Farnesoid X receptor agonist for the treatment of chronic hepatitis B: A safety study
Bibliographic record
Abstract
Abstract The nuclear farnesoid X receptor (FXR) regulates bile acid homeostasis and is a drug target for metabolic liver diseases. FXR also plays an important role in hepatitis B virus (HBV) DNA transcription. In vitro and in mice, FXR agonist treatment leads to inhibition of viral replication and a decline in viral proteins, pregenomic RNA (pgRNA) and HBV DNA levels. We aimed to translate this to a clinical use by primarily evaluating the safety and secondary the anti‐viral effect of Vonafexor, a FXR agonist, in chronic hepatitis B (CHB) patients. In total, 73 CHB patients were enrolled in a two‐part Phase Ib double‐blind, placebo‐controlled trial. Patients were randomized to receive oral Vonafexor (100, 200 and 400 mg once daily, or 200 mg twice daily), placebo, or entecavir (Part A, n = 48) or to receive Vonafexor (300 mg once daily or 150 mg twice daily), or placebo, combined with pegylated‐interferon‐α2a (Part B, n = 25) for 29 days. Patients were followed up for 35 days. Enrolled CHB patients were mostly HBeAg‐negative. Vonafexor was overall well tolerated and safe. The most frequent adverse events were moderate gastrointestinal events. Pruritus was more frequent with twice‐daily compared with once‐daily regimens (56%–67% vs. 16%, respectively, p < 0.05). Vonafexor monotherapy of 400 mg once daily decreased HBsAg concentrations (–0.1 log10 IU/mL, p < 0.05), and Vonafexor/pegylated‐IFN‐α2a combination therapy decreased HBcrAg and pgRNA. In conclusion, Vonafexor was safe with a decline in HBV markers observed in CHB patients suggesting a potential anti‐viral effect the therapeutic potential of which has to be evaluated in larger trials.
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 machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".