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Quantitative analysis of HBV cccDNA from clinical specimens: correlation with clinical and virological response during antiviral therapy

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Název: Quantitative analysis of HBV cccDNA from clinical specimens: correlation with clinical and virological response during antiviral therapy
Autoři: Kwiatkowski, RW, Sander, TJ, Hall, JG, Lopez, VA, Dienstag, JL, Bourne, EJ, Longlet, JM, Wright, T, Lai, CL, Condreay, LD
Zdroj: Journal of Viral Hepatitis. 14:55-63
Informace o vydavateli: Wiley, 2006.
Rok vydání: 2006
Témata: 0301 basic medicine, Hepatitis B virus, Biopsy, DNA, Circular - analysis - genetics, DNA Probes - genetics, Amino Acid Motifs, Biopsy, Fine-Needle, Pilot Projects, Hepatitis B e Antigens - blood, Virus Replication, Antiviral Agents, Hepatitis B virus - genetics, Interferon-alpha - therapeutic use, 03 medical and health sciences, Hepatitis B, Chronic, Drug Therapy, Antiviral Agents - therapeutic use, Humans, Hepatitis B e Antigens, Lamivudine - therapeutic use, Alanine Transaminase - blood, Interferon-alpha, Alanine Transaminase, DNA, Viral - genetics, Hepatitis B, 3. Good health, Lamivudine, Combination, DNA, Viral, Mutation, Fine-Needle, Chronic - blood - drug therapy - pathology - virology, Drug Therapy, Combination, Hepatitis B, Chronic - blood - drug therapy - pathology - virology, DNA, Circular, Circular - analysis - genetics, DNA Probes, DNA, Viral - genetics, Virus Replication - drug effects
Popis: Summary. Attempts to investigate changes in various forms of intrahepatic hepatitis B virus (HBV) DNA during antiviral therapy have been hampered by limitations in technologies and scarcity of adequate tissue for analysis. We used a sensitive, specific assay to detect and quantitate covalently closed circular DNA (cccDNA) from total intrahepatic HBV DNA in clinical liver specimens. Total HBV DNA and cccDNA from 21 needle‐biopsy specimens were quantified, with levels ranging from 0.1 to 9.8 copies/cell and 0.3 to 491.0 copies/cell, respectively. Then, we performed the same determinations on baseline and week‐52 liver needle‐biopsy specimens from eight patients enrolled in a clinical trial and evaluated the association between intrahepatic HBV DNA levels and serological and virological endpoints. In most patients, levels of intrahepatic HBV DNA, including cccDNA, decreased over the 52‐week study, regardless of therapy or serological outcome. Higher ratios of cccDNA to total HBV DNA were detected at week 52 than at baseline indicating a shift in predominance of nonreplicating virus in posttreatment specimens. In patients who achieved treatment‐related or spontaneous hepatitis B e antigen (HBeAg) responses, including those harbouring tyrosine‐methionine‐aspartate‐aspartate‐mutant HBV, levels of intrahepatic and serum HBV DNA suppression were greater than those in patients without HBeAg responses. In conclusion, this pilot study of intrahepatic HBV replicative forms in patients with chronic hepatitis B indicated that total intrahepatic and, specifically, cccDNA levels are not static but change as a reflection of serological and virological events.
Druh dokumentu: Article
Jazyk: English
ISSN: 1365-2893
1352-0504
DOI: 10.1111/j.1365-2893.2006.00775.x
Přístupová URL adresa: https://pubmed.ncbi.nlm.nih.gov/17212645
https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2893.2006.00775.x
https://www.ncbi.nlm.nih.gov/pubmed/17212645
http://hub.hku.hk/handle/10722/78602
https://core.ac.uk/display/37909118
https://europepmc.org/article/MED/17212645
http://hdl.handle.net/10722/78602
Rights: Wiley Online Library User Agreement
Přístupové číslo: edsair.doi.dedup.....efc6e15db413b5de65dc9783fa3afc70
Databáze: OpenAIRE
Popis
Abstrakt:Summary. Attempts to investigate changes in various forms of intrahepatic hepatitis B virus (HBV) DNA during antiviral therapy have been hampered by limitations in technologies and scarcity of adequate tissue for analysis. We used a sensitive, specific assay to detect and quantitate covalently closed circular DNA (cccDNA) from total intrahepatic HBV DNA in clinical liver specimens. Total HBV DNA and cccDNA from 21 needle‐biopsy specimens were quantified, with levels ranging from 0.1 to 9.8 copies/cell and 0.3 to 491.0 copies/cell, respectively. Then, we performed the same determinations on baseline and week‐52 liver needle‐biopsy specimens from eight patients enrolled in a clinical trial and evaluated the association between intrahepatic HBV DNA levels and serological and virological endpoints. In most patients, levels of intrahepatic HBV DNA, including cccDNA, decreased over the 52‐week study, regardless of therapy or serological outcome. Higher ratios of cccDNA to total HBV DNA were detected at week 52 than at baseline indicating a shift in predominance of nonreplicating virus in posttreatment specimens. In patients who achieved treatment‐related or spontaneous hepatitis B e antigen (HBeAg) responses, including those harbouring tyrosine‐methionine‐aspartate‐aspartate‐mutant HBV, levels of intrahepatic and serum HBV DNA suppression were greater than those in patients without HBeAg responses. In conclusion, this pilot study of intrahepatic HBV replicative forms in patients with chronic hepatitis B indicated that total intrahepatic and, specifically, cccDNA levels are not static but change as a reflection of serological and virological events.
ISSN:13652893
13520504
DOI:10.1111/j.1365-2893.2006.00775.x