{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T14:31:57Z","timestamp":1772721117396,"version":"3.50.1"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T00:00:00Z","timestamp":1757635200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T00:00:00Z","timestamp":1757635200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur Radiol"],"DOI":"10.1007\/s00330-025-11994-3","type":"journal-article","created":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T15:39:50Z","timestamp":1757691590000},"page":"2246-2258","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Large well-differentiated hepatocellular carcinoma in patients with HBV: gadoxetic acid-enhanced MR imaging features and prognosis"],"prefix":"10.1007","volume":"36","author":[{"given":"Yuhao","family":"Tao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingyue","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanjun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haoran","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingzhan","family":"Du","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingchuan","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunhong","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3977-9413","authenticated-orcid":false,"given":"Weiguo","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,9,12]]},"reference":[{"key":"11994_CR1","doi-asserted-by":"publisher","first-page":"2893","DOI":"10.1002\/ijc.25516","volume":"127","author":"J Ferlay","year":"2010","unstructured":"Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM (2010) Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127:2893\u20132917","journal-title":"Int J Cancer"},{"key":"11994_CR2","doi-asserted-by":"crossref","unstructured":"European Association for the Study of the Liver (2018) EASL clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 69:182\u2013236","DOI":"10.1016\/j.jhep.2018.03.019"},{"key":"11994_CR3","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1002\/1097-0142(195405)7:3<462::AID-CNCR2820070308>3.0.CO;2-E","volume":"7","author":"HA Edmondson","year":"1954","unstructured":"Edmondson HA, Steiner PE (1954) Primary carcinoma of the liver: a study of 100 cases among 48,900 necropsies. Cancer 7:462\u2013503","journal-title":"Cancer"},{"key":"11994_CR4","doi-asserted-by":"crossref","unstructured":"International Consensus Group for Hepatocellular Neoplasia, The International Consensus Group for Hepatocellular Neoplasia (2009) Pathologic diagnosis of early hepatocellular carcinoma: a report of the international consensus group for hepatocellular neoplasia. Hepatology 49:658\u2013664","DOI":"10.1002\/hep.22709"},{"key":"11994_CR5","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1159\/000078475","volume":"47","author":"M Kudo","year":"2004","unstructured":"Kudo M (2004) Atypical large well-differentiated hepatocellular carcinoma with benign nature: a new clinical entity. Intervirology 47:227\u2013237","journal-title":"Intervirology"},{"key":"11994_CR6","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1016\/j.hpb.2019.08.012","volume":"22","author":"M Okuno","year":"2020","unstructured":"Okuno M, Newhook TE, Joechle K et al (2020) Characteristics of atypical large well-differentiated hepatocellular carcinoma: A specific subtype of hepatocellular carcinoma?. HPB (Oxford) 22:545\u2013552","journal-title":"HPB (Oxford)"},{"key":"11994_CR7","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1016\/j.amjsurg.2021.03.065","volume":"223","author":"SH Lin","year":"2022","unstructured":"Lin SH, Eng HL, Liu YW et al (2022) Characteristics and prognosis of patients with large well-differentiated hepatocellular carcinoma who have undergone resection. Am J Surg 223:339\u2013345","journal-title":"Am J Surg"},{"key":"11994_CR8","doi-asserted-by":"publisher","first-page":"1701","DOI":"10.1007\/s00330-012-2421-6","volume":"22","author":"C An","year":"2012","unstructured":"An C, Park MS, Jeon HM et al (2012) Prediction of the histopathological grade of hepatocellular carcinoma using qualitative diffusion-weighted, dynamic, and hepatobiliary phase MRI. Eur Radiol 22:1701\u20131708","journal-title":"Eur Radiol"},{"key":"11994_CR9","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1002\/jso.20661","volume":"95","author":"K