Title: Time to Clarify Common Misconceptions about the Liver Imaging Reporting and Data System for Contrast-enhanced US
Abstract: HomeRadiologyVol. 295, No. 1 PreviousNext CommunicationsFree AccessLetters to the EditorTime to Clarify Common Misconceptions about the Liver Imaging Reporting and Data System for Contrast-enhanced USYuko Kono* , Claude B. Sirlin*, David T. Fetzer†, Tae K. Kim‡, Shuchi K. Rodgers§, Fabio Piscagliaǁ, Andrej Lyshchik#, Christoph F. Dietrich**, Stephanie R. Wilson††Yuko Kono* , Claude B. Sirlin*, David T. Fetzer†, Tae K. Kim‡, Shuchi K. Rodgers§, Fabio Piscagliaǁ, Andrej Lyshchik#, Christoph F. Dietrich**, Stephanie R. Wilson††Author AffiliationsDepartment of Medicine, Department of Radiology, University of California, San Diego, 200 W Arbor Dr, San Diego, CA 92103*Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Tex†Department of Medical Imaging, University Health Network, University of Toronto, Toronto, Canada‡Department of Radiology, Einstein Medical Center, Philadelphia, Pa§Division of Internal Medicine, University and General Hospital S. Orsola-Malpighi, University of Bologna, Bologna, ItalyǁDepartment of Radiology, Thomas Jefferson University, Philadelphia, Pa#Department of Internal Medicine 2, Caritas Krankenhaus, Bad Mergentheim, Germany**Department of Radiology, University of Calgary, Calgary, Canada††e-mail: [email protected]Yuko Kono* Claude B. Sirlin*David T. Fetzer†Tae K. Kim‡Shuchi K. Rodgers§Fabio PiscagliaǁAndrej Lyshchik#Christoph F. Dietrich**Stephanie R. Wilson††Published Online:Feb 18 2020https://doi.org/10.1148/radiol.2020192557MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In Editor:We read with interest the comprehensive review and commentary in the October 2019 issue of Radiology by Dr Emilio Quaia (1) and commend him on his work. However, that commentary includes a few incorrect or unsubstantiated points. As members of the contrast-enhanced (CE) US (CEUS) Liver Imaging Reporting and Data System (LI-RADS) Working Group and LI-RADS Steering Committee, we would like to take this opportunity to resolve some of these points:1."…the American Association for the Study of Liver Disease… [does] not recommend use of CEUS in hepatocellular nodule characterization because of the possibility that hepatocellular carcinoma (HCC) will be misdiagnosed as intrahepatic cholangiocarcinoma (ICC)." Studies published after the American Association for the Study of Liver Disease removed CE US from HCC diagnosis in 2011 have demonstrated that CE US helps to accurately differentiate ICC from HCC (2,3). American Association for the Study of Liver Disease updated its Practice Guidance in Hepatology in 2018 (4) to include CE US as a valid option for HCC diagnosis. Similarly, the European Association for the Study of Liver Disease also updated its practice guideline in 2018 to recognize CE US as part of the HCC diagnostic algorithm (5).2. "CEUS LI-RADS criteria were developed in the United States, where HCC histology, epidemiology, and imaging features are different from those in Europe and Asia (6)." We would like to clarify that CEUS LI-RADS was developed by an international working group of experts from North America and Europe with support of the American College of Radiology (ACR). We are unaware of data to suggest that HCCs have histologic findings or imaging appearance that is different in Europe or Asia than in the United States.3. "LR-3 category encompasses an excessively high number of observations with many different combinations of size and enhancement patterns and, consequently, an excessively high number of HCC nodules." Contrary to the statement that the LR-3 category includes an excessively high number of observations and an excessively high number of HCCs, emerging data suggest that the CEUS LR-3 category encompasses an appropriate number of observations, of which an appropriate proportion are HCC. In a large retrospective multicenter study for CEUS LI-RADS, which included more than 1000 observations (7), about 20% of observations were LR-3, of which 47% were HCC.4. "….. a variant of the original CEUS LI-RADS, named LI-RADS CE US, has been published in Europe (8). This algorithm includes four basic diagnostic categories instead of five, as in the original CE US LI-RADS (with the indeterminate category of LR-3 omitted from LI-RADS CE US)." This European publication came after the publication of the original CEUS LI-RADS document sanctioned by the ACR. We are concerned that differences between the two algorithms, despite near identical names, could confuse radiologists, other specialists, and patients. Readers should be aware that the European system cited by Dr Quaia is not sanctioned by the ACR and was not designed to achieve high specificity for HCC.5. "Nodules smaller than 10 mm with hyperenhancement in the arterial phase and washout in the late phase should be upgraded from CEUS LR-4 to CEUS LR-5." The value of the LR-5 category is its high specificity for HCC, approaching 100%, which facilitates management decisions without biopsy. We agree with Dr Quaia's inference that nodules smaller than 10 mm may indeed be HCC. However, there is no scientific evidence to support his recommendation because the positive predictive