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Causality: well established
Causality assessment · Causality: well established
Valproate and Hepatotoxicity: is the FAERS signal real?
A written Bradford Hill assessment of one drug–event pair. The grade is a judgement about the signal, not a statement that this drug causes this event in any one person; FAERS counts are reports, not rates.
Valproate ↔ Hepatotoxicity
n=65 co-reports · PRR 3.0 · ROR 3.0
Valproate can cause serious, sometimes fatal hepatotoxicity, with the highest risk in children under two and in polytherapy; 65 co-reports give PRR 3.0. A boxed warning mandates baseline and periodic liver-function testing, and the drug is stopped if hepatic injury is suspected.
Regulatory basis: valproate prescribing information — boxed warning for hepatotoxicity; liver-function monitoring.
| Bradford Hill viewpoint | Status | Note |
|---|---|---|
| Temporality (necessary) | met | Can be rapid in high-risk patients |
| Strength | met | PRR 3.0 with 65 co-reports |
| Consistency | met | Reproduced across cohorts |
| Specificity | met | Highest in defined risk groups |
| Biological gradient | met | Dose and age related |
| Plausibility | met | Known mitochondrial/β-oxidation toxicity |
| Coherence | met | Fits valproate's metabolic profile |
| Experiment | n/a | Too rare and severe for trial capture |
| Analogy | met | Analogous to other antiepileptic hepatotoxins |
This table is this page's own qualitative read of the literature cited above, not an automated or citation-gated assessment — see the note at the bottom of this page.
✗ No ClinicalTrials.gov results-posting trial in the top search hits for valproate captured hepatotoxicity as a tracked adverse event in a usable structure. Trials excluded the youngest, highest-risk children and were too small for rare hepatic failure.