Oishi","year":"2007","unstructured":"Oishi K, Itamoto T, Amano H et al (2007) Clinicopathologic features of poorly differentiated hepatocellular carcinoma. J Surg Oncol 95:311\u2013316","journal-title":"J Surg Oncol"},{"key":"11994_CR10","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.clinimag.2016.12.009","volume":"43","author":"HF Tong","year":"2017","unstructured":"Tong HF, Liang HB, Mo ZK, Guan TP, Yang J, Fang CH (2017) Quantitative analysis of gadoxetic acid-enhanced magnetic resonance imaging predicts histological grade of hepatocellular carcinoma. Clin Imaging 43:9\u201314","journal-title":"Clin Imaging"},{"key":"11994_CR11","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1007\/s00261-014-0227-5","volume":"40","author":"TA Hope","year":"2015","unstructured":"Hope TA, Fowler KJ, Sirlin CB et al (2015) Hepatobiliary agents and their role in LI-RADS. Abdom Imaging 40:613\u2013625","journal-title":"Abdom Imaging"},{"key":"11994_CR12","doi-asserted-by":"publisher","first-page":"1364","DOI":"10.1007\/s00330-022-09105-7","volume":"33","author":"H Cha","year":"2023","unstructured":"Cha H, Choi JY, Park YN et al (2023) Comparison of imaging findings of macrotrabecular-massive hepatocellular carcinoma using CT and gadoxetic acid-enhanced MRI. Eur Radiol 33:1364\u20131377","journal-title":"Eur Radiol"},{"key":"11994_CR13","doi-asserted-by":"publisher","first-page":"1847","DOI":"10.1007\/s00261-017-1372-4","volume":"43","author":"R Cannella","year":"2018","unstructured":"Cannella R, Furlan A (2018) Mosaic architecture of hepatocellular carcinoma. Abdom Radiol (NY) 43:1847\u20131848","journal-title":"Abdom Radiol (NY)"},{"key":"11994_CR14","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1159\/000078470","volume":"47","author":"M Kojiro","year":"2004","unstructured":"Kojiro M (2004) Nodule-in-nodule\u2019 appearance in hepatocellular carcinoma: its significance as a morphologic marker of dedifferentiation. Intervirology 47:179\u2013183","journal-title":"Intervirology"},{"key":"11994_CR15","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1002\/hep.20878","volume":"42","author":"SW Nam","year":"2005","unstructured":"Nam SW, Park JY, Ramasamy A et al (2005) Molecular changes from dysplastic nodule to hepatocellular carcinoma through gene expression profiling. Hepatology 42:809\u2013818","journal-title":"Hepatology"},{"key":"11994_CR16","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1053\/j.gastro.2009.06.003","volume":"137","author":"S Roayaie","year":"2009","unstructured":"Roayaie S, Blume IN, Thung SN et al (2009) A system of classifying microvascular invasion to predict outcome after resection in patients with hepatocellular carcinoma. Gastroenterology 137:850\u2013855","journal-title":"Gastroenterology"},{"key":"11994_CR17","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1002\/cncr.20798","volume":"103","author":"A Sasaki","year":"2005","unstructured":"Sasaki A, Kai S, Iwashita Y, Hirano S, Ohta M, Kitano S (2005) Microsatellite distribution and indication for locoregional therapy in small hepatocellular carcinoma. Cancer 103:299\u2013306","journal-title":"Cancer"},{"key":"11994_CR18","doi-asserted-by":"publisher","DOI":"10.1186\/s13027-020-00337-0","volume":"15","author":"YQ Si","year":"2020","unstructured":"Si YQ, Wang XQ, Fan G et al (2020) Value of AFP and PIVKA-II in diagnosis of HBV-related hepatocellular carcinoma and prediction of vascular invasion and tumor differentiation. Infect Agent Cancer 15:70","journal-title":"Infect Agent Cancer"},{"key":"11994_CR19","doi-asserted-by":"publisher","first-page":"59","DOI":"10.18632\/oncoscience.115","volume":"2","author":"M Zhu","year":"2015","unstructured":"Zhu M, Guo J, Xia H et al (2015) Alpha-fetoprotein activates AKT\/mTOR signaling to promote CXCR4 expression and migration of hepatoma cells. Oncoscience 2:59\u201370","journal-title":"Oncoscience"},{"key":"11994_CR20","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-1036-5","volume":"9","author":"S Wang","year":"2018","unstructured":"Wang S, Zhu M, Wang Q et al (2018) Alpha-fetoprotein inhibits autophagy to promote malignant behaviour in hepatocellular carcinoma cells by activating