Trial reportScience translational medicine2017
RNAi-based treatment of chronically infected patients and chimpanzees reveals that integrated hepatitis B virus DNA is a source of HBsAg.
Trial report in Science translational medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 262 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
262 citing papers in PubMed, 1 synthesis or guideline pooled it, 480 citations in OpenAlex.
- HBV RNA Predicts the Risk of Off-Treatment Relapse in Chronic Hepatitis B Patients With NAs Therapy: A Systematic Review and Meta-Analysis.Journal of viral hepatitis · 2026Pooled it
- Safety and efficacy of libevitug in patients with chronic hepatitis B and D virus coinfection: A single-center, open-label, phase IIa trial in China.Hepatology communications · 2026Trial
- Safety, pharmacokinetics, and pharmacodynamics of the antisense oligonucleotide RO7239958 in healthy volunteers and adults with chronic hepatitis B infection.Antimicrobial agents and chemotherapy · 2025Trial
- Trial
- A randomized phase 1b trial of the active site polymerase inhibitor nucleotide ATI-2173 in patients with chronic hepatitis B virus infection.Journal of viral hepatitis · 2023Trial
- Farnesoid X receptor agonist for the treatment of chronic hepatitis B: A safety study.Journal of viral hepatitis · 2021Trial
- Comparison of HBV RNA and Hepatitis B Core Related Antigen With Conventional HBV Markers Among Untreated Adults With Chronic Hepatitis B in North America.Hepatology (Baltimore, Md.) · 2021Trial
- Clinical Study of Single-Stranded Oligonucleotide RO7062931 in Healthy Volunteers and Patients With Chronic Hepatitis B.Hepatology (Baltimore, Md.) · 2021Trial
- Safety, tolerability, pharmacokinetics, and pharmacodynamics of a TLR7 agonist prodrug RO6870868 in healthy volunteers.Clinical and translational science · 2021Trial
- Hepatitis B Virus: Epidemiology, Prophylaxis, Therapy, Clinical Outcomes, and Novel Therapeutic Directions.Biomolecules · 2026Review
- Differential Hepatitis B Surface Antigen Glycan Isomer Kinetics Between Tenofovir Alafenamide and Entecavir: Hepatocellular Carcinoma Risk Stratification in Hepatitis B e Antigen-Positive Patients.Journal of viral hepatitis · 2026Article
- Genomic and transcriptomic features of HBV integration in treatment-naïve, HBeAg-positive children with chronic HBV infection.EBioMedicine · 2026Article
- Hepatitis B virus RNA levels and clinical characteristics of persistent viremia in HBsAg-positive patients undergoing nucleos(t)ide analog.Virus research · 2026Article
- [Clinical significance and occurrence mechanism of hepatitis B virus DNA integration].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Review
- Spatial-quantitative profiling of intrahepatic HBsAg heterogeneity and clustered distribution in chronic HBV infection.JHEP reports : innovation in hepatology · 2026Article
- Article
- Combination therapy with tobevibart and elebsiran potently reduces hepatitis B virus surface antigen levels in preclinicalAntimicrobial agents and chemotherapy · 2026Article
- Hepatocyte-Targeted Drug Delivery Strategies for Chronic Hepatitis B: Overcoming Delivery Barriers Toward Functional Cure.Pharmaceutics · 2026Review
- Nanoparticle approaches for hepatitis therapy and clinical translation.Discover nano · 2026Review
- Insight into the Biology of Hepatitis B Virus and Recent Therapeutic Approaches.Current microbiology · 2026Review
202 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 8 institutions in 5 countries.
Funding
Abstract
Chronic hepatitis B virus (HBV) infection is a major health concern worldwide, frequently leading to liver cirrhosis, liver failure, and hepatocellular carcinoma. Evidence suggests that high viral antigen load may play a role in chronicity. Production of viral proteins is thought to depend on transcription of viral covalently closed circular DNA (cccDNA). In a human clinical trial with an RNA interference (RNAi)-based therapeutic targeting HBV transcripts, ARC-520, HBV S antigen (HBsAg) was strongly reduced in treatment-naïve patients positive for HBV e antigen (HBeAg) but was reduced significantly less in patients who were HBeAg-negative or had received long-term therapy with nucleos(t)ide viral replication inhibitors (NUCs). HBeAg positivity is associated with greater disease risk that may be moderately reduced upon HBeAg loss. The molecular basis for this unexpected differential response was investigated in chimpanzees chronically infected with HBV. Several lines of evidence demonstrated that HBsAg was expressed not only from the episomal cccDNA minichromosome but also from transcripts arising from HBV DNA integrated into the host genome, which was the dominant source in HBeAg-negative chimpanzees. Many of the integrants detected in chimpanzees lacked target sites for the small interfering RNAs in ARC-520, explaining the reduced response in HBeAg-negative chimpanzees and, by extension, in HBeAg-negative patients. Our results uncover a heretofore underrecognized source of HBsAg that may represent a strategy adopted by HBV to maintain chronicity in the presence of host immunosurveillance. These results could alter trial design and endpoint expectations of new therapies for chronic HBV.
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What OpenQuestion holds
Registered trials
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 OpenQuestion graph.