ReviewBiomedicines2026
HBx-Associated Reactivation of the IGF2 Locus in Chronic HBV Infection and HBV-Related Hepatocarcinogenesis: Evidence Boundaries and Biomarker Implications.
Review in Biomedicines, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
0 citing papers in PubMed.
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Corrections and comments
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Authors and funding
2 authors.
Funding
Abstract
Chronic hepatitis B virus (HBV) infection remains one of the main causes of hepatocellular carcinoma (HCC), even though vaccination and long-term viral suppression have reduced new infections and circulating viral replication. This residual cancer risk suggests that serum HBV DNA alone does not capture the full biology of HBV-related carcinogenesis. Hepatitis B virus X protein (HBx) is a relevant entry point because it maintains the transcriptional competence of covalently closed circular DNA (cccDNA), engages host chromatin regulators, and may persist in tumors as cccDNA-derived, integration-derived, full-length, truncated, or fusion forms. This review focuses on a specific question: does the available literature support HBx-associated reactivation of the IGF2 locus in chronic HBV infection and HBV-related hepatocarcinogenesis, and, if so, at which regulatory layer is the claim defensible? The most direct evidence remains promoter-proximal. Classic mechanistic work shows acute HBx-dependent activation of IGF2 promoter P4 through Sp1- and PKC/ERK-dependent signaling. Human tissue and cell-based studies also support a broader fetal-promoter compartment, including P3/P4 transcript enrichment, local promoter hypomethylation, MBD2-HBx-CBP/p300 recruitment, and increased histone H3/H4 acetylation. These observations do not, however, establish HBV exclusivity, uniform loss of imprinting, or direct HBx-mediated rewiring of the human IGF2/H19 topological domain. Recent integration-aware and long-read studies further argue against treating tumor-stage HBx as a single biological variable. In the present evidence framework, HBx-associated IGF2 locus reactivation is therefore more appropriately viewed as a stage-aware, promoter-resolved, biomarker-oriented hypothesis than as a universal mechanism or a treatment algorithm for HBV-related HCC.
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Registered trials
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