{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:47:39Z","timestamp":1760150859136,"version":"build-2065373602"},"reference-count":37,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,1,29]],"date-time":"2022-01-29T00:00:00Z","timestamp":1643414400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100018688","name":"Korea Disease Control and Prevention Agency","doi-asserted-by":"publisher","award":["2019ER510202"],"award-info":[{"award-number":["2019ER510202"]}],"id":[{"id":"10.13039\/100018688","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Antiviral therapy (AVT) induces the regression of non-invasive fibrosis markers (NFMs) and reduces hepatocellular carcinoma (HCC) risk among chronic hepatitis B (CHB) patients. We externally validated the predictive performance of the FSAC prediction model for HCC using on-therapy NFM responses. Our multicenter study consecutively recruited treatment-na\u00efve CHB patients (n = 3026; median age, 50.0 years; male predominant (61.3%); cirrhosis in 1391 (46.0%) patients) receiving potent AVTs for &gt;18 months between 2007 and 2018. During follow-up (median 64.0 months), HCC developed in 303 (10.0%) patients. Patients with low FIB-4 or APRI levels at 12 months showed significantly lower HCC risk than those with high NFM levels at 12 months (all p &lt; 0.05). Cumulative 3-, 5-, and 8-year HCC probabilities were 0.0%, 0.3% and 1.2% in the low-risk group (FSAC \u2264 2); 2.1%, 5.2%, and 11.1% in the intermediate-risk group (FSAC 3\u22128); and 5.2%, 15.5%, and 29.8% in the high-risk group (FSAC \u2265 9) (both p &lt; 0.001 between each adjacent pair). Harrell\u2019s c-index value for FSAC score (0.770) was higher than those for PAGE-B (0.725), modified PAGE-B (0.738), modified REACH-B (0.737), LSM-HCC (0.734), and CAMD (0.742). Our study showed that the FSAC model, which incorporates on-therapy changes in NFMs, had better predictive performance than other models using only baseline parameters.<\/jats:p>","DOI":"10.3390\/cancers14030711","type":"journal-article","created":{"date-parts":[[2022,1,29]],"date-time":"2022-01-29T23:02:06Z","timestamp":1643497326000},"page":"711","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["External Validation of the FSAC Model Using On-Therapy Changes in Noninvasive Fibrosis Markers in Patients with Chronic Hepatitis B: A Multicenter Study"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2371-0967","authenticated-orcid":false,"given":"Jae Seung","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea"},{"name":"Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Korea"},{"name":"Yonsei Liver Center, Severance Hospital, Seoul 03722, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyun Woong","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea"},{"name":"Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Korea"},{"name":"Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tae Seop","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea"},{"name":"Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Korea"},{"name":"Department of Internal Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin-si 16995, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"In Kyung","family":"Min","sequence":"additional","affiliation":[{"name":"Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul 03722, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3552-3560","authenticated-orcid":false,"given":"Hye Won","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea"},{"name":"Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Korea"},{"name":"Yonsei Liver Center, Severance Hospital, Seoul 03722, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9658-8050","authenticated-orcid":false,"given":"Seung Up","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea"},{"name":"Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Korea"},{"name":"Yonsei Liver Center, Severance Hospital, Seoul 03722, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6324-2224","authenticated-orcid":false,"given":"Jun Yong","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea"},{"name":"Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Korea"},{"name":"Yonsei Liver Center, Severance Hospital, Seoul 03722, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8327-3439","authenticated-orcid":false,"given":"Do Young","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea"},{"name":"Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Korea"},{"name":"Yonsei Liver Center, Severance Hospital, Seoul 03722, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang Hoon","family":"Ahn","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea"},{"name":"Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Korea"},{"name":"Yonsei Liver Center, Severance Hospital, Seoul 03722, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beom Kyung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea"},{"name":"Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Korea"},{"name":"Yonsei Liver Center, Severance Hospital, Seoul 03722, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"172","DOI":"10.3350\/cmh.2018.0106","article-title":"Unmet need in chronic hepatitis B management","volume":"25","author":"Liang","year":"2019","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3350\/cmh.2019.0065","article-title":"Trends in the prevalence of chronic liver disease in the Korean adult population, 1998\u20132017","volume":"26","author":"Park","year":"2020","journal-title":"Clin. Mol. Hepatol."