{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T07:15:20Z","timestamp":1789802120425,"version":"4.0.1"},"reference-count":33,"publisher":"The Korean Association for the Study of the Liver","issue":"2","license":[{"start":{"date-parts":[[2020,12,3]],"date-time":"2020-12-03T00:00:00Z","timestamp":1606953600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/3.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2019R1A2C4070136"],"award-info":[{"award-number":["2019R1A2C4070136"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Science and ICT"}],"content-domain":{"domain":["e-cmh.org"],"crossmark-restriction":true},"short-container-title":["Clin Mol Hepatol"],"published-print":{"date-parts":[[2021,4,1]]},"abstract":"<jats:p>Background\/Aims: The immune-tolerant (IT) phase of chronic hepatitis B (CHB) patients is not generally indicative of antiviral therapy (AVT). We assessed and compared the risk of hepatocellular carcinoma (HCC) during the IT-phase stringently defined by a low fibrosis-4 (FIB-4) index, compared to that in patients undergoing AVT.Methods: Among 125 untreated patients that were hepatitis B e-antigen positive, hepatitis B virus-DNA &gt;20,000 IU\/mL, with normal alanine aminotransferase level from 2012 to 2018, those with a FIB-4 index of &lt;1.45 were classified into the IT-group. The cumulative probability of HCC was estimated using Kaplan-Meier analysis. All patients were assessed until HCC development (intention-to-treat [ITT] analysis), whereas those suspected of experiencing CHB phase switch were assessed using the per-protocol (PP) and censored at the time of phase switch.Results: The cumulative probability of HCC at 1-, 3-, and 5-years among the IT-group was zero, compared to AVT-treated patients with FIB-4 indices &lt;1.45 during the same period: 0.2%, 0.6%, and 1.4%, respectively (P=0.264 for ITT and P=0.533 for PP). Among the initially screened 125 untreated patients, those with a FIB-4 index of \u22651.45 had a higher risk of HCC compared to the IT-group (P=0.005). Furthermore, among AVT-treated patients, those with a FIB-4 index of \u22651.45 had a higher risk of HCC compared to their counterpart (P&lt;0.001).Conclusions: The risk of HCC was negligible in the IT-group stringently defined by a low FIB-4 index. However, given that a higher HCC risk exists among untreated patients with higher FIB-4, appropriate criteria for AVT should be established.<\/jats:p>","DOI":"10.3350\/cmh.2020.0216","type":"journal-article","created":{"date-parts":[[2020,12,15]],"date-time":"2020-12-15T07:09:46Z","timestamp":1608016186000},"page":"295-304","update-policy":"https:\/\/doi.org\/10.3350\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Negligible risks of hepatocellular carcinoma during biomarker-defined immune-tolerant phase for patients with chronic hepatitis B"],"prefix":"10.3350","volume":"27","author":[{"given":"Mi Young","family":"Jeon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beom Kyung","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae 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