scholarly journals Serum HBV RNA composition dynamics as a marker for intrahepatic HBV cccDNA turnover

2020 ◽  
Vol 92 (8) ◽  
pp. 935-937
Author(s):  
Xupeng Hong ◽  
Jianming Hu
Keyword(s):  
Hbv Cccdna ◽  
Intrahepatic Hbv

scholarly journals Hepatitis B Core-Related Antigen as Surrogate Biomarker of Intrahepatic Hepatitis B Virus Covalently-Closed-Circular DNA in Patients with Chronic Hepatitis B: A Meta-Analysis

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 187
Author(s):  
Gian Paolo Caviglia ◽  
Angelo Armandi ◽  
Chiara Rosso ◽  
Davide Giuseppe Ribaldone ◽  
Rinaldo Pellicano ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hepatitis B Surface Antigen ◽  
Meta Analysis ◽  
Circular Dna ◽  
Non Invasive ◽  
Hbv Cccdna ◽  
B Virus ◽  
Chronic Hbv ◽  
Intrahepatic Hbv

Hepatitis B virus (HBV) covalently-closed-circular (ccc)DNA is the key molecule responsible for viral persistence within infected hepatocytes. The evaluation of HBV cccDNA is crucial for the management of patients with chronic HBV infection and for the personalization of treatment. However, the need for liver biopsy is the principal obstacle for the assessment of intrahepatic HBV cccDNA. In the last decade, several studies have investigated the performance of hepatitis B core-related antigen (HBcrAg) as a surrogate of HBV cccDNA amount in the liver. In this meta-analysis, we collected 14 studies (1271 patients) investigating the correlation between serum HBcrAg and intrahepatic HBV cccDNA. Serum HBcrAg showed a high correlation with intrahepatic HBV cccDNA (r = 0.641, 95% confidence interval (CI) 0.510–0.743, p < 0.001). In a head-to-head comparison, we observed that the performance of HBcrAg was significantly superior to that of hepatitis B surface antigen (r = 0.665 vs. r = 0.475, respectively, p < 0.001). Subgroup analysis showed that the correlation between HBcrAg and intrahepatic HBV cccDNA was high, both in hepatitis B e antigen-positive and -negative patients (r = 0.678, 95% CI 0.403–0.840, p < 0.001, and r = 0.578, 95% CI 0.344–0.744, p < 0.001, respectively). In conclusion, the measurement of serum HBcrAg qualifies as a reliable non-invasive surrogate for the assessment of an intrahepatic HBV cccDNA reservoir.

scholarly journals Diagnostic Value of Detection of Pregenomic RNA in Sera of Hepatitis B Virus-Infected Patients with Different Clinical Outcomes

2019 ◽  
Vol 58 (2) ◽  
Author(s):  
Ni Lin ◽  
Aizhu Ye ◽  
Jinpiao Lin ◽  
Can Liu ◽  
Jinlan Huang ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Clinical Outcomes ◽  
Hepatitis B Surface Antigen ◽  
Surrogate Marker ◽  
Diagnostic Value ◽  
Hbv Dna ◽  
Hbv Cccdna ◽  
B Virus ◽  
Intrahepatic Hbv

ABSTRACT Pregenomic RNA (pgRNA) is a direct transcription product of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA), and it plays important roles in viral genome amplification and replication. This study was designed to investigate whether serum pgRNA is a strong alternative marker for reflecting HBV cccDNA levels and to analyze the correlation between serum pgRNA, serum HBV DNA, and hepatitis B surface antigen (HBsAg). A total of 400 HBV-infected patients who received nucleos(t)ide analog (NA) therapy with different clinical outcomes were involved in this research. Case groups included asymptomatic hepatitis B virus carrier (ASC), chronic hepatitis B (CHB), liver cirrhosis (LC), and hepatocellular carcinoma (HCC) patients, with 100 patients in each group. The results showed that the levels of HBV pgRNA had significant differences between these 4 groups. Serum pgRNA levels correlated well with serum HBV DNA and HBsAg levels (HBV pgRNA levels versus HBV DNA levels, r = 0.58, P < 0.001; HBV pgRNA levels versus HBsAg levels, r = 0.47, P < 0.001). In addition, we focused on the 108 HBV-infected patients with HBV DNA levels of <500 IU/ml; it was surprising to find that in 17.57% (13/74) of cases, HBV pgRNA could be detected even when the HBV DNA level was below 20 IU/ml. In conclusion, HBV pgRNA levels in serum can be a surrogate marker for intrahepatic HBV cccDNA compared with serum HBV DNA and HBsAg. The detection of serum HBV pgRNA levels may provide a reference for clinical monitoring of cccDNA levels and the selection of appropriate timing for discontinuing antiviral therapy, especially when HBV DNA levels are below the detection limit.