PI3K\/AKT\/mTOR signalling. Cell Death Dis 9:1027","journal-title":"Cell Death Dis"},{"key":"11994_CR21","doi-asserted-by":"publisher","first-page":"1136","DOI":"10.1016\/j.prp.2018.06.011","volume":"214","author":"H B\u00f6sm\u00fcller","year":"2018","unstructured":"B\u00f6sm\u00fcller H, Pfefferle V, Bittar Z et al (2018) Microvessel density and angiogenesis in primary hepatic malignancies: Differential expression of CD31 and VEGFR-2 in hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Pathol Res Pract 214:1136\u20131141","journal-title":"Pathol Res Pract"},{"key":"11994_CR22","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1097\/01.rct.0000236417.82395.57","volume":"31","author":"Y Asayama","year":"2007","unstructured":"Asayama Y, Yoshimitsu K, Irie H et al (2007) Poorly versus moderately differentiated hepatocellular carcinoma: vascularity assessment by computed tomographic hepatic angiography in correlation with histologically counted number of unpaired arteries. J Comput Assist Tomogr 31:188\u2013192","journal-title":"J Comput Assist Tomogr"},{"key":"11994_CR23","doi-asserted-by":"publisher","first-page":"379","DOI":"10.2147\/JHC.S364742","volume":"ume 9","author":"X Li","year":"2022","unstructured":"Li X, Yao Q, Liu C et al (2022) Macrotrabecular-massive hepatocellular carcinoma: What should we know? J Hepatocell Carcinoma ume 9:379\u2013387","journal-title":"J Hepatocell Carcinoma"},{"key":"11994_CR24","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.humpath.2021.04.008","volume":"113","author":"D Kumar","year":"2021","unstructured":"Kumar D, Hafez O, Jain D, Zhang X (2021) Can primary hepatocellular carcinoma histomorphology predict extrahepatic metastasis? Hum Pathol 113:39\u201346","journal-title":"Hum Pathol"},{"key":"11994_CR25","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/S1470-2045(08)70284-5","volume":"10","author":"V Mazzaferro","year":"2009","unstructured":"Mazzaferro V, Llovet JM, Miceli R et al (2009) Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. Lancet Oncol 10:35\u201343","journal-title":"Lancet Oncol"},{"key":"11994_CR26","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1245\/s10434-012-2513-1","volume":"20","author":"M Rodr\u00edguez-Per\u00e1lvarez","year":"2013","unstructured":"Rodr\u00edguez-Per\u00e1lvarez M, Luong TV, Andreana L, Meyer T, Dhillon AP, Burroughs AK (2013) A systematic review of microvascular invasion in hepatocellular carcinoma: diagnostic and prognostic variability. Ann Surg Oncol 20:325\u2013339","journal-title":"Ann Surg Oncol"},{"key":"11994_CR27","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1007\/s00432-016-2286-1","volume":"143","author":"LH Feng","year":"2017","unstructured":"Feng LH, Dong H, Lau WY et al (2017) Novel microvascular invasion-based prognostic nomograms to predict survival outcomes in patients after R0 resection for hepatocellular carcinoma. J Cancer Res Clin Oncol 143:293\u2013303","journal-title":"J Cancer Res Clin Oncol"},{"key":"11994_CR28","doi-asserted-by":"publisher","first-page":"730","DOI":"10.1007\/s12072-010-9245-8","volume":"5","author":"S Enomoto","year":"2011","unstructured":"Enomoto S, Tamai H, Shingaki N et al (2011) Assessment of hepatocellular carcinomas using conventional magnetic resonance imaging correlated with histological differentiation and a serum marker of poor prognosis. Hepatol Int 5:730\u2013737","journal-title":"Hepatol Int"},{"key":"11994_CR29","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1002\/jmri.1880040117","volume":"4","author":"Y Yamashita","year":"1994","unstructured":"Yamashita Y, Fan ZM, Yamamoto H et al (1994) Spin-echo and dynamic gadolinium-enhanced FLASH MR imaging of hepatocellular carcinoma: correlation with histopathologic findings. J Magn Reson Imaging 4:83\u201390","journal-title":"J Magn Reson Imaging"},{"key":"11994_CR30","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1159\/000315235","volume":"78","author":"M Kudo","year":"2010","unstructured":"Kudo M (2010) Will Gd-EOB-MRI change the diagnostic algorithm in hepatocellular carcinoma?. Oncology 78:87\u201393","journal-title":"Oncology"},{"key":"11994_CR31","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.mri.2010.07.019","volume":"29","author":"SA