ArticleClinical and molecular hepatology2021
Persistence of intrahepatic hepatitis B virus DNA integration in patients developing hepatocellular carcinoma after hepatitis B surface antigen seroclearance.
Article in Clinical and molecular hepatology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- KASL clinical practice guidelines for management of chronic hepatitis B.Clinical and molecular hepatology · 2022Guideline
- Efficacy of Antiviral Prophylaxis up to 6 or 12 Months From Completion of Rituximab in Resolved Hepatitis B Patients: A Multicenter, Randomized Study.Journal of Korean medical science · 2023Trial
- The Investigation of Hepatitis B Vaccine Immune Responses in Occult Hepatitis B Virus-Infected Patients.Frontiers in immunology · 2022Trial
- KASL clinical practice guidelines for management of chronic hepatitis B Endorsed by the East Asia Liver Alliance (EALA).Clinical and molecular hepatology · 2026Article
- Article
- Prediction of long-term HBsAg seroclearance in patients with HBeAg-negative chronic hepatitis B.JHEP reports : innovation in hepatology · 2025Article
- Statistical Cure After Hepatectomy for Hepatitis B Virus-Associated Hepatocellular Carcinoma: A Risk-Stratification Model.Annals of surgical oncology · 2025Article
- Male preference for TERT alterations and HBV integration in young-age HBV-related HCC: implications for sex disparity.Clinical and molecular hepatology · 2025Article
- Update on the treatment navigation for functional cure of chronic hepatitis B: Expert consensus 2.0.Clinical and molecular hepatology · 2025Review
- Surveillance Following Hepatitis B Surface Antigen Loss: An Issue Requiring Attention.Pathogens (Basel, Switzerland) · 2024Review
- Core protein inhibitors: Opportunities and challenges at the forefront of hepatitis B cure: Editorial on "Phase 1 trial of the safety, pharmacokinetics, and antiviral activity of EDP-514 in untreated viremic chronic hepatitis B patients".Clinical and molecular hepatology · 2024Article
- The impact of integrated hepatitis B virus DNA on oncogenesis and antiviral therapy.Biomarker research · 2024Review
- Detection of HBV DNA integration in plasma cell-free DNA of different HBV diseases utilizing DNA capture strategy.Virologica Sinica · 2024Article
- Hepatocellular carcinoma in HBsAg seroclearance: clinical features, recurrence, and prognosis following curative hepatectomy.Therapeutic advances in medical oncology · 2024Article
- Reduction in Intrahepatic cccDNA and Integration of HBV in Chronic Hepatitis B Patients with a Functional Cure.Journal of clinical and translational hepatology · 2023Article
- The role of different viral biomarkers on the management of chronic hepatitis B.Clinical and molecular hepatology · 2023Review
- Effects of hepatitis B virus infection and strategies for preventing mother-to-child transmission on maternal and fetal T-cell immunity.Frontiers in immunology · 2023Review
- Suboptimal Performance of Hepatocellular Carcinoma Prediction Models in Patients with Hepatitis B Virus-Related Cirrhosis.Diagnostics (Basel, Switzerland) · 2022Article
- Article
- Hepatitis B virus DNA integration as a novel biomarker of hepatitis B virus-mediated pathogenetic properties and a barrier to the current strategies for hepatitis B virus cure.Frontiers in microbiology · 2022Review
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND/
aimsThe role of hepatitis B virus (HBV) integration into the host genome in hepatocarcinogenesis following hepatitis B surface antigen (HBsAg) seroclearance remains unknown. Our study aimed to investigate and characterize HBV integration events in chronic hepatitis B (CHB) patients who developed hepatocellular carcinoma (HCC) after HBsAg seroclearance.
methodsUsing probe-based HBV capturing followed by next-generation sequencing technology, HBV integration was examined in 10 samples (seven tumors and three non-tumor tissues) from seven chronic carriers who developed HCC after HBsAg loss. Genomic locations and patterns of HBV integration were investigated.
resultsHBV integration was observed in six patients (85.7%) and eight (80.0%) of 10 tested samples. HBV integration breakpoints were detected in all of the non-tumor (3/3, 100%) and five of the seven (71.4%) tumor samples, with an average number of breakpoints of 4.00 and 2.43, respectively. Despite the lower total number of tumoral integration breakpoints, HBV integration sites in the tumors were more enriched within the genic area. In contrast, non-tumor tissues more often showed intergenic integration. Regarding functions of the affected genes, tumoral genes with HBV integration were mostly associated with carcinogenesis. At enrollment, patients who did not remain under regular HCC surveillance after HBsAg seroclearance had a large HCC, while those on regular surveillance had a small HCC.
conclusionThe biological functions of HBV integration are almost comparable between HBsAg-positive and HBsAgserocleared HCCs, with continuing pro-oncogenic effects of HBV integration. Thus, ongoing HCC surveillance and clinical management should continue even after HBsAg seroclearance in patients with CHB.
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