Hepatitis B Virus DNA Integration Drives Carcinogenesis and Provides a New Biomarker for HBV-related HCC

Yeh, Shiou–Hwei; Li, Chiao-Ling; Lin, Yu‐Hui; Ho, Ming-Chih; Wang, Ya-Chun; Tseng, Sheng-Tai; Chen, Pei‐Jer

doi:10.1016/j.jcmgh.2023.01.001

Cited by 24 publications

(16 citation statements)

References 72 publications

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“…As HBV integrations may be specific biomarkers for prediction of clinical outcomes, However, rapid, reliable and stable HBV integration site detection processes are rare [ 26 ]. In this study, a new HBV integration site detection tool based on feature coding called ViroISDC is presented, which is a natural language processing method.…”

Section: Discussionmentioning

confidence: 99%

ViroISDC: a method for calling integration sites of hepatitis B virus based on feature encoding

Qiao,

Li,

Lin

et al. 2024

BMC Bioinformatics

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Background Hepatitis B virus (HBV) integrates into human chromosomes and can lead to genomic instability and hepatocarcinogenesis. Current tools for HBV integration site detection lack accuracy and stability. Results This study proposes a deep learning-based method, named ViroISDC, for detecting integration sites. ViroISDC generates corresponding grammar rules and encodes the characteristics of the language data to predict integration sites accurately. Compared with Lumpy, Pindel, Seeksv, and SurVirus, ViroISDC exhibits better overall performance and is less sensitive to sequencing depth and integration sequence length, displaying good reliability, stability, and generality. Further downstream analysis of integrated sites detected by ViroISDC reveals the integration patterns and features of HBV. It is observed that HBV integration exhibits specific chromosomal preferences and tends to integrate into cancerous tissue. Moreover, HBV integration frequency was higher in males than females, and high-frequency integration sites were more likely to be present on hepatocarcinogenesis- and anti-cancer-related genes, validating the reliability of the ViroISDC. Conclusions ViroISDC pipeline exhibits superior precision, stability, and reliability across various datasets when compared to similar software. It is invaluable in exploring HBV infection in the human body, holding significant implications for the diagnosis, treatment, and prognosis assessment of HCC.

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Section: Discussionmentioning

confidence: 99%

ViroISDC: a method for calling integration sites of hepatitis B virus based on feature encoding

Qiao,

Li,

Lin

et al. 2024

BMC Bioinformatics

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“… 13 – 16 HCC from chronic hepatitis B infection is a result of the pro-oncogenic properties of the virus that can occur both directly ( integration of the virus genome in the host DNA) and indirectly because of rounds of liver cell necrosis and regeneration. 17 – 20 HBV infection is often acquired perinatally in Asia; therefore, older age usually means long-standing infection and increases HCC risk by both the direct and indirect mechanisms. Our study suggested that achieving recompensation can attenuate but not completely eliminate the occurrence of HCC.…”

Section: Discussionmentioning

confidence: 99%

Risk of HCC decreases in HBV-related patients with cirrhosis acquired recompensation: A retrospective study based on Baveno VII criteria

Zhang,

Liu,

et al. 2023

Hepatology Communications

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Background: Antiviral therapy improves the clinical outcomes of patients with HBV-related cirrhosis. In this study, we aimed to evaluate the incidence rate of HCC in patients with HBV-related recompensated, compensated, or decompensated cirrhosis based on the latest Baveno VII criteria. Methods: In this two-center retrospective study, HBV-related patients with cirrhosis were enrolled and treated with first-line nucleos(t)ide analogues therapy for at least 12 months. Participants were classified into 3 groups: (1) compensated group, (2) decompensated group, or (3) recompensated group according to Baveno VII criteria. Multivariate regression models and propensity score matching were used to identify the predictors of HCC. Results: Of the 404 patients recruited, during a median follow-up of 44.5 months (interquartile range 26.8, 57.0 months), 233 (57.7%), 100 (24.8%), and 71(17.6%) patients had compensated, recompensated, and decompensated cirrhosis. In total, 38 developed HCC. The cumulative incidence of HCC development at 2, 4, and 6 years was 1.3%, 5.4%, and 20.0% in the compensated group, 1.2%, 5.2%, and 24.5% in the recompensated group, and 2.1%, 23.6%, and 41.8% in the decompensated group, respectively. In the multivariate Cox regression model, compared with the recompensated group, the decompensated group had a significant increased risk for the development of HCC (aHR 2.55; 95% CI: 1.240–5.240; p = 0.027), while the compensated group had similar HCC risk for the development of HCC (aHR 1.41; 95% CI: 0.540–3.730; p = 0.835). Propensity score-matching analysis between the recompensated and compensated groups (84 pairs) and propensity score-matching analysis between the recompensated and decompensated groups (62 pairs) showed similar results. Conclusions: Achieving recompensation reduced the risk of HCC in patients with HBV-related decompensated cirrhosis, while the risk remained comparable to that of compensated cirrhosis.

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“…By regulating its gene expression, HBV genome integration is a key step in HBVinduced hepatocarcinogenesis (Figure 2) [86,87]. Indeed, the integration of HBV DNA into the host cell genome has shown a close association with the risk of HCC.…”

Section: Hbv-host Interactions In Oncogenesismentioning

confidence: 99%

HBV Infection and Host Interactions: The Role in Viral Persistence and Oncogenesis

Nevola

Beccia

Rosato³

et al. 2023

IJMS

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Hepatitis B virus (HBV) is a major cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Despite the advent of vaccines and potent antiviral agents able to suppress viral replication, recovery from chronic HBV infection is still an extremely difficult goal to achieve. Complex interactions between virus and host are responsible for HBV persistence and the risk of oncogenesis. Through multiple pathways, HBV is able to silence both innate and adaptive immunological responses and become out of control. Furthermore, the integration of the viral genome into that of the host and the production of covalently closed circular DNA (cccDNA) represent reservoirs of viral persistence and account for the difficult eradication of the infection. An adequate knowledge of the virus–host interaction mechanisms responsible for viral persistence and the risk of hepatocarcinogenesis is necessary for the development of functional cures for chronic HBV infection. The purpose of this review is, therefore, to analyze how interactions between HBV and host concur in the mechanisms of infection, persistence, and oncogenesis and what are the implications and the therapeutic perspectives that follow.

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Hepatitis B Virus DNA Integration Drives Carcinogenesis and Provides a New Biomarker for HBV-related HCC

Cited by 24 publications

References 72 publications

ViroISDC: a method for calling integration sites of hepatitis B virus based on feature encoding

ViroISDC: a method for calling integration sites of hepatitis B virus based on feature encoding

Risk of HCC decreases in HBV-related patients with cirrhosis acquired recompensation: A retrospective study based on Baveno VII criteria

HBV Infection and Host Interactions: The Role in Viral Persistence and Oncogenesis

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