Korean Journal of Radiology

The Korean Society of Radiology (대한영상의학회)
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Emerging Role of Hepatobiliary Magnetic Resonance Contrast Media and Contrast-Enhanced Ultrasound for Noninvasive Diagnosis of Hepatocellular Carcinoma: Emphasis on Recent Updates in Major Guidelines

  • Tae-Hyung Kim (Department of Radiology, Seoul National University College of Medicine) ;
  • Jeong Hee Yoon (Department of Radiology, Seoul National University College of Medicine) ;
  • Jeong Min Lee (Department of Radiology, Seoul National University College of Medicine)
  • Received : 2018.07.14
  • Accepted : 2019.02.03
  • Published : 2019.06.01
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Abstract

Hepatocellular carcinoma (HCC) can be noninvasively diagnosed on the basis of its characteristic imaging findings of arterial phase enhancement and portal/delayed "washout" on computed tomography (CT) and magnetic resonance imaging (MRI) in cirrhotic patients. However, different specific diagnostic criteria have been proposed by several countries and major academic societies. In 2018, major guideline updates were proposed by the Association for the Study of Liver Diseases, European Association for the Study of the Liver (EASL), Korean Liver Cancer Association and National Cancer Center (KLCA-NCC) of Korea. In addition to dynamic CT and MRI using extracellular contrast media, these new guidelines now include magnetic resonance imaging (MRI) using hepatobiliary contrast media as the first-line diagnostic test, while the KLCA-NCC and EASL guidelines also include contrast-enhanced ultrasound (CEUS) as the second-line diagnostic test. Therefore, hepatobiliary MR contrast media and CEUS will be increasingly used for the noninvasive diagnosis and staging of HCC. In this review, we discuss the emerging role of hepatobiliary phase MRI and CEUS for the diagnosis of HCC and also review the changes in the HCC diagnostic criteria in major guidelines, including the KLCA-NCC practice guidelines version 2018. In addition, we aimed to pay particular attention to some remaining issues in the noninvasive diagnosis of HCC.

Keywords

References

  1. Choo SP, Tan WL, Goh BKP, Tai WM, Zhu AX. Comparison of hepatocellular carcinoma in Eastern versus Western populations. Cancer 2016;122:3430-3446 https://doi.org/10.1002/cncr.30237
  2. Altekruse SF, McGlynn KA, Reichman ME. Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from 1975 to 2005. J Clin Oncol 2009;27:1485-1491 https://doi.org/10.1200/JCO.2008.20.7753
  3. 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
  4. Trevisani F, De Notariis S, Rapaccini G, Farinati F, Benvegnu L, Zoli M, et al. Semiannual and annual surveillance of cirrhotic patients for hepatocellular carcinoma: effects on cancer stage and patient survival (Italian experience). Am J Gastroenterol 2002;97:734-744 https://doi.org/10.1111/j.1572-0241.2002.05557.x
  5. Ando E, Kuromatsu R, Tanaka M, Takada A, Fukushima N, Sumie S, et al. Surveillance program for early detection of hepatocellular carcinoma in Japan: results of specialized department of liver disease. J Clin Gastroenterol 2006;40:942-948 https://doi.org/10.1097/01.mcg.0000225675.14594.d6
  6. Noda I, Kitamoto M, Nakahara H, Hayashi R, Okimoto T, Monzen Y, et al. Regular surveillance by imaging for early detection and better prognosis of hepatocellular carcinoma in patients infected with hepatitis C virus. J Gastroenterol 2010;45:105-112 https://doi.org/10.1007/s00535-009-0131-x
  7. Lopez PM, Villanueva A, Llovet JM. Systematic review: evidence-based management of hepatocellular carcinoma--an updated analysis of randomized controlled trials. Aliment Pharmacol Ther 2006;23:1535-1547 https://doi.org/10.1111/j.1365-2036.2006.02932.x
