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This review\u2019s objective is to re-analyze the relationship between the precore\/core mutations of HBV-DNA and HBV reactivation in HCC patients receiving targeted therapy. Further, to re-analyze clinically significant precore\/core mutations affecting pregenomic RNA initiation and synthesis, and their regulation of viral and cellular gene expressions. This review shed light on the mechanism of HBV reactivation. We analyze the effects of antivirals lamivudine, entecavir, tenofovir alafenamide, tenofovir disoproxil fumarate and immune-based strategies on reactivation after treatment for HBV-related HCC. We proposed future directions for studying mutations in the precore\/core region that are likely to cause relapse. This review recommends comparing the genome\/proteome of blood from overt and relapsed HCC-related chronic HBV patients. This helps identifying persistent genetic\/epigenetic profiles of HBV resistant variants, thus accurately selecting the appropriate antiviral therapy and eliminating the risk of viral reactivation.<\/jats:p>","DOI":"10.4331\/wjbc.v17.i2.120297","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:48:20Z","timestamp":1780447700000},"source":"Crossref","is-referenced-by-count":0,"title":["Precore\/core mutation relatedness to viral reactivation in patients undergoing targeted therapy for hepatitis B virus-related hepatocellular carcinoma"],"prefix":"10.4331","volume":"17","author":[{"given":"Mohammed S","family":"Abdulrahman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omnia","family":"Aboelmagd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samy","family":"Zaky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dina","family":"Johar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2060","published-online":{"date-parts":[[2026,6,5]]},"reference":[{"key":"B1","unstructured":"World Health Organization.   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