Molecular mechanistic insight of hepatitis B virus mediated hepatocellular carcinoma

Chaturvedi, Vivek K.; Singh, Anshuman; Dubey, Shikha; Hetta, Helal F; John, James; Singh, Maneet

doi:10.1016/j.micpath.2019.01.004

Cited by 82 publications

(72 citation statements)

References 118 publications

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“…The intra-nuclear dslDNA HBV genomes can then be integrated into the host cell genome at the site of double-stranded DNA breaks via DNA repair pathways [24]. Integrated viral sequences are essential for the production of mutated HBx or preS2/S proteins, contributing to tumorigenesis [25]. The promotion of genomic instability as the result of both the integration of viral DNA into the host genome and the activity of viral proteins is one of the mechanisms that have been reported [25][26][27][28].…”

Section: Discussionmentioning

confidence: 99%

“…Integrated viral sequences are essential for the production of mutated HBx or preS2/S proteins, contributing to tumorigenesis [25]. The promotion of genomic instability as the result of both the integration of viral DNA into the host genome and the activity of viral proteins is one of the mechanisms that have been reported [25][26][27][28]. Another direct mechanism of HBV carcinogenesis is based on the ability of viral proteins (HBx, HBc, and preS) to affect cell functions, including cell proliferation and cell viability, and to sensitize liver cells to mutagens [25][26][27][28].…”

Section: Discussionmentioning

confidence: 99%

“…The promotion of genomic instability as the result of both the integration of viral DNA into the host genome and the activity of viral proteins is one of the mechanisms that have been reported [25][26][27][28]. Another direct mechanism of HBV carcinogenesis is based on the ability of viral proteins (HBx, HBc, and preS) to affect cell functions, including cell proliferation and cell viability, and to sensitize liver cells to mutagens [25][26][27][28]. The third reported mechanism is the insertional mutagenesis, which can integrate the viral DNA into host cancer genes (telomerase reverse transcriptase (TERT), myeloid/lymphoid or mixed-lineage leukemia 4 (MLL4), and cyclin E1 (CCNE1)).…”

Section: Discussionmentioning

confidence: 99%

“…The third reported mechanism is the insertional mutagenesis, which can integrate the viral DNA into host cancer genes (telomerase reverse transcriptase (TERT), myeloid/lymphoid or mixed-lineage leukemia 4 (MLL4), and cyclin E1 (CCNE1)). HBV can thus promote heptocarcinogenesis [25][26][27][28]. Previous studies have indicated that patients with HBV integration in the TERT gene had significantly poorer survival rates [28].…”

Section: Discussionmentioning

confidence: 99%

“…In the cytoplasm, HBx regulates protein degradation, cellular transcription, apoptosis, and cell proliferation. HBx stimulates the replication of HBV in the nucleus [25]. There are five suggested mechanisms through which HBx induces parthenogenesis [29].…”

Section: Discussionmentioning

confidence: 99%

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Chronic Hepatitis B Virus Infection Associated with Increased Colorectal Cancer Risk in Taiwanese Population

Muo

et al. 2020

Viruses

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Chronic hepatitis B virus (HBV) infections and colorectal cancer (CRC) are prevalent in Taiwan. We carried out a population-based case-control study to assess the association between HBV infection and CRC risk. Using the National Health Insurance Research Database of Taiwan, we identified 69,478 newly diagnosed patients with CRC from 2005 to 2011. We further randomly selected 69,478 age- and gender-matched controls without CRC from the same database. Odds ratios (ORs) were calculated to evaluate the association between chronic HBV infection and CRC using a logistic regression analysis. HBV infection was found to be associated with the risk of CRC (OR = 1.27, 95% confidence interval (CI) = 1.20–1.33). This relationship was similar in men and women. Age-specific analysis revealed that the CRC risk associated with HBV decreased with age. The adjusted ORs for patients aged <55, 55–64, and 65–74 years were 1.63 (95% CI = 1.48–1.79), 1.24 (95% CI = 1.13–1.37), and 1.02 (95% = 0.92–1.13), respectively. In conclusion, this study suggests that chronic HBV infection is significantly associated with an increased risk of CRC. Monitoring the risk of CRC development in young patients with HBV infection is crucial.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Chronic Hepatitis B Virus Infection Associated with Increased Colorectal Cancer Risk in Taiwanese Population

