Contrast-enhanced ultrasound for hepatocellular carcinoma detection and diagnosis in the context of nonalcoholic fatty liver disease

Abstract

The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide and is projected to become a major etiology of cirrhosis and hepatocellular carcinoma (HCC). HCC occurs more commonly in NAFLD patients who develop cirrhosis, though HCC is known to occur in the setting of noncirrhotic NAFLD as well. This is of particular importance given that the American College of Radiology (ACR) CT/MRI Liver Reporting and Data System (LI-RADS) algorithm may only be applied to a certain population of patients, and this population does not include those with noncirrhotic NAFLD. Conventional ultrasound (US) has long been in use for HCC surveillance, but contrast-enhanced US (CEUS) is a relatively newer modality, growing in use for assessment of liver lesions, and its use in HCC diagnosis has been formalized with CEUS LI-RADS. The use of US and CEUS in the assessment of liver lesions in NAFLD patients involves the consideration of certain particular nuances, and familiarity with these considerations will continue increasing in importance as the disease becomes more common.

Keywords

Hepatocellular carcinoma / contrast-enhanced ultrasound / nonalcoholic fatty liver disease

References

[1] Eslam M,George J.International Consensus PanelMAFLD: a consensus-driven proposed nomenclature for metabolic associated fatty liver disease.Gastroenterology2020;158:1999-2014.e1

[2] Fouad Y,Bollipo S,Ajlouni Y.What’s in a name? Renaming ‘NAFLD’ to ‘MAFLD’..Liver Int2020;40:1254-61

[3] Lazo M,Eberhardt MS.Prevalence of nonalcoholic fatty liver disease in the United States: the Third National Health and Nutrition Examination Survey, 1988-1994.Am J Epidemiol2013;178:38-45 PMCID:PMC3698993

[4] Williams CD,Asike MI.Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy: a prospective study.Gastroenterology2011;140:124-31

[5] Huang DQ,Loomba R.Global epidemiology of NAFLD-related HCC: trends, predictions, risk factors and prevention.Nat Rev Gastroenterol Hepatol2021;18:223-38 PMCID:PMC8016738

[6] Benhammou JN,Aby ES.Nonalcoholic fatty liver disease-related hepatocellular carcinoma growth rates and their clinical outcomes.Hepatoma Res2021;7:70 PMCID:PMC8713558

[7] Kanwal F,Li L.Effect of metabolic traits on the risk of cirrhosis and hepatocellular cancer in nonalcoholic fatty liver disease.Hepatology2020;71:808-19

[8] Yasui K,Komorizono Y.Japan NASH Study GroupMinistry of HealthLabourWelfare of JapanCharacteristics of patients with nonalcoholic steatohepatitis who develop hepatocellular carcinoma.Clin Gastroenterol Hepatol2011;9:428-33;quiz e50

[9] Piscaglia F,Barchetti A.HCC-NAFLD Italian Study GroupClinical patterns of hepatocellular carcinoma in nonalcoholic fatty liver disease: a multicenter prospective study.Hepatology2016;63:827-38

[10] Omata M,Kokudo N.Asia-Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update.Hepatol Int2017;11:317-70 PMCID:PMC5491694

[11] Marrero JA,Sirlin CB.Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the american association for the study of liver diseases.Hepatology2018;68:723-50

[12] Association for the Study of the Liver. Electronic address: [e-mail], European Association for the Study of the Liver. EASL clinical practice guidelines: management of hepatocellular carcinoma.J Hepatol2018;69:182-236

[13] Loomba R,Patton H.AGA clinical practice update on screening and surveillance for hepatocellular carcinoma in patients with nonalcoholic fatty liver disease: expert review.Gastroenterology2020;158:1822-30 PMCID:PMC8012107

[14] ACR Education Center. Ultrasound LI-RADS v2017. Available from: https://www.acr.org/Clinical-Resources/Reporting-and-Data-Systems/LI-RADS [Last accessed on 17 Mar 2023]

[15] Tanaka H.Current role of ultrasound in the diagnosis of hepatocellular carcinoma.J Med Ultrason (2001)2020;47:239-55 PMCID:PMC7181430

[16] D'Onofrio M,De Robertis R,Mucelli RP.Contrast-enhanced ultrasound of focal liver lesions.AJR Am J Roentgenol2015;205:W56-66

[17] Wei K,Carson L.The safety of deFinity and Optison for ultrasound image enhancement: a retrospective analysis of 78,383 administered contrast doses.J Am Soc Echocardiogr2008;21:1202-6

[18] Main ML,Ryan A,Miller P.Acute mortality in critically ill patients undergoing echocardiography with or without an ultrasound contrast agent.JACC Cardiovasc Imaging2014;7:40-8

[19] Xue LY,Huang BJ.Contrast-enhanced ultrasonography for evaluation of cystic renal mass: in comparison to contrast-enhanced CT and conventional ultrasound.Abdom Imaging2014;39:1274-83

[20] Wilson SR,Piscaglia F.CEUS LI-RADS: algorithm, implementation, and key differences from CT/MRI.Abdom Radiol (NY)2018;43:127-42

[21] ACR Education Center. CT/MRI LI-RADS® v2017 CORE. Available from: https://www.acr.org/-/media/ACR/Files/RADS/LI-RADS/LIRADS_2017_Core.pdf [Last accessed on 17 Mar 2023]

[22] Ding J,Zhou Y.Impact of revision of the LR-M criteria on the diagnostic performance of contrast-enhanced ultrasound LI-RADS.Ultrasound Med Biol2021;47:3403-10

