Korean J Gastroenterol.  2019 Aug;74(2):101-109. 10.4166/kjg.2019.74.2.101.

2018 Korean Liver Cancer Association and National Cancer Center for Clinical Practice Guidelines of Hepatocellular Carcinoma: What's Different from 2014?

  • 1Department of Internal Medicine, Korea University Guro Hospital, Seoul, Korea. kjhhepar@naver.com


The Korean clinical practice guidelines for the management of hepatocellular carcinoma (HCC) was originally enacted in 2004 by the Korean Liver Cancer Association (KLCA)-National Cancer Center (NCC) Korea in order to provide medical practitioners with specific medical information regarding HCC to help them facilitate their understanding of the disease and treatment of the patients. KLCA-NCC Korea practice guidelines for the management of HCC have been revised entirely two times in 2009, and 2014. Although several major international liver association have established and revised clinical practice guidelines, since the medical environment in each country is somewhat different depending on race, region, institution, and economic conditions, it is necessary to revise the Korean guidelines to that reflect our medical environments and own research results. In this review, major change and its background will be summarized about 2018 updated clinical practice guidelines for the management of HCC.


Carcinoma, hepatocellular; Guideline; Therapeutics

MeSH Terms

Carcinoma, Hepatocellular*
Continental Population Groups
Liver Neoplasms*


  • Fig. 1 Diagnostic algorithm and recall policy in patients with a high risk of hepatocellular carcinoma.1 HCC, hepatocellular carcinoma. *Major imaging features for “definite” diagnosis of HCC are defined as arterial phase hyperenhancement with washout in portal venous, delayed or hepatobiliary phases. These criteria should be applied only to lesion which does not show either marked T2 hyperintensity or targetoid appearance on diffusion-weighted images or contrastenhanced sequence on contrast-enhanced US as second line exams, major imaging features include arterial hyperenhancement and mild washout with late onset (≥60 seconds); **In nodule(s) with some but not all of aforementioned major imaging features of HCC, category of “probable” HCC can be assigned only when lesion fulfills at least one item from each of following two categories of ancillary imaging features. Two categories which make up ancillary imaging features are findings favoring malignancy in general (mild-to-moderate T2 hyperintensity, restricted diffusion, hepatobiliary phase hypointensity, interval growth) and those favoring HCC in particular (non-enhancing capsule, mosaic architecture, nodule-innodule appearance, fat or blood products in mass). These criteria should be applied only to lesion which shows neither marked T2 hyperintensity nor targetoid appearance on diffusion-weighted images or contrast-enhanced sequences.

  • Fig. 2 Therapeutic strategy in advanced hepatocellular carcinoma based on present evidence. HCC, hepatocellular carcinoma; PD, progressed disease; PVT, portal vein thrombosis; AFP, alpha-fetoprotein. *In patients without main PVT and <50% tumor load; #In patients with AFP >400 ng/mL; ?Cabozantinib trial included one patient of lenvatinib failure but the one had been assigned to placebo.