  8. Cruite I, Tang A, Sirlin CB. Imaging-based diagnostic systems for hepatocellular carcinoma. AJR Am J Roentgenol 2013;201:41-55 https://doi.org/10.2214/AJR.13.10570
  9. Tang A, Cruite I, Sirlin CB. Toward a standardized system for hepatocellular carcinoma diagnosis using computed tomography and MRI. Expert Rev Gastroenterol Hepatol 2013;7:269-279 https://doi.org/10.1586/egh.13.3
  10. Tang A, Cruite I, Mitchell DG, Sirlin CB. Hepatocellular carcinoma imaging systems: why they exist, how they have evolved, and how they differ. Abdom Radiol (NY) 2018;43:3-12 https://doi.org/10.1007/s00261-017-1292-3
  11. Heimbach JK, Kulik LM, Finn RS, Sirlin CB, Abecassis MM, Roberts LR, et al. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology 2018;67:358-380 https://doi.org/10.1002/hep.29086
  12. Yu JS, Kim KW, Kim EK, Lee JT, Yoo HS. Contrast enhancement of small hepatocellular carcinoma: usefulness of three successive early image acquisitions during multiphase dynamic MR imaging. AJR Am J Roentgenol 1999;173:597-604 https://doi.org/10.2214/ajr.173.3.10470886
  13. Torzilli G, Minagawa M, Takayama T, Inoue K, Hui AM, Kubota K, et al. Accurate preoperative evaluation of liver mass lesions without fine-needle biopsy. Hepatology 1999;30:889-893 https://doi.org/10.1002/hep.510300411
  14. Choi JY, Lee JM, Sirlin CB. CT and MR imaging diagnosis and staging of hepatocellular carcinoma: part I. Development, growth, and spread: key pathologic and imaging aspects. Radiology 2014;272:635-654 https://doi.org/10.1148/radiol.14132361
  15. 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;68:723-750 https://doi.org/10.1002/hep.29913
  16. European Association for the Study of the Liver. EASL clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 2018;69:182-236 https://doi.org/10.1016/j.jhep.2018.03.019
  17. 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;11:317-370 https://doi.org/10.1007/s12072-017-9799-9
  18. CT/MRI LI-RADS®, version 2017. American College of Radiology Web site. https://www.acr.org/Clinical-Resources/Reporting-and-Data-Systems/LI-RADS/CT-MRI-LI-RADS-v2017, Accessed April 3, 2019
  19. New: CT/MRI LI-RADS®, version 2018. American College of Radiology Web site. https://www.acr.org/Clinical-Resources/Reporting-and-Data-Systems/LI-RADS/CT-MRI-LI-RADS-v2018, Accessed April 3, 2019
  20. Wald C, Russo MW, Heimbach JK, Hussain HK, Pomfret EA, Bruix J. New OPTN/UNOS policy for liver transplant allocation: standardization of liver imaging, diagnosis, classification, and reporting of hepatocellular carcinoma. Radiology 2013;266:376-382 https://doi.org/10.1148/radiol.12121698
  21. Kudo M, Matsui O, Izumi N, Iijima H, Kadoya M, Imai Y, et al. JSH consensus-based clinical practice guidelines for the management of hepatocellular carcinoma: 2014 update by the liver cancer study group of Japan. Liver Cancer 2014;3:458-468 https://doi.org/10.1159/000343875
  22. Korean Liver Cancer Study Group (KLCSG), National Cancer Center, Korea (NCC). 2014 Korean Liver Cancer Study Group-National Cancer Center Korea practice guideline for the management of hepatocellular carcinoma. Korean J Radiol 2015;16:465-522 https://doi.org/10.3348/kjr.2015.16.3.465
  23. Gavriilidis P, Roberts KJ, Askari A, Sutcliffe RP, Huo TL, Liu PH, et al. Evaluation of the current guidelines for resection of hepatocellular carcinoma using the appraisal of guidelines for research and evaluation II instrument. J Hepatol 2017;67:991-998 https://doi.org/10.1016/j.jhep.2017.06.028
  24. Korean Liver Cancer Association and National Cancer Center (KLCA-NCC) Korea. 2018 Korean liver cancer association-national cancer center Korea practice guidelines for management of hepatocellular carcinoma. Gut Liver 2019;13:227-299 https://doi.org/10.5009/gnl19024
