{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T10:05:03Z","timestamp":1784196303691,"version":"3.55.0"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To investigate the predictive value of contrast-enhanced ultrasound (CEUS) features combined with Liver Imaging Reporting and Data System (LI-RADS) categorization for microvascular invasion (MVI) in hepatocellular carcinoma (HCC) \u22645 cm.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This multicenter retrospective study enrolled adult patients with HCC \u22645 cm who underwent CEUS between January 2018 and December 2025. Least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic analysis were employed to screen risk factors and establish the MVI prediction model. Three models were developed: a clinical model, an ultrasound model, and a combined model. The performance of the combined model was evaluated and validated using the area under the receiver operating characteristic (AUC), calibration curves, decision curve analysis (DCA), and the Hosmer-Lemeshow test.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 261 patients with HCC \u22645 cm were enrolled. Patients were divided into a derivation cohort (n=209) and an external validation cohort (n=52). 85 patients (32.57%) were MVI-positive. LASSO regression and multivariate analysis revealed that AFP, tumor margin, enhanced homogeneity, mosaic, and LI-RADS were significantly associated with MVI. The combined model showed an AUC of 0.880 (95% CI: 0.832\u20130.929) in the derivation cohort and 0.832 (95% CI: 0.703\u20130.960) in the external validation cohort. Calibration curves revealed excellent agreement between the model\u2019s predicted probability of MVI and the actual observed outcomes. DCA confirmed the excellent net benefits.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This model can noninvasive preoperative prediction of MVI risk in patients with HCC \u22645 cm, offering a reliable reference for clinicians in developing personalized treatment strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1901674","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T09:11:43Z","timestamp":1784193103000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Preoperative prediction of microvascular invasion in hepatocellular carcinoma \u22645 cm based on contrast-enhanced ultrasound features and LI-RADS categorization: a multicenter study"],"prefix":"10.3389","volume":"16","author":[{"given":"Qian","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Interventional Ultrasound, First Hospital of Shanxi Medical University","place":["Taiyuan, Shanxi, China"]},{"name":"Department of Medical Imaging, Shanxi Medical University","place":["Taiyuan, Shanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan","family":"Pang","sequence":"additional","affiliation":[{"name":"Department of Interventional Ultrasound, Fifth Medical Center of Chinese PLA General Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhilong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Interventional Ultrasound, First Hospital of Shanxi Medical University","place":["Taiyuan, Shanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruining","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Interventional Ultrasound, First Hospital of Shanxi Medical University","place":["Taiyuan, Shanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenwen","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Interventional Ultrasound, First Hospital of Shanxi Medical University","place":["Taiyuan, Shanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Interventional Ultrasound, First Hospital of Shanxi Medical University","place":["Taiyuan, Shanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanjing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Interventional Ultrasound, First Hospital of Shanxi Medical University","place":["Taiyuan, Shanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Interventional Ultrasound, First Hospital of Shanxi Medical University","place":["Taiyuan, Shanxi, China"]},{"name":"Department of Interventional Ultrasound, Fifth Medical Center of Chinese PLA General Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Interventional Ultrasound, First Hospital of Shanxi Medical University","place":["Taiyuan, Shanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J Clin"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2021.11.023","article-title":"Global, regional and national burden of primary liver cancer by subtype","volume":"161","author":"Rumgay","year":"2022","journal-title":"Eur J Cancer"},{"key":"B3","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1159\/000546574","article-title":"China liver cancer guidelines for the diagnosis and treatment of hepatocellular carcinoma (2024 edition)","volume":"14","author":"Zhou","year":"2025","journal-title":"Liver Cancer"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhepr.2026.101732","article-title":"HCC recurrence in liver transplants treated with hypothermic oxygenated machine perfusion: An international matched cohort study","volume":"8","author":"Eden","year":"2026","journal-title":"JHEP Rep"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0000000000002889","article-title":"Liver transplantation and hepatic resection can achieve cure for hepatocellular carcinoma","volume":"268","author":"Pinna","year":"2018","journal-title":"Ann Surg"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0000000000000710","article-title":"Recurrence of hepatocellular cancer after resection: patterns, treatments, and prognosis","volume":"261","author":"Tabrizian","year":"2015","journal-title":"Ann Surg"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.06.003","article-title":"A system of classifying microvascular invasion to predict outcome after resection in patients with hepatocellular carcinoma","volume":"137","author":"Roayaie","year":"2009","journal-title":"Gastroenterology"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.14218\/JCTH.2022.00013S","article-title":"Roles and molecular mechanisms of biomarkers in hepatocellular carcinoma with microvascular invasion: a review","volume":"11","author":"Zhao","year":"2023","journal-title":"J Clin Transl Hepatol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1007\/s12029-020-00487-9","article-title":"Microvascular venous invasion in hepatocellular carcinoma: why do recurrences occur","volume":"51","author":"Isik","year":"2020","journal-title":"J