1. 2018 Korean practice guidelines for the management of hepatocellular carcinoma. [Internet]. Seoul: The Korean Liver Cancer Association and National Cancer Center;2018. 06. cited 2019 Aug 1. Available from: http://livercancer.or.kr/file/2018_guidelines_20190315_v4.pdf.
2. Reig M, Mariño Z, Perelló C, et al. Unexpected high rate of early tumor recurrence in patients with HCV-related HCC undergoing interferon-free therapy. J Hepatol. 2016; 65:719–726.
3. Calvaruso V, Cabibbo G, Cacciola I, et al. Incidence of hepatocellular carcinoma in patients with HCV-associated cirrhosis treated with direct-acting antiviral agents. Gastroenterology. 2018; 155:411–421.e4.
4. Singal AG, Rich NE, Mehta N, et al. Direct-acting antiviral therapy not associated with recurrence of hepatocellular carcinoma in a multicenter North American cohort study. Gastroenterology. 2019; 156:1683–1692.e1.
5. Singal AG, Rich NE, Mehta N, et al. Direct-acting antiviral therapy for HCV infection is associated with increased survival in patients with a history of hepatocellular carcinoma. Gastroenterology. 2019; 07. 30. [Epub ahead of print].
6. Bravi F, Bosetti C, Tavani A, Gallus S, La Vecchia C. Coffee reduces risk for hepatocellular carcinoma: an updated meta-analysis. Clin Gastroenterol Hepatol. 2013; 11:1413–1421.e1.
7. Inoue M, Yoshimi I, Sobue T, Tsugane S. JPHC Study Group. Influence of coffee drinking on subsequent risk of hepatocellular carcinoma: a prospective study in Japan. J Natl Cancer Inst. 2005; 97:293–300.
8. European Association for the Study of the Liver. EASL clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2018; 69:182–236.
9. Marrero JA, Kulik LM, Sirlin CB, 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.
10. Khalili K, Kim TK, Jang HJ, 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.
11. Sangiovanni A, Manini MA, Iavarone 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.
12. Yoon SH, Lee JM, So YH, et al. Multiphasic MDCT enhancement pattern of hepatocellular carcinoma smaller than 3 cm in diameter: tumor size and cellular differentiation. AJR Am J Roentgenol. 2009; 193:W482–W489.
13. Bolondi L, Gaiani S, Celli N, et al. Characterization of small nodules in cirrhosis by assessment of vascularity: the problem of hypovascular hepatocellular carcinoma. Hepatology. 2005; 42:27–34.
14. Choi SH, Byun JH, Lim YS, et al. Diagnostic criteria for hepatocellular carcinoma ≤3 cm with hepatocyte-specific contrast-enhanced magnetic resonance imaging. J Hepatol. 2016; 64:1099–1107.
15. 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.
16. Lee YJ, Lee JM, Lee JS, et al. Hepatocellular carcinoma: diagnostic performance of multidetector CT and MR imaging-a systematic review and meta-analysis. Radiology. 2015; 275:97–109.
17. Uchino K, Tateishi R, Shiina S, et al. Hepatocellular carcinoma with extrahepatic metastasis: clinical features and prognostic factors. Cancer. 2011; 117:4475–4483.
18. Cho Y, Lee DH, Lee YB, et al. Does 18F-FDG positron emission tomography-computed tomography have a role in initial staging of hepatocellular carcinoma? PLoS One. 2014; 9:e105679.
19. Azoulay D, Audureau E, Bhangui P, et al. Living or brain-dead donor liver transplantation for hepatocellular carcinoma: a multicenter, Western, intent-to-treat cohort study. Ann Surg. 2017; 266:1035–1044.
20. Bhangui P, Vibert E, Majno P, et al. Intention-to-treat analysis of liver transplantation for hepatocellular carcinoma: living versus deceased donor transplantation. Hepatology. 2011; 53:1570–1579.
21. Wang C, Wang H, Yang W, et al. Multicenter randomized controlled trial of percutaneous cryoablation versus radiofrequency ablation in hepatocellular carcinoma. Hepatology. 2015; 61:1579–1590.
22. Yu J, Yu XL, Han ZY, et al. Percutaneous cooled-probe microwave versus radiofrequency ablation in early-stage hepatocellular carcinoma: a phase III randomised controlled trial. Gut. 2017; 66:1172–1173.
23. Kim GA, Shim JH, Yoon SM, et al. Comparison of chemoembolization with and without radiation therapy and sorafenib for advanced hepatocellular carcinoma with portal vein tumor thrombosis: a propensity score analysis. J Vasc Interv Radiol. 2015; 26:320–329.e6.
24. Yoon SM, Ryoo BY, Lee SJ, et al. Efficacy and safety of transarterial chemoembolization plus external beam radiotherapy vs sorafenib in hepatocellular carcinoma with macroscopic vascular invasion: a randomized clinical trial. JAMA Oncol. 2018; 4:661–669.
25. Kudo M, Finn RS, Qin S, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018; 391:1163–1173.
26. Lee JH, Lee JH, Lim YS, et al. Adjuvant immunotherapy with autologous cytokine-induced killer cells for hepatocellular carcinoma. Gastroenterology. 2015; 148:1383–1391.e6.
27. Wang H, Liu A, Bo W, et al. Adjuvant immunotherapy with autologous cytokine-induced killer cells for hepatocellular carcinoma patients after curative resection, a systematic review and meta-analysis. Dig Liver Dis. 2016; 48:1275–1282.
28. Bruix J, Qin S, Merle P, et al. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017; 389:56–66.
29. El-Khoueiry AB, Sangro B, Yau T, et al. Nivolumab in patients with advanced hepatocellular carcinoma (checkmate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet. 2017; 389:2492–2502.
30. Abou-Alfa GK, Meyer T, Cheng AL, et al. Cabozantinib in patients with advanced and progressing hepatocellular carcinoma. N Engl J Med. 2018; 379:54–63.
31. Zhu AX, Kang YK, Yen CJ, et al. Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased α-fetoprotein concentrations (REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019; 20:282–296.
Full Text Links
  • KJG
export Copy
  • Twitter
  • Facebook
Similar articles
Copyright © 2023 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr