–90.CrossRefGoogle Scholar
  24. 24.
    Yu NC, Chaudhari V, Raman SS, Lassman C, Tong MJ, Busuttil RW, et al. CT and MRI improve detection of hepatocellular carcinoma, compared with ultrasound alone, in patients with cirrhosis. Clin Gastroenterol Hepatol. 2011;9(2):161–7.CrossRefGoogle Scholar
  25. 25.
    Pocha C, Dieperink E, McMaken KA, Knott A, Thuras P, Ho SB. Surveillance for hepatocellular cancer with ultrasonography versus computed tomography: a randomised study. Aliment Pharmacol Ther. 2013;38(3):303–12.CrossRefGoogle Scholar
  26. 26.
    Kim SY, An J, Lim YS, Han S, Lee JY, Byun JH, et al. MRI with liver-specific contrast for surveillance of patients with cirrhosis at high risk of hepatocellular carcinoma. JAMA Oncol. 2017;3(4):456–63.CrossRefGoogle Scholar
  27. 27.
    Gulani V, Calamante F, Shellock FG, Kanal E, Reeder SB, Medicine ISfMRi. Gadolinium deposition in the brain: summary of evidence and recommendations. Lancet Neurol. 2017;16(7):564–70.CrossRefGoogle Scholar
  28. 28.
    Besa C, Lewis S, Pandharipande PV, Chhatwal J, Kamath A, Cooper N, et al. Hepatocellular carcinoma detection: diagnostic performance of a simulated abbreviated MRI protocol combining diffusion-weighted and T1-weighted imaging at the delayed phase post gadoxetic acid. Abdom Radiol. 2017;42(1):179–90.CrossRefGoogle Scholar
  29. 29.
    Lee JY, Huo EJ, Weinstein S, Santos C, Monto A, Corvera CU, et al. Evaluation of an abbreviated screening MRI protocol for patients at risk for hepatocellular carcinoma. Abdom Radiol. 2018;43(7):1627–33.CrossRefGoogle Scholar
  30. 30.
    Kudo M, Hatanaka K, Kumada T, Toyoda H, Tada T. Double-contrast ultrasound: a novel surveillance tool for hepatocellular carcinoma. Am J Gastroenterol. 2011;106(2):368–70.CrossRefGoogle Scholar
  31. 31.
    Park JH, Park MS, Lee SJ, Jeong WK, Lee JY, Park MJ, et al. Contrast-enhanced US with perfluorobutane (sonazoid) used as a surveillance test for hepatocellular carcinoma (HCC) in cirrhosis (SCAN): an exploratory cross-sectional study for a diagnostic trial. BMC Cancer. 2017;17(1):279.CrossRefGoogle Scholar
  32. 32.
    Dietrich C, Fetzer D, Jang H-J, Kim T-K, Kono Y, Lyshchik A. CEUS LI-RADS; 2017.Google Scholar
  33. 33.
    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(1):169–77.CrossRefGoogle Scholar
  34. 34.
    Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53(3):1020–2.CrossRefGoogle Scholar
  35. 35.
    Neumann PJ, Cohen JT, Weinstein MC. Updating cost-effectiveness: the curious resilience of the $50,000-per-QALY threshold. N Engl J Med. 2014;371(9):796–7.CrossRefGoogle Scholar
  36. 36.
    Bertram MY, Lauer JA, De Joncheere K, Edejer T, Hutubessy R, Kieny MP, et al. Cost-effectiveness thresholds: pros and cons. Bull World Health Organ. 2016;94(12):925–30.CrossRefGoogle Scholar
  37. 37.
    Cucchetti A, Cescon M, Erroi V, Pinna AD. Cost-effectiveness of liver cancer screening. Best Pract Res Clin Gastroenterol. 2013;27(6):961–72.CrossRefGoogle Scholar
  38. 38.
    Ruggeri M. Hepatocellular carcinoma: cost-effectiveness of screening. A systematic review. Risk Manag Healthc Policy. 2012;5:49–54.CrossRefGoogle Scholar
  39. 39.
    Cadier B, Bulsei J, Nahon P, Seror O, Laurent A, Rosa I, et al. Early detection and curative treatment of hepatocellular carcinoma: a cost-effectiveness analysis in France and in the United States. Hepatology. 2017;65(4):1237–48.CrossRefGoogle Scholar
  40. 40.
    Arguedas MR, Chen VK, Eloubeidi MA, Fallon MB. Screening for hepatocellular carcinoma in patients with hepatitis C cirrhosis: a cost-utility analysis. Am J Gastroenterol. 2003;98(3):679–90.CrossRefGoogle Scholar
  41. 41.
    Lin OS, Keeffe EB, Sanders GD, Owens DK. Cost-effectiveness of screening for hepatocellular carcinoma in patients with cirrhosis due to chronic hepatitis C. Aliment Pharmacol Ther. 2004;19(11):1159–72.CrossRefGoogle Scholar