Gastrointest Cancer"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.hpb.2019.02.003","article-title":"Effect of microvascular invasion on the postoperative long-term prognosis of solitary small HCC: a systematic review and meta-analysis","volume":"21","author":"Chen","year":"2019","journal-title":"HPB"},{"key":"B11","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1186\/s12880-024-01426-x","article-title":"Ultrasomics differentiation of Malignant and benign focal liver lesions based on contrast-enhanced ultrasound","volume":"24","author":"Hu","year":"2024","journal-title":"BMC Med Imaging"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1055\/s-0042-124369","article-title":"Contrast enhanced ultrasound (CEUS) liver imaging reporting and data system (LI-RADS\u00ae): the official version by the American College of Radiology (ACR)","volume":"38","author":"Kono","year":"2017","journal-title":"Ultraschall Med"},{"key":"B13","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1186\/s13244-024-01688-7","article-title":"Correlation between CEUS LI-RADS categorization of HCC\u2009< 20 mm and clinic-pathological features","volume":"15","author":"Yang","year":"2024","journal-title":"Insights Imaging"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1007\/s00330-020-07660-5","article-title":"Pathological considerations of CEUS LI-RADS correlation with fibrosis stage and tumour histological grade","volume":"31","author":"Cheng","year":"2021","journal-title":"Eur Radiol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1159\/000527498","article-title":"Contrast-enhanced ultrasound liver imaging reporting and data system in hepatocellular carcinoma \u22645 cm: biological characteristics and patient outcomes","volume":"12","author":"Cai","year":"2023","journal-title":"Liver Cancer"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-012-2513-1","article-title":"A systematic review of microvascular invasion in hepatocellular carcinoma: diagnostic and prognostic variability","volume":"20","author":"Rodr\u00edguez-Per\u00e1lvarez","year":"2013","journal-title":"Ann Surg Oncol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1001744","article-title":"Critical appraisal and data extraction for systematic reviews of prediction modelling studies: the CHARMS checklist","volume":"11","author":"Moons","year":"2014","journal-title":"PloS Med"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0000000000003781","article-title":"Subclassification of microscopic vascular invasion in hepatocellular carcinoma","volume":"274","author":"Kang","year":"2021","journal-title":"Ann Surg"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2021.11.018","article-title":"BCLC strategy for prognosis prediction and treatment recommendation: the 2022 update","volume":"76","author":"Reig","year":"2022","journal-title":"J Hepatol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-1203","article-title":"Targeting alpha-fetoprotein (AFP)-MHC complex with CAR T-cell therapy for liver cancer","volume":"23","author":"Liu","year":"2017","journal-title":"Clin Cancer Res"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.2147\/JHC.S272762","article-title":"Serum tumor markers for early diagnosis of primary hepatocellular carcinoma","volume":"7","author":"Zong","year":"2020","journal-title":"J Hepatocell Carcinoma"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2023.216240","article-title":"AFP deletion leads to anti-tumorigenic but pro-metastatic roles in liver cancers with concomitant CTNNB1 mutations","volume":"566","author":"Xu","year":"2023","journal-title":"Cancer Lett"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejrad.2025.112477","article-title":"Quantitative sonazoid contrast-enhanced ultrasound features for predicting microvascular invasion of hepatocellular carcinoma","volume":"194","author":"Yang","year":"2026","journal-title":"Eur J Radiol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3350\/cmh.2023.0034","article-title":"Classification of microvascular invasion of hepatocellular carcinoma: correlation with prognosis and magnetic resonance imaging","volume":"29","author":"Hwang","year":"2023","journal-title":"Clin Mol Hepatol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1055\/a-1177-0530","article-title":"Guidelines and good clinical practice recommendations for contrast enhanced ultrasound in the liver-update 2020-WFUMB in cooperation with EFSUMB, AFSUMB, AIUM, and FLAUS","volume":"41","author":"Dietrich","year":"2020","journal-title":"Ultraschall Med"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1186\/s13244-019-0819-2","article-title":"CEUS LI-RADS: a pictorial review","volume":"11","author":"Bartolotta","year":"2020","journal-title":"Insights Imaging"},{"key":"B27","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1055\/a-1168-6321","article-title":"Contrast-enhanced ultrasound liver imaging reporting and data system in diagnosing hepatocellular carcinoma: diagnostic performance and interobserver agreement","volume":"43","author":"Zhou","year":"2022","journal-title":"Ultraschall Med"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.hbpd.2022.05.008","article-title":"Contrast-enhanced ultrasound predicts microvascular invasion in patients with hepatocellular carcinoma","volume":"21","author":"Huang","year":"2022","journal-title":"Hepatobiliary Pancreat Dis Int"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejrad.2025.112535","article-title":"LI-RADS categories and clinicopathological features predict recurrence-free survival in patients with radical resected hepatocellular carcinoma","volume":"194","author":"Cao","year":"2026","journal-title":"Eur J Radiol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1186\/s13244-024-01821-6","article-title":"Value of high frame rate contrast-enhanced ultrasound in predicting microvascular invasion of hepatocellular carcinoma","volume":"15","author":"Fei","year":"2024","journal-title":"Insights Imaging"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1901674\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T09:11:44Z","timestamp":1784193104000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1901674\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,16]]},"references-count":30,"alternative-id":["10.3389\/fonc.2026.1901674"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2026.1901674","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,16]]},"article-number":"1901674"}}