{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T10:06:45Z","timestamp":1776766005809,"version":"3.51.2"},"reference-count":35,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2022,10,16]],"date-time":"2022-10-16T00:00:00Z","timestamp":1665878400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004606","name":"Chang Gung Memorial Hospital, Taiwan","doi-asserted-by":"publisher","award":["CMRPG8K1101"],"award-info":[{"award-number":["CMRPG8K1101"]}],"id":[{"id":"10.13039\/501100004606","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004606","name":"Chang Gung Memorial Hospital, Taiwan","doi-asserted-by":"publisher","award":["109-2314-B-039-020"],"award-info":[{"award-number":["109-2314-B-039-020"]}],"id":[{"id":"10.13039\/501100004606","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Science and Technology, Taiwan","award":["CMRPG8K1101"],"award-info":[{"award-number":["CMRPG8K1101"]}]},{"name":"Ministry of Science and Technology, Taiwan","award":["109-2314-B-039-020"],"award-info":[{"award-number":["109-2314-B-039-020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Mac-2 binding protein glycosylation isomer (M2BPGi) has not been used in a risk score to predict hepatocellular carcinoma (HCC). We enrolled 1003 patients with chronic hepatitis B and cirrhosis receiving entecavir or tenofovir therapy for more than12 months to construct an HCC risk score. In the development cohort, Cox regression analysis identified male gender, age, platelet count, AFP and M2BPGi levels at 12 months of treatment as independent risk factors of HCC. We developed the HCC risk prediction model, the ASPAM-B score, based on age, sex, platelet count, AFP and M2BPGi levels at 12 months of treatment, with the total scores ranging from 0 to 11.5. This risk model accurately classified patients into low (0\u20133.5), medium (4\u20137), and high (&gt;7) risk in the development and validation groups (p &lt; 0.001). The areas under the receiver operating characteristic curve (AUROC) of 3-, 5- and 9-year risks of HCC were 0.742, 0.728 and 0.719, respectively, in the development cohort. All AUROC between the ASPAM-B and APA-B, PAGE-B, RWS-HCC and THRI scores at 3\u20139 years were significantly different. The M2BPGi-based risk model exhibited good discriminant function in predicting HCC in cirrhotic patients who received long-term antiviral treatment.<\/jats:p>","DOI":"10.3390\/cancers14205063","type":"journal-article","created":{"date-parts":[[2022,10,16]],"date-time":"2022-10-16T21:10:10Z","timestamp":1665954610000},"page":"5063","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A Mac-2 Binding Protein Glycosylation Isomer-Based Risk Model Predicts Hepatocellular Carcinoma in HBV-Related Cirrhotic Patients on Antiviral Therapy"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8896-8133","authenticated-orcid":false,"given":"Chien-Hung","family":"Chen","sequence":"first","affiliation":[{"name":"Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Kaohsiung 833253, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsung-Hui","family":"Hu","sequence":"additional","affiliation":[{"name":"Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Kaohsiung 833253, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing-Houng","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Kaohsiung 833253, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsueh-Chou","family":"Lai","sequence":"additional","affiliation":[{"name":"Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung 404022, Taiwan"},{"name":"School of Chinese Medicine, China Medical University, Taichung 404022, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao-Hung","family":"Hung","sequence":"additional","affiliation":[{"name":"Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Kaohsiung 833253, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheng-Nan","family":"Lu","sequence":"additional","affiliation":[{"name":"Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Kaohsiung 833253, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9030-6086","authenticated-orcid":false,"given":"Cheng-Yuan","family":"Peng","sequence":"additional","affiliation":[{"name":"Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung 404022, Taiwan"},{"name":"School of Medicine, China Medical University, Taichung 404022, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1002\/hep.23785","article-title":"Long-term entecavir therapy results in the reversal of fibrosis\/cirrhosis and continued histological improvement in patients with chronic hepatitis B","volume":"52","author":"Chang","year":"2010","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/S0140-6736(12)61425-1","article-title":"Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: A 5-year open-label follow-up study","volume":"381","author":"Marcellin","year":"2013","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1111\/liv.13253","article-title":"Four-year entecavir therapy reduces hepatocellular carcinoma, cirrhotic events and mortality in chronic hepatitis B patients","volume":"36","author":"Su","year":"2016","journal-title":"Liver Int."