Differential HBV replicative markers and covalently closed circular DNA transcription in immune-active chronic hepatitis B with and without HBeAg.

Autor: Kim HS; The Catholic University Liver Research Center, Collage of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.; Department of Biomedicine & Health Sciences, Graduate School, The Catholic University of Korea, Seoul, Republic of Korea.; Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea., Kim JS; The Catholic University Liver Research Center, Collage of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.; Department of Biomedicine & Health Sciences, Graduate School, The Catholic University of Korea, Seoul, Republic of Korea.; Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea., Kim JM; The Catholic University Liver Research Center, Collage of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.; Department of Biomedicine & Health Sciences, Graduate School, The Catholic University of Korea, Seoul, Republic of Korea.; Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea., Han JW; The Catholic University Liver Research Center, Collage of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.; Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea., Lee SK; The Catholic University Liver Research Center, Collage of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.; Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea., Nam H; The Catholic University Liver Research Center, Collage of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.; Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea., Sung PS; The Catholic University Liver Research Center, Collage of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.; Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea., Kwon JH; The Catholic University Liver Research Center, Collage of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.; Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea., Bae SH; The Catholic University Liver Research Center, Collage of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.; Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea., Choi JY; The Catholic University Liver Research Center, Collage of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.; Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea., Yoon SK; The Catholic University Liver Research Center, Collage of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.; Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea., Jang JW; The Catholic University Liver Research Center, Collage of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.; Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.; Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Jazyk: angličtina
Zdroj: Liver international : official journal of the International Association for the Study of the Liver [Liver Int] 2024 Oct; Vol. 44 (10), pp. 2753-2762. Date of Electronic Publication: 2024 Jul 29.
DOI: 10.1111/liv.16032
Abstrakt: Background and Aims: Molecular processes driving immune-active chronic hepatitis B (CHB) with and without hepatitis B e antigen (HBeAg) remain incompletely understood. This study aimed to investigate expression profiles of serum and intrahepatic HBV markers and replicative activity of HBV in CHB patients with or without HBeAg.
Methods: This study recruited 111 untreated immune-active CHB (60 HBeAg-positive and 51 HBeAg-negative) patients and quantified intrahepatic covalently closed circular DNA (cccDNA), pre-genomic RNA (pgRNA), total HBV DNA (tDNA), and replicative intermediates as well as serum HBV markers (HBV DNA, hepatitis B surface antigen, hepatitis B core-related antigen). Correlations between HBV markers and clinico-virological factors influencing expression levels of HBV markers were analysed.
Results: Levels of all serum markers and intrahepatic cccDNA/tDNA as well as cccDNA transcriptional activity and virion productivity were significantly reduced in HBeAg-negative patients compared to those in HBeAg-positive patients. Additionally, correlations between intrahepatic cccDNA/pgRNA and serum markers were impaired in HBeAg-negative individuals. Aminotransferase levels were positively correlated with cccDNA transcriptional activity in HBeAg-positive patients, but not in HBeAg-negative patients. Notably, among HBeAg-positive patients, there was a progressive decline in pgRNA level, transcriptional activity, and serum HBV markers as liver fibrosis advanced, which was not observed in HBeAg-negative patients.
Conclusions: HBeAg loss is correlated with diminished intrahepatic HBV reservoirs and cccDNA transcription, leading to decreased serum HBV marker levels. Circulating HBV markers are not reliable indicators of intrahepatic HBV replicative activity for HBeAg-negative patients. Our findings reveal distinct disease phenotypes between immune-active CHB with and without HBeAg, highlighting the need to establish optimal surrogate biomarkers that can accurately mirror intrahepatic viral activity to aid in decision-making for antiviral therapy for immune-active CHB.
(© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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