Epigenetic regulation of hepatitis B virus covalently closed circular DNA: Implications for epigenetic therapy against chronic hepatitis B

Hong, Xupeng; Kim, Elena S.; Guo, Haitao

doi:10.1002/hep.29479

Cited by 171 publications

(180 citation statements)

References 75 publications

(199 reference statements)

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“…Hepatitis B virus (HBV) infection is an important factor for HCC occurrence. The association between HBV and HCC has been demonstrated by multiple epidemiological studies: High HBV prevalence may result in a high frequency of occurrence of HCC, and the risk of HCC in HBV carriers is significantly increased compared with that of non-carriers [10]. Thus, the occurrence of hepatocellular carcinoma (HCC) is decreased but not eliminated.…”

Section: Introductionmentioning

confidence: 99%

Circulating LncRNAs Serve as Diagnostic Markers for Hepatocellular Carcinoma

Yuan¹,

Sun²,

Liu³

et al. 2017

Cell Physiol Biochem

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Background/Aims: Circulating (serous or plasmic) long non-coding RNA (lncRNA) as biomarkers for predicting the diagnosis or prognosis of human disease have been well documented. Due to the sensibility or specificity limitation of Alpha Fetoprotein (AFP), a cluster lncRNAs were revealed as fingerprints for hepatocellular carcinoma (HCC). In this study, we enrolled all the reported circulating lncRNAs in HCC as candidate targets and examined in an independent cohort. Methods: The candidate lncRNAs were determined by qRT-PCR divided into training and validation sets. The risk score analysis was employed to evaluate the potential diagnosis ability of the lncRNAs independently or combining with AFP value. The receiver operating characteristic curve (ROC) was applied for presentation of sensibility or specificity. Results: Among the ten candidate circulating lncRNA, LINC00152, RP11-160H22.5, XLOC014172 and LOC149086 were screened with significant difference in training set. Further investigation in validation set indicated LINC00152, RP11-160H22.5 and XLOC014172 might be the fingerprints for HCC comparing with chronic hepatitis (CH) patients or healthy controls. The risk score analysis revealed the combination of three lncRNAs with AFP could distinguish the HCC from either CH or healthy control with the area under curve value (AUC) of 0.986 and 0.985, respectively. Conclusion: The three lncRNAs may act as novel biomarkers for acting as fingerprint in HCC combining with AFP.

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Section: Introductionmentioning

confidence: 99%

Circulating LncRNAs Serve as Diagnostic Markers for Hepatocellular Carcinoma

Yuan¹,

Sun²,

Liu³

et al. 2017

Cell Physiol Biochem

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“…The amount and transcriptional activity of cccDNA are important for evaluating disease activity and treatment response. The cccDNA pool is highly stable in the hepatocyte nucleus because cccDNA is hard to eliminate and new hepatocytes are infected persistently . In the presence of an inadequate immune system and without suitable drug, a small amount of cccDNA may cause a comprehensive HBV infection or CHB relapse.…”

Section: Application Of Viral Markers In Chb Clinical Practicementioning

confidence: 99%

Insights for clinical diagnostic indicators of virus and host in chronic hepatitis B infection

Guo

Zeng

et al. 2020

Journal of Viral Hepatitis

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Covalently closed circular DNA (cccDNA), which is stably present in the nucleus of hepatocytes, is an important indicator for evaluating antiviral efficacy. Since cccDNA quantification requires an invasive procedure, serum biological markers that can effectively reflect the transcriptional activity of intrahepatic virus and the efficacy of treatment are required. Here, from the aspects of virus and host, we outline the focus of clinical research of HBV in recent years, including HBV RNA, empty virus, hepatitis B core‐related antigen and changes in the immune response. We briefly discuss their significance in predicting disease activity and monitoring treatment response in chronic hepatitis B. On this basis, some issues worthy of attention in laboratory diagnosis are proposed.

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“…In contrast, inhibition of HBx binding to cccDNA leads to suppression of its transcription and virus replication by modifying the epigenetic regulation of cccDNA function with host restriction factors, including Smc5/6 complex and protein arginine methyltransferase PRMT1. HBV core inhibitors targeting cccDNA‐bound HBc may potentially alter the epigenetics of cccDNA and in combination with HBx inhibitors could in theory lead to a stronger synergistic effect on cccDNA transcriptional silencing and HBV replication …”

Section: Novel Therapeutic Strategies In Developmentmentioning

confidence: 99%

Towards HBV curative therapies

Schinazi

Ehteshami

Bassit

et al. 2018

Liver International

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Tremendous progress has been made over the last 2 decades to discover and develop approaches to control hepatitis B virus (HBV) infections and to prevent the development of hepatocellular carcinoma using various interferons and small molecules as antiviral agents. However, none of these agents have significant impact on eliminating HBV from infected cells. Currently the emphasis is on silencing or eliminating cccDNA, which could lead to a cure for HBV. Various approaches are being developed including the development of capsid effectors, CRISPR/Cas9, TALENS, siRNA, entry and secretion inhibitors, as well as immunological approaches. It is very likely that a combination of these modalities will need to be employed to successfully eliminate HBV or prevent virus rebound on discontinuation of therapy. In the next 5 years clinical data will emerge which will provide insight on the safety and feasibility of these approaches and if they can be applied to eradicate HBV infections globally. In this review, we summarize current treatments and we highlight and examine recent therapeutic strategies that are currently being evaluated at the preclinical and clinical stage. K E Y W O R D Santiviral agents, cccDNA, HBV cure, immunotherapy

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Epigenetic regulation of hepatitis B virus covalently closed circular DNA: Implications for epigenetic therapy against chronic hepatitis B

Cited by 171 publications

References 75 publications

Circulating LncRNAs Serve as Diagnostic Markers for Hepatocellular Carcinoma

Circulating LncRNAs Serve as Diagnostic Markers for Hepatocellular Carcinoma

Insights for clinical diagnostic indicators of virus and host in chronic hepatitis B infection

Towards HBV curative therapies

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