value for HCC for nodules smaller than 10 mm with hyperenhancement in the arterial phase and washout in the late phase is, to our knowledge, not yet known though likely to be substantially lower than 100%. Due to the difficulty in characterizing tiny nodules and the unknown benefit of treating them, to our knowledge no Western societal guidelines, including LI-RADS for CT and MRI, endorse noninvasive imaging diagnosis of HCC nodules smaller than 10 mm.LR-4 is an important category, with an intended probability of HCC of about 70%–95%. Focal liver observations characterized as CEUS LR-4 are concerning for HCC, although not meeting the stringent criteria for LR-5. Thus, all LR-4 nodules (including those <10 mm with hyperenhancement in the arterial phase and washout in the late phase) are scrutinized closely and deserve short-term follow-up, biopsy, or even treatment after multidisciplinary discussion, however there would be no evidence-based benefit to categorizing these as LR-5.6. "Even LR-M criteria should be revised…should be maintained as the more specific criterion for LR-M." The LR-M category helps to preserve the specificity for HCC while also maintaining sensitivity for malignancy. It is a common misconception that LR-M refers only to a non-HCC malignancy. Rather, LR-M is "probably or definitely malignant, not necessarily HCC," as described in the official LI-RADS document. Whereas this important category is intended to encompass most nonhepatocellular malignancies, HCCs with atypical imaging features such as rim arterial phase hyperenhancement or rapid washout will also be categorized as LR-M. This is unavoidable because of overlap in imaging features. Moreover, miscategorizing atypical HCCs as LR-M is generally not clinically problematic because such lesions usually proceed to biopsy, enabling histologic analysis to provide the correct diagnosis and ensuring appropriate patient management.7. "Unfortunately, the overall accuracy of LR-M in nodules 2 cm or smaller was as low as 11%. These issues should suggest a revision of LR-M criteria. Most likely, the time criterion for the onset of contrast material washout should be reduced to less than 60 seconds." We feel Dr Quaia's recommendation to change the time cutoff for differentiating rapid versus late washout is premature. The single study cited to support his recommendation was a small cohort of 56 patients with a total of 44 HCCs and two ICCs (9).Moreover, whereas reducing the cutoff to less than 60 seconds would increase the specificity of LR-M for nonhepatocellular malignancy, it would decrease the specificity of LR-5 for HCC. The reason is that ICCs and other nonhepatocelluar malignancies with washout onset above the new cutoff would be miscategorized as LR-5. This would increase the number of nonhepatocellular malignancies incorrectly diagnosed as HCC, potentially leading to serious management errors and adverse patient outcomes. The CEUS LI-RADS working group intentionally selected the cutoff of 60 seconds to prevent this miscategorization and preserve high specificity of LR-5 for HCC. Dr Quaia's recommendation cannot be endorsed.8. "In addition, marked washout within 2 minutes should be shifted to 3–4 minutes, and marked washout within 2 minutes should be considered typical of HCCs to increase specificity…" Dr Quaia's proposal to change the cutoff for marked washout to 3–4 minutes will have the opposite effect of what he intends; namely, it would decrease the specificity of LR-5 for HCC. For the same reasons as Terzi et al (7), this recommendation cannot be endorsed.9. "The variability of US equipment in terms of sensitivity to microbubble signal, interreader variability… and wide washout temporal range for LR-M observations are limitations." There is no evidence that variability in bubble sensitivity between machines is more deleterious to diagnostic performance than variations between CT and MRI equipment (10). Further, interreader variability is not unique to CE US and is found in the application of LI-RADS in both CT and MRI (11–13).In summary, we are aware that LI-RADS is imperfect. CEUS LI-RADS is a newer component of LI-RADS that will invariably undergo future evidence-based revisions. Our international expert working group welcomes constructive valid suggestions, proposals, and criticism. We await the results of an international multicenter prospective validation study for CEUS LI-RADS, the data from which will inform future evidence-based modifications (possibly including washout cutoff for LR-5 vs LR-M, and timing for marked washout) and potentially increase sensitivity of LR-5 without compromising specificity (Figure).Figure: CEUS LI-RADS categories. HCC = hepatocellular carcinoma.Figure:Download as PowerPointOpen in Image Viewer Disclosures of Conflicts of Interest: Y.K. