Evidence map›Paper›PMID 39478672›Full record

Trial reportThe Journal of infectious diseases2025

Hepatitis B Virus RNA as a Biomarker for Safe Antiviral Discontinuation: A Prospective Study of Nucleos(t)ide Analogue Withdrawal.

Norah A Terrault, Richard Sterling, Anna S Lok, Marc G Ghany, Jordan J Feld, Gavin Cloherty, Abdus S Wahed, Xue Yang

Registry-linked trialAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The Journal of infectious diseases, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01369212 (Combination Therapy of Pegylated Interferon Alfa-2a and Tenofovir Versus Tenofovir Monotherapy in HBeAg-positive and HBeAg-negative Chronic Hepatitis B), which is not on this map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

NCT01369212 phase3completednot on this map

Combination Therapy of Pegylated Interferon Alfa-2a and Tenofovir Versus Tenofovir Monotherapy in HBeAg-positive and HBeAg-negative Chronic Hepatitis B

TypeinterventionalSponsorNational Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)Ran2012 to 2021Enrolled201ConditionsHepatitis BArmsTenofovir, Peginterferon-alfa 2a and tenofovir
3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Norah A TerraultDivision of Gastrointestinal and Liver Diseases, University of Southern California, Los Angeles.ORCID 0000-0003-4143-1950
Richard SterlingDivision of Gastroenterology and Hepatology, Virginia Commonwealth University, Richmond.ORCID 0000-0002-8637-2475
Anna S LokDivision of Gastroenterology and Hepatology, University of Michigan, Ann Arbor.ORCID 0000-0002-5811-6845
Marc G GhanyLiver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.ORCID 0000-0003-2837-0188
Jordan J FeldToronto Centre for Liver Disease, Toronto General Hospital, University Health Network, University of Toronto, Ontario, Canada.ORCID 0000-0003-2640-2211
Gavin ClohertyInfectious Disease Research, Abbott Diagnostics, Abbott Park, Illinois.
Abdus S WahedDepartment of Biostatistics and Computational Biology, University of Rochester, New York.ORCID 0000-0001-6911-7221
Xue YangDepartment of Biostatistics, University of Pittsburgh, Philadelphia.ORCID 0000-0002-6290-1117

Funding

Abbott DiagnosticsHepatitis B Research NetworkIntramural Research Program of the National Institute of Diabetes and Digestive Diseases and Kidney DiseasesNIH HHS
6 · The paper itself

Abstract

backgroundWithdrawal of nucleos(t)ide analogue therapy is associated with hepatitis B surface antigen (HBsAg) loss and sustained off-therapy partial cure (normal alanine aminotransferase [ALT] ≤30 U/L for males and ≤20 U/L for females with hepatitis B virus [HBV] DNA <2000 IU/mL) but should be offered only to those most likely to benefit. HBV RNA may be useful for risk stratification.

methodsThe Hepatitis B Research Network Immune-Active Trial prospectively evaluated treatment with tenofovir disoproxil fumarate (TDF) for 192 weeks ± peginterferon alfa-2a for the initial 24 weeks, followed by protocolized withdrawal of TDF among eligible participants (ClinicalTrials.gov NCT01369212). HBV RNA was evaluated as a predictor of ALT flares and sustained partial cure (HBV DNA <2000 IU/mL) 48 weeks after TDF withdrawal.

resultsOf 93 participants discontinuing TDF (n = 52, TDF + peginterferon alfa-2a; n = 41, TDF alone), 52 (55.9%) had unquantifiable HBV RNA at end of treatment. ALT flares >5 times the upper limit of normal at 48 weeks off therapy occurred in 33.3%, with pretreatment age (≥35 years) and quantifiable HBV RNA at end of treatment the best predictors (area under the receiver operating characteristic curves, 0.74 and 0.85 for training and test sets, respectively). A total of 26 (28.3%) had sustained partial cure, 3 (11.5%) with ALT flare. Nonquantifiable HBV RNA and quantitative HBsAg <100 IU/mL at end of treatment were the best predictors of sustained partial cure (area under the receiver operating characteristic curves, 0.84 and 0.93 for training and test sets). If HBV RNA was quantifiable at end of treatment, the likelihood of sustained partial cure was only 3%, whereas if HBV RNA was unquantifiable and quantitative HBsAg was <100 IU/mL, this likelihood was 73%.

conclusionsHBV RNA is a useful biomarker in predicting likelihood of achieving sustained partial cure and safe withdrawal of nucleos(t)ide analogues.

Indexed as

Antiviral AgentsHepatitis BHepatitis B, ChronicHepatitis B virusRNA, ViralTenofovirAdultAlanine TransaminaseBiomarkersDNA, ViralFemaleHepatitis B Surface AntigensHumansInterferon-alphaMaleMiddle AgedAlanine TransaminaseAntiviral AgentsBiomarkersDNA, ViralHepatitis B Surface AntigensInterferon-alphapeginterferon alfa-2aPolyethylene GlycolsRecombinant ProteinsRNA, ViralTenofovirALT flarefunctional cureHBsAg losspartial curepeginterferon

Identifiers

PMID39478672
PMCPMC12128069

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.