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What this is
This is a case report discussing potential long-term liver safety concern in some children treated with high-dose pyridoxal-5′-phosphate (PLP). CurePDE shares this to keep our community informed, not to provide treatment guidance.
Paper links:
Key points
- A small report described 4 children with vitamin B6-dependent epilepsies who received long-term, high-dose oral PLP.
- The children had different underlying diagnoses (PNPO deficiency and ALDH7A1 deficiency), but shared prolonged PLP exposure.
- Three of the four children developed hepatocellular carcinoma (a type of liver cancer) after several years of PLP treatment; one had severe liver injury that was reversible.
- The paper cannot prove PLP caused these outcomes, but it raises an important safety signal that deserves attention and follow-up research.
- The authors recommend regular liver monitoring for patients receiving chronic PLP and call for standardized, high-quality PLP preparations.
- Do not start, stop, or change any medication based on this post; if you have questions, discuss them with your clinical team (for example: what formulation is used, how dosing is scheduled, and what liver monitoring is appropriate).
Technical appendix
What was studied
A case series of four pediatric patients treated with long-term high-dose PLP for vitamin B6-dependent epilepsies. Two had genetically confirmed PNPO deficiency and two were later diagnosed with ALDH7A1 deficiency. The report describes liver outcomes over years of treatment and notes frequent formulation changes due to availability.
What was found
Across the four patients:
- 3 developed hepatocellular carcinoma after several years of PLP therapy.
- 1 developed severe hepatotoxicity that was reported as fully reversible.
The authors discuss plausible mechanisms for PLP-related toxicity (including mitochondrial dysfunction and reactive degradation products) and note that, in two patients, increasing dosing frequency allowed a >30% reduction in total daily PLP dose without apparent loss of seizure control.
Limitations
- Very small sample size (n=4) and observational design; it cannot establish causation.
- Potential confounding (including underlying disease factors and other exposures) is difficult to fully rule out in a case series.
- Formulation variability and dose history details may affect interpretation and generalizability.
What this does NOT mean
- This is not medical advice.
- This does not mean any treatment should be started, stopped, or changed.
- This does not mean PLP is unsafe for every patient or that any individual patient will have the same outcome.
References
- Hepatocellular Carcinoma: A Critical Complication in Patients Treated with Pyridoxal Phosphate. DOI: 10.1055/a-2773-6076. PMID: 41429136. Source: https://pubmed.ncbi.nlm.nih.gov/41429136/
