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However, some patients cannot be classified into one of the stages and are said to fall into an \u2018indeterminate phase\u2019 or \u2018grey zone\u2019. Exact definitions of the indeterminate phase vary from guideline to guideline as a result of different cut\u2010off values for biomarker measurements. Data suggest that as many as 50% of HBV patients may be in an indeterminate phase and may not rapidly transition out of this phase. Clinical data that suggest these patients are at increased risk of hepatocellular carcinoma (HCC) are complemented by molecular evidence of integrations of HBV\u2010DNA into the host genome, chromosomal translocations and immune activation despite liver enzymes that may suggest lack of inflammation. Antiviral therapy reduces these hepatocarcinogenic mechanisms and is reflected in a reduction of fibrosis and HCC risk. We review key data on patients in the indeterminate phase, with emphasis on HCC as an outcome. We take a holistic approach and link new biological data with clinical observations as well as examine the potential role of antiviral therapy in reducing HCC risk among patients in the indeterminate phase. With the availability of safe and effective oral antivirals, consideration must be given as to how much residual risk of HCC should be tolerated among patients in the indeterminate phase.<\/jats:p>","DOI":"10.1111\/jvh.13914","type":"journal-article","created":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T12:41:37Z","timestamp":1715172097000},"page":"27-35","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Hepatocellular carcinoma among patients with chronic hepatitis B in the indeterminate phase"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2266-3935","authenticated-orcid":false,"given":"Lung\u2010Yi","family":"Mak","sequence":"first","affiliation":[{"name":"Department of Medicine, Queen Mary Hospital The University of Hong Kong  Hong Kong Special Administrative Region China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0369-5878","authenticated-orcid":false,"given":"Leland J.","family":"Yee","sequence":"additional","affiliation":[{"name":"Gilead Sciences  Foster City California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8923-2806","authenticated-orcid":false,"given":"Robert J.","family":"Wong","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Stanford University School of Medicine  Palo Alto California USA"},{"name":"Division of Gastroenterology and Hepatology Veterans Affairs Palo Alto Health Care System  Palo Alto California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian B.","family":"Ramers","sequence":"additional","affiliation":[{"name":"Laura Rodriguez Research Institute Family Health Centers of San Diego  San Diego California USA"},{"name":"University of California San Diego School of Medicine  La Jolla California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine","family":"Frenette","sequence":"additional","affiliation":[{"name":"Gilead Sciences  Foster City California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8984-5103","authenticated-orcid":false,"given":"Yao\u2010Chun","family":"Hsu","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology E\u2010Da Hospital  Kaohsiung Taiwan"},{"name":"School of Medicine, College of Medicine I\u2010Shou University  Kaohsiung Taiwan"},{"name":"Institute of Biomedical Informatics National Yang Ming Chiao Tung University  Taipei Taiwan"},{"name":"Division of Gastroenterology and Hepatology Fu\u2010Jen Catholic University Hospital  New Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,5,8]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-023-00760-9"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(23)00197-8"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.36.2335"},{"key":"e_1_2_10_5_1","unstructured":"Foundation HB.Hepatitis B Facts and Figures. 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