{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T21:25:44Z","timestamp":1774387544691,"version":"3.50.1"},"reference-count":49,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T00:00:00Z","timestamp":1750118400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality and often develops in the context of liver cirrhosis (LC). Its detection remains a clinical challenge, particularly with limited sensitivity of the current serum biomarkers and qualitative imaging tools. The aim of this pilot study is to evaluate the application of a combined model based on the use of Liver to Spleen Volume Ratio (LSVR), a score of regional liver remodeling, and Liver Vein to Cava Attenuation (LVCA), a computed tomography (CT)-based perfusion-related parameter, to diagnose HCC in patients with LC. Methods: In this observational retrospective pilot study, 36 patients with LC, with or without HCC, were enrolled from a single tertiary care center between 2021 and 2024. Demographic, clinical, biochemical, and imaging data were collected. LSVR and LVCA were calculated from contrast-enhanced CT scans. Predictors of HCC were assessed using conditional inference trees and multivariate logistic regression. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC). A p-value &lt; 0.05 was considered statistically significant. Results: LVCA and LSVR levels were significantly higher in the HCC group (p &lt; 0.001). In multivariate analysis, LVCA was significantly associated with HCC onset (Odds Ratio = 2.88, p = 0.0075). The final model incorporating both LVCA and LSVR achieved excellent discrimination (AUC = 0.967), with 91% sensitivity and 88% specificity. The combined model outperformed LSVR alone (p = 0.030), though not LVCA alone. Conclusions: Our pilot study suggests the utility of LVCA and LSVR as potential non-invasive imaging tools for HCC diagnosis. External validation in multicenter cohorts and longitudinal studies assessing the temporal evolution of LSVR and LVCA are necessary to better evaluate their application in clinical practice.<\/jats:p>","DOI":"10.3390\/jcm14124306","type":"journal-article","created":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T07:04:52Z","timestamp":1750143892000},"page":"4306","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Combined Model for the Diagnosis of Hepatocellular Carcinoma: A Pilot Study Comparing the Liver to Spleen Volume Ratio and Liver Vein to Cava Attenuation"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5922-1524","authenticated-orcid":false,"given":"Ludovico","family":"Abenavoli","sequence":"first","affiliation":[{"name":"Department of Health Sciences, University \u201cMagna Graecia\u201d, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7084-8264","authenticated-orcid":false,"given":"Giuseppe Guido Maria","family":"Scarlata","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University \u201cMagna Graecia\u201d, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Luisa","family":"Gambardella","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University \u201cMagna Graecia\u201d, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caterina","family":"Battaglia","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University \u201cMagna Gr\u00e6cia\u201d, Viale Europa, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6461-6563","authenticated-orcid":false,"given":"Massimo","family":"Borelli","sequence":"additional","affiliation":[{"name":"UMG School of PhD Programmes \u201cLife Sciences and Technologies\u201d, University \u201cMagna Graecia\u201d, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Manti","sequence":"additional","affiliation":[{"name":"Radiology Unit, Renato Dulbecco University Hospital, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9158-0140","authenticated-orcid":false,"given":"Domenico","family":"Lagan\u00e0","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University \u201cMagna Gr\u00e6cia\u201d, Viale Europa, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,17]]},"reference":[{"key":"ref_1","first-page":"19","article-title":"Impact of diet and gut microbiota changes in the development of hepatocellular carcinoma","volume":"10","author":"Scarlata","year":"2024","journal-title":"Hepatoma Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"102406","DOI":"10.1016\/j.jceh.2024.102406","article-title":"Evolving Global Etiology of Hepatocellular Carcinoma (HCC): Insights and Trends for 2024","volume":"15","author":"Koshy","year":"2025","journal-title":"J. Clin. Exp. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1038\/s41575-019-0186-y","article-title":"A global view of hepatocellular carcinoma: Trends, risk, prevention and management","volume":"16","author":"Yang","year":"2019","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Phoolchund, A.G.S., and Khakoo, S.I. (2024). MASLD and the Development of HCC: Pathogenesis and Therapeutic Challenges. Cancers, 16.","DOI":"10.3390\/cancers16020259"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"516","DOI":"10.14218\/JCTH.2024.00018","article-title":"Ultrasonography of Hepatocellular Carcinoma: From Diagnosis to Prognosis","volume":"12","author":"Hu","year":"2024","journal-title":"J. Clin. Transl. Hepatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"209","DOI":"10.5152\/dir.2014.13370","article-title":"MRI of hepatocellular carcinoma: An update of current practices","volume":"20","author":"Kalb","year":"2014","journal-title":"Diagn. Interv. Radiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"976","DOI":"10.3390\/gastroent15040068","article-title":"CT and MR Imaging of Hepatocellular Carcinoma and Liver Cirrhosis","volume":"15","author":"Okada","year":"2024","journal-title":"Gastroenterol. Insights"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2697","DOI":"10.1007\/s12033-023-00890-0","article-title":"An Insight into the Role of Alpha-Fetoprotein (AFP) in the Development and Progression of Hepatocellular Carcinoma","volume":"66","author":"Samban","year":"2024","journal-title":"Mol. Biotechnol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"513","DOI":"10.2147\/JHC.S499966","article-title":"The Diagnostic Performance of AFP, AFP-L3, DCP, CA199, and Their Combination for Primary Liver Cancer","volume":"12","author":"Liu","year":"2025","journal-title":"J. Hepatocell. Carcinoma"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Schlosser, S., T\u00fcmen, D., Volz, B., Neumeyer, K., Egler, N., Kunst, C., Tews, H.C., Schmid, S., Kandulski, A., and M\u00fcller, M. (2022). HCC biomarkers\u2014State of the old and outlook to future promising biomarkers and their potential in everyday clinical practice. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.1016952"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Scarlata, G.G.M., Ismaiel, A., Gambardella, M.L., Leucuta, D.C., Luzza, F., Dumitrascu, D.L., and Abenavoli, L. (2024). Use of Non-Invasive Biomarkers and Clinical Scores to Predict the Complications of Liver Cirrhosis: A Bicentric Experience. Medicina, 60.","DOI":"10.3390\/medicina60111854"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Ismaiel, A., Katell, E., Leucuta, D.C., Popa, S.L., Catana, C.S., Dumitrascu, D.L., and Surdea-Blaga, T. (2025). The Impact of Non-Invasive Scores and Hemogram-Derived Ratios in Differentiating Chronic Liver Disease from Cirrhosis. J. Clin. Med., 14.","DOI":"10.3390\/jcm14093072"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.gendis.2020.01.014","article-title":"Advances in the early diagnosis of hepatocellular carcinoma","volume":"7","author":"Wang","year":"2020","journal-title":"Genes. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.1002\/jmri.27962","article-title":"A New Reporting System for Diagnosis of Hepatocellular Carcinoma in Chronic Hepatitis B With Clinical and Gadoxetic Acid-Enhanced MRI Features","volume":"55","author":"Hwang","year":"2022","journal-title":"J. Magn. Reson. Imaging"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.mric.2021.05.002","article-title":"Computed Tomography Techniques, Protocols, Advancements, and Future Directions in Liver Diseases","volume":"29","author":"Kulkarni","year":"2021","journal-title":"Magn. Reson. Imaging Clin. N. Am."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Obmann, V.C., Mertineit, N., Berzigotti, A., Marx, C., Ebner, L., Kreis, R., Vermathen, P., Heverhagen, J.T., Christe, A., and Huber, A.T. (2018). CT predicts liver fibrosis: Prospective evaluation of morphology- and attenuation-based quantitative scores in routine portal venous abdominal scans. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0199611"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1007\/s00535-021-01788-x","article-title":"Evidence-based clinical practice guidelines for Liver Cirrhosis 2020","volume":"56","author":"Yoshiji","year":"2021","journal-title":"J. Gastroenterol."