Lee","year":"2011","unstructured":"Lee SA, Lee CH, Jung WY et al (2011) Paradoxical high signal intensity of hepatocellular carcinoma in the hepatobiliary phase of Gd-EOB-DTPA enhanced MRI: initial experience. Magn Reson Imaging 29:83\u201390","journal-title":"Magn Reson Imaging"},{"key":"11994_CR32","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1055\/s-0039-1693512","volume":"40","author":"J Rimola","year":"2020","unstructured":"Rimola J (2020) Heterogeneity of hepatocellular carcinoma on imaging. Semin Liver Dis 40:61\u201369","journal-title":"Semin Liver Dis"},{"key":"11994_CR33","doi-asserted-by":"publisher","first-page":"e2458","DOI":"10.1097\/MD.0000000000002458","volume":"95","author":"M Li","year":"2016","unstructured":"Li M, Xin Y, Fu S et al (2016) Corona enhancement and mosaic architecture for prognosis and selection between of liver resection versus transcatheter arterial chemoembolization in single hepatocellular carcinomas >5\u200acm without extrahepatic metastases: an imaging-based retrospective study. Medicine (Baltimore) 95:e2458","journal-title":"Medicine (Baltimore)"},{"key":"11994_CR34","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/j.critrevonc.2015.01.009","volume":"94","author":"KS Jeng","year":"2015","unstructured":"Jeng KS, Chang CF, Jeng WJ, Sheen IS, Jeng CJ (2015) Heterogeneity of hepatocellular carcinoma contributes to cancer progression. Crit Rev Oncol Hematol 94:337\u2013347","journal-title":"Crit Rev Oncol Hematol"},{"key":"11994_CR35","doi-asserted-by":"publisher","first-page":"7561","DOI":"10.3748\/wjg.v12.i47.7561","volume":"12","author":"M Minagawa","year":"2006","unstructured":"Minagawa M, Makuuchi M (2006) Treatment of hepatocellular carcinoma accompanied by portal vein tumor thrombus. World J Gastroenterol 12:7561\u20137567","journal-title":"World J Gastroenterol"},{"key":"11994_CR36","doi-asserted-by":"publisher","first-page":"821","DOI":"10.2214\/AJR.19.21168","volume":"213","author":"J Chen","year":"2019","unstructured":"Chen J, Zhou J, Kuang S et al (2019) Liver imaging reporting and data system category 5: MRI predictors of microvascular invasion and recurrence after hepatectomy for hepatocellular carcinoma. AJR Am J Roentgenol 213:821\u2013830","journal-title":"AJR Am J Roentgenol"}],"container-title":["European Radiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00330-025-11994-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00330-025-11994-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00330-025-11994-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T13:20:12Z","timestamp":1772716812000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00330-025-11994-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,12]]},"references-count":36,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["11994"],"URL":"https:\/\/doi.org\/10.1007\/s00330-025-11994-3","relation":{},"ISSN":["1432-1084"],"issn-type":[{"value":"1432-1084","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,12]]},"assertion":[{"value":"30 October 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 July 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 August 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 September 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The scientific guarantor of this publication is Weiguo Zhang.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Guarantor"}},{"value":"The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Ruirui Ma, a statistician who comes from the School of Public Health, Suzhou Medical College of Soochow University, kindly provided statistical advice for this manuscript. She is not one of the authors.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Statistics and biometry"}},{"value":"Written informed consent was waived by the Institutional Review Board.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}},{"value":"Institutional Review Board approval was obtained.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"No study subjects or cohorts overlap.","order":7,"name":"Ethics","group":{"name":"EthicsHeading","label":"Study subjects or cohorts overlap"}},{"order":8,"name":"Ethics","group":{"name":"EthicsHeading","label":"Methodology"}}]}}