ArticlePloS one2022
Ongoing viral replication and production of infectious virus in patients with chronic hepatitis B virus suppressed below the limit of quantitation on long-term nucleos(t)ide therapy.
Article in PloS one, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Droplet Digital PCR Measurement of HBV DNA in On-Treatment Chronic HBV Patients: Association With HCC Development and Outcomes.Journal of viral hepatitis · 2026Article
- Spatial transcriptional profiling of CHB liver biopsies reveals an undetected population of zonally biased HBV-integrated cells.JHEP reports : innovation in hepatology · 2026Article
- HBVZ10, an AAV8 vector-based new HBV therapy candidate for cccDNA elimination.Molecular therapy. Methods & clinical development · 2025Article
- Targeting HBV with RNA interference: Paths to cure.Science translational medicine · 2025Review
- New potent HBV replication inhibitors for the management of chronic hepatitis B are needed.Nature reviews. Gastroenterology & hepatology · 2025Article
- Hyperendemicity and genotype diversity of hepatitis B virus among patients attending the University of Abuja Teaching Hospital, Nigeria.GMS hygiene and infection control · 2025Article
- Review
- Is HBV RNA a new endpoint of HBV cure?Saudi journal of gastroenterology : official journal of the Saudi Gastroenterology Association · 2024Article
- Safety, pharmacodynamics, and antiviral activity of selgantolimod in viremic patients with chronic hepatitis B virus infection.JHEP reports : innovation in hepatology · 2024Article
- Development of hepatocellular carcinoma in treated and untreated patients with chronic hepatitis B virus infection.Clinical and molecular hepatology · 2023Review
- Early intrahepatic recurrence of HBV infection in liver transplant recipients despite antiviral prophylaxis.JHEP reports : innovation in hepatology · 2023Article
- Intrahepatic quantification of HBV antigens in chronic hepatitis B reveals heterogeneity and treatment-mediated reductions in HBV core-positive cells.JHEP reports : innovation in hepatology · 2023Article
- Characterization of a Novel Capsid Assembly Modulator for the Treatment of Chronic Hepatitis B Virus Infection.Antimicrobial agents and chemotherapy · 2023Article
- Review
- Targeting the hepatitis B cccDNA with a sequence-specific ARCUS nuclease to eliminate hepatitis B virus in vivo.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nucleos(t)ide analogs are standard-of-care for the treatment of chronic hepatitis B and can effectively reduce hepatitis B virus (HBV) replication but rarely leads to cure. Nucleos(t)ide analogs do not directly eliminate the viral episome, therefore treatment cessation typically leads to rapid viral rebound. While treatment is effective, HBV DNA is still detectable (although not quantifiable) in the periphery of the majority of nucleos(t)ide analog treated HBV patients, even after prolonged treatment. Addressing whether the detectable HBV DNA represents infectious virus is a key unknown and has important implications for the development of a curative treatment for HBV. The minimum HBV genome equivalents required to establish infection in human liver chimeric mice was determined by titration of HBV patient sera and the infectivity in chimeric mice of serum from patients (n = 7) suppressed to the limit of detection on nucleos(t)ide analog therapy was evaluated. A minimum of 5 HBV genome equivalents were required to establish infection in the chimeric mice, confirming this model has sufficient sensitivity to determine whether serum from virally suppressed patients contains infectious virus. Strikingly, serum from 75% (n = 3 out of 4) of nucleos(t)ide-treated HBV patients with DNA that was detectable, but below the lower limit of quantitation, also established infection in the chimeric mice. These results demonstrate that infectious virus is still present in some HBV patients on suppressive nucleos(t)ide therapy. This residual virus may support viral persistence via continuous infection and explain the ongoing risk for HBV-related complications despite long-term suppression on therapy. Thus, additional treatment intensification may facilitate HBV cure.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.