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Record W4391053435 · doi:10.1111/jvh.13918

Addition of PEG‐interferon to long‐term nucleos(t)ide analogue therapy enhances HBsAg decline and clearance in HBeAg‐negative chronic hepatitis B

2024· article· en· W4391053435 on OpenAlexaffabout
Mina Farag, Margo J. H. van Campenhout, Milan J. Sonneveld, Scott Fung, Karel J. van Erpecum, David Wong, Elke Verhey, Robert de Man, Robert J. de Knegt, Johannes T. Brouwer, Hubertus C. Baak, Jordan J. Feld, Kin Seng Liem, André Boonstra, Bettina E. Hansen, Harry L.A. Janssen

Bibliographic record

VenueJournal of Viral Hepatitis · 2024
Typearticle
Languageen
FieldMedicine
TopicHepatitis B Virus Studies
Canadian institutionsUniversity of TorontoToronto General HospitalUniversity Health Network
FundersF. Hoffmann-La Roche
KeywordsHBsAgMedicineHBeAgGastroenterologyInternal medicinePEG ratioCombination therapyChronic hepatitisHepatitis B virusImmunologyVirus

Abstract

fetched live from OpenAlex

Abstract We studied whether 48 weeks of PEG‐IFN alfa‐2a add‐on increases HBsAg‐decline and clearance in HBeAg‐negative patients on long‐term nucleo(s)tide analogue (NA) therapy. In this investigator‐initiated, randomized, controlled trial conducted in Europe and Canada, HBeAg‐negative patients treated with NA > 12 months, with HBVDNA < 200 IU/mL, were enrolled. Patients were randomized 2:1 to 48 weeks of PEG‐IFN alfa‐2a add‐on (180 μg per week) or continued NA‐monotherapy with subsequent follow‐up to Week 72. Endpoints were HBsAg decline (≥1 log 10 IU/mL) and HBsAg clearance at Week 48. Of the 86 patients in the modified‐intention‐to‐treat analysis, 58 patients received PEG‐IFN add‐on, and 28 continued NA monotherapy. At Week 48, 16(28%) patients achieved HBsAg decline ≥1 log 10 in the add‐on arm versus none on NA‐monotherapy ( p < .001), and HBsAg clearance was observed in 6 (10%) PEG‐IFN add‐on patients versus 0% NA‐monotherapy ( p = .01). HBVRNA was only detected in 2% after PEG‐IFN treatment versus 19% in NA‐monotherapy ( p = .002) at Week 48. PEG‐IFN add‐on therapy was well tolerated in majority of patients. Low baseline HBsAg levels (<10 IU/mL) identified patients most likely to achieve HBsAg loss with PEG‐IFN add‐on, whereas an HBsAg level > 200 IU/mL at on‐treatment Week 12 was highly predictive of non‐response (NPV = 100%). Addition of PEG‐IFN to long‐term NA enhanced HBsAg decline and increased the chance of HBsAg clearance in HBeAg‐negative patients on long‐term NA. On‐treatment HBsAg levels >200 IU/mL identify patients unlikely to benefit from PEG‐IFN add‐on and could be used as a potential stopping‐rule for PEG‐IFN therapy. Our findings support further exploration of immune modulation add‐on to antiviral therapy, preferably using response‐guided strategies, to increase functional cure rates in patients with CHB.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.193
Threshold uncertainty score0.970

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.017
GPT teacher head0.313
Teacher spread0.295 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations16
Published2024
Admission routes2
Has abstractyes

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