  25. Choi JY, Lee JM, Sirlin CB. CT and MR imaging diagnosis and staging of hepatocellular carcinoma: part II. Extracellular agents, hepatobiliary agents, and ancillary imaging features. Radiology 2014;273:30-50 https://doi.org/10.1148/radiol.14132362
  26. Kitao A, Matsui O, Yoneda N, Kozaka K, Shinmura R, Koda W, et al. The uptake transporter OATP8 expression decreases during multistep hepatocarcinogenesis: correlation with gadoxetic acid enhanced MR imaging. Eur Radiol 2011;21:2056-2066 https://doi.org/10.1007/s00330-011-2165-8
  27. Kogita S, Imai Y, Okada M, Kim T, Onishi H, Takamura M, et al. Gd-EOB-DTPA-enhanced magnetic resonance images of hepatocellular carcinoma: correlation with histological grading and portal blood flow. Eur Radiol 2010;20:2405-2413 https://doi.org/10.1007/s00330-010-1812-9
  28. Lee YJ, Lee JM, Lee JS, Lee HY, Park BH, Kim YH, et al. Hepatocellular carcinoma: diagnostic performance of multidetector CT and MR imaging-a systematic review and meta-analysis. Radiology 2015;275:97-109 https://doi.org/10.1148/radiol.14140690
  29. Kim HD, Lim YS, Han S, An J, Kim GA, Kim SY, et al. Evaluation of early-stage hepatocellular carcinoma by magnetic resonance imaging with gadoxetic acid detects additional lesions and increases overall survival. Gastroenterology 2015;148:1371-1382 https://doi.org/10.1053/j.gastro.2015.02.051
  30. Joo I, Lee JM, Lee DH, Jeon JH, Han JK, Choi BI. Noninvasive diagnosis of hepatocellular carcinoma on gadoxetic acid-enhanced MRI: can hypointensity on the hepatobiliary phase be used as an alternative to washout? Eur Radiol 2015;25:2859-2868 https://doi.org/10.1007/s00330-015-3686-3
  31. Choi SH, Byun JH, Lim YS, Yu E, Lee SJ, Kim SY, et al. Diagnostic criteria for hepatocellular carcinoma 3 cm with hepatocyte-specific contrast-enhanced magnetic resonance imaging. J Hepatol 2016;64:1099-1107 https://doi.org/10.1016/j.jhep.2016.01.018
  32. Sangiovanni A, Manini MA, Iavarone M, Romeo R, Forzenigo LV, Fraquelli M, et al. The diagnostic and economic impact of contrast imaging techniques in the diagnosis of small hepatocellular carcinoma in cirrhosis. Gut 2010;59:638-644 https://doi.org/10.1136/gut.2009.187286
  33. Khalili K, Kim TK, Jang HJ, Haider MA, Khan L, Guindi M, et al. Optimization of imaging diagnosis of 1-2 cm hepatocellular carcinoma: an analysis of diagnostic performance and resource utilization. J Hepatol 2011;54:723-728 https://doi.org/10.1016/j.jhep.2010.07.025
  34. Yoon JH, Park JW, Lee JM. Noninvasive diagnosis of hepatocellular carcinoma: elaboration on Korean Liver Cancer Study Group-National Cancer Center Korea practice guidelines compared with other guidelines and remaining issues. Korean J Radiol 2016;17:7-24 https://doi.org/10.3348/kjr.2016.17.1.7
  35. Korean Society of Abdominal Radiology. Diagnosis of hepatocellular carcinoma with gadoxetic acid-enhanced MRI: 2016 consensus recommendations of the Korean Society of Abdominal Radiology. Korean J Radiol 2017;18:427-443 https://doi.org/10.3348/kjr.2017.18.3.427
  36. Song KD, Kim SH, Lim HK, Jung SH, Sohn I, Kim HS. Subcentimeter hypervascular nodule with typical imaging findings of hepatocellular carcinoma in patients with history of hepatocellular carcinoma: natural course on serial gadoxetic acid-enhanced MRI and diffusion-weighted imaging. Eur Radiol 2015;25:2789-2796 https://doi.org/10.1007/s00330-015-3680-9
  37. Yoon JH, Lee JM, Yang HK, Lee KB, Jang JJ, Han JK, et al. Non-hypervascular hypointense nodules ≥ 1 cm on the hepatobiliary phase of gadoxetic acid-enhanced magnetic resonance imaging in cirrhotic livers. Dig Dis 2014;32:678-689 https://doi.org/10.1159/000368000
  38. Choi JW, Lee JM, Kim SJ, Yoon JH, Baek JH, Han JK, et al. Hepatocellular carcinoma: imaging patterns on gadoxetic acid-enhanced MR images and their value as an imaging biomarker. Radiology 2013;267:776-786 https://doi.org/10.1148/radiol.13120775