  42. 42.
    Patel D, Terrault NA, Yao FY, Bass NM, Ladabaum U. Cost-effectiveness of hepatocellular carcinoma surveillance in patients with hepatitis C virus-related cirrhosis. Clin Gastroenterol Hepatol. 2005;3(1):75–84.CrossRefGoogle Scholar
  43. 43.
    Thompson Coon J, Rogers G, Hewson P, Wright D, Anderson R, Cramp M, et al. Surveillance of cirrhosis for hepatocellular carcinoma: systematic review and economic analysis. Health Technol Assess. 2007;11(34):1–206.CrossRefGoogle Scholar
  44. 44.
    Andersson KL, Salomon JA, Goldie SJ, Chung RT. Cost effectiveness of alternative surveillance strategies for hepatocellular carcinoma in patients with cirrhosis. Clin Gastroenterol Hepatol. 2008;6(12):1418–24.CrossRefGoogle Scholar
  45. 45.
    Nouso K, Tanaka H, Uematsu S, Shiraga K, Okamoto R, Onishi H, et al. Cost-effectiveness of the surveillance program of hepatocellular carcinoma depends on the medical circumstances. J Gastroenterol Hepatol. 2008;23(3):437–44.CrossRefGoogle Scholar
  46. 46.
    Tanaka H, Iijima H, Nouso K, Aoki N, Iwai T, Takashima T, et al. Cost-effectiveness analysis on the surveillance for hepatocellular carcinoma in liver cirrhosis patients using contrast-enhanced ultrasonography. Hepatol Res. 2012;42(4):376–84.CrossRefGoogle Scholar
  47. 47.
    Cucchetti A, Trevisani F, Cescon M, Ercolani G, Farinati F, Poggio PD, et al. Cost-effectiveness of semi-annual surveillance for hepatocellular carcinoma in cirrhotic patients of the Italian Liver Cancer population. J Hepatol. 2012;56(5):1089–96.CrossRefGoogle Scholar
  48. 48.
    Harris RP, Sheridan SL, Lewis CL, Barclay C, Vu MB, Kistler CE, et al. The harms of screening: a proposed taxonomy and application to lung cancer screening. JAMA Intern Med. 2014;174(2):281–5.CrossRefGoogle Scholar
  49. 49.
    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(4):1196–205.CrossRefGoogle Scholar
  50. 50.
    Davila JA, Morgan RO, Richardson PA, Du XL, McGlynn KA, El-Serag HB. Use of surveillance for hepatocellular carcinoma among patients with cirrhosis in the United States. Hepatology. 2010;52(1):132–41.CrossRefGoogle Scholar
  51. 51.
    Tran SA, Le A, Zhao C, Hoang J, Yasukawa LA, Weber S, et al. Rate of hepatocellular carcinoma surveillance remains low for a large, real-life cohort of patients with hepatitis C cirrhosis. BMJ Open Gastroenterol. 2018;5(1):e000192.CrossRefGoogle Scholar
  52. 52.
    Wang C, Chen V, Vu V, Le A, Nguyen L, Zhao C, et al. Poor adherence and low persistency rates for hepatocellular carcinoma surveillance in patients with chronic hepatitis B. Medicine. 2016;95(35):e4744.CrossRefGoogle Scholar
  53. 53.
    Wong CR, Garcia RT, Trinh HN, Lam KD, Ha NB, Nguyen HA, et al. Adherence to screening for hepatocellular carcinoma among patients with cirrhosis or chronic hepatitis B in a community setting. Dig Dis Sci. 2009;54(12):2712–21.CrossRefGoogle Scholar
  54. 54.
    Singal AG, Yopp A, Skinner C, Packer M, Lee WM, Tiro JA. Utilization of hepatocellular carcinoma surveillance among American patients: a systematic review. J Gen Intern Med. 2012;27(7):861–7.CrossRefGoogle Scholar
  55. 55.
    Singal AG, Li X, Tiro J, Kandunoori P, Adams-Huet B, Nehra MS, et al. Racial, social, and clinical determinants of hepatocellular carcinoma surveillance. Am J Med. 2015;128(1):90.e1–7.CrossRefGoogle Scholar
  56. 56.
    Farvardin S, Patel J, Khambaty M, Yerokun OA, Mok H, Tiro JA, et al. Patient-reported barriers are associated with lower hepatocellular carcinoma surveillance rates in patients with cirrhosis. Hepatology. 2017;65(3):875–84.CrossRefGoogle Scholar
  57. 57.
    Dalton-Fitzgerald E, Tiro J, Kandunoori P, Halm EA, Yopp A, Singal AG. Practice patterns and attitudes of primary care providers and barriers to surveillance of hepatocellular carcinoma in patients with cirrhosis. Clin Gastroenterol Hepatol. 2015;13(4):791–8.CrossRefGoogle Scholar
