Analysis of HBsAg Immunocomplexes and cccDNA Activity During and Persisting After NAP-Based Therapy.
Adult
Alanine Transaminase
/ blood
Antiviral Agents
/ therapeutic use
Cross-Over Studies
DNA, Circular
/ blood
Drug Therapy, Combination
Female
Hepatitis B Core Antigens
/ blood
Hepatitis B Surface Antigens
/ blood
Hepatitis B virus
/ genetics
Hepatitis B, Chronic
/ blood
Humans
Interferons
/ therapeutic use
Male
Nucleic Acids
/ therapeutic use
Polymers
/ therapeutic use
RNA, Viral
/ blood
Seroconversion
/ drug effects
Tenofovir
/ therapeutic use
Treatment Outcome
Virus Inactivation
/ drug effects
Journal
Hepatology communications
ISSN: 2471-254X
Titre abrégé: Hepatol Commun
Pays: United States
ID NLM: 101695860
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
revised:
28
04
2021
received:
08
01
2021
accepted:
04
05
2021
pubmed:
25
9
2021
medline:
28
1
2022
entrez:
24
9
2021
Statut:
ppublish
Résumé
Therapy with nucleic acid polymers (NAPs), tenofovir disoproxil fumarate (TDF), and pegylated interferon (pegIFN) achieve high rates of HBsAg loss/seroconversion and functional cure in chronic hepatitis B virus (HBV) infection. The role of hepatitis B surface antigen (HBsAg) seroconversion and inactivation of covalently closed circular DNA (cccDNA) in establishing functional cure were examined. Archived serum from the REP 401 study was analyzed using the Abbott ARCHITECT HBsAg NEXT assay (Chicago, IL), Abbott research use-only assays for HBsAg immune complexes (HBsAg ICs), circulating HBV RNA, and the Fujirebio assay for hepatitis B core-related antigen (HBcrAg; Malvern, PA). HBsAg became < 0.005 IU/mL in 23 participants during NAP exposure, which persisted in all participants with functional cure. HBsAg IC declined during lead-in TDF monotherapy and correlated with minor declines in HBsAg. Following the addition of NAPs and pegIFN, minor HBsAg IC increases (n = 13) or flares (n = 2) during therapy were not correlated with HBsAg decline, hepatitis B surface antibody (anti-HBs) titers, or alanine aminotransferase. HBsAg IC universally declined during follow-up in participants with virologic control or functional cure. Universal declines in HBV RNA and HBcrAg during TDF monotherapy continued with NAP + pegIFN regardless of therapeutic outcome. At the end of therapy, HBV RNA was undetectable in only 5 of 14 participants with functional cure but became undetectable after removal of therapy in all participants with functional cure. Undetectable HBV RNA at the end of therapy in 5 participants was followed by relapse to virologic control or viral rebound. Conclusion: Anti-HBs-independent mechanisms contribute to HBsAg clearance during NAP therapy. Inactivation of cccDNA does not predict functional cure following NAP-based therapy; however, functional cure is accompanied by persistent inactivation of cccDNA. Persistent HBsAg loss with functional cure may also reflect reduction/clearance of integrated HBV DNA. Clinicaltrials.org number NCT02565719.
Identifiants
pubmed: 34558823
doi: 10.1002/hep4.1767
pmc: PMC8557319
pii: 02009842-202111000-00008
doi:
Substances chimiques
Antiviral Agents
0
DNA, Circular
0
Hepatitis B Core Antigens
0
Hepatitis B Surface Antigens
0
Nucleic Acids
0
Polymers
0
RNA, Viral
0
Interferons
9008-11-1
Tenofovir
99YXE507IL
Alanine Transaminase
EC 2.6.1.2
Banques de données
ClinicalTrials.gov
['NCT02565719']
Types de publication
Clinical Trial, Phase II
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1873-1887Informations de copyright
© 2021 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.
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