Letter: Unmasking the Risks—The Need for Robust Data on Baclofen in Cirrhotic Patients. Authors' Reply

We thank Dr. Salman for their interest in our study and for highlighting the ongoing challenges in managing alcohol-associated liver disease (ALD) [1]. We agree that alcohol abstinence remains the cornerstone in the management and treatment of patients with ALD. Pharmacotherapeutic options for alcohol use disorder (AUD) in patients with cirrhosis are limited. In this context, our study sought to provide comparative real-world safety data for baclofen and acamprosate, two medications often used in this population [2]. Our findings suggest that acamprosate may be associated with a lower risk of hepatic encephalopathy compared with baclofen, particularly in patients at higher baseline risk or those receiving concomitant medications such as gabapentin. Importantly, these findings are not and should not be interpreted as a blanket contraindication to baclofen use. Baclofen remains a pharmacotherapy option with strong evidence of safety and efficacy in patients with AUD and comorbid ALD (including cirrhosis) [3, 4] and is a valuable therapeutic option, particularly in patients for whom alternative agents are not suitable [5, 6]. Indeed, the American College of Gastroenterology (ACG) endorses baclofen, and the American Association for the Study of Liver Diseases (AASLD) endorses baclofen and acamprosate in patients with ALD [7, 8]. However, precision medicine approaches are critical for identifying subgroups of patients who may or may not benefit from a given medication, not only in terms of efficacy but also in safety and tolerability. Case in point, our results support a more individualized approach, where patient-specific factors, including prior encephalopathy, comorbidities, and concomitant medications, are carefully considered when selecting pharmacotherapy [9]. We agree that the available evidence remains limited and that further well-designed prospective studies are needed. In the meantime, given that patients with AUD rarely receive treatments, including pharmacotherapies, it is of paramount importance to increase the implementation of pharmacological treatments for AUD in clinical practice. Indeed, increasing the uptake of both pharmacological, behavioral, and psychosocial interventions in patients with AUD and ALD is particularly critical [10], as sustained abstinence offers a meaningful opportunity for clinical improvement and potential recompensation in patients with alcohol-associated cirrhosis. Yee Hui Yeo: writing – original draft. Juan Pablo Arab: writing – review and editing, supervision, conceptualization. Lorenzo Leggio: conceptualization, writing – review and editing, supervision. The authors have nothing to report. Dr. Leggio is supported by the Intramural Research Program of the National Institutes of Health (NIH). The contributions of the NIH author were made as part of their official duties as NIH federal employees, are in compliance with agency policy requirements, and are considered Works of the United States Government. However, the findings and conclusions presented in this paper are those of the authors and do not necessarily reflect the views of the NIH or the U.S. Department of Health and Human Services. This article is linked to Yeo et al. papers. To view these articles, visit https://doi.org/10.1111/apt.70619 and https://doi.org/10.1111/apt.70693. The data that support the findings of this study are available from the corresponding author upon reasonable request.