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1093\/infdis\/jiy391","article-title":"Reduced Incidence of Hepatocellular Carcinoma in Cirrhotic and Noncirrhotic Patients with Chronic Hepatitis B Treated With Tenofovir\u2014A Propensity Score\u2013Matched Study","volume":"219","author":"Nguyen","year":"2019","journal-title":"J. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1016\/j.jhep.2015.11.035","article-title":"PAGE-B predicts the risk of developing hepatocellular carcinoma in Caucasians with chronic hepatitis B on 5-year antiviral therapy","volume":"64","author":"Papatheodoridis","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"92431","DOI":"10.18632\/oncotarget.21369","article-title":"Prediction model of hepatocellular carcinoma risk in Asian patients with chronic hepatitis B treated with entecavir","volume":"8","author":"Chen","year":"2017","journal-title":"Oncotarget"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"170","DOI":"10.3350\/cmh.2016.0086","article-title":"Risk score model for the development of hepatocellular carcinoma in treatment-na\u00efve patients receiving oral antiviral treatment for chronic hepatitis B","volume":"23","author":"Sohn","year":"2017","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.jhep.2018.02.032","article-title":"Development of a scoring system to predict hepatocellular carcinoma in Asians on antivirals for chronic hepatitis B","volume":"69","author":"Hsu","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1016\/j.jhep.2018.07.018","article-title":"Modified PAGE-B score predicts the risk of hepatocellular carcinoma in Asians with chronic hepatitis B on antiviral therapy","volume":"69","author":"Kim","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1097\/MEG.0000000000001357","article-title":"Prediction model for hepatocellular carcinoma risk in treatment-naive chronic hepatitis B patients receiving entecavir\/tenofovir","volume":"31","author":"Yu","year":"2019","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1093\/infdis\/jiz477","article-title":"Real-World Effectiveness from the Asia Pacific Rim Liver Consortium for HBV Risk Score for the Prediction of Hepatocellular Carcinoma in Chronic Hepatitis B Patients Treated with Oral Antiviral Therapy","volume":"221","author":"Yang","year":"2020","journal-title":"J. Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1016\/j.jhep.2020.07.025","article-title":"aMAP risk score predicts hepatocellular carcinoma development in patients with chronic hepatitis","volume":"73","author":"Fan","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1652","DOI":"10.1111\/liv.14820","article-title":"Twelve-month post-treatment parameters are superior in predicting hepatocellular carcinoma in patients with chronic hepatitis B","volume":"41","author":"Ahn","year":"2021","journal-title":"Liver Int."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1136\/gutjnl-2015-310818","article-title":"Real-world risk score for hepatocellular carcinoma (RWS-HCC): A clinically practical risk predictor for HCC in chronic hepatitis B","volume":"65","author":"Poh","year":"2016","journal-title":"Gut"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.jhep.2021.09.009","article-title":"Comparative performance of risk prediction models for hepatitis B-related hepatocellular carcinoma in the United States","volume":"76","author":"Kim","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"16","DOI":"10.3343\/alm.2021.41.1.16","article-title":"Clinical Utility of Mac-2 Binding Protein Glycosylation Isomer in Chronic Liver Diseases","volume":"41","author":"Tamaki","year":"2021","journal-title":"Ann. Lab. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1111\/hepr.12703","article-title":"Clinical implications of serum Wisteria floribunda agglutinin-positive Mac-2-binding protein in treatment-naive chronic hepatitis B","volume":"47","author":"Ishii","year":"2017","journal-title":"Hepatol. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1111\/hepr.12712","article-title":"Serum Wisteria floribunda agglutinin-positive human Mac-2 binding protein may predict liver fibrosis and progression to hepatocellular carcinoma in patients with chronic hepatitis B virus infection","volume":"47","author":"Ichikawa","year":"2017","journal-title":"Hepatol. