scholarly journals How to Clear HBV cccDNA: CRISPR/Cas9 Might Be Promising

2017 ◽  
Author(s):  
Yan Qiu ◽  
Ying Liu ◽  
Wen Ren ◽  
Jing Ren
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Health Concern ◽  
Liver Carcinoma ◽  
Major Health ◽  
Circular Dna ◽  
Hbv Cccdna ◽  
B Virus

BACKGROUND: Chronic hepatitis B infected with Hepatitis B virus remains a major health concern worldwide. Despite standard interferon-α and nucleotide analogues have been shown to reduce the deterioration of liver disease among chronic hepatitis B patients, covalently closed circular DNA was still difficult to eradicate. METHODS: A literature search of Pubmed and Web of science was performed with the following key words: ‘CRISPR’, ‘CRISPR/Cas9’, ‘hepatitis B’, ‘HBV’, ‘chronic hepatitis B’ and ‘HBV cccDNA’. The information about CRISPR/Cas9 for the treatment of HBV cccDNA or hepatitis B was reviewed. RESULTS: CRISPR/Cas9 could treat hepatitis B through suppressing or clearing HBV cccDNA with different gRNAs. CONCLUSION: With the emergence of CRISPR/Cas9 (the RNA-guided clustered regulatory interspaced short palindromic repeats, CRISPR) editing technology, clearance of hepatitis B virus and better prevention of liver carcinoma seemed to be possible.

scholarly journals Clinical Implications of Hepatitis B Virus RNA and Covalently Closed Circular DNA in Monitoring Patients with Chronic Hepatitis B Today with a Gaze into the Future: The Field Is Unprepared for a Sterilizing Cure

Genes ◽  
2018 ◽  
Vol 9 (10) ◽  
pp. 483 ◽  
Author(s):  
Anastasiya Kostyusheva ◽  
Dmitry Kostyushev ◽  
Sergey Brezgin ◽  
Elena Volchkova ◽  
Vladimir Chulanov
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Splice Variants ◽  
Clinical Implications ◽  
Circular Dna ◽  
Covalently Closed Circular Dna ◽  
Chronic Hepatitis B Virus ◽  
B Virus

. Chronic hepatitis B virus (HBV) infection has long remained a critical global health issue. Covalently closed circular DNA (cccDNA) is a persistent form of the HBV genome that maintains HBV chronicity. Decades of extensive research resulted in the two therapeutic options currently available: nucleot(s)ide analogs and interferon (IFN) therapy. A plethora of reliable markers to monitor HBV patients has been established, including the recently discovered encapsidated pregenomic RNA in serum, which can be used to determine treatment end-points and to predict the susceptibility of patients to IFN. Additionally, HBV RNA splice variants and cccDNA and its epigenetic modifications are associated with the clinical course and risks of hepatocellular carcinoma (HCC) and liver fibrosis. However, new antivirals, including CRISPR/Cas9, APOBEC-mediated degradation of cccDNA, and T-cell therapies aim at completely eliminating HBV, and it is clear that the diagnostic arsenal for defining the long-awaited sterilizing cure is missing. In this review, we discuss the currently available tools for detecting and measuring HBV RNAs and cccDNA, as well as the state-of-the-art in clinical implications of these markers, and debate needs and goals within the context of the sterilizing cure that is soon to come.

scholarly journals Correlation of HBcrAg with Intrahepatic Hepatitis B Virus Total DNA and Covalently Closed Circular DNA in HBeAg-Positive Chronic Hepatitis B Patients

2018 ◽  
Vol 57 (1) ◽  
Author(s):  
Lin Wang ◽  
Xi Cao ◽  
Zhenzi Wang ◽  
Yuhua Gao ◽  
Juan Deng ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hbv Dna ◽  
Circular Dna ◽  
Hbv Cccdna ◽  
B Virus ◽  
Positive Chronic Hepatitis ◽  
Total Dna ◽  
Intrahepatic Hbv

ABSTRACT The purpose of this study was to explore the correlations of serum hepatitis B core-related antigen (HBcrAg) with intrahepatic Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) and HBV total DNA in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients. Serum HBcrAg and other parameters, including HBV DNA, HBV RNA, HBeAg, hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were quantitatively measured at baseline and follow-up time points. Intrahepatic HBV cccDNA and total DNA were quantitatively detected at baseline and 96 weeks. Grading of liver necroinflammation and staging of hepatic fibrosis were assessed at baseline and 96 weeks. Correlations between serum HBcrAg and other parameters were analyzed by Pearson’s correlation analysis. The results showed that pretreatment HBcrAg correlated significantly with HBV total DNA levels (r = 0.328, P = 0.003) in 82 CHB patients, and, after removing three outliers, with intrahepatic HBV cccDNA (r = 0.323, P = 0.004; n = 79). Serum HBcrAg correlated better with HBV cccDNA in patients with lower levels of serum HBV DNA (stratified by 7 log IU/ml of HBV DNA; r = 0.656, P = 0.003 versus r = −0.02, P = 0.866). Significant inverse correlations were found between HBcrAg and grade of liver necroinflammation (r = −0.245, P = 0.037), stage of hepatic fibrosis (r = −0.360, P = 0.002) at baseline. Serum HBcrAg presented significant correlation with intrahepatic HBV cccDNA in patients with HBeAg seroconversion at 96 weeks (r = 0.622, P = 0.006). The decrease in HBcrAg showed significant correlation with the decrease in HBV cccDNA after 96-week NA therapy (r = 0.282, P = 0.043). Serum HBcrAg also correlated significantly with other serum markers at baseline and 96 weeks of NA therapy. In conclusion, baseline HBcrAg and its decreased value were significantly correlated with the corresponding intrahepatic HBV cccDNA.

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