Comment on: 'Lanthanum carbonate possibly responsible for acute liver failure in a patient with Child-Pugh stage A liver cirrhosis'
Bibliographic record
Abstract
Sir, De Leeuw and colleagues reported decompensation of existing liver disease in a patient with a complex history including alcohol-induced liver cirrhosis, pancreatitis and secondary diabetes [1]. The patient required hospitalization due to decreased consciousness and somnolence. The authors, noting a temporal association with lanthanum carbonate therapy, proposed that there was a causal relationship. This patient report is highly confounded by a number of factors, including concomitant medication and hypophosphataemia, which are also credible explanations for the patient's presentation. Firstly, the patient was taking lorazepam, which can cause coma in patients with reduced hepatic metabolism. Secondly, following dialysis the patient was profoundly hypophosphataemic. This is a recognized cause of irritability, paraesthaesia, confusion, convulsions and coma [2]. Evaluation of the published data on lanthanum carbonate (FOSRENOL®, Shire Pharmaceuticals, Basingstoke, UK) shows that the bioavailability is ∼0.001% and the small fraction of lanthanum absorbed is not metabolized. Animal studies have demonstrated that the presence of lanthanum in the liver is consistent with hepatic excretion via a lysosomal transcellular transport mechanism [3,4]. A long-term follow-up of clinical trial cohorts has included liver function tests and has not demonstrated any evidence of acute or chronic liver toxicity during 2 years of therapy compared to standard therapy. In uncontrolled studies, subjects have been exposed to lanthanum carbonate for up to 6 years [5,6]. In addition to over 5000 subjects in clinical studies, there is now over 60000 patient-years of post-marketing experience with lanthanum carbonate. Although no specific studies were done in patients with liver impairment, there is insufficient evidence to assume that lanthanum carbonate may contribute to a worsening of liver function in this patient population. Conflict of interest statement. M.S., B.G. and R.D.P. are employees of Shire Pharmaceuticals. Editorial Note: Dr De Leeuw et al. had been invited to reply to this letter but we did not receive a response in time.
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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 | 0.015 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.001 | 0.003 |
| Open science | 0.003 | 0.001 |
| Research integrity | 0.029 | 0.020 |
| Insufficient payload (model declined to judge) | 0.006 | 0.004 |
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".