Performance of HCC diagnosis in the KLCA-NCC guidelines: a closer look at MRI contrast agents and HCC imaging hallmarks

Ji Hye Min; Young Kon Kim

doi:10.17998/jlc.2023.10.08

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Correspondence Performance of HCC diagnosis in the KLCA-NCC guidelines: a closer look at MRI contrast agents and HCC imaging hallmarks: Ji Hye Min, Young Kon Kim; Journal of Liver Cancer 2024;24(1):7-8.
DOI: https://doi.org/10.17998/jlc.2023.10.08
Published online: November 6, 2023

Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

Corresponding author: Young Kon Kim, Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea E-mail: youngkon0707.kim@samsung.com

• Received: September 4, 2023 • Accepted: October 8, 2023

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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We were glad to read the study entitled, “Diagnostic performance of the 2022 KLCA-NCC criteria for hepatocellular carcinoma on magnetic resonance imaging with extracellular contrast and hepatobiliary agents: comparison with the 2018 KLCA-NCC criteria” by Yoon et al.¹Unlike the definite hepatocellular carcinoma (HCC) category, the probable HCC category has been revised in the 2022 Korean Liver Cancer Association-National Cancer Center (KLCA-NCC) criteria.²Yoon et al.¹highlighted that in using extracellular contrast agent (ECA)-magnetic resonance imaging (MRI), the 2022 KLCA-NCC offers a high sensitivity in HCC diagnosis compared to that of the 2018 KLCA-NCC, particularly, in the definite and probable HCC categories. Moreover, their results reaffirmed that hepatobiliary agent (HBA)-MRI outperformed ECA-MRI in terms of sensitivity without sacrificing specificity across the 2018 and 2022 KLCA-NCC criteria. This aligns with our understanding, especially in the Korean medical environment, as HBA-MRI is predominantly used for liver cancer diagnosis, and there is a premium for high sensitivity. With this foundation, we wish to provide further insights into this topic.

Highlighting that the diagnostic ability for HCC may be influenced by the type of contrast medium as well as the specific diagnostic criteria is essential. Specifically, the washout definition or type of major features used can substantially influence the diagnostic performance for HCC. The main conclusion is that for the definite HCC category, HBA-MRI provides better sensitivity than ECA-MRI, in accordance with the intention of the KLCA-NCC versions. This is largely attributable to the expanded washout definition, which inherently favors HBA-MRI. Nevertheless, these findings need to be approached with caution; early contrast uptake into hepatocytes, even in the portal venous phase, may exaggerate washout on HBA-MRI,^3,⁴albeit not being associated with the study results. Furthermore, the enhancing capsule, a major feature in liver imaging reporting and data system (LI-RADS) that is better visualized in ECA-MRI than in HBA-MRI, is used only as an ancillary feature favoring HCC in the KLCA-NCC guidelines.⁵Thus, in interpreting the results of Yoon et al.,¹we should consider the expanded washout and undervaluing of enhancing capsules in the KLCA-NCC guidelines, as opposed to solely focusing on the intrinsic differences between the two MRI contrast agents. Consequently, the conclusions of this study should be interpreted as specifically applicable to the KLCA-NCC criteria used in clinical scenarios, emphasizing early HCC detection and treatment.