},{"key":"ref_18","unstructured":"European Association for the Study of the Liver (2025). EASL Clinical Practice Guidelines on the management of hepatocellular carcinoma. J. Hepatol., 82, 315\u2013374."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1016\/j.jhep.2021.12.022","article-title":"Baveno VII\u2014Renewing consensus in portal hypertension","volume":"76","author":"Bosch","year":"2022","journal-title":"J. Hepatol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Tajiri, T., Yoshida, H., Obara, K., Onji, M., Kage, M., Kitano, S., Kokudo, N., Kokubu, S., Sakaida, I., and Sata, M. (2010). General Rules for Recording Endoscopic Findings of Esophagogastric Varices, Wiley. [2nd ed.].","DOI":"10.1111\/j.1443-1661.2009.00929.x"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1016\/j.jhep.2021.09.003","article-title":"EASL Clinical Practice Guidelines on prevention and management of bleeding and thrombosis in patients with cirrhosis","volume":"76","author":"Villa","year":"2022","journal-title":"J. Hepatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"681","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":"ref_23","doi-asserted-by":"crossref","first-page":"e2877","DOI":"10.1097\/MD.0000000000002877","article-title":"Child-Pugh Versus MELD Score for the Assessment of Prognosis in Liver Cirrhosis: A Systematic Review and Meta-Analysis of Observational Studies","volume":"95","author":"Peng","year":"2016","journal-title":"Medicine"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1985","DOI":"10.3348\/kjr.2021.0348","article-title":"Liver-to-Spleen Volume Ratio Automatically Measured on CT Predicts Decompensation in Patients with B Viral Compensated Cirrhosis","volume":"22","author":"Kwon","year":"2021","journal-title":"Korean J. Radiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1912","DOI":"10.1007\/s00261-020-02834-7","article-title":"Liver segmental volume and attenuation ratio (LSVAR) on portal venous CT scans improves the detection of clinically significant liver fibrosis compared to liver segmental volume ratio (LSVR)","volume":"46","author":"Obmann","year":"2021","journal-title":"Abdom. Radiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1198\/106186006X133933","article-title":"Unbiased recursive partitioning: A conditional inference framework","volume":"15","author":"Hothorn","year":"2006","journal-title":"J. Comput. Graph. Stat."},{"key":"ref_27","unstructured":"Hothorn, T., Hornik, K., Strobl, C., and Zeileis, A. (2025, May 05). party: A Laboratory for Recursive Partytioning. R Package Version 1.3-13. Available online: https:\/\/CRAN.R-project.org\/package=party."},{"key":"ref_28","unstructured":"R Core Team (2024). R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing. Available online: https:\/\/www.R-project.org\/."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Scarpellini, E., Scarlata, G.G.M., Santori, V., Scarcella, M., Kobyliak, N., and Abenavoli, L. (2024). Gut Microbiota, Deranged Immunity, and Hepatocellular Carcinoma. Biomedicines, 12.","DOI":"10.3390\/biomedicines12081797"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"875","DOI":"10.14309\/ajg.0000000000002596","article-title":"Proportion of Time Covered by Hepatocellular Carcinoma Surveillance in Patients with Cirrhosis","volume":"119","author":"Daher","year":"2024","journal-title":"Am. J Gastroenterol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"S44","DOI":"10.1002\/lt.22365","article-title":"Milan criteria in liver transplantation for hepatocellular carcinoma: An evidence-based analysis of 15 years of experience","volume":"17","author":"Mazzaferro","year":"2011","journal-title":"Liver Transplant."