[23] Zheng W,Zou XB.Evaluation of contrast-enhanced US LI-RADS version 2017: application on 2020 liver nodules in patients with hepatitis B infection.Radiology2020;294:299-307

[24] Thompson SM,Ehman EC.Non-alcoholic fatty liver disease-associated hepatocellular carcinoma: effect of hepatic steatosis on major hepatocellular carcinoma features at MRI.Br J Radiol2018;91:20180345 PMCID:PMC6319849

[25] Garg I,Sheedy SP.CT of hepatocellular carcinoma in non-alcoholic fatty liver disease: imaging characteristics and inter-rater agreement.Hepatoma Res2019;2019

[26] Gaddikeri S,Wang CL.Hepatocellular carcinoma in the noncirrhotic liver.AJR Am J Roentgenol2014;203:W34-47

[27] Terzi E,Leoni S.CEUS LI-RADS are effective in predicting the risk hepatocellular carcinoma of liver nodules.Dig Liver Dis2017;49:e22

[28] Kim TK,Wilson SR.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 Hepatol2017;23:280-9 PMCID:PMC5760002

[29] Zhou Y,Ding J.Risk stratification and distribution of hepatocellular carcinomas in CEUS and CT/MRI LI-RADS: a meta-analysis.Front Oncol2022;12:873913 PMCID:PMC9001845

[30] Li L,Han J,Peng C.Clinical application of liver imaging reporting and data system for characterizing liver neoplasms: a meta-analysis.Diagnostics (Basel)2021;11:323 PMCID:PMC7921912

[31] Aubé C,Lonjon J.CHIC GroupEASL and AASLD recommendations for the diagnosis of HCC to the test of daily practice.Liver Int2017;37:1515-25

[32] Pan JM,Zheng YL.Tumor size-based validation of contrast-enhanced ultrasound liver imaging reporting and data system (CEUS LI-RADS) 2017 for hepatocellular carcinoma characterizing.Br J Radiol2021;94:20201359 PMCID:PMC9328060

[33] Huang JY,Lu Q.Diagnostic accuracy of CEUS LI-RADS for the characterization of liver nodules 20 mm or smaller in patients at risk for hepatocellular carcinoma.Radiology2020;294:329-39

[34] Mei Q,Chen Q.Clinical value of contrast-enhanced ultrasound in early diagnosis of small hepatocellular carcinoma (≤ 2 cm).World J Clin Cases2022;10:8525-34 PMCID:PMC9453369

[35] Kang JH,Lee JS,Jang JK.Inter-reader reliability of contrast-enhanced ultrasound liver imaging reporting and data system: a meta-analysis.Abdom Radiol (NY)2021;46:4671-81

[36] Hu YX,Han J.Diagnosis of non-hepatocellular carcinoma malignancies in patients with risks for hepatocellular carcinoma: CEUS LI-RADS versus CT/MRI LI-RADS.Front Oncol2021;11:641195 PMCID:PMC8074676

[37] Hai Y,Chong W,Lyshchik A.Meta-analysis and systematic review of contrast-enhanced ultrasound in evaluating the treatment response after locoregional therapy of hepatocellular carcinoma.Abdom Radiol (NY)2021;46:5162-79 PMCID:PMC8569603

[38] Faccia M,Ainora ME.Contrast-enhanced ultrasound for monitoring treatment response in different stages of hepatocellular carcinoma.Cancers (Basel)2022;14:481 PMCID:PMC8833342

[39] Meloni MF,Chiang J,Danzi R.Use of contrast-enhanced ultrasound in ablation therapy of hcc: planning, guiding, and assessing treatment response.J Ultrasound Med2021;40:879-94

[40] Francica G,Riccardi L.Ablation treatment of primary and secondary liver tumors under contrast-enhanced ultrasound guidance in field practice of interventional ultrasound centers. A multicenter study.Eur J Radiol2018;105:96-101

[41] Hwang JA,Kang HJ,Park HJ.Perfluorobutane-enhanced ultrasonography with a Kupffer phase: improved diagnostic sensitivity for hepatocellular carcinoma.Eur Radiol2022;32:8507-17

[42] Barr RG,Luo Y.Contrast-enhanced ultrasound imaging of the liver: a review of the clinical evidence for SonoVue and Sonazoid.Abdom Radiol (NY)2020;45:3779-88

[43] Li L,Wang J.Contrast-enhanced ultrasound using perfluorobutane: impact of proposed modified LI-RADS criteria on hepatocellular carcinoma detection.AJR Am J Roentgenol2022;219:434-43

[44] Kang HJ,Yoon JH,Kim H.Contrast-enhanced US with sulfur hexafluoride and perfluorobutane for the diagnosis of hepatocellular carcinoma in individuals with high risk.Radiology2020;297:108-16

[45] Park JH,Lee SJ.Contrast-enhanced US with Perfluorobutane for hepatocellular carcinoma surveillance: a multicenter diagnostic trial (SCAN).Radiology2019;292:638-46

[46] Kudo M,Izumi N.Liver Cancer Study Group of JapanJSH consensus-based clinical practice guidelines for the management of hepatocellular carcinoma: 2014 update by the Liver Cancer Study Group of Japan.Liver Cancer2014;3:458-68 PMCID:PMC4531423

[47] Yi Z,Orman ES,Hayashi PH.Trends in characteristics of patients listed for liver transplantation will lead to higher rates of waitlist removal due to clinical deterioration.Transplantation2017;101:2368-74 PMCID:PMC5667556