  39. Suh YJ, Kim MJ, Choi JY, Park YN, Park MS, Kim KW. Differentiation of hepatic hyperintense lesions seen on gadoxetic acid-enhanced hepatobiliary phase MRI. AJR Am J Roentgenol 2011;197:W44-W52 https://doi.org/10.2214/AJR.10.5845
  40. Davenport MS, Viglianti BL, Al-Hawary MM, Caoili EM, Kaza RK, Liu PS, et al. Comparison of acute transient dyspnea after intravenous administration of gadoxetate disodium and gadobenate dimeglumine: effect on arterial phase image quality. Radiology 2013;266:452-461 https://doi.org/10.1148/radiol.12120826
  41. Pietryga JA, Burke LM, Marin D, Jaffe TA, Bashir MR. Respiratory motion artifact affecting hepatic arterial phase imaging with gadoxetate disodium: examination recovery with a multiple arterial phase acquisition. Radiology 2014;271:426-434 https://doi.org/10.1148/radiol.13131988
  42. Bolondi L, Correas JM, Lencioni R, Weskott HP, Piscaglia F. New perspectives for the use of contrast-enhanced liver ultrasound in clinical practice. Dig Liver Dis 2007;39:187-195 https://doi.org/10.1016/j.dld.2006.08.008
  43. Strobel D, Bernatik T, Blank W, Schuler A, Greis C, Dietrich CF, et al. Diagnostic accuracy of CEUS in the differential diagnosis of small (≤ 20 mm) and subcentimetric (≤ 10 mm) focal liver lesions in comparison with histology. Results of the DEGUM multicenter trial. Ultraschall Med 2011;32:593-597 https://doi.org/10.1055/s-0031-1271114
  44. Kim TK, Noh SY, Wilson SR, Kono Y, Piscaglia F, Jang HJ, et al. Contrast-enhanced ultrasound (CEUS) liver imaging reporting and data system (LI-RADS) 2017 - a review of important differences compared to the CT/MRI system. Clin Mol Hepatol 2017;23:280-289 https://doi.org/10.3350/cmh.2017.0037
  45. Kudo M. Defect reperfusion imaging with Sonazoid®: a breakthrough in hepatocellular carcinoma. Liver Cancer 2016;5:1-7 https://doi.org/10.1159/000367760
  46. Maruyama H, Takahashi M, Ishibashi H, Yoshikawa M, Yokosuka O. Contrast-enhanced ultrasound for characterisation of hepatic lesions appearing non-hypervascular on CT in chronic liver diseases. Br J Radiol 2012;85:351-357 https://doi.org/10.1259/bjr/20440141
  47. Takahashi M, Maruyama H, Shimada T, Kamezaki H, Sekimoto T, Kanai F, et al. Characterization of hepatic lesions (≤ 30 mm) with liver-specific contrast agents: a comparison between ultrasound and magnetic resonance imaging. Eur J Radiol 2013;82:75-84 https://doi.org/10.1016/j.ejrad.2012.05.035
  48. Wilson SR, Kim TK, Jang HJ, Burns PN. Enhancement patterns of focal liver masses: discordance between contrast-enhanced sonography and contrast-enhanced CT and MRI. AJR Am J Roentgenol 2007;189:W7-W12 https://doi.org/10.2214/AJR.06.1060
  49. Itai Y, Furui S, Ohtomo K, Kokubo T, Yamauchi T, Minami M, et al. Dynamic CT features of arterioportal shunts in hepatocellular carcinoma. AJR Am J Roentgenol 1986;146:723-727 https://doi.org/10.2214/ajr.146.4.723
  50. Yu JS, Kim KW, Jeong MG, Lee JT, Yoo HS. Nontumorous hepatic arterial-portal venous shunts: MR imaging findings. Radiology 2000;217:750-756 https://doi.org/10.1148/radiology.217.3.r00dc13750
  51. Leoni S, Piscaglia F, Granito A, Borghi A, Galassi M, Marinelli S, et al. Characterization of primary and recurrent nodules in liver cirrhosis using contrast-enhanced ultrasound: which vascular criteria should be adopted? Ultraschall Med 2013;34:280-287 https://doi.org/10.1055/s-0033-1335024
  52. Claudon M, Dietrich CF, Choi BI, Cosgrove DO, Kudo M, Nolsoe CP, et al. Guidelines and good clinical practice recommendations for contrast enhanced ultrasound (CEUS) in the liver--update 2012: a WFUMB-EFSUMB initiative in cooperation with representatives of AFSUMB, AIUM, ASUM, FLAUS and ICUS. Ultraschall Med 2013;34:11-29