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"European Association for the Study of the Liver (2024). EASL Clinical Practice Guidelines on liver transplantation. J. Hepatol., 81, 1040\u20131086.","DOI":"10.1016\/j.jhep.2024.07.032"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.jhep.2018.09.014","article-title":"Burden of liver diseases in the world","volume":"70","author":"Asrani","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/hep.28431","article-title":"Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes","volume":"64","author":"Younossi","year":"2016","journal-title":"Hepatology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4853","DOI":"10.3748\/wjg.v17.i44.4853","article-title":"Hepatitis B virus infection and the risk of hepatocellular carcinoma","volume":"17","author":"Tan","year":"2011","journal-title":"World J. Gastroenterol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Attia, A.M., Rezaee-Zavareh, M.S., Hwang, S.Y., Kim, N., Adetyan, H., Yalda, T., Chen, P.J., Koltsova, E.K., and Yang, J.D. (2024). Novel Biomarkers for Early Detection of Hepatocellular Carcinoma. Diagnostics, 14.","DOI":"10.3390\/diagnostics14202278"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Oura, K., Morishita, A., Tani, J., and Masaki, T. (2021). Tumor Immune Microenvironment and Immunosuppressive Therapy in Hepatocellular Carcinoma: A Review. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22115801"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e17126","DOI":"10.1016\/j.heliyon.2023.e17126","article-title":"The relationship between the serum lipid profile and hepatocellular carcinoma in east Asian population: A mendelian randomization study","volume":"9","author":"Pan","year":"2023","journal-title":"Heliyon"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Fang, T., Long, G., Mi, X., Su, W., Mo, L., and Zhou, L. (2022). Splenic Volume, an Easy-To-Use Predictor of HCC Late Recurrence for HCC Patients After Hepatectomy. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.876668"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1016\/j.transproceed.2023.03.026","article-title":"Liver-Spleen Volume Ratio as a Predictor of Native Liver Survival in Patients with Biliary Atresia","volume":"55","author":"Takase","year":"2023","journal-title":"Transplant. Proc."},{"key":"ref_41","first-page":"100645","article-title":"CT-derived liver and spleen volume accurately diagnose clinically significant portal hypertension in patients with hepatocellular carcinoma","volume":"5","author":"Canales","year":"2022","journal-title":"JHEP Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"S63","DOI":"10.1016\/j.jceh.2014.06.009","article-title":"Radiological features of hepatocellular carcinoma","volume":"4","author":"Shah","year":"2014","journal-title":"J. Clin. Exp. Hepatol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1007\/s00432-004-0552-0","article-title":"Randomized controlled trial of screening for hepatocellular carcinoma","volume":"130","author":"Zhang","year":"2004","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1053\/j.gastro.2009.10.031","article-title":"Des-gamma-carboxy prothrombin and alpha-fetoprotein as biomarkers for the early detection of hepatocellular carcinoma","volume":"138","author":"Lok","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1706","DOI":"10.1053\/j.gastro.2018.01.064","article-title":"Surveillance Imaging and Alpha Fetoprotein for Early Detection of Hepatocellular Carcinoma in Patients with Cirrhosis: A Meta-analysis","volume":"154","author":"Tzartzeva","year":"2018","journal-title":"Gastroenterology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1097\/SLA.0000000000006386","article-title":"Tumor Mutational Burden from Circulating Tumor DNA Predicts Recurrence of Hepatocellular Carcinoma After Resection: An Emerging Biomarker for Surveillance","volume":"280","author":"Wehrle","year":"2024","journal-title":"Ann. Surg."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"111796","DOI":"10.1016\/j.ejrad.2024.111796","article-title":"ctDNA in the reading room: A guide for radiologists","volume":"181","author":"Pearce","year":"2024","journal-title":"Eur. J. Radiol."},{"key":"ref_48","first-page":"27","article-title":"Safety Considerations in MRI and CT","volume":"29","author":"Watson","year":"2023","journal-title":"Continuum"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Najjar, R. (2023). Redefining Radiology: A Review of Artificial Intelligence Integration in Medical Imaging. Diagnostics, 13.","DOI":"10.20944\/preprints202306.1124.v1"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/12\/4306\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:53:28Z","timestamp":1760032408000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/12\/4306"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,17]]},"references-count":49,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["jcm14124306"],"URL":"https:\/\/doi.org\/10.3390\/jcm14124306","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,17]]}}}