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.

scholarly journals Mechanism of Hepatitis B Virus cccDNA Formation

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1463
Author(s):  
Lei Wei ◽  
Alexander Ploss
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Medical Problem ◽  
Circular Dna ◽  
Critical Step ◽  
Hbv Cccdna ◽  
Double Stranded Dna ◽  
Cellular Environment ◽  
B Virus ◽  
Comprehensive Picture

Hepatitis B virus (HBV) remains a major medical problem affecting at least 257 million chronically infected patients who are at risk of developing serious, frequently fatal liver diseases. HBV is a small, partially double-stranded DNA virus that goes through an intricate replication cycle in its native cellular environment: human hepatocytes. A critical step in the viral life-cycle is the conversion of relaxed circular DNA (rcDNA) into covalently closed circular DNA (cccDNA), the latter being the major template for HBV gene transcription. For this conversion, HBV relies on multiple host factors, as enzymes capable of catalyzing the relevant reactions are not encoded in the viral genome. Combinations of genetic and biochemical approaches have produced findings that provide a more holistic picture of the complex mechanism of HBV cccDNA formation. Here, we review some of these studies that have helped to provide a comprehensive picture of rcDNA to cccDNA conversion. Mechanistic insights into this critical step for HBV persistence hold the key for devising new therapies that will lead not only to viral suppression but to a cure.

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-&alpha; 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: &lsquo;CRISPR&rsquo;, &lsquo;CRISPR/Cas9&rsquo;, &lsquo;hepatitis B&rsquo;, &lsquo;HBV&rsquo;, &lsquo;chronic hepatitis B&rsquo; and &lsquo;HBV cccDNA&rsquo;. 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 relevance of the in situ assay for HBV DNA: a cross-sectional study in patients with chronic hepatitis B

2020 ◽  
Vol 73 (12) ◽  
pp. 813-818
Author(s):  
Danping Liu ◽  
Tong Xu ◽  
Bisheng Shi ◽  
Wei Lu ◽  
Ye Zheng ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Viral Replication ◽  
Chronic Hepatitis B ◽  
In Situ Hybridisation ◽  
Collagen Fibre ◽  
Hbv Dna ◽  
Viral Antigens ◽  
Intrahepatic Hbv

AimsThe visualisation of HBV DNA in liver sections of patients with chronic hepatitis B (CHB) in our previous report uncovered a mosaic distribution of viral antigens and nucleic acids. Here we aim to further explore the clinical utility of the in situ hybridisation (ISH) assay for HBV DNA.MethodISH of HBV DNA along with immunohistochemistry (IHC) of HBsAg, HBcAg and routine histopathology analysis was performed in 313 treatment-naive patients with CHB. Serum HBcrAg and HBcAb titre were also measured in addition to basic biochemical and virological parameters.ResultsThe ISH of HBV DNA, HBsAg and HBcAg showed 95.2%, 97.1% and 42.8% positive rate, respectively. The staining pattern of HBV DNA differs significantly with that of HBsAg. Intrahepatic HBV DNA exhibited high-level of correlations with viral load, HBcrAg and HBsAg titre. In HBeAg-negative patients, higher intrahepatic HBV DNA is associated with histological evidence of liver inflammation and fibrosis, whereas no such trend was observed in HBeAg-positive patients. Finally, a triple staining protocol that combined the detection of HBV DNA, HBsAg and collagen fibre was developed to enable better evaluation of viral replication and antigen expression in the context of disease progression.ConclusionsThe ISH assay for HBV DNA reflects the vigour of intrahepatic viral replication. It is complementary to the routine IHC assay for viral antigens and also related to the histopathological progression of liver diseases. The application of the HBV DNA ISH assay may help a better evaluation of virological and pathological condition of patients with CHB.

Sign in / Sign up

Export Citation Format

Share Document