Subsequently, we are slightly concerned about the interpretation of HCC hallmark visualization based on MRI contrast agents because the details of the imaging features are missing. As highlighted in the editorial by Yoon,⁶the similar diagnostic performance of the ver. 2018 and ver. 2022 KLCA-NCC on HBA-MRI is likely attributed to the fact that most observations with arterial phase hyperenhancement (APHE) and washout (portal venous phase washout or hypointensity on transitional/hepatobiliary phase) can be classified as definite HCC, irrespective of the ancillary features. To confirm this, a more detailed depiction of imaging features is essential. Furthermore, application of ancillary features in the updated 2022 KLCA-NCC diagnostic flow for probable HCC differs according to the presence of APHE. In comparing the 2018 and 2022 KLCA-NCC using ECA-MRI, what combinations of APHE and ancillary features of both categories were included in probable HCC? We empirically presume that in ECA-MRI, observations showing APHE and mild-to-moderate T2 hyperintensity and/or restricted diffusion (with no other ancillary features favoring HCC in particular) would be responsible for a significant increase in the probable HCC category with ver. 2022, but not with ver. 2018. The observation of APHE, no washout, and ancillary features favoring malignancy in general may include other HCC mimickers, such as inflammatory lesions or other tumors like combined hepatocellular cholangiocarcinoma, angiomyolipoma, and neuroendocrine tumors. Further, in Yoon’s study,⁶non-surgical candidates were excluded from the final cohort, thus enriching the cohort for HCC. Although there was no significant sacrifice in specificity with ver. 2022 along with expanded washout, relaxing the criteria for probable HCC may inevitably inflate specificity. The difference in the upgraded number of probable HCC by using ver. 2022 between the two contrast agents used in the two patient cohorts might imply an introduced potential bias in Yoon’s study.⁶This issue should be re-evaluated because the motivation of revised version 2020 is not to increase probable HCC categorization with ECA-MRI but not with HBA-MRI. Therefore, caution should be exercised when applying probable HCC in ver. 2022 KLCA-NCC, especially in using ancillary features favoring malignancy in general, because non-HCC lesions can be misdiagnosed as HCC.

Notably, there is an inherent selection bias that should be emphasized. As previously mentioned, the study cohort is biased toward a large number of HCCs and a relatively small number of other malignancies or cirrhosis-related benign nodules. Further, specificity may have been overestimated. Additionally, the study may not have discerned subtle differences in specificity. Without individual comparisons, the reliability of the results may have been compromised. These factors should be considered when interpreting the results.

Yoon et al.¹provided insights into the evolving landscape of HCC diagnosis using MRI contrast agents within the KLCA-NCC guidelines. As with all studies, the clinical context and guideline specifics play a pivotal role in the interpretations. We appreciate their dedicated efforts and look forward to continued dialogue on this critical subject, fostering a more profound understanding and eventually refining the diagnostic approaches.

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Conflict of Interest

The authors have no conflicts of interest to disclose.

Ethics Statement

Not applicable.

Funding Statement

No funding to declare.

Data Availability

Not applicable.

Author Contribution

Conceptualization: JHM, YGK

Writing - original draft: JHM, YGK

References

1. Yoon JK, Lee S, Hwang JA, Lee JE, Kim SS, Kim MJ. Diagnostic performance of the 2022 KLCA-NCC criteria for hepatocellular carcinoma on magnetic resonance imaging with extracellular contrast and hepatobiliary agents: comparison with the 2018 KLCA-NCC criteria. J Liver Cancer 2023;23:157−165.Article PubMed PMC PDF
2. Korean Liver Cancer Association (KLCA), National Cancer Center (NCC) Korea. 2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma. Korean J Radiol 2022;23:1126−1240.Article PubMed PMC PDF
3. Vogl TJ, Kümmel S, Hammerstingl R, Schellenbeck M, Schumacher G, Balzer T, et al. Liver tumors: comparison of MR imaging with Gd-EOBDTPA and Gd-DTPA. Radiology 1996;200:59−67.Article PubMed
4. Paisant A, Vilgrain V, Riou J, Oberti F, Sutter O, Laurent V, et al. Comparison of extracellular and hepatobiliary MR contrast agents for the diagnosis of small HCCs. J Hepatol 2020;72:937−945.Article PubMed
5. Min JH, Kim JM, Kim YK, Kang TW, Lee SJ, Choi GS, et al. Prospective intraindividual comparison of magnetic resonance imaging with gadoxetic acid and extracellular contrast for diagnosis of hepatocellular carcinomas using the liver imaging reporting and data system. Hepatology 2018;68:2254−2266.Article PubMed PDF
6. Yoon JH. Impact of the updated KLCA-NCC criteria for diagnosis of “probable HCC” in liver MRI: comparisons between KLCA v2022 and v2018. J Liver Cancer 2023;23:124−126.Article PubMed PMC PDF

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Performance of HCC diagnosis in the KLCA-NCC guidelines: a closer look at MRI contrast agents and HCC imaging hallmarks

J Liver Cancer. 2024;24(1):7-8. Published online November 6, 2023

DOI: https://doi.org/10.17998/jlc.2023.10.08

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Performance of HCC diagnosis in the KLCA-NCC guidelines: a closer look at MRI contrast agents and HCC imaging hallmarks