  53. Bota S, Piscaglia F, Marinelli S, Pecorelli A, Terzi E, Bolondi L. Comparison of international guidelines for noninvasive diagnosis of hepatocellular carcinoma. Liver Cancer 2012;1:190-200 https://doi.org/10.1159/000343833
  54. Italian Association for the Study of the Liver (AISF); AISF Expert Panel; AISF Coordinating Committee; Bolondi L, Cillo U, Colombo M, Craxi A, Farinati F, Giannini EG, et al. Position paper of the Italian association for the study of the liver (AISF): the multidisciplinary clinical approach to hepatocellular carcinoma. Dig Liver Dis 2013;45:712-723 https://doi.org/10.1016/j.dld.2013.01.012
  55. Sherman M, Burak K, Maroun J, Metrakos P, Knox JJ, Myers RP, et al. Multidisciplinary Canadian consensus recommendations for the management and treatment of hepatocellular carcinoma. Curr Oncol 2011;18:228-240 https://doi.org/10.3747/co.v18i5.952
  56. Furlan A, Marin D, Cabassa P, Taibbi A, Brunelli E, Agnello F, et al. Enhancement pattern of small hepatocellular carcinoma (HCC) at contrast-enhanced us (CEUS), MDCT, and MRI: intermodality agreement and comparison of diagnostic sensitivity between 2005 and 2010 American Association for the Study of Liver Diseases (AASLD) guidelines. Eur J Radiol 2012;81:2099-2105 https://doi.org/10.1016/j.ejrad.2011.07.010
  57. Forner A, Vilana R, Ayuso C, Bianchi L, Sole M, Ayuso JR, et al. Diagnosis of hepatic nodules 20 mm or smaller in cirrhosis: prospective validation of the noninvasive diagnostic criteria for hepatocellular carcinoma. Hepatology 2008;47:97-104 https://doi.org/10.1002/hep.21966
  58. Terzi E, Iavarone M, Pompili M, Veronese L, Cabibbo G, Fraquelli M, et al. Contrast ultrasound LI-RADS LR-5 identifies hepatocellular carcinoma in cirrhosis in a multicenter restropective study of 1,006 nodules. J Hepatol 2018;68:485-492 https://doi.org/10.1016/j.jhep.2017.11.007
  59. Galassi M, Iavarone M, Rossi S, Bota S, Vavassori S, Rosa L, et al. Patterns of appearance and risk of misdiagnosis of intrahepatic cholangiocarcinoma in cirrhosis at contrast enhanced ultrasound. Liver Int 2013;33:771-779 https://doi.org/10.1111/liv.12124
  60. Vilana R, Forner A, Bianchi L, Garcia-Criado A, Rimola J, de Lope CR, et al. Intrahepatic peripheral cholangiocarcinoma in cirrhosis patients may display a vascular pattern similar to hepatocellular carcinoma on contrast-enhanced ultrasound. Hepatology 2010;51:2020-2029 https://doi.org/10.1002/hep.23600
  61. Li R, Zhang X, Ma KS, Li XW, Xia F, Zhong H, et al. Dynamic enhancing vascular pattern of intrahepatic peripheral cholangiocarcinoma on contrast-enhanced ultrasound: the influence of chronic hepatitis and cirrhosis. Abdom Imaging 2013;38:112-119 https://doi.org/10.1007/s00261-012-9854-x
  62. Chen LD, Xu HX, Xie XY, Xie XH, Xu ZF, Liu GJ, et al. Intrahepatic cholangiocarcinoma and hepatocellular carcinoma: differential diagnosis with contrast-enhanced ultrasound. Eur Radiol 2010;20:743-753 https://doi.org/10.1007/s00330-009-1599-8
  63. Wildner D, Bernatik T, Greis C, Seitz K, Neurath MF, Strobel D. CEUS in hepatocellular carcinoma and intrahepatic cholangiocellular carcinoma in 320 patients - early or late washout matters: a subanalysis of the DEGUM multicenter trial. Ultraschall Med 2015;36:132-139 https://doi.org/10.1055/s-0034-1399147
  64. Wildner D, Pfeifer L, Goertz RS, Bernatik T, Sturm J, Neurath MF, et al. Dynamic contrast-enhanced ultrasound (DCE-US) for the characterization of hepatocellular carcinoma and cholangiocellular carcinoma. Ultraschall Med 2014;35:522-527 https://doi.org/10.1055/s-0034-1385170
  65. Piscaglia F, Kudo M, Han KH, Sirlin C. Diagnosis of hepatocellular carcinoma with non-invasive imaging: a plea for worldwide adoption of standard and precise terminology for describing enhancement criteria. Ultraschall Med 2017;38:9-11 https://doi.org/10.1055/s-0042-124204
