ArticleWorld journal of gastroenterology2004
HBV cccDNA in patients' sera as an indicator for HBV reactivation and an early signal of liver damage.
Article in World journal of gastroenterology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Incidence and risk factors for hepatitis B virus reactivation in kidney transplant recipients: a systematic review and meta-analysis.BMC nephrology · 2026Pooled it
- Whole genome sequencing of hepatitis B virus using tiled amplicon (HEPTILE) and probe based enrichment on Illumina and Nanopore platforms.Scientific reports · 2025Article
- cccDNA-Targeted Drug Screen Reveals a Class of Antihistamines as Suppressors of HBV Genome Levels.Biomolecules · 2023Article
- DNA Repair Factor Poly(ADP-Ribose) Polymerase 1 Is a Proviral Factor in Hepatitis B Virus Covalently Closed Circular DNA Formation.Journal of virology · 2022Article
- Serum hepatitis B virus RNA detectability, composition and clinical significance in patients with ab initio hepatitis B e antigen negative chronic hepatitis B.Virology journal · 2022Article
- Intracellular interferon signalling pathways as potential regulators of covalently closed circular DNA in the treatment of chronic hepatitis B.World journal of gastroenterology · 2021Review
- Host-Directed Antiviral Therapy.Clinical microbiology reviews · 2020Review
- Novel Hepatitis B Virus Capsid Assembly Modulator Induces Potent Antiviral ResponsesAntimicrobial agents and chemotherapy · 2020Article
- Review
- Detection of HBV Covalently Closed Circular DNA.Viruses · 2017Review
- Relationship between genotypes and clinical manifestation, pathology, and cccDNA in Chinese children with hepatitis B virus-associated glomerulonephritis.World journal of pediatrics : WJP · 2016Article
- Article
- CRISPR/Cas9 nickase-mediated disruption of hepatitis B virus open reading frame S and X.Scientific reports · 2015Article
- Detection of Hepatitis B Virus Covalently Closed Circular DNA in the Plasma of Iranian HBeAg-Negative Patients With Chronic Hepatitis B.Hepatitis monthly · 2015Article
- [Intrahepatic hepatitis B virus covalently closed circular DNA correlation with serum HBV DNA, serum HBsAg, alanine aminotransferase and age].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2015Article
- Article
- Development of magnetic capture hybridization and quantitative polymerase chain reaction for hepatitis B virus covalently closed circular DNA.Hepatitis monthly · 2015Article
- Effects of entecavir on hepatitis B virus covalently closed circular DNA in hepatitis B e antigen-positive patients with hepatitis B.PloS one · 2015Article
- Levels of hepatitis B virus replicative intermediate in serum samples of chronic hepatitis B patients.Molecular biology reports · 2014Article
- The Human Bocavirus Is Associated with Some Lung and Colorectal Cancers and Persists in Solid Tumors.PloS one · 2013Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimTo evaluate the covalently closed circle DNA (cccDNA) level of hepatitis B virus (HBV) in patients' liver and sera.
methodsHBV DNA was isolated from patients' liver biopsies and sera. A sensitive real-time PCR method, which is capable of differentiation of HBV viral genomic DNA and cccDNA, was used to quantify the total HBV cccDNA. The total HBV viral DNA was quantitated by real-time PCR using a HBV diagnostic kit (PG Biotech, LTD, Shenzhen, China) described previously.
resultsFor the first time, we measured the level of HBV DNA and cccDNA isolated from ten HBV patients' liver biopsies and sera. In the liver biopsies, cccDNA was detected from all the biopsy samples. The copy number of cccDNA ranged from from 0.03 to 173.1 per cell, the copy number of total HBV DNA ranged from 0.08 to 3 717 per cell. The ratio of total HBV DNA to cccDNA ranged from 1 to 3 406. In the sera, cccDNA was only detected from six samples whereas HBV viral DNA was detected from all ten samples. The ratio of cccDNA to total HBV DNA ranged from 0 to 1.77%. To further investigate the reason why cccDNA could only be detected in some patients' sera, we performed longitudinal studies. The cccDNA was detected from the patients' sera with HBV reactivation but not from the patients' sera without HBV reactivation. The level of cccDNA in the sera was correlated with ALT and viral load in the HBV reactivation patients.
conclusionHBV cccDNA is actively transcribed and replicated in some patients' hepatocytes, which is reflected by a high ratio of HBV total DNA vs cccDNA. Detection of cccDNA in the liver biopsy will provide an end-point for the anti-HBV therapy. The occurrence of cccDNA in the sera is an early signal of liver damage, which may be another important clinical parameter.
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