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1007\/s00535-017-1386-2","article-title":"Serum Wisteria floribunda agglutinin-positive Mac-2 binding protein predicts hepatocellular carcinoma incidence and recurrence in nucleos(t)ide analogue therapy for chronic hepatitis B","volume":"53","author":"Kawaguchi","year":"2018","journal-title":"J. Gastroenterol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1007\/s00535-017-1424-0","article-title":"High levels of serum Mac-2-binding protein glycosylation isomer (M2BPGi) predict the development of hepatocellular carcinoma in hepatitis B patients treated with nucleot(s)ide analogues","volume":"53","author":"Shinkai","year":"2018","journal-title":"J. Gastroenterol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1111\/liv.12907","article-title":"Serum WFA+ -M2BP levels as a prognostic factor in patients with early hepatocellular carcinoma undergoing curative resection","volume":"36","author":"Toyoda","year":"2016","journal-title":"Liver Int."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"33","DOI":"10.3350\/cmh.2018.0073","article-title":"Serum Wisteria floribunda agglutinin-positive human Mac-2 binding protein level predicts recurrence of hepatitis B virus-related hepatocellular carcinoma after curative resection","volume":"26","author":"Kim","year":"2020","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1002\/hep.29913","article-title":"Diagnosis, Staging, and Management of Hepatocellular Carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases","volume":"68","author":"Marrero","year":"2018","journal-title":"Hepatology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4158\/EP15672.GLSUPPL","article-title":"American Association of Clinical Endocrinologists and American College of Endocrinology- clinical practice guidelines for developing a diabetes mellitus comprehensive care plan- 2015","volume":"21","author":"Handelsman","year":"2015","journal-title":"Endocr. Pract."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1038\/srep01065","article-title":"A serum \u201csweet-doughnut\u201d protein facilitates fibrosis evaluation and therapy assessment in patients with viral hepatitis","volume":"3","author":"Kuno","year":"2013","journal-title":"Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1111\/1469-0691.12739","article-title":"Linearized hepatitis B surface antigen and hepatitis B core-related antigen in the natural history of chronic hepatitis B","volume":"20","author":"Seto","year":"2014","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1002\/sim.4780100410","article-title":"Multiple imputation in health-care databases: An overview and some applications","volume":"10","author":"Rubin","year":"1991","journal-title":"Stat. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1002\/sim.1742","article-title":"Presentation of multivariate data for clinical use: The Framingham Study risk score functions","volume":"23","author":"Sullivan","year":"2004","journal-title":"Stat. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1002\/sim.4154","article-title":"On the C-statistics for evaluating overall adequacy of risk prediction procedures with censored survival data","volume":"30","author":"Uno","year":"2011","journal-title":"Stat Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"5381","DOI":"10.1002\/sim.5958","article-title":"Estimating and comparing time-dependent areas under receiver operating characteristic curves for censored event times with competing risks","volume":"32","author":"Blanche","year":"2013","journal-title":"Stat. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.jhep.2017.07.033","article-title":"Toronto HCC risk index: A validated scoring system to predict 10-year risk of HCC in patients with cirrhosis","volume":"68","author":"Sharma","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.jhep.2021.09.025","article-title":"An artificial intelligence model to predict hepatocellular carcinoma risk in Korean and Caucasian patients with chronic hepatitis B","volume":"76","author":"Kim","year":"2022","journal-title":"J. Hepatol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1002\/hep.21941","article-title":"Platelet count is not a predictor of the presence or development of gastroesophageal varices in cirrhosis","volume":"47","author":"Qamar","year":"2008","journal-title":"Hepatology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1016\/j.jhep.2009.01.014","article-title":"Hepatic venous pressure gradient predicts development of hepatocellular carcinoma independently of severity of cirrhosis","volume":"50","author":"Ripoll","year":"2009","journal-title":"J. Hepatol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1111\/apt.15108","article-title":"Impact of hepatitis B core-related antigen on the incidence of hepatocellular carcinoma in patients treated with nucleos(t)ide analogues","volume":"49","author":"Hosaka","year":"2019","journal-title":"Aliment. Pharmacol. Ther."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/20\/5063\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:55:03Z","timestamp":1760144103000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/20\/5063"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,16]]},"references-count":35,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["cancers14205063"],"URL":"https:\/\/doi.org\/10.3390\/cancers14205063","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,16]]}}}