Abdulrahman MS, Aboelmagd O, Zhang Y, Zaky S, Johar D. Precore/core mutation relatedness to viral reactivation in patients undergoing targeted therapy for hepatitis B virus-related hepatocellular carcinoma. World J Biol Chem 2026; 17(2): 120297 [DOI: 10.4331/wjbc.v17.i2.120297]
Corresponding Author of This Article
Dina Johar, PhD, Department of Biochemistry and Nutrition, Faculty of Women for Arts, Sciences and Education, Ain Shams University, Asma Fahme Street, Cairo 11757, Egypt. dinajohar@gu.edu.eg
Research Domain of This Article
Gastroenterology & Hepatology
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review-article
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Abdulrahman MS, Aboelmagd O, Zhang Y, Zaky S, Johar D. Precore/core mutation relatedness to viral reactivation in patients undergoing targeted therapy for hepatitis B virus-related hepatocellular carcinoma. World J Biol Chem 2026; 17(2): 120297 [DOI: 10.4331/wjbc.v17.i2.120297]
World J Biol Chem. Jun 5, 2026; 17(2): 120297 Published online Jun 5, 2026. doi: 10.4331/wjbc.v17.i2.120297
Precore/core mutation relatedness to viral reactivation in patients undergoing targeted therapy for hepatitis B virus-related hepatocellular carcinoma
Mohammed S Abdulrahman, Omnia Aboelmagd, Ying Zhang, Samy Zaky, Dina Johar
Mohammed S Abdulrahman, Department of Microbiology and Immunology, Faculty of Pharmacy, Al-Azhar University, Cairo 11651, Egypt
Mohammed S Abdulrahman, Department of Microbiology and Immunology, Faculty of Pharmacy, Menoufia National University, Menoufia 32658, Egypt
Omnia Aboelmagd, Department of Psychiatry, Faculty of Medicine, Cairo University, Cairo 11562, Egypt
Ying Zhang, School of Basic Medical Sciences, Binzhou Medical University, Yantai 264003, Shandong Province, China
Samy Zaky, Department of Hepatogastroenterology and Infectious Diseases, Faculty of Medicine, Al-Azhar University, Cairo 11651, Egypt
Dina Johar, Department of Biochemistry and Nutrition, Faculty of Women for Arts, Sciences and Education, Ain Shams University, Cairo 11757, Egypt
Author contributions: Johar D, Aboelmagd O contributed to conception, design, acquisition of data, literature analysis, discussion, writing and reviewing the manuscript; Abdulrahman MS, Zhang Y, Zaky S contributed to discussion, visualization, reviewing and editing the manuscript. All authors have read and approved the final manuscript for submission.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Dina Johar, PhD, Department of Biochemistry and Nutrition, Faculty of Women for Arts, Sciences and Education, Ain Shams University, Asma Fahme Street, Cairo 11757, Egypt. dinajohar@gu.edu.eg
Received: February 25, 2026 Revised: April 20, 2026 Accepted: May 26, 2026 Published online: June 5, 2026 Processing time: 101 Days and 19.9 Hours
Abstract
Hepatitis B virus (HBV) reactivation after targeted therapy or immunomodulating therapy leads to active or fulminant hepatitis, low response to prophylactic vaccination, premature discharge from therapy and death. The hypothesis that seroreactive viral infection is caused by mutation/s in the precore/core is invaluable to elucidating the mechanisms of HBV reactivation. Precore/core mutations may correlate with, or predict susceptibility to seroreactivation in HBV-related hepatocellular carcinoma (HCC) patients receiving targeted therapy. This review’s 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.
Core Tip: Current antiviral treatments can slow down hepatitis B virus (HBV) replication and help improve liver damage. However, they rarely fully clear chronic HBV infections. There is an urgent need for new drugs and better strategies to combat the virus. The hypothesis that seroreactive viral infection is caused by mutation/s in the precore/core is invaluable to elucidating the mechanisms of HBV reactivation. This review re-analyzes clinically significant HBV precore/core mutations affecting pregenomic RNA initiation and synthesis, and their regulation of viral and cellular gene expressions. Further, it analyzes the effects of antivirals lamivudine, entecavir, tenofovir alafenamide, and immune-based strategies on viral reactivation after treatment.