Muo

et al. 2020

Viruses

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Integrative analysis of highly mutated genes in hepatitis B virus‐related hepatic carcinoma

Kong

Yang

et al. 2020

Cancer Medicine

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Gene mutation is responsible for the development of hepatocellular carcinoma (HCC) with hepatitis B virus (HBV) infection; however, the characteristics and associated biological functions of highly mutated genes, in which the mutation frequencies are at least 5% in HCC patients with HBV infection, are not clearly evaluated. In the study, we analyzed the information regarding somatic mutation obtained by whole‐exome sequencing in 280 HBV‐related HCC tissues from public databases and published studies. Via integrative analysis, 78 genes, including TP53, TTN, MUC16, CTNNB1, and PCLO were summarized as highly mutated genes, and some of these mutated genes were further identified as cancer driver genes. Besides, we discovered that the highly mutated genes were enriched with various biological functions and pathways. The expression of many of highly mutated genes was found to be significantly altered in HBV‐related HCC, and several highly mutated genes were related to a variety of clinical factors and associated with the poor survival of the disease. Taken together, these results could enrich our understanding of highly mutated genes and their relationships with HBV‐related HCC. Some of the identified highly mutated genes might be used as novel biomarkers of disease prognosis, or as molecular targets for the treatment of HCC with HBV infection.

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A Semi‐mechanistic Model to Characterize the Long‐Term Dynamics of Hepatitis B Virus Markers During Treatment With Lamivudine and Pegylated Interferon

Messaoudi

Lemenuel‐Diot

Gonçalves

et al. 2023

Clin Pharma and Therapeutics

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Antiviral treatments against hepatitis B virus (HBV) suppress viral replication but do not eradicate the virus, and need therefore to be taken lifelong to avoid relapse. Mathematical models can be useful to support the development of curative anti-HBV agents; however, they mostly focus on short-term HBV DNA data and neglect the complex hostpathogen interaction. This work aimed to characterize the effect of treatment with lamivudine and/or pegylated interferon (Peg-IFN) in 1,300 patients (hepatitis B envelope antigen (HBeAg)-positive and HBeAg-negative) treated for 1 year. A mathematical model was developed incorporating two populations of infected cells, namely I 1 , with a high transcriptional activity, that progressively evolve into I 2 , at a rate tr , representing cells with integrated HBV DNA that have a lower transcriptional activity. Parameters of the model were estimated in patients treated with lamivudine or Peg-IFN alone (N = 894), and the model was then validated in patients treated with lamivudine plus Peg-IFN (N = 436) to predict the virological response after a year of combination treatment. Lamivudine had a larger effect in blocking viral production than Peg-IFN (99.4-99.9% vs. 91.8-95.1%); however, Peg-IFN had a significant immunomodulatory effect, leading to an enhancement of the loss rates of I 1 (×1.7 in HBeAg-positive patients), I 2 (> ×7 irrespective of HBeAg status), and tr (×4.6 and ×2.0 in HBeAg-positive and HBeAg-negative patients, respectively). Using this model, we were able to describe the synergy of the different effects occurring during treatment with combination and predicted an effect of 99.99% on blocking viral production. This framework can therefore support the optimization of combination therapy with new anti-HBV agents.Chronic hepatitis B virus (CHB) infection is a leading cause of liver disease, including cirrhosis and hepatocellular carcinoma. In 2021, nearly 300 million people were chronically infected worldwide, resulting in more than 800,000 deaths. 1 To reduce disease progression, antiviral treatments rely on two therapeutic classes, nucleoside analogs (NUCs) and pegylated interferons (Peg-IFNs), which are

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Molecular mechanistic insight of hepatitis B virus mediated hepatocellular carcinoma

Cited by 82 publications

References 118 publications

Chronic Hepatitis B Virus Infection Associated with Increased Colorectal Cancer Risk in Taiwanese Population

Chronic Hepatitis B Virus Infection Associated with Increased Colorectal Cancer Risk in Taiwanese Population

Integrative analysis of highly mutated genes in hepatitis B virus‐related hepatic carcinoma

A Semi‐mechanistic Model to Characterize the Long‐Term Dynamics of Hepatitis B Virus Markers During Treatment With Lamivudine and Pegylated Interferon

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