  66. Piscaglia F, Wilson SR, Lyshchik A, Cosgrove D, Dietrich CF, Jang HJ, et al. American College of Radiology Contrast enhanced ultrasound Liver Imaging Reporting and Data System (CEUS LI-RADS) for the diagnosis of hepatocellular carcinoma: a pictorial essay. Ultraschall Med 2017;38:320-324 https://doi.org/10.1055/s-0042-124661
  67. Aube C, Oberti F, Lonjon J, Pageaux G, Seror O, N'Kontchou G, et al. EASL and AASLD recommendations for the diagnosis of HCC to the test of daily practice. Liver Int 2017;37:1515-1525 https://doi.org/10.1111/liv.13429
  68. American College of Radiology. Ultrasound LI-RADS® v2017. American College of Radiology Web site. https://www.acr.org/clinical-resources/reporting-and-data-systems/li-rads/ultrasound-li-rads-v2017. Accessed January 1, 2019
  69. Joo I, Lee JM, Lee DH, Jeon JH, Han JK. Retrospective validation of a new diagnostic criterion for hepatocellular carcinoma on gadoxetic acid-enhanced MRI: can hypointensity on the hepatobiliary phase be used as an alternative to washout with the aid of ancillary features? Eur Radiol 2019;29:1724-1732 https://doi.org/10.1007/s00330-018-5727-1
  70. Farinati F, Sergio A, Baldan A, Giacomin A, Di Nolfo MA, Del Poggio P, et al. Early and very early hepatocellular carcinoma: when and how much do staging and choice of treatment really matter? A multi-center study. BMC Cancer 2009;9:33
  71. Kim YY, An C, Kim S, Kim MJ. Diagnostic accuracy of prospective application of the liver imaging reporting and data system (LI-RADS) in gadoxetate-enhanced MRI. Eur Radiol 2018;28:2038-2046 https://doi.org/10.1007/s00330-017-5188-y
  72. Joo I, Lee JM, Lee DH, Ahn SJ, Lee ES, Han JK. Liver imaging reporting and data system v2014 categorization of hepatocellular carcinoma on gadoxetic acid-enhanced MRI: comparison with multiphasic multidetector computed tomography. J Magn Reson Imaging 2017;45:731-740 https://doi.org/10.1002/jmri.25406
  73. Choi SH, Lee SS, Kim SY, Park SH, Park SH, Kim KM, et al. Intrahepatic cholangiocarcinoma in patients with cirrhosis: differentiation from hepatocellular carcinoma by using gadoxetic acid-enhanced MR imaging and dynamic CT. Radiology 2017;282:771-781 https://doi.org/10.1148/radiol.2016160639
  74. Bolondi L. Screening for hepatocellular carcinoma in cirrhosis. J Hepatol 2003;39:1076-1084 https://doi.org/10.1016/S0168-8278(03)00349-0
  75. 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;30:37-47 https://doi.org/10.1111/j.1365-2036.2009.04014.x
  76. 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 (NY) 2017;42:179-190 https://doi.org/10.1007/s00261-016-0841-5
  77. 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;204:527-535 https://doi.org/10.2214/AJR.14.12986
  78. 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;42:376-384 https://doi.org/10.1111/j.1872-034X.2011.00936.x
  79. Jang KM, Kim SH, Kim YK, Choi D. Imaging features of subcentimeter hypointense nodules on gadoxetic acid-enhanced hepatobiliary phase MR imaging that progress to hypervascular hepatocellular carcinoma in patients with chronic liver disease. Acta Radiol 2015;56:526-535 https://doi.org/10.1177/0284185114534652
  80. Wang JH, Changchien CS, Hu TH, Lee CM, Kee KM, Lin CY, et al. The efficacy of treatment schedules according to Barcelona clinic liver cancer staging for hepatocellular carcinoma - survival analysis of 3892 patients. Eur J Cancer 2008;44:1000-1006 https://doi.org/10.1016/j.ejca.2008.02.018
  81. Hatanaka K, Kudo M, Minami Y, Maekawa K. Sonazoid-enhanced ultrasonography for diagnosis of hepatic malignancies: comparison with contrast-enhanced CT. Oncology 2008;75 Suppl 1:42-47 https://doi.org/10.1159/000173423