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: disclosed money to author's institution for grant from Canon Medical Systems; disclosed money paid to author for research support funding from Bracco. Other relationships: disclosed research support from GE Healthcare, Bracco, and Lantheus. C.B.S. Activities related to the present article: author is the co-chair of the LI-RADS Steering Committee and co-chair of the LI-RADS Lexicon and Writing Group. Activities not related to the present article: disclosed money paid to author's institution for advisory board memberships from AMRA, Guerbet, Bristol Meyers Squibb; consultancies for GE Healthcare, Bayer, AMRA, Fulcrum Therapeutics, and IBM/Watson Health; grants/grants pending from Gilead, GE Healthcare, GE MRI, Bayer, GE Digital, GE US, ACR Innovation, Philips, and Celgene; payment for lectures including service on speakers bureaus from GE Healthcare and Bayer; royalties from Wolters Kluwer Health; payment for development of educational presentations from Medscape and Resoundant; lab service agreements with Enanta, ICON Medical Imaging, Gilead, Shire, Virtualscopics, Intercept, Synageva, Takeda, Genzyme, Janssen, NuSirt, Celgene-Parexel, Organovo; independent consulting contracts with Epigenomics and Blade Therapeutics; board of directors for Society of Abdominal Radiology. Other relationships: disclosed that author is the cochair of the LI-RADS Steering Committee. D.T.F. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: disclosed money paid to author for lectures from Philips Healthcare; research agreement with Philips Healthcare; and speaker's bureau fees from Siemens Medical Solutions. Other relationships: disclosed no relevant relationships. T.K.K. disclosed no relevant relationships. S.K.R. disclosed no relevant relationships. F.P. Activities related to the present article: disclosed money paid to author for consulting from AstraZeneca, Bayer, Bracco, BMS, EISAI, GE, IPSEN, La Force Guerbet, Tiziana Life Sciences; writing assistance from Bayer; and a research contract with ESAOTE. Activities not related to the present article: disclosed board membership with the International Contrast Ultrasound Society. Other relationships: disclosed no relevant relationships. A.L. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: disclosed money paid to author for consultancies from GE Healthcare and Bioclinica; grants/grants pending from GE Healthcare, Canon, and Siemens; payment for lectures from GE Healthcare; and royalties from Elsevier. Other relationships: disclosed no relevant relationships. C.F.D. disclosed no relevant relationships. S.R.W. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: disclosed money paid to author's institution for grants/grants pending from Lantheus and Samsung; disclosed money paid to author for lectures from Philips. Other relationships: disclosed no relevant relationships.References1. Quaia E. State of the Art: LI-RADS for Contrast-enhanced US. Radiology 2019;293(1):4–14. Link, Google Scholar2. Liu GJ, Wang W, Lu MD, et al. Contrast-Enhanced Ultrasound for the Characterization of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma. 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Crossref, Medline, Google ScholarArticle HistoryPublished online: Feb 18 2020Published in print: Apr 2020 FiguresReferencesRelatedDetailsCited ByFocal liver lesions other than hepatocellular carcinoma in cirrhosis: Diagnostic challengesKathleenMöller, EhsanSafai Zadeh, ChristianGörg, YiDong, XinwuCui, AdrianLim, Chiara deMolo, CarlaSerra, AnaMartín Algíbez, AnalisaBerzigotti, FabioPiscaglia, SiegbertFaiss, Christoph F.Dietrich2023 | Journal of Translational Internal Medicine, Vol. 10, No. 4Contrast-enhanced ultrasonography for the evaluation of malignant focal liver lesionsMaria CristinaChammas, André LeopoldinoBordini2022 | Ultrasonography, Vol. 41, No. 1LR-M Observations on Contrast-Enhanced Ultrasound: Detection of Hepatocellular Carcinoma Using Additional Features in Comparison With Current LI-RADS CriteriaYangHuang, Meng-FeiXian, Wen-XuanXie, Kang-MingPan, DanZeng, HuiHuang, Ming-DeLi, Xiao-YanXie, MingKuang, Ming-DeLu, Li-DaChen, WeiWang2022 | American Journal of Roentgenology, Vol. 219, No. 1Diagnostic value of CEUS LI-RADS and serum tumor markers for combined hepatocellular-cholangiocarcinomaRongWen, PengLin, YuquanWu, HaihuiYin, WeicheHuang, DanxiaGuo, YuyePeng, DunLiu, YunHe, HongYang2022 | European Journal of Radiology, Vol. 154Diagnosis of Non-Hepatocellular Carcinoma Malignancies in Patients With Risks for Hepatocellular Carcinoma: CEUS LI-RADS Versus CT/MRI LI-RADSYi-XinHu, Jing-XianShen, JingHan, Si-YueMao, Ru-ShuangMao, QingLi, FeiLi, Zhi-XingGuo, Jian-HuaZhou2021 | Frontiers in Oncology, Vol. 11CEUS LI-RADS Categories to Distinguish Hepatocellular Carcinoma and Non–Hepatocellular Carcinoma MalignanciesAntonio Giorgio, Massimo De Luca, Pietro Gatti, Paolo Matteucci, Valentina Giorgio, 12 May 2020 | Radiology, Vol. 296, No. 2Guidelines and Good Clinical Practice Recommendations for Contrast-Enhanced Ultrasound (CEUS) in the Liver–Update 2020 WFUMB in Cooperation with EFSUMB, AFSUMB, AIUM, and FLAUSChristoph F.Dietrich, Christian PállsonNolsøe, Richard G.Barr, AnnalisaBerzigotti, Peter N.Burns, VitoCantisani, Maria CristinaChammas, NitinChaubal, Byung IhnChoi, Dirk-AndréClevert, XinwuCui, YiDong, MirkoD'Onofrio, J. 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Publication Year: 2020
Publication Date: 2020-02-18
Language: en
Type: letter
Indexed In: ['crossref', 'pubmed']
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Cited By Count: 14
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