Skip to main content

Advertisement

SpringerLink
Log in

Ultrasound Screening and Surveillance in Hepatocellular Carcinoma

  • Ultrasound (M Hahn and M Shiemorteza, Section Editors)
  • Published:
Current Radiology Reports Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

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

  1. Wilson JMG, Jungner G. Principles and practice of screening for disease. Geneva: World Health Organization; 1968.

    Google Scholar 

  2. World Health Organization IAfRoC. Liver Cancer Fact Sheet; 2018.

  3. El-Serag HB. Hepatocellular carcinoma. N Engl J Med. 2011;365(12):1118–27.

    Article  CAS  Google Scholar 

  4. Colombo M. Natural history of hepatocellular carcinoma. Cancer Imaging. 2005;5:85–8.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

  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.

  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.

  9. Collier J, Sherman M. Screening for hepatocellular carcinoma. Hepatology. 1998;27(1):273–8.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  12. Bruix J, Sherman M. Practice guidelines committee AeAftSoLD. Management of hepatocellular carcinoma. Hepatology. 2005;42(5):1208–36.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  14. Liver EAFTSOT, Cancer EOFRATO. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012;56(4):908–43.

    Article  Google Scholar 

  15. Goodman ZD. Grading and staging systems for inflammation and fibrosis in chronic liver diseases. J Hepatol. 2007;47(4):598–607.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  32. Dietrich C, Fetzer D, Jang H-J, Kim T-K, Kono Y, Lyshchik A. CEUS LI-RADS; 2017.

  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.

    Article  CAS  Google Scholar 

  34. Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53(3):1020–2.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  38. Ruggeri M. Hepatocellular carcinoma: cost-effectiveness of screening. A systematic review. Risk Manag Healthc Policy. 2012;5:49–54.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  58. Simmons OL, Feng Y, Parikh ND, Singal AG. Primary care provider practice patterns and barriers to hepatocellular carcinoma surveillance. Clin Gastroenterol Hepatol; 2018.

  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. 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.

  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.

    Article  Google Scholar 

  62. Lederle FA, Pocha C. Screening for liver cancer: the rush to judgment. Ann Intern Med. 2012;156(5):387–9.

    Article  Google Scholar 

  63. Singal AG. CON: hepatocellular carcinoma surveillance: in need of higher-quality data. Am J Gastroenterol. 2017;112(11):1634–5.

    Article  Google Scholar 

  64. Cooper GS. Should we abandon current hepatocellular carcinoma screening practices? Gastroenterology. 2018;155(4):972–4.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  66. Parikh ND. PRO: hepatocellular carcinoma surveillance: a useful tool against the rising tide of HCC. Am J Gastroenterol. 2017;112(11):1632–3.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  73. Younes R, Bugianesi E. Should we undertake surveillance for HCC in patients with NAFLD? J Hepatol. 2018;68(2):326–34.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Radiology, Abdominal Division, Vancouver General Hospital, 899 West 12th Ave, Room G861, Vancouver, BC, V5Z 1M9, USA

    Emily H. T. Pang & Alison C. Harris

Authors
  1. Emily H. T. Pang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alison C. Harris
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Emily H. T. Pang.

Ethics declarations

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.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical collection on Ultrasound.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pang, E.H.T., Harris, A.C. Ultrasound Screening and Surveillance in Hepatocellular Carcinoma. Curr Radiol Rep 7, 8 (2019). https://doi.org/10.1007/s40134-019-0317-9

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s40134-019-0317-9

Keywords

Search

Navigation