cccDNA
乙型肝炎表面抗原
HBeAg
病毒学
核糖核酸
乙型肝炎病毒
乙型肝炎
医学
分子生物学
生物
病毒
基因
生物化学
作者
Barbara Testoni,Caroline Scholtès,Marie-Laure Plissonnier,Alexia Paturel,Françoise Berby,F. Facchetti,François Villeret,Elisabetta Degasperi,Beth Scott,Aaron Hamilton,Marintha Heil,Pietro Lampertico,Massimo Levrero,Fabien Zoulim
出处
期刊:Gut
[BMJ]
日期:2023-10-25
卷期号:: gutjnl-330644
被引量:11
标识
DOI:10.1136/gutjnl-2023-330644
摘要
Objective A convenient, reproducible biomarker of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) transcriptional activity is lacking. We measured circulating HBV RNA (cirB-RNA) in untreated and nucleos(t)ide analogues (NUC) treated chronic hepatitis B (CHB) patients to define its correlation with intrahepatic viral markers and HBV core-related antigen (HBcrAg). Design Paired liver biopsy and serum samples were collected from 122 untreated and 30 NUC-treated CHB patients. We measured cirB-RNA, HBV DNA, hepatitis B surface antigen (HBsAg), HBcrAg and alanine aminotransferase levels. cirB-RNA was quantified using an investigational HBV RNA assay for use on the cobas 6800 system. The test detects a region spanning the HBV canonical polyadenylation site. cccDNA and 3.5 kb RNA in liver tissue were assessed by quantitative PCR and droplet digital PCR. Results cirB-RNA was detectable in 100% of HBeAg(+) chronic hepatitis (CH), 57% and 14% of HBeAg(−) CH and chronic infection untreated patients and 47% of NUC-treated patients. cirB-RNA undetectability was associated with lower intrahepatic cccDNA transcriptional activity, as well as serum HBcrAg, but no significant differences in HBsAg, in both untreated and treated patients. In untreated HBeAg(−) patients, cirB-RNA correlated with intrahepatic 3.5 kb RNA and cccDNA transcriptional activity, serum HBV DNA and HBcrAg, but not with HBsAg or total cccDNA levels. Combined undetectability of both cirB-RNA and HBcrAg detection in untreated HBeAg(−) patients identified a subgroup with the lowest levels of intrahepatic transcriptionally active cccDNA. Conclusion Our results support the usefulness of quantification of circulating HBV RNA expressed from cccDNA as an indicator of intrahepatic active viral reservoir in both untreated and NUC-treated CHB patients. Trial registration number NCT02602847 .
科研通智能强力驱动
Strongly Powered by AbleSci AI