},{"doi-asserted-by":"crossref","unstructured":"European Association for the Study of the Liver (2017). EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J. Hepatol., 67, 370\u2013398.","key":"ref_3","DOI":"10.1016\/j.jhep.2017.03.021"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"411","DOI":"10.3350\/cmh.2020.0049","article-title":"Comparison of clinical practice guidelines for the management of chronic hepatitis B: When to start, when to change, and when to stop","volume":"26","author":"Yim","year":"2020","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1002\/hep.28156","article-title":"AASLD guidelines for treatment of chronic hepatitis B","volume":"63","author":"Terrault","year":"2016","journal-title":"Hepatology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"352","DOI":"10.3350\/cmh.2019.0044n","article-title":"Entecavir+tenofovir vs. lamivudine\/telbivudine+adefovir in chronic hepatitis B patients with prior suboptimal response","volume":"26","author":"Woo","year":"2020","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"529","DOI":"10.3350\/cmh.2019.0056n","article-title":"Inhibition of PI3K\/Akt signaling suppresses epithelial-to-mesenchymal transition in hepatocellular carcinoma through the Snail\/GSK-3\/beta-catenin pathway","volume":"26","author":"Lee","year":"2020","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"606","DOI":"10.3350\/cmh.2020.0169","article-title":"Autophagy and liver cancer","volume":"26","author":"Chao","year":"2020","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"742","DOI":"10.3350\/cmh.2020.0178","article-title":"Hepatic Hippo signaling inhibits development of hepatocellular carcinoma","volume":"26","author":"Liu","year":"2020","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"364","DOI":"10.3350\/cmh.2020.0012","article-title":"Low-level viremia and cirrhotic complications in patients with chronic hepatitis B according to adherence to entecavir","volume":"26","author":"Lee","year":"2020","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"516","DOI":"10.3350\/cmh.2020.0016","article-title":"Substantial risk of recurrence even after 5 recurrence-free years in early-stage hepatocellular carcinoma patients","volume":"26","author":"Kim","year":"2020","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"506","DOI":"10.3350\/cmh.2020.0038","article-title":"Stereotactic body radiation therapy for small (\u22645 cm) hepatocellular carcinoma not amenable to curative treatment: Results of a single-arm, phase II clinical trial","volume":"26","author":"Yoon","year":"2020","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_13","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_14","doi-asserted-by":"crossref","first-page":"340","DOI":"10.3350\/cmh.2020.0004","article-title":"Comparison of LI-RADS 2018 and KLCA-NCC 2018 for noninvasive diagnosis of hepatocellular carcinoma using magnetic resonance imaging","volume":"26","author":"Lee","year":"2020","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_15","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_16","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1016\/j.jhep.2020.01.007","article-title":"Hepatocellular carcinoma prediction beyond year 5 of oral therapy in a large cohort of Caucasian patients with chronic hepatitis B","volume":"72","author":"Papatheodoridis","year":"2020","journal-title":"J. Hepatol."},{"doi-asserted-by":"crossref","unstructured":"Chon, H.Y., Lee, J.S., Lee, H.W., Chun, H.S., Kim, B.K., Tak, W.Y., Park, J.Y., Kweon, Y.O., Kim, D.Y., and Ahn, S.H. (2021). Predictive Performance of CAGE-B and SAGE-B Models in Asian Treatment-Naive Patients Who Started Entecavir for Chronic Hepatitis B. Clin. Gastroenterol. Hepatol.","key":"ref_17","DOI":"10.1016\/j.cgh.2021.06.001"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"467","DOI":"10.2147\/JHC.S300382","article-title":"The Prognostic Role of On-Treatment Liver Stiffness for Hepatocellular Carcinoma Development in Patients with Chronic Hepatitis B","volume":"8","author":"Lee","year":"2021","journal-title":"J. Hepatocell. Carcinoma"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1097\/MEG.0000000000001794","article-title":"Dynamics of liver stiffness-based risk prediction model during antiviral therapy in patients with chronic hepatitis B","volume":"33","author":"Chon","year":"2021","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1002\/jum.14822","article-title":"Dynamic Changes of the Aspartate Aminotransferase-to-Platelet Ratio and Transient Elastography in