“Comment on: Does Prior Bariatric Surgery Predispose to Acetaminophen-Related Acute Liver Failure?”

We read with great interest the article titled “Does Prior Bariatric Surgery Predispose to Acetaminophen-Related Acute Liver Failure?” by Tujios et al (1). The topic is highly relevant and timely, particularly in light of the increasing use of glucagon-like peptide-1 (GLP-1) receptor agonists as non-surgical alternatives for weight loss and metabolic regulation. This study not only contributes to our understanding of drug-induced liver injury in patients with altered gastrointestinal physiology after bariatric surgery but also opens new avenues for future research in populations undergoing pharmacologic interventions with similar effects. While the study is commendable in its scope and importance, we would like to express a few concerns. First, the absence of detailed surgical data in most cases—specifically, the type of procedure and the time elapsed since surgery—limits interpretation. Different types of bariatric surgery may have distinct metabolic and pharmacokinetic consequences, which could affect acetaminophen absorption and hepatotoxicity. For instance, studies have demonstrated altered acetaminophen pharmacokinetics after Roux-en-Y gastric bypass, including faster absorption and higher peak plasma levels compared with preoperative values (2). Furthermore, acetaminophen dose estimations were based primarily on patient or caregiver recollection, which is particularly problematic in cases involving hepatic encephalopathy. The potential for recall bias and inaccurate dosing history may have affected the reliability of key findings (3). In such critical clinical scenarios, objective drug level assessments would enhance the accuracy of exposure estimations. In addition, the inclusion of patients with alcohol use complicates the attribution of liver injury solely to acetaminophen. Alcohol is a known inducer of CYP2E1 and may increase the production of the toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI) (4). Moreover, the study did not provide information regarding coadministered medications. Many commonly used drugs (e.g., isoniazid, anticonvulsants) are known to exacerbate acetaminophen hepatotoxicity through various mechanisms (5). A more comprehensive medication history could have helped to control for confounding variables and better delineate the role of bariatric surgery in the observed hepatotoxicity. CONFLICTS OF INTEREST Guarantor of the article: Mehmet Akif Yağli, MD. Specific author contributions: M.A.Y.: conceived the idea for the letter, conducted the literature review, drafted the initial version, and approved the final manuscript. A.Ç.Ö. and S.K.: contributed to the scientific content, performed critical revisions, and approved the final version of the manuscript. Financial support: The authors received no financial support from any institution or organization for the research, authorship, or publication of this article. Potential competing interests: The authors declare no potential conflicts of interest with respect to the research, authorship, or publication of this article.