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Record W2790860083 · doi:10.1111/liv.13716

<scp>ALT</scp> flares during nucleotide analogue therapy are associated with <scp>HB</scp>sAg loss in genotype A <scp>HB</scp>eAg‐positive chronic hepatitis B

2018· article· en· W2790860083 on OpenAlexaff
Darren Wong, Margaret Littlejohn, Rosalind Edwards, Kathy Merlock Jackson, Peter Revill, Anuj Gaggar, Kathryn M. Kitrinos, Mani Subramanian, Patrick Marcellin, Marı́a Buti, Harry L.A. Janssen, Ed Gane, Stephen Locarnini, Alexander Thompson

Bibliographic record

VenueLiver International · 2018
Typearticle
Languageen
FieldMedicine
TopicHepatitis B Virus Studies
Canadian institutionsUniversity of TorontoUniversity Health Network
FundersGilead Sciences
KeywordsMedicineGastroenterologyInternal medicineFlareAlanine aminotransferaseGenotypeChemistry

Abstract

fetched live from OpenAlex

Abstract Background Alanine aminotransferase ( ALT ) flares during NA therapy are uncommon but occur. Evaluation of ALT flares during nucleos(t)ide analogue ( NA ) therapy is important as new immunomodulatory therapies for hepatitis B virus ( HBV ) are developed. We evaluated the association between ALT flares and HB sAg loss during long‐term therapy for genotype A CHB . Methods This analysis included genotype A subjects from a phase III study of tenofovir vs adefovir in HB eAg‐positive HBV . ALT flare was defined as (i) a rise in ALT &gt;2x ULN from normal ALT levels; or (ii) a rise in ALT &gt;2x baseline ALT level. HB sAg response at week 384 was recorded as one of HB sAg loss vs HB sAg decline (≥1 log 10 IU /mL decline) vs non‐response. The primary analysis evaluated the association between ALT flare and HB sAg response. Results 54 subjects were included. 23/54 (43%) subjects experienced an on‐treatment ALT flare. 45% achieved an HB sAg reduction ≥1 log 10 IU / mL , and of these 67% achieved HB sAg loss at a median of 102 weeks [ IQR : 64‐156]. Flare was associated with HB sAg decline vs non‐response (67% vs 23%, P = .002), and were more common in subjects who achieved HB sAg loss vs non‐response (56% vs 23%), P = .049). There was a median delay of 56 weeks [ IQR : 40‐80] between a flare and HB sAg loss. Conclusion In genotype A subjects undergoing long‐term NA therapy, ALT flares predict for HB sAg response. The delay between ALT flare and HB sAg loss has implications for clinical trial design for early phase development of immunomodulatory strategies aiming for HB sAg loss.

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)0.003
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.049
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.003
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0010.001
Science and technology studies0.0000.001
Scholarly communication0.0000.001
Open science0.0010.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.001

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 head0.015
GPT teacher head0.253
Teacher spread0.237 · 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.

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

Citations36
Published2018
Admission routes1
Has abstractyes

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