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This study aimed to evaluate its diagnostic efficacy for early and alpha\u2010fetoprotein (AFP)\u2010negative HCC, and its potential role in assessing radical resection and early recurrence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A large\u2010scale multicentre clinical study enrolled 1 352 subjects from three medical centres, including HCC, benign liver diseases, and non\u2010hepatocyte cancers. Serum samples were collected for AKR1B10 and AFP testing, and clinical and imaging data were collected for analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Serum AKR1B10 markedly increased in HCC patients to 1419.51\u2009\u00b1\u200989.09\u2009pg\/mL, compared to 177.96\u2009\u00b1\u20099.78\u2009pg\/mL in healthy controls. Receiver operating characteristic (ROC) curve analysis showed that for HCC diagnosis, AKR1B10 had an Area under the curve (AUC) of 0.866, sensitivity of 73.10%, and specificity of 95.24%, compared to AFP with 0.750, 64.27%, and 82.14%, respectively. In early HCC, AKR1B10 yielded an AUC of 0.800, a sensitivity of 65.8%, and a specificity of 91.67%, better than AFP (0.717, 59.83%, and 88.1%, respectively). AKR1B10 was positive in 69.27% of AFP\u2010negative HCC cases and showed an AUC of 0.852, a sensitivity of 72.2%, and a specificity of 90.48%. In patients with HCC undergoing curative resection, serum AKR1B10 levels declined to normal within 3\u20135\u2009days. At 1\u20133\u2009months after surgery, serum AKR1B10 had a concordance of 94.41% with imaging data, compared to 70.63% for AFP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>AKR1B10 is a useful serum marker for the diagnosis of early and AFP\u2010negative HCC and shows potential in assessing curative resection and early recurrence.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.70732","type":"journal-article","created":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T04:40:00Z","timestamp":1782535200000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Diagnostic Performance of Serum\n                    <scp>AKR1B10<\/scp>\n                    in Early\u2010Stage and\n                    <scp>AFP<\/scp>\n                    \u2010Negative Hepatocellular Carcinoma: A Multicentre Study"],"prefix":"10.1111","volume":"46","author":[{"given":"Zhe","family":"Cao","sequence":"first","affiliation":[{"name":"Hunan Engineering Technology Research Center of Veterinary Drugs Hunan Agricultural University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9335-0381","authenticated-orcid":false,"given":"Ming","family":"Xie","sequence":"additional","affiliation":[{"name":"Hunan Engineering Research Center for Early Diagnosis and Treatment of Liver Cancer, Hunan Province Key Laboratory of Tumor Cellular &amp; Molecular Pathology, Cancer Research Institute, Hengyang Medical School University of South China  Hengyang Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Ye","sequence":"additional","affiliation":[{"name":"The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University\/Hunan Cancer Hospital  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Wu","sequence":"additional","affiliation":[{"name":"Hunan Light of Life Biotechnology Co., Ltd.  Hunan Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiqing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Hepatopancreatobiliary Surgery The First Affiliated Hospital, Hengyang Medical School, University of South China  Hengyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guodong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Hepatopancreatobiliary Surgery The First Affiliated Hospital, Hengyang Medical School, University of South China  Hengyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deliang","family":"Cao","sequence":"additional","affiliation":[{"name":"Hunan Engineering Research Center for Early Diagnosis and Treatment of Liver Cancer, Hunan Province Key Laboratory of Tumor Cellular &amp; Molecular Pathology, Cancer Research Institute, Hengyang Medical School University of South China  Hengyang Hunan 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