Predicting a Histologic Response in Patients With Chronic Hepatitis B After Entecavir Treatment","volume":"38","author":"Sun","year":"2019","journal-title":"J. Ultrasound Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.14309\/ajg.0000000000001219","article-title":"Prediction of Hepatocellular Carcinoma by On-Therapy Response of Noninvasive Fibrosis Markers in Chronic Hepatitis B","volume":"116","author":"Nam","year":"2021","journal-title":"Am. J. Gastroenterol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1002\/hep.21178","article-title":"Development of a simple noninvasive index to predict significant fibrosis in patients with HIV\/HCV coinfection","volume":"43","author":"Sterling","year":"2006","journal-title":"Hepatology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1111\/j.1478-3231.2009.02192.x","article-title":"Validation of FIB-4 and comparison with other simple noninvasive indices for predicting liver fibrosis and cirrhosis in hepatitis B virus-infected patients","volume":"30","author":"Kim","year":"2010","journal-title":"Liver Int."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1053\/jhep.2003.50346","article-title":"A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C","volume":"38","author":"Wai","year":"2003","journal-title":"Hepatology"},{"doi-asserted-by":"crossref","unstructured":"Korean Association for the Study of the Liver (2020). KASL clinical practice guidelines for liver cirrhosis: Varices, hepatic encephalopathy, and related complications. Clin. Mol. Hepatol., 26, 83\u2013127.","key":"ref_25","DOI":"10.3350\/cmh.2019.0010n"},{"doi-asserted-by":"crossref","unstructured":"Korean Association for the Study of the Liver (2016). KASL clinical practice guidelines: Management of chronic hepatitis B. Clin. Mol. Hepatol., 22, 18\u201375.","key":"ref_26","DOI":"10.3350\/cmh.2016.22.1.18"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"54","DOI":"10.3350\/cmh.2019.0039","article-title":"Sensitivity of ultrasound in detecting hepatocellular carcinoma in obese patients compared to explant pathology as the gold standard","volume":"26","author":"Esfeh","year":"2020","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"160","DOI":"10.3350\/cmh.2018.1013","article-title":"Advances in ultrasound diagnosis in chronic liver diseases","volume":"25","author":"Maruyama","year":"2019","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"390","DOI":"10.3350\/cmh.2018.0103","article-title":"Risk assessment of hepatocellular carcinoma development for indeterminate hepatic nodules in patients with chronic hepatitis B","volume":"25","author":"Shin","year":"2019","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"335","DOI":"10.3350\/cmh.2019.0010","article-title":"Detect or not to detect very early stage hepatocellular carcinoma? The western perspective","volume":"25","author":"Yang","year":"2019","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1002\/hep.29086","article-title":"AASLD guidelines for the treatment of hepatocellular carcinoma","volume":"67","author":"Heimbach","year":"2018","journal-title":"Hepatology"},{"unstructured":"European Association for the Study of the Liver (2018). EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J. Hepatol., 69, 182\u2013236.","key":"ref_32"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"223","DOI":"10.3350\/cmh.2018.0107","article-title":"Gadoxetic acid-enhanced magnetic resonance imaging: Hepatocellular carcinoma and mimickers","volume":"25","author":"Kim","year":"2019","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1038\/ajg.2014.157","article-title":"Prediction of development of liver-related events by transient elastography in hepatitis B patients with complete virological response on antiviral therapy","volume":"109","author":"Lee","year":"2014","journal-title":"Am. J. Gastroenterol."},{"key":"ref_35","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_36","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.jhep.2013.09.029","article-title":"Liver stiffness-based optimization of hepatocellular carcinoma risk score in patients with chronic hepatitis B","volume":"60","author":"Wong","year":"2014","journal-title":"J. Hepatol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1148\/radiol.2021202804","article-title":"Three-dimensional MR Elastography Depicts Liver Inflammation, Fibrosis, and Portal Hypertension in Chronic Hepatitis B or C","volume":"301","author":"Shi","year":"2021","journal-title":"Radiology"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/3\/711\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:11:13Z","timestamp":1760134273000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/3\/711"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,29]]},"references-count":37,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["cancers14030711"],"URL":"https:\/\/doi.org\/10.3390\/cancers14030711","relation":{},"ISSN":["2072-6694"],"issn-type":[{"type":"electronic","value":"2072-6694"}],"subject":[],"published":{"date-parts":[[2022,1,29]]}}}