  58. 58.
    Simmons OL, Feng Y, Parikh ND, Singal AG. Primary care provider practice patterns and barriers to hepatocellular carcinoma surveillance. Clin Gastroenterol Hepatol; 2018.Google Scholar
  59. 59.
    • Dahiya N, Dehkordy SF, Desser T, Fetzer D, Harris A, Hong W, et al. Ultrasound liver imaging data and reporting system (US LI-RADS): American College of Radiology; 2017. https://www.acr.org/-/media/ACR/Files/RADS/LI-RADS/LI-RADS-US-Algorithm-Portrait-2017.pdf?la=en. American College of Radiology Ultrasound LI-RADS document.
  60. 60.
    Dahiya N, Dehkordy SF, Desser T, Fetzer D, Harris A, Hong W, et al. Ultrasound Liver Imaging Data and Reporting System (US LI-RADS); 2017.Google Scholar
  61. 61.
    Wells ML, Fenstad ER, Poterucha JT, Hough DM, Young PM, Araoz PA, et al. Imaging findings of congestive hepatopathy. Radiographics. 2016;36(4):1024–37.CrossRefGoogle Scholar
  62. 62.
    Lederle FA, Pocha C. Screening for liver cancer: the rush to judgment. Ann Intern Med. 2012;156(5):387–9.CrossRefGoogle Scholar
  63. 63.
    Singal AG. CON: hepatocellular carcinoma surveillance: in need of higher-quality data. Am J Gastroenterol. 2017;112(11):1634–5.CrossRefGoogle Scholar
  64. 64.
    Cooper GS. Should we abandon current hepatocellular carcinoma screening practices? Gastroenterology. 2018;155(4):972–4.CrossRefGoogle Scholar
  65. 65.
    Sherman M, Bruix J, Porayko M, Tran T, Committee APG. Screening for hepatocellular carcinoma: the rationale for the American Association for the Study of Liver Diseases recommendations. Hepatology. 2012;56(3):793–6.CrossRefGoogle Scholar
  66. 66.
    Parikh ND. PRO: hepatocellular carcinoma surveillance: a useful tool against the rising tide of HCC. Am J Gastroenterol. 2017;112(11):1632–3.CrossRefGoogle Scholar
  67. 67.
    Berhane S, Toyoda H, Tada T, Kumada T, Kagebayashi C, Satomura S, et al. Role of the GALAD and BALAD-2 serologic models in diagnosis of hepatocellular carcinoma and prediction of survival in patients. Clin Gastroenterol Hepatol. 2016;14(6):875–86.CrossRefGoogle Scholar
  68. 68.
    Marks RM, Ryan A, Heba ER, Tang A, Wolfson TJ, Gamst AC, et al. Diagnostic per-patient accuracy of an abbreviated hepatobiliary phase gadoxetic acid-enhanced MRI for hepatocellular carcinoma surveillance. AJR Am J Roentgenol. 2015;204(3):527–35.CrossRefGoogle Scholar
  69. 69.
    Wong GL, Chan HL, Wong CK, Leung C, Chan CY, Ho PP, et al. Liver stiffness-based optimization of hepatocellular carcinoma risk score in patients with chronic hepatitis B. J Hepatol. 2014;60(2):339–45.CrossRefGoogle Scholar
  70. 70.
    Wong VW, Janssen HL. Can we use HCC risk scores to individualize surveillance in chronic hepatitis B infection? J Hepatol. 2015;63(3):722–32.CrossRefGoogle Scholar
  71. 71.
    Motosugi U, Ichikawa T, Koshiishi T, Sano K, Morisaka H, Ichikawa S, et al. Liver stiffness measured by magnetic resonance elastography as a risk factor for hepatocellular carcinoma: a preliminary case-control study. Eur Radiol. 2013;23(1):156–62.CrossRefGoogle Scholar
  72. 72.
    Masuzaki R, Tateishi R, Yoshida H, Goto E, Sato T, Ohki T, et al. Prospective risk assessment for hepatocellular carcinoma development in patients with chronic hepatitis C by transient elastography. Hepatology. 2009;49(6):1954–61.CrossRefGoogle Scholar
  73. 73.
    Younes R, Bugianesi E. Should we undertake surveillance for HCC in patients with NAFLD? J Hepatol. 2018;68(2):326–34.CrossRefGoogle Scholar

Copyright information

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

Authors and Affiliations

  1. 1.Department of Radiology, Abdominal DivisionVancouver General HospitalVancouverUSA

Personalised recommendations