To the Editor:
We read with interest the article by McGovern et al. in which they studied the ratio of aspartate aminotransferase (AST) to alanine aminotransferase (ALT) when examining recovery from paracetamol poisoning in 37 patients, and determining when to stop treatment with acetylcysteine (NAC).Citation1 These patients are described as having “severe paracetamol poisoning” based on the ALT or AST level > 1000 IU/L. As such they are a small proportion of all paracetamol overdose patients. In patients with more severe liver injury ALT is a weak marker of prognosis, and it is normal to consider markers that reflect hepatic synthetic function, normally international normalized ratio (INR), or other organ damage, particularly renal injury.Citation2,Citation3 The authors limit the ability of others to assess their work by not including such additional data, which should ideally be provided.
They have used a receiver operating characteristic or ROC methodology, but exclude 296 patients of their series, as they had ALT less than 1000 IU/L. This makes the interpretation even more challenging.
AST in relatively non-specific, being present in multiple cell types outside the liver. This is likely to limit its utility and new biomarkers with enhanced liver specificity are in clinical development (e.g., miR-122).Citation4 In many countries AST is not routinely measured, and decisions to stop NAC rely on whether patients’ ALT is improving and the progression of INR is in a favorable direction. Decisions on when to stop NAC are in general made in patients with far less severe liver injury than that reported here. It would be useful to know whether any patients in whom ALT began to decline subsequently deteriorated again, and how the patients’ INR related to the findings in this paper. Obviously, NAC may impair INRCitation5 and this information on the case series would be informative.
Declaration of interest
The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.
References
- McGovern AJ, Vitkovitsky IV, Jones DL, Mullins ME. Can AST/ALT ratio indicate recovery after acute paracetamol poisoning? Clin Toxicol 2015; 53:164–167.
- Ferner RE, Dear JW, Bateman DN. Management of paracetamol poisoning. BMJ 2011; 342:d2218.
- Pakravan N, Simpson KJ, Waring WS, Bates CM, Bateman DN. Renal injury at first presentation as a predictor for poor outcome in severe paracetamol poisoning referred to a liver transplant unit. EurJ Clin Pharmacol 2009; 65:163–168.
- Antoine DJ, Dear JW, Lewis PS, Platt V, Coyle J, Masson M, et al. Mechanistic biomarkers provide early and sensitive detection of acetaminophen-induced acute liver injury at first presentation to hospital. Hepatology 2013; 58:777–787.
- Whyte IM, Buckley NA, Reith DM, Goodhew I, Seldon M, Dawson AH. Acetaminophen causes an increased international normalized ratio by reducing functional factor VII. Ther Drug Monit 2000; 22:742–748.